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Lin F, Luo H, Wang J, Li Q, Zha L. Macrophage-derived extracellular vesicles as new players in chronic non-communicable diseases. Front Immunol 2025; 15:1479330. [PMID: 39896803 PMCID: PMC11782043 DOI: 10.3389/fimmu.2024.1479330] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2024] [Accepted: 12/23/2024] [Indexed: 02/04/2025] Open
Abstract
Macrophages are innate immune cells present in all tissues and play an important role in almost all aspects of the biology of living organisms. Extracellular vesicles (EVs) are released by cells and transport their contents (micro RNAs, mRNA, proteins, and long noncoding RNAs) to nearby or distant cells for cell-to-cell communication. Numerous studies have shown that macrophage-derived extracellular vesicles (M-EVs) and their contents play an important role in a variety of diseases and show great potential as biomarkers, therapeutics, and drug delivery vehicles for diseases. This article reviews the biological functions and mechanisms of M-EVs and their contents in chronic non-communicable diseases such as cardiovascular diseases, metabolic diseases, cancer, inflammatory diseases and bone-related diseases. In addition, the potential application of M-EVs as drug delivery systems for various diseases have been summarized.
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Affiliation(s)
- Fengjuan Lin
- Department of Nutrition and Food Hygiene, Guangdong Provincial Key Laboratory of Tropical Disease Research, National Medical Products Administration (NMPA) Key Laboratory for Safety Evaluation of Cosmetics, School of Public Health, Southern Medical University, Guangzhou, Guangdong, China
| | - Huiyu Luo
- Department of Nutrition and Food Hygiene, Guangdong Provincial Key Laboratory of Tropical Disease Research, National Medical Products Administration (NMPA) Key Laboratory for Safety Evaluation of Cosmetics, School of Public Health, Southern Medical University, Guangzhou, Guangdong, China
| | - Jiexian Wang
- Department of Nutrition and Food Hygiene, Guangdong Provincial Key Laboratory of Tropical Disease Research, National Medical Products Administration (NMPA) Key Laboratory for Safety Evaluation of Cosmetics, School of Public Health, Southern Medical University, Guangzhou, Guangdong, China
| | - Qing Li
- Department of Clinical Nutrition, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Longying Zha
- Department of Nutrition and Food Hygiene, Guangdong Provincial Key Laboratory of Tropical Disease Research, National Medical Products Administration (NMPA) Key Laboratory for Safety Evaluation of Cosmetics, School of Public Health, Southern Medical University, Guangzhou, Guangdong, China
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Joseph EA, Allen CJ. Long-Term Quality of Life and Survivorship Priorities in Esophageal Cancer Patients: A Survey-Based Assessment. J Surg Oncol 2024. [PMID: 39702855 DOI: 10.1002/jso.28045] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2024] [Revised: 11/04/2024] [Accepted: 12/03/2024] [Indexed: 12/21/2024]
Abstract
BACKGROUND AND OBJECTIVES This study examines the long-term quality of life (QOL) and priorities of survivors who underwent management for esophageal cancer (EC). METHODS We cross-sectionally surveyed EC patients through online support groups to assess the relative importance of their overall survival, experience, costs of care, and QOL. Kendall's co-efficient of Concordance (W) was utilized to assess agreement among respondents. RESULTS Among 100 respondents (age 57.2 ± 10.4 years, 54% male, 90% Caucasian), median overall survival was 18.0 (7.8-49.8) months, with a maximum survivorship of 48.3 years. Respondents ranked overall survival most important, followed by functional independence, emotional well-being, treatment experience, and costs of care (W = 0.342, p < 0.001). Some survivors ranked treatment experience (4%) or costs (6%) as their most important priority. The cohort's physical QOL (P-QOL; 39.79 ± 10.16) and mental QOL (M-QOL; 42.29 ± 15.43) were below that of the general population (50.00 ± 10.00); both p < 0.050. There was no difference in P-QOL and M-QOL based on the presence of metastatic disease (both p > 0.050). Patients who underwent curative surgery had superior M-QOL (45.00 ± 15.22 vs. 36.70 ± 14.53, p = 0.010). Although P-QOL was similar based on duration of survival (40.30 ± 9.75 [< 1 year], 39.33 ± 10.52 [1-5 years], 39.81 ± 10.68 [> 5 years], p = 0.873), M-QOL was higher in patients with extended survivorship (36.87 ± 14.24 [< 1 year], 45.05 ± 14.94 [1-5 years], 47.30 ± 16.36 [> 5 years], p = 0.008). CONCLUSIONS Despite enduring physical health impairments, a majority of EC survivors prioritized their survival. However, a few survivors prioritized costs and treatment experience, underscoring the importance of tailoring treatments to ensure alignment with individual patient-driven priorities.
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Affiliation(s)
- Edward A Joseph
- Division of Surgical Oncology, Allegheny Health Network Singer Research Institute, Pittsburgh, Pennsylvania, USA
| | - Casey J Allen
- Division of Surgical Oncology, Institute of Surgery, Allegheny Health Network Cancer Institute, Pittsburgh, Pennsylvania, USA
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Mudiyanselage SB, Nguyen D, Tang B, Williams R, Kamal M, Zhao FL, Gao L. The epidemiological trends and predictions of esophageal squamous cell carcinoma and gastroesophageal junction carcinoma: an Australian population-based study. BMC Cancer 2024; 24:1498. [PMID: 39639209 PMCID: PMC11619256 DOI: 10.1186/s12885-024-13151-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2024] [Accepted: 11/05/2024] [Indexed: 12/07/2024] Open
Abstract
BACKGROUND Gastroesophageal junction carcinoma (GEJC) and esophageal squamous cell carcinoma (ESCC) are increasing in Australia and other Western countries. We aimed to investigate past trends and predict the future direction of GEJC and ESCC cases. METHODS Data on GEJC and ESCC were extracted from the Australian Cancer Database, and the National Mortality Database for the Australian states of Victoria, Queensland, Tasmania, and the Australian Capital Territory. The new number of cases were predicted up to 2039 by fitting a least squares linear regression using the Australian incidence rates trend from 2009 to 2018. Past trends were analyzed for prevalence and mortality. Kaplan-Meier curves generated the survival trend for up to 10 years. RESULTS Between 2009 and 2018, the overall incidences of GEJC showed an increasing trend (annual change [β1] = 0.87, P < 0.05). For GEJC, the rates of incidence, prevalence, and mortality were higher in men (β1 = 1.86, 95% CI: 1.29-2.43, P < 0.05; β1 = 14.45, 95% CI: 12.93-15.98, P < 0.05; β1 = 1.04, 95% CI: - 0.68 to 2.76, P = 0.195, respectively) than in women. By 2039, it is estimated that 6 in 100,000 population will be newly diagnosed with GEJC. Notably, the rate of new GEJC cases decreased in women during the study period (β1=-0.08, 95% CI: - 0.39 to 0.24, P = 0.596). For ESCC, the incidence rate increased, albeit at a slower rate compared with GEJC (β1 = 0.87, 95% CI: 0.6-1.15, P < 0.05; β1 = 0.03, 95% CI: - 0.28 to 0.34, P = 0.805, respectively). New cases of ESCC in men declined (β1=-0.03, 95% CI: - 0.46 to 0.4, P = 0.884). By 2039, it is predicted that 2 in 100,000 people will be newly diagnosed. The 10-year survival rate for GEJC and ESCC was low (11% and 20%, respectively), while the survival rate for women was relatively higher than for men. CONCLUSION The incidence, prevalence, and mortality would be predicted to increase in 2039 if there were no significant changes in risk factors, diagnosis, treatment, and management compared with 2009-2018. Strategies to identify early signs and enable earlier diagnosis and early and new treatment options are essential in GEJC and ESCC.
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Affiliation(s)
- Shalika Bohingamu Mudiyanselage
- School of Health and Social Development and Deakin Health Economics, Institute for Health Transformation, Deakin University, Geelong, VIC, Australia
| | - Dieu Nguyen
- School of Health and Social Development and Deakin Health Economics, Institute for Health Transformation, Deakin University, Geelong, VIC, Australia
| | | | | | - Mostafa Kamal
- Deakin Business School, Deakin University, Geelong, VIC, Australia
| | - Fei-Li Zhao
- BeiGene AUS PTY Ltd, Sydney, NSW, Australia.
| | - Lan Gao
- School of Health and Social Development and Deakin Health Economics, Institute for Health Transformation, Deakin University, Geelong, VIC, Australia.
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Wang YK, Karmakar R, Mukundan A, Men TC, Tsao YM, Lu SC, Wu IC, Wang HC. Computer-aided endoscopic diagnostic system modified with hyperspectral imaging for the classification of esophageal neoplasms. Front Oncol 2024; 14:1423405. [PMID: 39687890 PMCID: PMC11646837 DOI: 10.3389/fonc.2024.1423405] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2024] [Accepted: 11/04/2024] [Indexed: 12/18/2024] Open
Abstract
Introduction The early detection of esophageal cancer is crucial to enhancing patient survival rates, and endoscopy remains the gold standard for identifying esophageal neoplasms. Despite this fact, accurately diagnosing superficial esophageal neoplasms poses a challenge, even for seasoned endoscopists. Recent advancements in computer-aided diagnostic systems, empowered by artificial intelligence (AI), have shown promising results in elevating the diagnostic precision for early-stage esophageal cancer. Methods In this study, we expanded upon traditional red-green-blue (RGB) imaging by integrating the YOLO neural network algorithm with hyperspectral imaging (HSI) to evaluate the diagnostic efficacy of this innovative AI system for superficial esophageal neoplasms. A total of 1836 endoscopic images were utilized for model training, which included 858 white-light imaging (WLI) and 978 narrow-band imaging (NBI) samples. These images were categorized into three groups, namely, normal esophagus, esophageal squamous dysplasia, and esophageal squamous cell carcinoma (SCC). Results An additional set comprising 257 WLI and 267 NBI images served as the validation dataset to assess diagnostic accuracy. Within the RGB dataset, the diagnostic accuracies of the WLI and NBI systems for classifying images into normal, dysplasia, and SCC categories were 0.83 and 0.82, respectively. Conversely, the HSI dataset yielded higher diagnostic accuracies for the WLI and NBI systems, with scores of 0.90 and 0.89, respectively. Conclusion The HSI dataset outperformed the RGB dataset, demonstrating an overall diagnostic accuracy improvement of 8%. Our findings underscored the advantageous impact of incorporating the HSI dataset in model training. Furthermore, the application of HSI in AI-driven image recognition algorithms significantly enhanced the diagnostic accuracy for early esophageal cancer.
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Affiliation(s)
- Yao-Kuang Wang
- Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Riya Karmakar
- Department of Mechanical Engineering, National Chung Cheng University, Chiayi, Taiwan
| | - Arvind Mukundan
- Department of Mechanical Engineering, National Chung Cheng University, Chiayi, Taiwan
| | - Ting-Chun Men
- Department of Mechanical Engineering, National Chung Cheng University, Chiayi, Taiwan
| | - Yu-Ming Tsao
- Department of Mechanical Engineering, National Chung Cheng University, Chiayi, Taiwan
| | - Song-Cun Lu
- Department of Mechanical Engineering, National Chung Cheng University, Chiayi, Taiwan
| | - I-Chen Wu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Hsiang-Chen Wang
- Department of Mechanical Engineering, National Chung Cheng University, Chiayi, Taiwan
- Department of Medical Research, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
- Technology Development, Hitspectra Intelligent Technology Co., Ltd., Kaohsiung, Taiwan
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Kunath BJ, De Rudder C, Laczny CC, Letellier E, Wilmes P. The oral-gut microbiome axis in health and disease. Nat Rev Microbiol 2024; 22:791-805. [PMID: 39039286 DOI: 10.1038/s41579-024-01075-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/25/2024] [Indexed: 07/24/2024]
Abstract
The human body hosts trillions of microorganisms throughout many diverse habitats with different physico-chemical characteristics. Among them, the oral cavity and the gut harbour some of the most dense and diverse microbial communities. Although these two sites are physiologically distinct, they are directly connected and can influence each other in several ways. For example, oral microorganisms can reach and colonize the gastrointestinal tract, particularly in the context of gut dysbiosis. However, the mechanisms of colonization and the role that the oral microbiome plays in causing or exacerbating diseases in other organs have not yet been fully elucidated. Here, we describe recent advances in our understanding of how the oral and intestinal microbiota interplay in relation to their impact on human health and disease.
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Affiliation(s)
- Benoit J Kunath
- Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg.
| | - Charlotte De Rudder
- Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
| | - Cedric C Laczny
- Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
| | - Elisabeth Letellier
- Department of Life Sciences and Medicine, Faculty of Science, Technology and Medicine, University of Luxembourg, Belvaux, Luxembourg
| | - Paul Wilmes
- Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg.
- Department of Life Sciences and Medicine, Faculty of Science, Technology and Medicine, University of Luxembourg, Belvaux, Luxembourg.
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Mylonakis A, Frountzas M, Lidoriki I, Kozadinos A, Kalfoutzou A, Karanikki E, Tsikrikou I, Kyriakidou M, Theodorou D, Toutouzas KG, Schizas D. The Role of Chemerin in Upper Gastrointestinal Cancer. Metabolites 2024; 14:599. [PMID: 39590835 PMCID: PMC11596733 DOI: 10.3390/metabo14110599] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2024] [Revised: 10/20/2024] [Accepted: 10/29/2024] [Indexed: 11/28/2024] Open
Abstract
Background/Objectives: Chemerin, which is a multifunctional cytokine and adipokine, has been implicated in inflammatory and metabolic processes and might play a role in upper gastrointestinal (GI) malignancies, particularly gastric and esophageal cancer. The aim of this review is to explore the role of chemerin in the pathophysiology of upper GI cancers, as well as its potential as a biomarker for early detection and as a therapeutic target. Methods: A comprehensive review of recent studies about chemerin's biochemical properties and interaction with its receptors, as well as its effects on inflammatory responses, immune regulation, and metabolic processes, was conducted. The clinical implications of chemerin for gastric and esophageal cancer were analyzed, whereas the potential therapeutic strategies targeting chemerin were discussed. Results: Elevated chemerin levels are associated with poor prognosis in gastric cancer and promote invasiveness and metastasis in esophageal cancer. Chemerin receptor antagonists show promising results in inhibiting cancer cell migration, invasion, and progression. Conclusions: Chemerin could represent a valuable prognostic biomarker and therapeutic target for upper GI cancers. Future observational studies should validate its clinical applications and investigate the efficacy of chemerin inhibitors as potential therapeutic targets.
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Affiliation(s)
- Adam Mylonakis
- First Department of Surgery, Laikon General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece; (A.M.); (A.K.); (I.T.); (M.K.); (D.S.)
| | - Maximos Frountzas
- First Propaedeutic Department of Surgery, Hippocration General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece; (M.F.); (D.T.); (K.G.T.)
| | - Irene Lidoriki
- First Department of Surgery, Laikon General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece; (A.M.); (A.K.); (I.T.); (M.K.); (D.S.)
- Department of Environmental, Occupational Medicine and Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02139, USA
- Department of Occupational Medicine, Cambridge Health Alliance, Harvard Medical School, Cambridge, MA 02139, USA
| | - Alexandros Kozadinos
- First Department of Surgery, Laikon General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece; (A.M.); (A.K.); (I.T.); (M.K.); (D.S.)
| | - Areti Kalfoutzou
- Department of Oncology, 251 Air Force General Hospital, 11525 Athens, Greece
| | - Eva Karanikki
- First Propaedeutic Department of Surgery, Hippocration General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece; (M.F.); (D.T.); (K.G.T.)
| | - Iliana Tsikrikou
- First Department of Surgery, Laikon General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece; (A.M.); (A.K.); (I.T.); (M.K.); (D.S.)
| | - Maria Kyriakidou
- First Department of Surgery, Laikon General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece; (A.M.); (A.K.); (I.T.); (M.K.); (D.S.)
| | - Dimitrios Theodorou
- First Propaedeutic Department of Surgery, Hippocration General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece; (M.F.); (D.T.); (K.G.T.)
| | - Konstantinos G. Toutouzas
- First Propaedeutic Department of Surgery, Hippocration General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece; (M.F.); (D.T.); (K.G.T.)
| | - Dimitrios Schizas
- First Department of Surgery, Laikon General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece; (A.M.); (A.K.); (I.T.); (M.K.); (D.S.)
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Tahaseen SM, Kirti R, Kumar R, Pandey S, Rao R, Kumar A, Arya R, Maji T, Biswas R. Gastrointestinal pathology in patients presenting with iron deficiency anaemia: A single-centre cross-sectional study. J Family Med Prim Care 2024; 13:5341-5348. [PMID: 39722951 PMCID: PMC11668466 DOI: 10.4103/jfmpc.jfmpc_1150_24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Revised: 08/13/2024] [Accepted: 08/20/2024] [Indexed: 12/28/2024] Open
Abstract
Background About a third of the world's population is estimated to suffer from anaemia, and iron deficiency is expected to account for about half of all anaemia cases. This study was designed to get an estimate of the proportion of patients with iron deficiency anaemia (IDA) who have a significant gastrointestinal (GI) pathology, in particular a GI malignancy, and to identify any risk factors or predictors for the same. Methods This cross-sectional study was conducted at a hospital in Eastern India. The study population comprised males above the age of 18 and postmenopausal females with IDA, excluding those haemodynamically unstable or with chronic diseases. Data collection included a detailed history, sociodemographic details, dietary habits, GI symptoms, and severity of anaemia. Faecal occult blood tests (OBTs) were conducted, and patients were referred for upper and lower GI endoscopy with biopsies. Results Out of the 257 patients, 50.97% (n = 131) had a significant GI pathology, and 25.68% (n = 66) had a GI malignancy. Male gender (AOR: 5.203, 95% CI: 1.725-15.698) and a positive stool OBT (AOR: 6.516, 95% CI: 2.255-18.828) were found to be independent risk factors for any GI pathology. Age 40 years or above (AOR: 11.376, 95% CI: 1.199-107.946), loss of appetite (AOR: 15.548, 95% CI: 1.416-170.735), pain abdomen (AOR: 5.566, 95% CI: 1.149-26.953), dysphagia (AOR: 7.945, 95% CI: 1.036-60.915), family history of malignancy (AOR: 46.726, 95% CI: 4.076-535.645), and positive OBT (AOR: 22.430, 95% CI: 3.933-127.915) were found to be independent risk factors of GI malignancy. Conclusions This study shows that a large proportion of adult males and postmenopausal females presenting with IDA in India have significant GI pathology. Furthermore, a significant proportion of them have GI malignancies. Thus, bidirectional endoscopy should be considered for these patients. Male patients, age >40, those with history of loss of appetite or weight, pain abdomen or dysphagia, positive family history, and positive OBT should be prioritised for the investigation.
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Affiliation(s)
- Shaik Mohammad Tahaseen
- Department of General Medicine, All India Institute of Medical Sciences, Patna, Bihar, India
| | - Ravi Kirti
- Department of General Medicine, All India Institute of Medical Sciences, Patna, Bihar, India
| | - Ramesh Kumar
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna, Bihar, India
| | - Sanjay Pandey
- Department of Community and Family Medicine, All India Institute of Medical Sciences, Patna, Bihar, India
| | - Rajath Rao
- Department of Community Medicine, Kasturba Medical College, Mangalore, Karnataka, India
| | - Anjani Kumar
- Department of General Medicine, All India Institute of Medical Sciences, Patna, Bihar, India
| | - Rahul Arya
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna, Bihar, India
| | - Tanmoy Maji
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna, Bihar, India
| | - Ratnadeep Biswas
- Department of General Medicine, All India Institute of Medical Sciences, Patna, Bihar, India
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He J, Liang G, Yu H, Shen W, Pimiento JM, Anker CJ, Koyanagi K, Liu J, Hu J. Two versus three to four cycles of neoadjuvant immunochemotherapy for locally advanced esophageal squamous cell carcinoma in real-world practice. J Thorac Dis 2024; 16:6999-7015. [PMID: 39552907 PMCID: PMC11565352 DOI: 10.21037/jtd-24-1365] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2024] [Accepted: 09/25/2024] [Indexed: 11/19/2024]
Abstract
Background There is currently no consensus on whether intensive cycles of neoadjuvant immunochemotherapy provide greater benefit than do less intensive cycles (two cycles) in esophageal cancer (EC). Therefore, in this study, we assessed the efficacy and safety of three to four cycles of neoadjuvant immunochemotherapy compared to two cycles for treating patients with locally advanced esophageal squamous cell carcinoma (ESCC). Methods This is a retrospective study of patients enrolled on previous clinical studies involving locally/regionally advanced ESCC (St. II-IVA) who received preoperative immunochemotherapy at the Department of Thoracic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine from 2019 to 2021. In this study, patients were planned to receive 2-4 cycles of chemoimmunotherapy. In this secondary analysis, patients who received three to four cycles of neoadjuvant immunochemotherapy were compared to those receiving two cycles in terms of safety and oncologic outcomes. The follow-up duration required for inclusion was at least one year following surgery, or until the patient died or independently elected to cease treatment if less than one year. Results Our study identified a total of 142 participants, who were categorized into two groups based on the number of neoadjuvant treatment cycles: the two cycles group (2 cycles) (n=65) and the three to four cycles group (3-4 cycles) (n=77). Regarding the rate of major pathologic response (MPR), the rates for the 3-4 cycles and 2 cycles groups were 22.1% and 20.0%, respectively, although this difference was not statistically significant (P=0.25). Similarly, the rate of pathologic complete remission (pCR) was higher in the 3-4 cycles group at 14.3% compared to 7.7% in the 2 cycles group, but the difference did not reach statistical significance (P=0.07). However, the incidence of adverse events (AEs) classified as grade 3 or 4 was significantly higher in the 3-4 cycles group than in the 2 cycles group (36.4% vs. 18.5%; P=0.02). The median disease-free survival (DFS) for the 3-4 cycles group was 30.8 months [95% confidence interval (CI): not reached to not reached] and was not reached in the 2 cycles group (hazard ratio 2.35, 95% CI: 1.134-4.86; P=0.02). The 2 cycles group did not reach the median overall survival (OS) (hazard ratio 2.47, 95% CI: 1.08-5.53; P=0.045), with that in the 3-4 cycles group 34.9 months (95% CI: 24.5 to not reached). Interestingly, the survival outcomes were more favorable in the 2 cycles group for certain subgroups of patients: those who were male, those with a history of smoking, those with a history of drinking, and those who did not achieve MPR. Conclusions Two cycles of neoadjuvant immunochemotherapy can be considered in locally advanced ESCC at high risk of developing toxicity with 3-4 cycles with similar oncologic outcomes.
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Affiliation(s)
- Jinxian He
- Department of Thoracic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Department of Thoracic Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo University, Ningbo, China
| | - Gaofeng Liang
- Department of Thoracic Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo University, Ningbo, China
| | - Hongyan Yu
- Department of Thoracic Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo University, Ningbo, China
| | - Weiyu Shen
- Department of Thoracic Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo University, Ningbo, China
| | - Jose M. Pimiento
- Department of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, FL, USA
| | - Christopher J. Anker
- Division of Radiation Oncology, University of Vermont Cancer Center, Burlington, VT, USA
| | - Kazuo Koyanagi
- Department of Gastroenterological Surgery, Tokai University School of Medicine, Kanagawa, Japan
| | - Jiacong Liu
- Department of Thoracic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jian Hu
- Department of Thoracic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Key Laboratory of Clinical Evaluation Technology for Medical Device of Zhejiang Province, Hangzhou, China
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Cao Y, Hu Q, Zhang Y, Li C, Zhou Y, Zhang Y, Qiu H, Li H. A propensity score-matched analysis to evaluate the benefit of adjuvant therapy on disease recurrence of esophageal squamous cell carcinoma after R0 esophagectomy. J Thorac Dis 2024; 16:6651-6663. [PMID: 39552908 PMCID: PMC11565312 DOI: 10.21037/jtd-24-806] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2024] [Accepted: 08/30/2024] [Indexed: 11/19/2024]
Abstract
Background Esophageal squamous cell carcinoma (ESCC) is common in China and has a poor prognosis despite radical surgery. Guidelines around the use of adjuvant therapy (AT) in ESCC are indecisive. We assessed the benefit of AT on recurrence-free survival (RFS) in Chinese patients with ESCC using propensity score (PS) matching. Methods This retrospective cohort study used hospital electronic medical records (EMRs) of 523 adults diagnosed between 2013 to 2019 with pathologically confirmed ESCC after R0 esophagectomy without neoadjuvant therapy. PSs were calculated using a generalized linear regression model based on demographic, clinical, and pathologic features. Patients with and without AT were matched using nearest neighbor method and caliper value 0.05. Subgroup analyses were stratified by PS. Results Younger patients with more advanced/poorly differentiated disease were more likely to receive AT (P<0.05). There were 137 matched pairs in the AT/No AT groups. After matching, the AT group tended to have longer median RFS [95% confidence interval (CI): 2.21 years (1.54-3.20)] than the No AT group [1.75 years (1.37-2.21)] (P=0.18). The benefit was significant in patients with PS ≥0.40 [hazard ratio 0.55, 95% CI: 0.32-0.87, median RFS (95% CI): 2.22 years (1.30-3.52) versus 1.23 years (0.90-1.64), P=0.03]. In other PS subgroups, median RFS was similar in AT and No AT groups. Conclusions After adjusting for baseline characteristics, AT tended to improve RFS after R0 esophagectomy in Chinese patients, with significant benefit associated with a higher PS score. The utility of PS to guide patient selection for AT in clinical practice needs further investigation.
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Affiliation(s)
- Yuqin Cao
- Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Qingqing Hu
- Global Epidemiology, Office of Chief Medical Officer, Johnson & Johnson, Shanghai, China
| | - Yajie Zhang
- Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Chengqiang Li
- Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yuan Zhou
- Johnson & Johnson Medical (Shanghai) Ltd., Shanghai, China
| | - Yongjing Zhang
- Global Epidemiology, Office of Chief Medical Officer, Johnson & Johnson, Shanghai, China
| | - Hong Qiu
- Global Epidemiology, Office of Chief Medical Officer, Johnson & Johnson, Titusville, NJ, USA
| | - Hecheng Li
- Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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10
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Zhang S, Zhang X, Xiahou Z, Zuo S, Xue J, Zhang Y. Unraveling the ecological landscape of mast cells in esophageal cancer through single-cell RNA sequencing. Front Immunol 2024; 15:1470449. [PMID: 39430754 PMCID: PMC11486721 DOI: 10.3389/fimmu.2024.1470449] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2024] [Accepted: 09/13/2024] [Indexed: 10/22/2024] Open
Abstract
Background Esophageal cancer (EC) is a major health issue, ranking seventh in incidence and sixth in mortality worldwide. Despite advancements in multidisciplinary treatment approaches, the 5-year survival rate for EC remains low at 21%. Challenges in EC treatment arise from late-stage diagnosis, high malignancy, and poor prognosis. Understanding the tumor microenvironment is critical, as it includes various cellular and extracellular components that influence tumor behavior and treatment response. Mast cells (MCs), as tissue-resident immune cells, play dual roles in tumor dynamics. High-throughput single-cell RNA sequencing offers a powerful tool for analyzing tumor heterogeneity and immune interactions, although its application in EC is limited. Methods In this study, we investigated the immune microenvironment of EC using single-cell RNA sequencing and established a comprehensive immune profile. We also performed analysis of upstream transcription factors and downstream pathway enrichment to further comprehensively decipher MCs in EC. Besides, we performed knockdown experiments to explore the role of epidermal growth factor receptor (EGFR) signaling pathway in MCs-tumor cell interactions, highlighting its potential as a prognostic marker. Finally, we constructed a prognostic model for EC, which provided valuable suggestions for the diagnosis and prognosis of EC. Results Our analysis identified 11 major cell types, of which MCs were particularly present in pericarcinoma tissues. Further grouping of the 5,001 MCs identified 8 distinct subtypes, including SRSF7-highly expressed MCs, which showed strong tumor preference and potential tumor-promoting properties. Moreover, we identified the key signaling receptor EGFR and validated it by in vitro knockdown experiments, demonstrating its cancer-promoting effects. In addition, we established an independent prognostic indicator, SRSF7+ MCs risk score (SMRS), which showed a correlation between high SMRS group and poor prognosis. Conclusion These findings illuminate the complex interactions within the tumor microenvironment of EC and suggest that targeting specific MCs subtypes, particularly via the EGFR signaling pathway, may present novel therapeutic strategies. This study establishes a comprehensive immune map of EC, offering insights for improved treatment approaches.
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Affiliation(s)
- Shengyi Zhang
- Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xinyi Zhang
- Clinical Medical College, Southwest Medical University, Luzhou, China
| | - Zhikai Xiahou
- China Institute of Sport and Health Science, Beijing Sport University, Beijing, China
| | - Shunqing Zuo
- Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jialong Xue
- Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yi Zhang
- Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
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11
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Tustumi F, Eri RY, Wende KW, Nakamura ET, Usón Junior PLS, Szor DJ. Disparities in esophageal cancer care: a population-based study. J Gastrointest Surg 2024; 28:1674-1681. [PMID: 39079844 DOI: 10.1016/j.gassur.2024.07.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2024] [Revised: 06/22/2024] [Accepted: 07/04/2024] [Indexed: 10/06/2024]
Abstract
BACKGROUND Vulnerable populations potentially have a worse prognosis for cancer. The present study aimed to identify individual and municipal characteristics of access to health, including education, use of health insurance, gross domestic product per capita (GDPpc), and urban aspects, which could impact the prognosis of patients with esophageal cancer. METHODS Data on urban concentration, administrative hierarchy, GDPpc, individual patient characteristics, and access to healthcare were collected from national and state public databases spanning between 2013 and 2022. The study included cities in the state of Sao Paulo, Brazil. Independent variables such as GDPpc, urban concentration, municipal administrative hierarchy, health insurance status, education level, and individual cancer and patient characteristics were evaluated against the outcomes of overall survival (OS), likelihood of undergoing surgical treatment, and time-to-treatment initiation. RESULTS A total of 9280 patients with esophageal cancer (85% squamous cell carcinoma and 15% adenocarcinoma) treated in 42 cities were included in the study. In univariate analysis, higher education (hazard ratio [HR] = 0.6; P < .001), female gender (HR = 0.85; P < .001), and having private health insurance (HR = 0.65; P < .001) were identified as protective factors for OS in esophageal cancer. After adjusting for other variables in multivariate analysis, higher education (HR = 0.77; P = .009), female gender (HR = 0.82; P < .001), and private insurance (HR = 0.65; P < .001) remained protective factors. GDPpc was not associated with OS. Urban concentration and hierarchy influenced the likelihood of receiving surgical treatment. Patients from high urban concentrations had shorter time-to-treatment initiation intervals. CONCLUSION Populations at risk, particularly those with limited access to education and healthcare, face a worse prognosis for esophageal cancer.
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Affiliation(s)
- Francisco Tustumi
- Department of Health Sciences, Hospital Israelita Albert Einstein, Sao Paulo, Brazil; Department of Gastroenterology, Universidade de São Paulo, Sao Paulo, Brazil.
| | - Ricardo Yugi Eri
- Department of Health Sciences, Hospital Israelita Albert Einstein, Sao Paulo, Brazil
| | - Klaus Werner Wende
- Department of Health Sciences, Hospital Israelita Albert Einstein, Sao Paulo, Brazil
| | | | | | - Daniel José Szor
- Department of Health Sciences, Hospital Israelita Albert Einstein, Sao Paulo, Brazil; Department of Gastroenterology, Universidade de São Paulo, Sao Paulo, Brazil
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12
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Ayoub M, Aibani R, Dodd T, Ceesay M, Bhinder M, Faris C, Amin N, Daglilar E. Risk of Esophageal and Gastric Cancer in Patients with Type 2 Diabetes Receiving Glucagon-like Peptide-1 Receptor Agonists (GLP-1 RAs): A National Analysis. Cancers (Basel) 2024; 16:3224. [PMID: 39335195 PMCID: PMC11430483 DOI: 10.3390/cancers16183224] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2024] [Revised: 09/17/2024] [Accepted: 09/20/2024] [Indexed: 09/30/2024] Open
Abstract
INTRODUCTION Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are becoming more popular in managing type 2 diabetes mellitus (T2DM). Concerns linger over potential links to malignancies like pancreatic and thyroid cancers, requiring more research to clarify their safety profiles. Additionally, evidence suggests GLP-1 RAs may lower colorectal and pancreatic cancer risk, especially in obese and overweight individuals, indicating a protective effect beyond weight loss. Current studies leave a gap in comprehensively understanding cancer risks associated with GLP-1 RAs, which prompts further research to enhance our understanding of their overall safety. METHODS We queried the US Collaborative Network (63 health care organizations) of the TriNetX research database. Patients with T2DM were identified and divided into two cohorts: patients on GLP-1 RAs and patients not on GLP-1 RAs. We excluded tobacco use and alcohol use disorders, obese patients with a body mass index (BMI) of >25 kg/m2, and those with a family history of gastrointestinal malignancy, infectious mononucleosis, chronic gastritis, pernicious anemia, helicobacter pylori infection, or gastroesophageal reflux disease (GERD). We used a 1:1 propensity score matching (PSM) model using patients' baseline characteristics, medications, labs, and genetics. We compared the rate of gastric cancer and esophageal cancer at the seven-year mark. RESULTS A total of 2,748,431 patients with T2DM were identified. Of those, 6% (n = 167,077) were on a GLP-1 RA and 94% (n = 2,581,354) were not on a GLP-1 RA. After PSM, both cohorts included 146,277 patients. Patients with T2DM who were on a GLP-1 RA, compared to those who were not, had a statistically significant lower risk of both gastric cancer (0.05% vs. 0.13%, p < 0.0001) and esophageal cancer (0.04% vs. 0.13%, p < 0.0001) at the seven-year mark. CONCLUSION The use of GLP-1 RAs in patients with T2DM does not significantly increase the risk of gastric or esophageal cancer. This finding supports the continued use of GLP-1 analogues as a therapeutic option in managing T2DM, considering their well-established benefits and low risk of complications. Based on the study results, these medications may even have a protective effect against these malignancies.
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Affiliation(s)
- Mark Ayoub
- Department of Internal Medicine, Charleston Area Medical Center, West Virginia University, Charleston, WV 25304, USA; (R.A.); (T.D.); (M.C.); (M.B.); (N.A.)
| | - Rafi Aibani
- Department of Internal Medicine, Charleston Area Medical Center, West Virginia University, Charleston, WV 25304, USA; (R.A.); (T.D.); (M.C.); (M.B.); (N.A.)
| | - Tiana Dodd
- Department of Internal Medicine, Charleston Area Medical Center, West Virginia University, Charleston, WV 25304, USA; (R.A.); (T.D.); (M.C.); (M.B.); (N.A.)
| | - Muhammed Ceesay
- Department of Internal Medicine, Charleston Area Medical Center, West Virginia University, Charleston, WV 25304, USA; (R.A.); (T.D.); (M.C.); (M.B.); (N.A.)
| | - Muhammad Bhinder
- Department of Internal Medicine, Charleston Area Medical Center, West Virginia University, Charleston, WV 25304, USA; (R.A.); (T.D.); (M.C.); (M.B.); (N.A.)
| | - Carol Faris
- Department of Internal Medicine, Bayonne Medical Center, Bayonne, NJ 07002, USA;
| | - Nisar Amin
- Department of Internal Medicine, Charleston Area Medical Center, West Virginia University, Charleston, WV 25304, USA; (R.A.); (T.D.); (M.C.); (M.B.); (N.A.)
| | - Ebubekir Daglilar
- Division of Gastroenterology and Hepatology, Charleston Area Medical Center, West Virginia University, Charleston, WV 25304, USA
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13
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Hassan MS, Johnson C, Ponna S, Scofield D, Awasthi N, von Holzen U. Inhibition of Insulin-like Growth Factor 1 Receptor/Insulin Receptor Signaling by Small-Molecule Inhibitor BMS-754807 Leads to Improved Survival in Experimental Esophageal Adenocarcinoma. Cancers (Basel) 2024; 16:3175. [PMID: 39335147 PMCID: PMC11430189 DOI: 10.3390/cancers16183175] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2024] [Revised: 09/04/2024] [Accepted: 09/10/2024] [Indexed: 09/30/2024] Open
Abstract
The insulin-like growth factor-1 (IGF-1) and insulin axes are upregulated in obesity and obesity-associated esophageal adenocarcinoma (EAC). Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) is a contemporary nanotechnology-based paclitaxel (PT) bound to human albumin, ensuring its solubility in water rather than a toxic solvent. Here, we examined the benefits of inhibiting insulin-like growth factor-1 receptor/insulin receptor (IGF-1/IR) signaling and the enhancement of nab-paclitaxel effects by inclusion of the small-molecule inhibitor BMS-754807 using both in vitro and in vivo models of EAC. Using multiple EAC cell lines, BMS-754807 and nab-paclitaxel were evaluated as mono and combination therapies for in vitro effects on cell proliferation, cell death, and cell movement. We then analyzed the in vivo anticancer potency with survival improvement with BMS-754807 and nab-paclitaxel mono and combination therapies. BMS-754807 monotherapy suppressed in vitro cell proliferation and wound healing while increasing apoptosis. BMS-754807, when combined with nab-paclitaxel, enhanced those effects on the inhibition of cell proliferation, increment in cell apoptosis, and inhibition of wound healing. BMS-754807 with nab-paclitaxel produced substantially greater antitumor effects by increasing in vivo apoptosis, leading to increased mice survival compared to those of BMS-754807 or nab-paclitaxel monotherapy. Our outcomes support the use of BMS-754807, alone and in combination with nab-paclitaxel, as an efficient and innovative treatment choice for EAC.
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Affiliation(s)
- Md Sazzad Hassan
- Department of Surgery, Indiana University School of Medicine, South Bend, IN 46617, USA; (N.A.)
- Harper Cancer Research Institute, South Bend, IN 46617, USA
| | - Chloe Johnson
- Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA
| | - Saisantosh Ponna
- Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA
| | - Dimitri Scofield
- Department of Biology, Indiana University, South Bend, IN 47405, USA
| | - Niranjan Awasthi
- Department of Surgery, Indiana University School of Medicine, South Bend, IN 46617, USA; (N.A.)
- Harper Cancer Research Institute, South Bend, IN 46617, USA
| | - Urs von Holzen
- Department of Surgery, Indiana University School of Medicine, South Bend, IN 46617, USA; (N.A.)
- Harper Cancer Research Institute, South Bend, IN 46617, USA
- Goshen Center for Cancer Care, Goshen, IN 46526, USA
- School of Medicine, University of Basel, 4056 Basel, Switzerland
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14
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Yang Z, Liu H, Song Y, Gao N, Gao P, Hui Y, Li Y, Fan T. Luteolin enhances drug chemosensitivity by downregulating the FAK/PI3K/AKT pathway in paclitaxel‑resistant esophageal squamous cell carcinoma. Int J Mol Med 2024; 54:77. [PMID: 38994756 PMCID: PMC11265837 DOI: 10.3892/ijmm.2024.5401] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2024] [Accepted: 06/12/2024] [Indexed: 07/13/2024] Open
Abstract
Drug resistance is a key factor underlying the failure of tumor chemotherapy. It enhances the stem‑like cell properties of cancer cells, tumor metastasis and relapse. Luteolin is a natural flavonoid with strong anti‑tumor effects. However, the mechanism(s) by which luteolin protects against paclitaxel (PTX)‑resistant cancer cell remains to be elucidated. The inhibitory effect of luteolin on the proliferation of EC1/PTX and EC1 cells was detected by cell counting kit‑8 assay. Colony formation and flow cytometry assays were used to assess clonogenic capacity, cell cycle and apoptosis. Wound healing and Transwell invasion tests were used to investigate the effects of luteolin on the migration and invasion of EC1/PTX cells. Western blotting was used to detect the protein levels of EMT‑related proteins and stem cell markers after sphere formation. Parental cells and drug‑resistant cells were screened by high‑throughput sequencing to detect the differential expression of RNA and differential genes. ELISA and western blotting were used to verify the screened PI3K/Akt signaling pathway, key proteins of which were explored by molecular docking. Hematoxylin and eosin staining and TUNEL staining were used to observe tumor xenografts on morphology and apoptosis in nude mice. The present study found that luteolin inhibited tumor resistance (inhibited proliferation, induced cell cycle arrest and apoptosis and hindered migration invasion, EMT and stem cell spherification) in vitro in PTX‑resistant esophageal squamous cell carcinoma (ESCC) cells. In addition, luteolin enhanced drug sensitivity and promoted the apoptosis of drug‑resistant ESCC cells in combination with PTX. Mechanistically, luteolin may inhibit the PI3K/AKT signaling pathway by binding to the active sites of focal adhesion kinase (FAK), Src and AKT. Notably, luteolin lowered the tumorigenic potential of PTX‑resistant ESCC cells but did not show significant toxicity in vivo. Luteolin enhanced drug chemosensitivity by downregulating the FAK/PI3K/AKT pathway in PTX‑resistant ESCC and could be a promising agent for the treatment of PTX‑resistant ESCC cancers.
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Affiliation(s)
- Zhenzhen Yang
- The Fifth Clinical Medical College of Henan University of Chinese Medicine (Zhengzhou People's Hospital), Zhengzhou, Henan 450003, P.R. China
- School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China
| | - Hongtao Liu
- School of Life Sciences, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China
| | - Yinsen Song
- The Fifth Clinical Medical College of Henan University of Chinese Medicine (Zhengzhou People's Hospital), Zhengzhou, Henan 450003, P.R. China
| | - Na Gao
- The Fifth Clinical Medical College of Henan University of Chinese Medicine (Zhengzhou People's Hospital), Zhengzhou, Henan 450003, P.R. China
- School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China
| | - Pan Gao
- The Fifth Clinical Medical College of Henan University of Chinese Medicine (Zhengzhou People's Hospital), Zhengzhou, Henan 450003, P.R. China
- School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China
| | - Yiran Hui
- School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China
- University of Chinese Academy of Sciences Shenzhen Hospital, Shenzhen, Guangdong 518107, P.R. China
| | - Yueheng Li
- School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China
| | - Tianli Fan
- School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China
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15
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Hu A, Li K. Erianin Impedes the Proliferation and Metastatic Migration Through Suppression of STAT-3 Phosphorylation in Human Esophageal Cancer Cells. Appl Biochem Biotechnol 2024; 196:5859-5874. [PMID: 38165593 DOI: 10.1007/s12010-023-04829-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/19/2023] [Indexed: 01/04/2024]
Abstract
In this study, we have investigated erianin, a natural phenolic drug that impedes proliferation and metastatic migration through suppression of STAT-3 phosphorylation in human esophageal cancer cells. Eca-109 cells were treated with different concentrations of erianin (4, 8, 12 µM) for 24 h, and then cell proliferation, apoptosis, and metastatic markers were evaluated. Erianin-induced cytotoxicity and cell proliferation were examined using MTT and crystal violet staining techniques. The measurement of reactive oxygen species (ROS) and the study of apoptotic changes were conducted through flow cytometry. Furthermore, protein expression analyses via western blotting included an evaluation of JAK-STAT3, cell survival, cell cycle, proliferation, and apoptosis-related proteins. Moreover, erianin treatment-associated MMP expressions were studied by RT-PCR. In this study, erianin treatment induces substantial cytotoxicity and ROS production based on the concentrations in Eca-109 cells. Moreover, erianin inhibits the MAPK phosphorylation, proliferation, and metastatic protein in Eca-109 cells. STAT-3 is a crucial transcriptional factor that regulates numerous downstream proteins, such as proliferation, anti-apoptosis, and metastatic proteins. In this study, erianin treatment inhibited the protein expression of IL-6, IL-10, JAK-1, and p-STAT-3 expressions leading to induce apoptosis in Eca-109 cells. Moreover, erianin inhibited the expression of proliferation, metastatic, and anti-apoptotic markers in Eca-109 cells. Hence, erianin suppressed the JAK/STAT-3 signaling pathway and demonstrates potential as a chemotherapeutic agent for the treatment of esophageal cancer.
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Affiliation(s)
- Anxi Hu
- Department of Thoracic Surgery, Zhengzhou Central Hospital, Affiliated to Zhengzhou University, Zhengzhou City, 450001, Henan Province, China
| | - Kunkun Li
- Department of Gastroenterology, Zhengzhou Central Hospital, Affiliated to Zhengzhou University, Zhengzhou City, 450001, Henan Province, China.
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16
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Li C, Shu P, Shi T, Chen Y, Mei P, Zhang Y, Wang Y, Du X, Wang J, Zhang Y, Liu B, Sheng Z, Chan S, Dan Z. Predicting the potential deterioration of Barrett's esophagus based on gut microbiota: a Mendelian randomization analysis. Mamm Genome 2024; 35:399-413. [PMID: 38886201 DOI: 10.1007/s00335-024-10042-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2023] [Accepted: 05/14/2024] [Indexed: 06/20/2024]
Abstract
Esophageal adenocarcinoma (EAC) is one of the most malignant tumors in the digestive system. To make thing worse, the scarcity of treatment options is disheartening. However, if detected early, there is a possibility of reversing the condition. Unfortunately, there is still a lack of relevant early screening methods. Considering that Barrett's esophagus (BE), a precursor lesion of EAC, has been confirmed as the only known precursor of EAC. Analyzing which BE cases will progress to EAC and understanding the processes and mechanisms involved is of great significance for early screening of such patients. Considering the significant alterations in the gut microbiota of patients with BE and its potential role in the progression to EAC, this study aims to analyze the relationship between BE, EAC, and GM to identify potential diagnostic biomarkers and therapeutic targets. This study utilized comprehensive statistical data on gut microbiota from a large-scale genome-wide association meta-analysis conducted by the MiBioGen consortium (n = 18,340). Subsequently, we selected a set of single nucleotide polymorphisms (SNPs) that fell below the genome-wide significance threshold (1 × 10-5) as instrumental variables. To investigate the causal relationship between gut microbiota and BE and EAC, we employed various MR analysis methods, including Inverse Variance Weighting (IVW), MR-Egger regression, weighted median (WM), and weighted mean. Additionally, we assessed the level of pleiotropy, heterogeneity, and stability of genetic variations through MR-Egger intercept test, MR-PRESSO, Cochran's Q test, and "leave-one-out" sensitivity analysis. Furthermore, we conducted reverse MR analysis to identify the causal relationships between gut microbiota and BE and EAC. The results from the Inverse Variance-Weighted (IVW) analysis indicate that Alistipes (P = 4.86 × 10-2), Lactobacillus (P = 2.11 × 10-2), Prevotella 7 (P = 4.28 × 10-2), and RuminococcaceaeUCG004 (P = 4.34 × 10-2) are risk factors for Barrett's esophagus (BE), while Flavonifractor (P = 8.81 × 10-3) and RuminococcaceaeUCG004 (P = 4.99 × 10-2) are risk factors for esophageal adenocarcinoma (EAC). On the other hand, certain gut microbiota genera appear to have a protective effect against both BE and EAC. These include Eubacterium (nodatum group) (P = 4.51 × 10-2), Holdemania (P = 1.22 × 10-2), and Lactococcus (P = 3.39 × 10-2) in the BE cohort, as well as Eubacterium (hallii group) (P = 4.07 × 10-2) and Actinomyces (P = 3.62 × 10-3) in the EAC cohort. According to the results of reverse MR analysis, no significant causal effects of BE and EAC on gut microbiota were observed. Furthermore, no significant heterogeneity or pleiotropy was detected in the instrumental variables. We have established a causal relationship between the gut microbiota and BE and EAC. This study holds profound significance for screening BE patients who may be at risk of deterioration, as it can provide them with timely medical interventions to reverse the condition.
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Affiliation(s)
- Conghan Li
- First Clinical Medical College (First Affiliated Hospital), Anhui Medical University, 81 Meishan Road, Hefei, 230032, China
| | - Panyin Shu
- State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, No. 37 Guoxue Lane, Wuhou District, Chengdu, Sichuan Province, 610041, China
| | - Taiyu Shi
- First Clinical Medical College (First Affiliated Hospital), Anhui Medical University, 81 Meishan Road, Hefei, 230032, China
| | - Yuerong Chen
- First Clinical Medical College (First Affiliated Hospital), Anhui Medical University, 81 Meishan Road, Hefei, 230032, China
| | - Ping Mei
- Department of Radiology, Anqing Municipal Hospital, Anqing, Anhui Province, 246000, China
| | - Yizhong Zhang
- College of Anesthesia, Wannan Medical College, No. 22 Wenchang West Road, Yijiang District, Wuhu City, 241002, Anhui, China
| | - Yan Wang
- College of Life Sciences, Anhui Medical University, 81 Meishan Road, Hefei, 230032, China
| | - Xinyan Du
- First Clinical Medical College (First Affiliated Hospital), Anhui Medical University, 81 Meishan Road, Hefei, 230032, China
| | - Jianning Wang
- First Clinical Medical College (First Affiliated Hospital), Anhui Medical University, 81 Meishan Road, Hefei, 230032, China
| | - Yixin Zhang
- First Clinical Medical College (First Affiliated Hospital), Anhui Medical University, 81 Meishan Road, Hefei, 230032, China
| | - Bin Liu
- First Clinical Medical College (First Affiliated Hospital), Anhui Medical University, 81 Meishan Road, Hefei, 230032, China
| | - Zhijin Sheng
- Department of Physical Education, College of Humanistic Medicine, Anhui Medical University, Hefei, Anhui, China.
| | - Shixin Chan
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, No. 218, Jixi Road, Shushan District, Hefei, 230032, China.
| | - Zhangyong Dan
- Laboratory of Molecular Biology, Department of Biochemistry, Anhui Medical University, 81 Meishan Road, Hefei, 230032, Anhui, China.
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Wang L, Du J, Sun H. Evolution of Esophageal Cancer Incidence Patterns in Hong Kong, 1992-2021: An Age-Period-Cohort and Decomposition Analysis. Int J Public Health 2024; 69:1607315. [PMID: 39170811 PMCID: PMC11335483 DOI: 10.3389/ijph.2024.1607315] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2024] [Accepted: 07/15/2024] [Indexed: 08/23/2024] Open
Abstract
Objective To elucidate the historical trends, underlying causes and future projections of esophageal cancer incidence in Hong Kong. Methods Utilizing the Age-Period-Cohort (APC) model, we analyzed data from the Hong Kong Cancer Registry (1992-2021) and United Nations World Population Prospects 2022 Revision. Age-standardized incidence rates were computed, and APC models evaluated age, period, and cohort effects. Bayesian APC modeling, coupled with decomposition analysis, projected future trends and identified factors influencing incidence. Results Between 1992 and 2021, both crude and age-standardized incidence rates of esophageal cancer witnessed significant declines. Net drifts exhibited pronounced downward trends for both sexes, with local drift diminishing across all age groups. Period and cohort rate ratios displayed a consistent monotonic decline for both sexes. Projections indicate a continued decline in esophageal cancer incidence. Population decomposition analysis revealed that epidemiological changes offset the increase in esophageal cancer cases due to population growth and aging. Conclusion The declining trend of esophageal cancer in Hong Kong is influenced by a combination of age, period, and cohort. Sustaining and enhancing these positive trends requires continuous efforts in public health interventions.
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Affiliation(s)
- Lijun Wang
- Department of Orthopaedics, Xijing Hospital, Fourth Military Medical University, Xi’an, China
| | - Jianqiang Du
- Key Laboratory of Biomedical Information Engineering, Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an, China
| | - Haifeng Sun
- Third Department of Medical Oncology, Shaanxi Provincial Cancer Hospital Affiliated to Medical College of Xi’an Jiaotong University, Xi’an, China
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van der Zijden CJ, Olthof PB, van der Sluis PC, Wijnhoven BPL, Erodotou M, Hartgrink HH, van Etten B, van Esser S, Lagarde SM, Dekker JWT. N3 Disease in Esophageal Cancer: Results from a Nationwide Registry. Dig Surg 2024; 41:133-140. [PMID: 39097966 PMCID: PMC11382634 DOI: 10.1159/000540468] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2024] [Accepted: 07/17/2024] [Indexed: 08/06/2024]
Abstract
BACKGROUND Patients with extensive lymph node metastases have a poor prognosis. Clinical staging of lymph node metastases poses significant challenges given the limited sensitivity and specificity of imaging techniques. The aim of this study was to investigate the overall survival (OS) of patients with N3 disease in a real-world Dutch population and the added value of surgery in these patients. METHODS Patients with cN3M0 esophageal or gastroesophageal cancer were identified from the Netherlands Cancer Registry (2012-2019). Treatment consisted of neoadjuvant chemo(radio)therapy followed by resection or chemo(radio)therapy, radiotherapy, or esophagectomy alone. OS was calculated using the Kaplan-Meier method. RESULTS Some 21,566 patients were diagnosed with esophageal cancer of whom 359 (1.7%) had cN3M0 disease. Median OS of these patients was 12.5 months (95% CI: 10.7-14.3). Median OS following chemoradiotherapy alone and neoadjuvant therapy plus surgery was 13.3 months (95% CI: 10.7-15.9) and 23.7 months (95% CI: 18.3-29.2), respectively. Of all patients who underwent esophagectomy, 391 (2.8%) had (y)pN3 disease, and median OS was 16.1 months (95% CI: 14.8-17.4). Twenty-one patients (5.4%) were correctly classified as cN3, and 3-year OS was 21%. CONCLUSION(S) Clinical staging appears to be difficult, apparently in patients with N3 esophageal cancer. Surgery seems to be of benefit to these patients. More research is required to address the ongoing challenges in clinical staging and the best neoadjuvant therapy.
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Affiliation(s)
| | - Pim B Olthof
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
- Department of Surgery, Reinier de Graaf Group, Delft, The Netherlands
- Department of Surgery, University Medical Center Groningen, Groningen, The Netherlands
| | | | - Bas P L Wijnhoven
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - Maria Erodotou
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - Henk H Hartgrink
- Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
| | - Boudewijn van Etten
- Department of Surgery, University Medical Center Groningen, Groningen, The Netherlands
| | - Stijn van Esser
- Department of Surgery, Reinier de Graaf Group, Delft, The Netherlands
| | - Sjoerd M Lagarde
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
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19
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Fang P, Zhou J, Liang Z, Yang Y, Luan S, Xiao X, Li X, Shang Q, Zhang H, Zeng X, Yuan Y. The prognostic value of controlling nutritional status score on esophageal squamous cell carcinoma patients with neoadjuvant therapy followed by esophagectomy-a retrospective research. J Thorac Dis 2024; 16:4460-4473. [PMID: 39144298 PMCID: PMC11320261 DOI: 10.21037/jtd-24-187] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2024] [Accepted: 06/07/2024] [Indexed: 08/16/2024]
Abstract
Background A variety of nutritional evaluation parameters has been documented as prognostic indicators in some malignancies. However, the prognostic significance of the controlling nutritional status (CONUT) score, as one of these nutritional indices, in patients with esophageal squamous cell carcinoma (ESCC) remains unclear and warrants investigation. Our study sought to elucidate the prognostic value of this nutritional index in ESCC patients who underwent neoadjuvant therapy followed by esophagectomy. Methods This retrospective study encompassed 314 patients diagnosed with ESCC who underwent neoadjuvant therapy followed by esophagectomy at West China Hospital of Sichuan University between August 2016 and August 2021. CONUT scores were computed at two specific time points: prior to neoadjuvant therapy initiation and before surgery, utilizing serum albumin, total lymphocyte, and cholesterol levels of ESCC patients. Furthermore, the delta CONUT (ΔCONUT) score was derived by subtracting the preoperative CONUT score from the pretreatment CONUT score. The associations between CONUT scores and various survival outcomes were evaluated using Kaplan-Meier methods and Cox regression analysis. Results Patients with a high preoperative CONUT score demonstrated a higher postoperative complication rate [odds ratio (OR) =2.009, 95% confidence interval (CI): 1.150-3.510, P=0.01] compared to those in the low CONUT group. Multivariate analysis revealed that a ΔCONUT score ≥0 served as an independent negative prognostic indicator for increased postoperative complications (OR =3.008, 95% CI: 1.509-5.999, P=0.002) and poorer overall survival [hazard ratio (HR) =2.388, 95% CI: 1.052-5.422, P=0.04] in ESCC patients who underwent neoadjuvant therapy combined with esophagectomy. Conclusions A high preoperative CONUT score and a ΔCONUT score ≥0 were indicative of a poor prognostic nutritional status in ESCC patients who had undergone neoadjuvant therapy followed by esophagectomy.
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Affiliation(s)
- Pinhao Fang
- Department of Thoracic Surgery, Med+X Center for Informatics, West China Hospital, Sichuan University, Chengdu, China
| | - Jianfeng Zhou
- Department of Thoracic Surgery, Med+X Center for Informatics, West China Hospital, Sichuan University, Chengdu, China
| | - Zhiwen Liang
- Department of Thoracic Surgery, Med+X Center for Informatics, West China Hospital, Sichuan University, Chengdu, China
| | - Yushang Yang
- Department of Thoracic Surgery, Med+X Center for Informatics, West China Hospital, Sichuan University, Chengdu, China
| | - Siyuan Luan
- Department of Thoracic Surgery, Med+X Center for Informatics, West China Hospital, Sichuan University, Chengdu, China
| | - Xin Xiao
- Department of Thoracic Surgery, Med+X Center for Informatics, West China Hospital, Sichuan University, Chengdu, China
| | - Xiaokun Li
- Department of Thoracic Surgery, Med+X Center for Informatics, West China Hospital, Sichuan University, Chengdu, China
| | - Qixin Shang
- Department of Thoracic Surgery, Med+X Center for Informatics, West China Hospital, Sichuan University, Chengdu, China
| | - Hanlu Zhang
- Department of Thoracic Surgery, Med+X Center for Informatics, West China Hospital, Sichuan University, Chengdu, China
| | - Xiaoxi Zeng
- Biomedical Big Data Center of West China Hospital, Med+X Center for Informatics, Sichuan University, Chengdu, China
| | - Yong Yuan
- Department of Thoracic Surgery, Med+X Center for Informatics, West China Hospital, Sichuan University, Chengdu, China
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20
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Zemanova P, Vocka M, Vanickova Z, Liska F, Krizova L, Kalab J, Votruba J. Does Extraesophageal Reflux Support the Development of Lung Adenocarcinoma? Analysis of Pepsin in Bronchoalveolar Lavage in Non-Smoker Patients. Cancers (Basel) 2024; 16:2687. [PMID: 39123415 PMCID: PMC11312250 DOI: 10.3390/cancers16152687] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Revised: 07/20/2024] [Accepted: 07/25/2024] [Indexed: 08/12/2024] Open
Abstract
The significance of extraesophageal reflux as a risk factor in lung adenocarcinoma has been understudied. In this study, we investigated whether extraesophageal reflux leads to higher pepsin concentrations in bronchoalveolar lavage (BAL) in patients with lung adenocarcinoma compared to controls. Subjects were recruited from non-smoker patients (lifelong non-smokers and ex-smokers with more than 5 years of non-smoking history) who had undergone bronchoscopy due to pulmonary abnormalities on a CT scan and met the inclusion criteria. Based on histological verification of the lung process, the patients were divided into three groups: (1) lung adenocarcinoma, (2) pulmonary metastases, and (3) lung sarcoidosis. Lung adenocarcinoma cases were further categorized as central or peripheral. BAL samples collected during bronchoscopy were quantitatively analyzed by enzyme-linked immunosorbent assay (ELISA) to measure pepsin levels. No statistically significant difference in pepsin concentration was observed between the lung adenocarcinoma group and control groups (p = 0.135). After excluding hemorrhagic BAL samples, the pepsin concentration was significantly the lowest in patients with lung adenocarcinoma (p = 0.023) compared to the control groups. The results of the study do not support the hypothesis of a higher occurrence of extraesophageal reflux (evaluated as the amount of pepsin in BAL) in non-smoker patients with lung adenocarcinoma.
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Affiliation(s)
- Petra Zemanova
- First Clinic of Tuberculosis and Respiratory Diseases, First Faculty of Medicine, Charles University in Prague, General University Hospital in Prague, U Nemocnice 2, 12808 Prague, Czech Republic; (J.K.); (J.V.)
- Department of Oncology, First Faculty of Medicine, Charles University in Prague, General University Hospital in Prague, U Nemocnice 2, Prague 2, 12808 Prague, Czech Republic; (M.V.); (L.K.)
| | - Michal Vocka
- Department of Oncology, First Faculty of Medicine, Charles University in Prague, General University Hospital in Prague, U Nemocnice 2, Prague 2, 12808 Prague, Czech Republic; (M.V.); (L.K.)
| | - Zdislava Vanickova
- Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University in Prague, General University Hospital in Prague, U Nemocnice 2, 12808 Prague, Czech Republic;
| | - Frantisek Liska
- Institute of Biology and Medical Genetics, Purkyne Institute, First Faculty of Medicine, Charles University in Prague, Albertov 4, 12800 Prague, Czech Republic;
| | - Ludmila Krizova
- Department of Oncology, First Faculty of Medicine, Charles University in Prague, General University Hospital in Prague, U Nemocnice 2, Prague 2, 12808 Prague, Czech Republic; (M.V.); (L.K.)
| | - Josef Kalab
- First Clinic of Tuberculosis and Respiratory Diseases, First Faculty of Medicine, Charles University in Prague, General University Hospital in Prague, U Nemocnice 2, 12808 Prague, Czech Republic; (J.K.); (J.V.)
| | - Jiri Votruba
- First Clinic of Tuberculosis and Respiratory Diseases, First Faculty of Medicine, Charles University in Prague, General University Hospital in Prague, U Nemocnice 2, 12808 Prague, Czech Republic; (J.K.); (J.V.)
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21
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Tasoudis P, Manaki V, Iwai Y, Buckeridge SA, Khoury AL, Agala CB, Haithcock BE, Mody GN, Long JM. The Role of Immunotherapy in the Management of Esophageal Cancer in Patients Treated with Neoadjuvant Chemoradiation: An Analysis of the National Cancer Database. Cancers (Basel) 2024; 16:2460. [PMID: 39001522 PMCID: PMC11240428 DOI: 10.3390/cancers16132460] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2024] [Revised: 06/26/2024] [Accepted: 06/26/2024] [Indexed: 07/16/2024] Open
Abstract
BACKGROUND The current National Comprehensive Cancer Network advises neoadjuvant chemoradiotherapy followed by surgery for locally advanced cases of esophageal cancer. The role of immunotherapy in this context is under heavy investigation. METHODS Patients with esophageal adenocarcinoma were identified in the National Cancer Database (NCDB) from 2004 to 2019. Three groups were generated as follows: (a) no immunotherapy, (b) neoadjuvant immunotherapy, and (c) adjuvant immunotherapy. Overall survival was evaluated using the Kaplan-Meier method and Cox proportional hazard analysis, adjusting for previously described risk factors for mortality. RESULTS Of the total 14,244 patients diagnosed with esophageal adenocarcinoma who received neoadjuvant chemoradiation, 14,065 patients did not receive immunotherapy, 110 received neoadjuvant immunotherapy, and 69 received adjuvant immunotherapy. When adjusting for established risk factors, adjuvant immunotherapy was associated with significantly improved survival compared to no immunotherapy and neoadjuvant immunotherapy during a median follow-up period of 35.2 months. No difference was noted among patients who received no immunotherapy vs. neoadjuvant immunotherapy in the same model. CONCLUSIONS In this retrospective analysis of the NCDB, receiving adjuvant immunotherapy offered a significant survival advantage compared to no immunotherapy and neoadjuvant immunotherapy in the treatment of esophageal adenocarcinoma. The addition of neoadjuvant immunotherapy to patients treated with neoadjuvant chemoradiation did not improve survival in this cohort. Further studies are warranted to investigate the long-term outcomes of immunotherapy in esophageal cancer.
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Affiliation(s)
- Panagiotis Tasoudis
- Division of Cardiothoracic Surgery, Department of Surgery, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA
| | - Vasiliki Manaki
- School of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
| | - Yoshiko Iwai
- Division of Cardiothoracic Surgery, Department of Surgery, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA
| | - Steven A Buckeridge
- Division of Cardiothoracic Surgery, Department of Surgery, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA
| | - Audrey L Khoury
- Division of Cardiothoracic Surgery, Department of Surgery, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA
| | - Chris B Agala
- Department of Surgery, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA
| | - Benjamin E Haithcock
- Division of Cardiothoracic Surgery, Department of Surgery, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA
| | - Gita N Mody
- Division of Cardiothoracic Surgery, Department of Surgery, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA
| | - Jason M Long
- Division of Cardiothoracic Surgery, Department of Surgery, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA
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22
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Maiyulan A, Matsumoto Y, Wang H, Murakami K, Toyozumi T, Otsuka R, Shiraishi T, Kinoshita K, Hu J, Iida S, Morishita H, Makiyama T, Nishioka Y, Kano M, Matsubara H. Hypoxia‑regulated exosomal miR‑185 inhibits esophageal squamous cell carcinoma progression and predicts prognosis. Oncol Lett 2024; 28:334. [PMID: 38827568 PMCID: PMC11140231 DOI: 10.3892/ol.2024.14467] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2024] [Accepted: 04/18/2024] [Indexed: 06/04/2024] Open
Abstract
Despite advances in treatment and diagnosis, the prognosis of patients with esophageal squamous cell carcinoma (ESCC) remains poor. MicroRNAs (miRNAs/miRs) are associated with prognosis in esophageal cancer, indicating that they may help guide treatment decisions. The aim of the present study was to explore exosomal miR-185 as a candidate prognostic biomarker and therapeutic target in ESCC, to investigate its biological function and clinical significance, and to ascertain the applicability of circulating exosomal miR-185 for the development of targeted drugs for ESCC treatment. A GeneChip miRNA array was used to compare exosomal miRNA expression in ESCC cell lines under hypoxia with those under normoxia. Exosomal miR-185 expression was then confirmed by reverse transcription-quantitative PCR. Patient background and prognosis were compared between high and low miR-185 expression groups. Functional analyses were performed to evaluate the antitumor effects of miR-185 in ESCC cells. Global Gene Set Enrichment Analysis of The Cancer Genome Atlas data was also performed, and differentially expressed exosomal miRNAs under hypoxia were identified compared to those under normoxia. Hypoxia markedly decreased the expression of exosomal miR-185 in KYSE-960 and T.Tn cell culture media. Overexpression of miR-185 suppressed the migration, invasion and colony-forming abilities of ESCC lines, and also suppressed cell cycle progression and promoted apoptosis after cisplatin treatment. Notably, high miR-185 expression was associated with signaling pathways related to cell death, DNA damage and p53. Furthermore, circulating exosomal miR-185 levels were associated with cN and cStage, and could predict progression-free survival and disease-specific survival of patients with ESCC after initial treatment. In conclusion, miR-185 holds potential as a prognostic biomarker and therapeutic target in ESCC.
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Affiliation(s)
- Abula Maiyulan
- Department of Frontier Surgery, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan
| | - Yasunori Matsumoto
- Department of Frontier Surgery, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan
| | - Huan Wang
- Department of Frontier Surgery, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan
| | - Kentaro Murakami
- Department of Frontier Surgery, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan
| | - Takeshi Toyozumi
- Department of Frontier Surgery, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan
| | - Ryota Otsuka
- Department of Frontier Surgery, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan
| | - Tadashi Shiraishi
- Department of Frontier Surgery, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan
| | - Kazuya Kinoshita
- Department of Frontier Surgery, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan
| | - Jie Hu
- Department of Frontier Surgery, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan
| | - Shinichiro Iida
- Department of Frontier Surgery, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan
| | - Hiroki Morishita
- Department of Frontier Surgery, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan
| | - Tenshi Makiyama
- Department of Frontier Surgery, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan
| | - Yuri Nishioka
- Department of Frontier Surgery, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan
| | - Masayuki Kano
- Department of Frontier Surgery, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan
| | - Hisahiro Matsubara
- Department of Frontier Surgery, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan
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23
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Ricardo J, Alkayali T, Shridhar R, Huston J, Meredith K. Esophageal cancer in Hispanics: a demographic analysis of the National Cancer Database. J Gastrointest Surg 2024; 28:1126-1131. [PMID: 38740256 DOI: 10.1016/j.gassur.2024.05.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2024] [Revised: 05/03/2024] [Accepted: 05/08/2024] [Indexed: 05/16/2024]
Abstract
BACKGROUND Hispanics are the fastest-growing minority and the second largest ethnic group in the United States, accounting for 18% of the national population. The American Cancer Society estimated 18,440 new cases of esophageal cancer (EC) in the United States in 2020. Hispanics are reported to be at high risk of EC. We sought to interrogate the demographic patterns of EC in Hispanics. Secondary objective was to examine evidence of socioeconomic disparities and differential therapy. METHODS We identified Hispanic vs non-Hispanic patients with EC in the National Cancer Database between 2005 and 2015. Groups were statistically equated through propensity score-matched analysis. RESULTS A total of 3205 Hispanics (3.8%) were identified among 85,004 patients with EC. We identified significant disparities between Hispanic and non-Hispanic groups. Disparities among Hispanics included higher prevalence of squamous EC, higher likelihood of stage IV cancer diagnosis, younger age, uninsured status, and income< $38,000. Hispanics were less likely to have surgical intervention or any type of treatment when compared to non-Hispanics. Multivariate analysis showed that age, ethnicity, treatment, histology, grade, stage, and Charlson-Deyo scores were independent predictors of survival. Treated Hispanics survived longer than non-Hispanics. CONCLUSION Despite the lower prevalence of EC, there is a disproportionately higher prevalence of metastatic and untreated cases among Hispanics. This disparity may be explained by Hispanics' limited access to medical care, exacerbated by their socioeconomic and insurance status. Further study is warranted to examine these health disparities among Hispanics.
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Affiliation(s)
- Juan Ricardo
- Florida State University College of Medicine, Surgical Oncology, Sarasota, Florida, United States
| | - Talal Alkayali
- Florida State University College of Medicine, Surgical Oncology, Sarasota, Florida, United States
| | - Ravi Shridhar
- Advent Health Cancer Institute, Radiation Oncology, Orlando, Florida, United States
| | - Jamie Huston
- Sarasota Memorial Cancer Institute, Gastrointestinal Oncology, Sarasota, Florida, United States
| | - Kenneth Meredith
- Florida State University College of Medicine, Surgical Oncology, Sarasota, Florida, United States; Sarasota Memorial Cancer Institute, Gastrointestinal Oncology, Sarasota, Florida, United States.
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24
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Goufman EI, Tikhonova NB, Aleksankin AP, Gershkovich KB, Stepanov AA, Stepanova II, Mikhaleva LM, Nizyaeva NV, Kovaleva OV, Alferov AA, Kuzmin YB, Kushlinskii NE. Circulating IgG Fragments for Gastric Cancer and Esophageal Cancer. Diagnostics (Basel) 2024; 14:1396. [PMID: 39001286 PMCID: PMC11241629 DOI: 10.3390/diagnostics14131396] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2024] [Revised: 06/26/2024] [Accepted: 06/27/2024] [Indexed: 07/16/2024] Open
Abstract
Blood serum of patients with gastric (n = 68) and esophageal (n = 43) cancer was assessed for proteolytic fragments of IgG. Serum samples of 20 healthy donors were used as a control. We analyzed indicators of hemostasis (prothrombin time, fibrinogen, plasminogen activity, a2-antiplasmin activity, protein C activity) in blood plasma and the level of total IgG in the blood serum. The median IgG-LysK of healthy donors was lower than in esophageal cancer and in patients with gastric cancer. ROC-analysis showed high sensitivity (91%) and specificity (85%) in the group with esophageal cancer but 68% and 85%, respectively, in patients with gastric cancer. Analysis of false negatives IgG-LysK in cancer patients showed that most patients had an advanced stage of cancer accompanied by metastases. Total IgG in the plasma of patients with false-negative IgG-LysK values was 30% lower than in samples with positive values, while the level of a2-antiplasmin was increased and the prothrombin time was shorter. These changes in blood homeostasis may be the reason for an increase in the proportion of false-negative values of the IgG-LysK coefficient. Circulatory IgG-LysK levels increase in the early stages of such cancers as gastric and esophageal cancers. Thus, when used in a panel with other more specific markers for these pathologies, this indicator can significantly increase the early detection of cancer.
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Affiliation(s)
- Eugene I Goufman
- Avtsyn Research Institute of Human Morphology of Federal State Budgetary Scientific Institution "Petrovsky National Research Centre of Surgery", 117418 Moscow, Russia
| | - Nataliia B Tikhonova
- Avtsyn Research Institute of Human Morphology of Federal State Budgetary Scientific Institution "Petrovsky National Research Centre of Surgery", 117418 Moscow, Russia
| | - Andrey P Aleksankin
- Avtsyn Research Institute of Human Morphology of Federal State Budgetary Scientific Institution "Petrovsky National Research Centre of Surgery", 117418 Moscow, Russia
| | - Karina B Gershkovich
- N. M. Emanuel Institute for Biochemical Physics, Russian Academy of Sciences, 119334 Moscow, Russia
| | - Alexander A Stepanov
- Avtsyn Research Institute of Human Morphology of Federal State Budgetary Scientific Institution "Petrovsky National Research Centre of Surgery", 117418 Moscow, Russia
| | - Irina I Stepanova
- Avtsyn Research Institute of Human Morphology of Federal State Budgetary Scientific Institution "Petrovsky National Research Centre of Surgery", 117418 Moscow, Russia
| | - Liudmila M Mikhaleva
- Avtsyn Research Institute of Human Morphology of Federal State Budgetary Scientific Institution "Petrovsky National Research Centre of Surgery", 117418 Moscow, Russia
| | - Natalia V Nizyaeva
- Avtsyn Research Institute of Human Morphology of Federal State Budgetary Scientific Institution "Petrovsky National Research Centre of Surgery", 117418 Moscow, Russia
| | - Olga V Kovaleva
- Federal State Budgetary Institution «N.N. Blokhin National Medical Research Center of Oncology», 115478 Moscow, Russia
| | - Alexander A Alferov
- Federal State Budgetary Institution «N.N. Blokhin National Medical Research Center of Oncology», 115478 Moscow, Russia
| | - Yury B Kuzmin
- Federal State Budgetary Institution «N.N. Blokhin National Medical Research Center of Oncology», 115478 Moscow, Russia
| | - Nikolay E Kushlinskii
- Federal State Budgetary Institution «N.N. Blokhin National Medical Research Center of Oncology», 115478 Moscow, Russia
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25
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Zou W, Kuang W, Cai C, Qian Y. Prognostic Nutritional Index as a Prognostic Indicator for the Occurrence of Postoperative Complications in Patients with Esophageal Squamous Cell Carcinoma Following Neoadjuvant Immunochemotherapy. Cancer Manag Res 2024; 16:643-650. [PMID: 38919874 PMCID: PMC11197999 DOI: 10.2147/cmar.s465501] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2024] [Accepted: 06/18/2024] [Indexed: 06/27/2024] Open
Abstract
Background & Aims The objective of this study was to evaluate the prognostic nutritional index (PNI) as a predictor of short-term postoperative complications in esophageal squamous cell carcinoma patients undergoing neoadjuvant immunochemotherapy. Methods Clinical data were collected from 77 patients undergoing radical esophageal cancer surgery after neoadjuvant immunochemotherapy at Tongji Hospital from January 2022 to January 2023. The receiver operating characteristic curve (ROC) was utilized to establish the optimal cut-off point for the PNI. Subsequently, patients were stratified into low and high PNI groups according to this cut-off point, and comparisons were made between the two groups in terms of clinical data and postoperative complications. Results Out of the 77 patients included in the study, 31 were categorized in the low PNI group and 46 in the high PNI group, with a defined cutoff point of 47.38. Significant statistical variances were noted in the occurrence rates of general complications (P < 0.001), pulmonary infections (P < 0.001), and anastomotic fistula (P = 0.034) between the two groups. The low PNI group displayed elevated rates of these complications in comparison to the high PNI group. Conclusion The research findings indicate that preoperative nutritional assessment using the PNI can effectively predict short-term postoperative complications in esophageal squamous cell carcinoma patients who have undergone neoadjuvant therapy. Furthermore, the results suggest that implementing nutritional interventions for patients with moderate-to-severe malnutrition, as indicated by preoperative PNI evaluation, may help reduce the incidence of postoperative complications.
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Affiliation(s)
- Wenbin Zou
- Department of Thoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China
| | - Wan Kuang
- Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China
| | - Chun Cai
- Department of Thoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China
| | - Yan Qian
- Department of Thoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China
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26
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Day F, Sridharan S, Johnson C, Quah GT, Mallesara G, Kumar M, Poulter AL, Morrison A, van der Westhuizen A, Fraser A, Oldmeadow C, Martin J. Esophageal chemoradiotherapy with concurrent nivolumab: Pilot results in the palliative treatment of oligometastatic disease. Asia Pac J Clin Oncol 2024; 20:416-422. [PMID: 38512856 DOI: 10.1111/ajco.14057] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Accepted: 03/07/2024] [Indexed: 03/23/2024]
Abstract
AIMS Many patients diagnosed with esophageal cancer have dysphagia from their primary tumor and de novo metastatic disease. The purpose of this study was to test the safety and efficacy of nivolumab given concurrently with hypofractionated chemoradiotherapy to patients with oligometastatic and obstructing esophageal tumors. METHODS Patients were enrolled in a planned single-arm, phase 2 clinical trial. Eligible participants had previously untreated oligometastatic (≤5 metastases on fludeoxyglucose-18 positron emission tomography scan outside the primary tumor radiotherapy field) esophageal or gastroesophageal carcinoma, dysphagia, and Eastern Cooperative Oncology Group performance status 0-1. Treatment was with 2 weeks of concurrent hypofractionated radiotherapy (30 Gy/10#) to the primary tumor, weekly carboplatin AUC2, weekly paclitaxel 50 mg/m2, and q2weekly nivolumab 240 mg, followed by nivolumab 480 mg continuing q4weekly until disease progression or 24 months total. A single metastasis was treated with stereotactic radiotherapy (SBRT) (24 Gy/3#) in week 7. RESULTS Five patients were recruited before trial closure to new participants for logistical reasons. Existing participants continued treatment per protocol as a pilot study at one center. All five patients completed chemoradioimmunotherapy and SBRT. All patients derived an improvement in their dysphagia. Two patients completed 24 months of nivolumab without disease progression. Grade 3 adverse events (AEs) occurred in 3 patients, however, there were no grade 4 AEs, AEs due to SBRT, or AEs of special interest as defined by the protocol. CONCLUSION Pilot results from five patients at one center found that treatment was well tolerated and effective for dysphagia relief. The efficacy of hypofractionated chemoradiotherapy with concurrent checkpoint inhibition should be tested in a multicentre study.
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Affiliation(s)
- Fiona Day
- Department of Medical Oncology, Calvary Mater Newcastle, Waratah, Australia
- School of Medicine and Public Health, University of Newcastle, Callaghan, Australia
| | - Swetha Sridharan
- School of Medicine and Public Health, University of Newcastle, Callaghan, Australia
- Department of Radiation Oncology, Calvary Mater Newcastle, Waratah, Australia
| | - Catherine Johnson
- Department of Medical Oncology, Calvary Mater Newcastle, Waratah, Australia
| | - Gaik T Quah
- Department of Medical Oncology, Calvary Mater Newcastle, Waratah, Australia
- School of Medicine and Public Health, University of Newcastle, Callaghan, Australia
| | - Girish Mallesara
- Department of Medical Oncology, Calvary Mater Newcastle, Waratah, Australia
- School of Medicine and Public Health, University of Newcastle, Callaghan, Australia
| | - Mahesh Kumar
- School of Medicine and Public Health, University of Newcastle, Callaghan, Australia
- Department of Radiation Oncology, Calvary Mater Newcastle, Waratah, Australia
| | | | - Anthony Morrison
- Department of Medical Oncology, Calvary Mater Newcastle, Waratah, Australia
| | - Andre van der Westhuizen
- Department of Medical Oncology, Calvary Mater Newcastle, Waratah, Australia
- School of Medicine and Public Health, University of Newcastle, Callaghan, Australia
| | - Allison Fraser
- Department of Medical Oncology, Calvary Mater Newcastle, Waratah, Australia
- Department of Radiation Oncology, Calvary Mater Newcastle, Waratah, Australia
| | - Christopher Oldmeadow
- School of Medicine and Public Health, University of Newcastle, Callaghan, Australia
- Clinical Research Design, Information Technology and Statistical Support Unit, Hunter Medical Research Institute, New Lambton Heights, Australia
| | - Jarad Martin
- School of Medicine and Public Health, University of Newcastle, Callaghan, Australia
- Department of Radiation Oncology, Calvary Mater Newcastle, Waratah, Australia
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Du R, Fan S, Yang D, Wang X, Hou X, Zeng C, Guo D, Tian R, Jiang L, Dong X, Yu R, Yu H, Zhu S, Li J, Shi A. Exploration of lymph node recurrence patterns and delineation guidelines of radiation field in middle thoracic oesophageal carcinomas after radical surgery: a real-world study. BMC Cancer 2024; 24:596. [PMID: 38755542 PMCID: PMC11097414 DOI: 10.1186/s12885-024-12297-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2023] [Accepted: 04/22/2024] [Indexed: 05/18/2024] Open
Abstract
BACKGROUND Oesophageal squamous cell carcinoma is one of the most commonly diagnosed carcinomas in China, and postoperative radiotherapy plays an important role in improving the prognosis of patients. Carcinomas in different locations of the oesophagus could have different patterns of lymph node metastasis after surgery. METHODS In this multicentric retrospective study, we enrolled patients with middle thoracic oesophageal squamous cell carcinomas from 3 cancer centres, and none of the patients underwent radiotherapy before or after surgery. We analysed the lymph node recurrence rates in different stations to explore the postoperative lymphatic recurrence pattern. RESULTS From January 1st, 2014, to December 31st, 2019, 132 patients met the criteria, and were included in this study. The lymphatic recurrence rate was 62.1%. Pathological stage (P = 0.032) and lymphadenectomy method (P = 0.006) were significant predictive factors of lymph node recurrence. The recurrence rates in the supraclavicular, upper and lower paratracheal stations of lymph nodes were 32.6%, 28.8% and 16.7%, respectively, showing a high incidence. The recurrence rate of the subcarinal node station was 9.8%, while 8.3% (upper, middle and lower) thoracic para-oesophageal nodes had recurrences. CONCLUSIONS We recommend including the supraclavicular, upper and lower paratracheal stations of lymph nodes in the postoperative radiation field in middle thoracic oesophageal carcinomas. Subcarinal station is also potentially high-risk, while whether to include thoracic para-oesophageal or abdominal nodes needs careful consideration.
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Affiliation(s)
- Rongxu Du
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Songqing Fan
- Oncology Division I, China Pingmei Shenma Medical Group General Hospital, Kuanggongzhong Rd.1, Xinhua District, Pingdingshan Henan, 450052, China
| | - Dan Yang
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Xiaobin Wang
- Department of Radiation Oncology, Hebei Cancer Hospital, The Fourth Hospital of Hebei Medical University, JianKang Rd.12, Shijiazhuang Hebei, 050011, China
| | - Xia Hou
- Department of Radiation Oncology, Shanxi Provincial Cancer Hospital, No.3 Workers New Village, Xinghualing District, Taiyuan, Shanxi, 030013, China
| | - Cheng Zeng
- Department of Radiation Oncology, Central Theater General Hospital, Wuluo Rd. 627, Wuchang District, Wuhan Hubei, 430061, China
| | - Dan Guo
- Department of Radiation Oncology, Shanxi Provincial Cancer Hospital, No.3 Workers New Village, Xinghualing District, Taiyuan, Shanxi, 030013, China
| | - Rongrong Tian
- Department of Radiation Oncology, Shanxi Provincial Cancer Hospital, No.3 Workers New Village, Xinghualing District, Taiyuan, Shanxi, 030013, China
| | - Leilei Jiang
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Xin Dong
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Rong Yu
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Huiming Yu
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Shuchai Zhu
- Department of Radiation Oncology, Hebei Cancer Hospital, The Fourth Hospital of Hebei Medical University, JianKang Rd.12, Shijiazhuang Hebei, 050011, China.
| | - Jie Li
- Department of Radiation Oncology, Shanxi Provincial Cancer Hospital, No.3 Workers New Village, Xinghualing District, Taiyuan, Shanxi, 030013, China.
| | - Anhui Shi
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing, 100142, China.
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Soroush A, Pourhossein S, Hosseingholizadeh D, Hjazi A, Shahhosseini R, Kavoosi H, Kermanshahi N, Behnamrad P, Ghavamikia N, Dadashpour M, Karkon Shayan S. Anti-cancer potential of zerumbone in cancer and glioma: current trends and future perspectives. Med Oncol 2024; 41:125. [PMID: 38652207 DOI: 10.1007/s12032-024-02327-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2023] [Accepted: 02/05/2024] [Indexed: 04/25/2024]
Abstract
Plant-derived immunomodulators and antitumor factors have appealed lots of attention from natural product scientists for their efficiency and safety and their important contribution to well-designed targeted drug action and delivery mechanisms. Zerumbone (ZER), the chief component of Zingiber zerumbet rhizomes, has been examined for its wide-spectrum in the treatment of multi-targeted diseases. The rhizomes have been used as food flavoring agents in numerous cuisines and in flora medication. Numerous in vivo and in vitro experiments have prepared confirmation of ZER as a potent immunomodulator as well as a potential anti-tumor agent. This review is an interesting compilation of all the important results of the research carried out to date to investigate the immunomodulatory and anticancer properties of ZER. The ultimate goal of this comprehensive review is to supply updated information and a crucial evaluation on ZER, including its chemistry and immunomodulating and antitumour properties, which may be of principal importance to supply a novel pathway for subsequent investigation to discover new agents to treat cancers and immune-related sickness. In addition, updated information on the toxicology of ZER has been summarized to support its safety profile.
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Affiliation(s)
| | - Siavash Pourhossein
- Department of Pharmacy, Eastern Mediterranean University, via Mersin 10, Famagusta, North Cyprus, Turkey
| | | | - Ahmed Hjazi
- Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Al-Kharj, 11942, Saudi Arabia
| | | | - Haniyeh Kavoosi
- Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran
| | - Nazgol Kermanshahi
- Faculty of Pharmacy, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Parisa Behnamrad
- Department of Pharmaceutics, Faculty of Pharmacy, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Nima Ghavamikia
- Cardiology Department, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran.
| | - Mehdi Dadashpour
- Department of Medical Biotechnology, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran.
- Semnan University of Medical Sciences, Semnan, Iran.
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Li B, Li M, Qi X, Tong T, Zhang G. The causal associations of circulating lipids with Barrett's Esophagus and Esophageal Cancer: a bi-directional, two sample mendelian randomization analysis. Hum Genomics 2024; 18:37. [PMID: 38627859 PMCID: PMC11020202 DOI: 10.1186/s40246-024-00608-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2024] [Accepted: 04/08/2024] [Indexed: 04/19/2024] Open
Abstract
OBJECTIVE The causal associations of circulating lipids with Barrett's Esophagus (BE) and Esophageal Cancer (EC) has been a topic of debate. This study sought to elucidate the causality between circulating lipids and the risk of BE and EC. METHODS We conducted two-sample Mendelian randomization (MR) analyses using single nucleotide polymorphisms (SNPs) of circulating lipids (n = 94,595 - 431,167 individuals), BE (218,792 individuals), and EC (190,190 individuals) obtained from the publicly available IEU OpenGWAS database. The robustness and reliability of the results were ensured by employing inverse-variance weighted (IVW), weighted median, MR-Egger, and MR-PRESSO methods. The presence of horizontal pleiotropy, heterogeneities, and stability of instrumental variables were assessed through MR-Egger intercept test, Cochran's Q test, and leave-one-out sensitivity analysis. Additionally, bidirectional MR and multivariable MR (MVMR) were performed to explore reverse causality and adjust for known confounders, respectively. RESULTS None of the testing methods revealed statistically significant horizontal pleiotropy, directional pleiotropy, or heterogeneity. Univariate MR analyses using IVW indicated a robust causal relationship between increased triglycerides and BE (odds ratio [OR] = 1.79, p-value = 0.009), while no significant association with EC was observed. Inverse MR analysis indicated no evidence of reverse causality in the aforementioned outcomes. In MVMR analyses, elevated triglycerides (TRG) were significantly and positively associated with BE risk (OR = 1.79, p-value = 0.041). CONCLUSION This MR study suggested that genetically increased triglycerides were closely related to an elevated risk of BE, potentially serving as a biomarker for the diagnosis of BE in the future.
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Affiliation(s)
- Baofeng Li
- Department of Thoracic Surgery, The Second Hospital of Jilin University, Changchun, Jilin, 130021, China
| | - Meng Li
- Department of Thoracic Surgery, The Second Hospital of Jilin University, Changchun, Jilin, 130021, China
| | - Xiao Qi
- Department of Thoracic Surgery, The Second Hospital of Jilin University, Changchun, Jilin, 130021, China
| | - Ti Tong
- Department of Thoracic Surgery, The Second Hospital of Jilin University, Changchun, Jilin, 130021, China.
| | - Guangxin Zhang
- Department of Thoracic Surgery, The Second Hospital of Jilin University, Changchun, Jilin, 130021, China.
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Cheng L, Chen L, Shi Y, Gu W, Ding W, Zheng X, Liu Y, Jiang J, Zheng Z. Efficacy and safety of bispecific antibodies vs. immune checkpoint blockade combination therapy in cancer: a real-world comparison. Mol Cancer 2024; 23:77. [PMID: 38627681 PMCID: PMC11020943 DOI: 10.1186/s12943-024-01956-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2023] [Accepted: 02/07/2024] [Indexed: 04/19/2024] Open
Abstract
Emerging tumor immunotherapy methods encompass bispecific antibodies (BSABs), immune checkpoint inhibitors (ICIs), and adoptive cell immunotherapy. BSABs belong to the antibody family that can specifically recognize two different antigens or epitopes on the same antigen. These antibodies demonstrate superior clinical efficacy than monoclonal antibodies, indicating their role as a promising tumor immunotherapy option. Immune checkpoints are also important in tumor immunotherapy. Programmed cell death protein-1 (PD-1) is a widely acknowledged immune checkpoint target with effective anti-tumor activity. PD-1 inhibitors have demonstrated notable therapeutic efficacy in treating hematological and solid tumors; however, more than 50% of patients undergoing this treatment exhibit a poor response. However, ICI-based combination therapies (ICI combination therapies) have been demonstrated to synergistically increase anti-tumor effects and immune response rates. In this review, we compare the clinical efficacy and side effects of BSABs and ICI combination therapies in real-world tumor immunotherapy, aiming to provide evidence-based approaches for clinical research and personalized tumor diagnosis and treatment.
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Affiliation(s)
- Linyan Cheng
- Department of Hematology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu Province, China
| | - Lujun Chen
- Department of Tumor Biological Treatment, the Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu Province, China
- Jiangsu Engineering Research Center for Tumor Immunotherapy, Changzhou, China
- Institute for Cell Therapy of Soochow University, Changzhou, China
| | - Yuan Shi
- Laboratory of Hematology, The Third Affiliated Hospital of Soochow University, Changzhou, China
| | - Weiying Gu
- Department of Hematology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu Province, China
| | - Weidong Ding
- Department of Hematology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China
- Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Xiao Zheng
- Department of Tumor Biological Treatment, the Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu Province, China.
- Jiangsu Engineering Research Center for Tumor Immunotherapy, Changzhou, China.
- Institute for Cell Therapy of Soochow University, Changzhou, China.
| | - Yan Liu
- Department of Hematology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu Province, China.
| | - Jingting Jiang
- Department of Tumor Biological Treatment, the Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu Province, China.
- Jiangsu Engineering Research Center for Tumor Immunotherapy, Changzhou, China.
- Institute for Cell Therapy of Soochow University, Changzhou, China.
| | - Zhuojun Zheng
- Department of Hematology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu Province, China.
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31
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Nayerpour Dizaj T, Doustmihan A, Sadeghzadeh Oskouei B, Akbari M, Jaymand M, Mazloomi M, Jahanban-Esfahlan R. Significance of PSCA as a novel prognostic marker and therapeutic target for cancer. Cancer Cell Int 2024; 24:135. [PMID: 38627732 PMCID: PMC11020972 DOI: 10.1186/s12935-024-03320-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2023] [Accepted: 03/30/2024] [Indexed: 04/20/2024] Open
Abstract
One of the contributing factors in the diagnosis and treatment of most cancers is the identification of their surface antigens. Cancer tissues or cells have their specific antigens. Some antigens that are present in many cancers elicit different functions. One of these antigens is the prostate stem cell antigen (PSCA) antigen, which was first identified in the prostate. PSCA is a cell surface protein that has different functions in different tissues. It can play an inhibitory role in cell proliferation as well as a tumor-inducing role. PSCA has several genetic variants involved in cancer susceptibility in some tissues, so identifying the characteristics of this antigen and its relationship with clinical features can provide more information on diagnosis and treatment of patients with cancers. Most studies on the PSCA have focused on prostate cancer. While it is also expressed in other cancers, little attention has been paid to its role as a valuable diagnostic, prognostic, and therapeutic tool in other cancers. PSCA has several genetic variants that seem to play a significant role in cancer susceptibility in some tissues, so identifying the characteristics of this antigen and its relationship and variants with clinical features can be beneficial in concomitant cancer therapy and diagnosis, as theranostic tools. In this study, we will review the alteration of the PSCA expression and its polymorphisms and evaluate its clinical and theranostics significance in various cancers.
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Affiliation(s)
- Tina Nayerpour Dizaj
- Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Abolfazl Doustmihan
- Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Behnaz Sadeghzadeh Oskouei
- Department of Reproductive Biology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Morteza Akbari
- Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mehdi Jaymand
- Nano Drug Delivery Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
- Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - MirAhmad Mazloomi
- Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Rana Jahanban-Esfahlan
- Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
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Qu HT, Li Q, Hao L, Ni YJ, Luan WY, Yang Z, Chen XD, Zhang TT, Miao YD, Zhang F. Esophageal cancer screening, early detection and treatment: Current insights and future directions. World J Gastrointest Oncol 2024; 16:1180-1191. [PMID: 38660654 PMCID: PMC11037049 DOI: 10.4251/wjgo.v16.i4.1180] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2023] [Revised: 01/09/2024] [Accepted: 02/19/2024] [Indexed: 04/10/2024] Open
Abstract
Esophageal cancer ranks among the most prevalent malignant tumors globally, primarily due to its highly aggressive nature and poor survival rates. According to the 2020 global cancer statistics, there were approximately 604000 new cases of esophageal cancer, resulting in 544000 deaths. The 5-year survival rate hovers around a mere 15%-25%. Notably, distinct variations exist in the risk factors associated with the two primary histological types, influencing their worldwide incidence and distribution. Squamous cell carcinoma displays a high incidence in specific regions, such as certain areas in China, where it meets the cost-effectiveness criteria for widespread endoscopy-based early diagnosis within the local population. Conversely, adenocarcinoma (EAC) represents the most common histological subtype of esophageal cancer in Europe and the United States. The role of early diagnosis in cases of EAC originating from Barrett's esophagus (BE) remains a subject of controversy. The effectiveness of early detection for EAC, particularly those arising from BE, continues to be a debated topic. The variations in how early-stage esophageal carcinoma is treated in different regions are largely due to the differing rates of early-stage cancer diagnoses. In areas with higher incidences, such as China and Japan, early diagnosis is more common, which has led to the advancement of endoscopic methods as definitive treatments. These techniques have demonstrated remarkable efficacy with minimal complications while preserving esophageal functionality. Early screening, prompt diagnosis, and timely treatment are key strategies that can significantly lower both the occurrence and death rates associated with esophageal cancer.
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Affiliation(s)
- Hong-Tao Qu
- Department of Emergency, Yantai Mountain Hospital, Yantai 264000, Shandong Province, China
| | - Qing Li
- Cancer Center, Yantai Affiliated Hospital of Binzhou Medical University, The 2nd Medical College of Binzhou Medical University, Yantai 264100, Shandong Province, China
| | - Liang Hao
- Cancer Center, Yantai Affiliated Hospital of Binzhou Medical University, The 2nd Medical College of Binzhou Medical University, Yantai 264100, Shandong Province, China
| | - Yan-Jing Ni
- Cancer Center, Yantai Affiliated Hospital of Binzhou Medical University, The 2nd Medical College of Binzhou Medical University, Yantai 264100, Shandong Province, China
| | - Wen-Yu Luan
- Cancer Center, Yantai Affiliated Hospital of Binzhou Medical University, The 2nd Medical College of Binzhou Medical University, Yantai 264100, Shandong Province, China
| | - Zhe Yang
- Cancer Center, Yantai Affiliated Hospital of Binzhou Medical University, The 2nd Medical College of Binzhou Medical University, Yantai 264100, Shandong Province, China
| | - Xiao-Dong Chen
- Cancer Center, Yantai Affiliated Hospital of Binzhou Medical University, The 2nd Medical College of Binzhou Medical University, Yantai 264100, Shandong Province, China
| | - Tong-Tong Zhang
- Cancer Center, Yantai Affiliated Hospital of Binzhou Medical University, The 2nd Medical College of Binzhou Medical University, Yantai 264100, Shandong Province, China
| | - Yan-Dong Miao
- Cancer Center, Yantai Affiliated Hospital of Binzhou Medical University, The 2nd Medical College of Binzhou Medical University, Yantai 264100, Shandong Province, China
| | - Fang Zhang
- Cancer Center, Yantai Affiliated Hospital of Binzhou Medical University, The 2nd Medical College of Binzhou Medical University, Yantai 264100, Shandong Province, China
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Zhou X, Bao W, Zhu X, Wang D, Zeng P, Xia G, Xing M, Zhan Y, Yan J, Yuan M, Zhao Q. Molecular characteristics and multivariate survival analysis of 43 patients with locally advanced or metastatic esophageal squamous cell carcinoma. J Thorac Dis 2024; 16:1843-1853. [PMID: 38617776 PMCID: PMC11009591 DOI: 10.21037/jtd-23-1601] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2023] [Accepted: 01/12/2024] [Indexed: 04/16/2024]
Abstract
Background Esophageal cancer (EC) is an aggressive malignant tumor with poor prognosis and high incidence. It is the sixth leading cause of cancer-related death in the world, and the 5-year overall survival (OS) rate is only 12-20%. The rapid development of next-generation sequencing (NGS) has provided powerful help for the treatment and management of EC patients. Methods Tumor tissue and blood samples of 43 Chinese patients with nonsurgical esophageal squamous cell carcinoma (ESCC) were sequenced using a 425 gene-panel. Genomic profiling was explored and and the Cox proportional hazards model was used to analyze the correlations between gene or signaling pathway alterations and prognosis. Results In this study, the most common mutated genes were TP53 (90.5%), CCND1 (45.2%), FGF19 (38.1%), NOTCH1 (26.2%), PI3KCA (21.4%) and CDKN2A (19%). Among these mutations, PI3KCA and NOTCH1 showed mutual exclusion to some extent. In the univariate model, mutations in NOTCH1, CBLB and TSC2 genes and tumor mutation burden (TMB) ≥7 were independent biomarkers of OS. NOTCH1 (P=0.007, HR =2.87), CBLB (P=0.011, HR =4.68) and TSC2 (P=0.024, HR =3.7) were significantly associated with poorer OS, and patients with TMB ≥7 had longer OS (P=0.151, HR =0.31). In addition, patients who carried alteration in NOTCH signaling pathway had reduced OS (P=0.014, HR =2.54). Conclusions NOTCH1, CBLB and TSC2 alterations were found to be potential indicators of poor prognosis in patients with ESCC. TMB was also positively correlated with the OS of ESCC patients, providing valuable insights for their treatment strategies.
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Affiliation(s)
- Xia Zhou
- Department of Thoracic Radiotherapy, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, China
| | - Wuan Bao
- Department of Thoracic Radiotherapy, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, China
| | - Xiang Zhu
- Department of Thoracic Radiotherapy, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, China
| | - Di Wang
- Medical Department, Nanjing Geneseeq Technology Inc., Nanjing, China
| | - Pengfei Zeng
- Department of Digestology, Zhejiang Medical & Health Group, Hangzhou Hospital of Hangzhou Medical College, Hangzhou, China
| | - Guojie Xia
- Department of Medical Oncology, Traditional Chinese Medical Hospital of Huzhou, Huzhou, China
| | - Minyan Xing
- Department of Medical Oncology, Haining Branch, The First Affiliated Hospital, Zhejiang University, Haining, China
| | - Yanyan Zhan
- Medical Department, Nanjing Geneseeq Technology Inc., Nanjing, China
| | - Junrong Yan
- Medical Department, Nanjing Geneseeq Technology Inc., Nanjing, China
| | - Minchi Yuan
- Department of Oncology, The First People’s Hospital of Jiashan, Jiashan, China
| | - Qiang Zhao
- Department of Thoracic Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, China
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Tian Z, Han C, Xu L, Teng Z, Song W. MGCNSS: miRNA-disease association prediction with multi-layer graph convolution and distance-based negative sample selection strategy. Brief Bioinform 2024; 25:bbae168. [PMID: 38622356 PMCID: PMC11018511 DOI: 10.1093/bib/bbae168] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2023] [Revised: 03/14/2024] [Accepted: 03/31/2024] [Indexed: 04/17/2024] Open
Abstract
Identifying disease-associated microRNAs (miRNAs) could help understand the deep mechanism of diseases, which promotes the development of new medicine. Recently, network-based approaches have been widely proposed for inferring the potential associations between miRNAs and diseases. However, these approaches ignore the importance of different relations in meta-paths when learning the embeddings of miRNAs and diseases. Besides, they pay little attention to screening out reliable negative samples which is crucial for improving the prediction accuracy. In this study, we propose a novel approach named MGCNSS with the multi-layer graph convolution and high-quality negative sample selection strategy. Specifically, MGCNSS first constructs a comprehensive heterogeneous network by integrating miRNA and disease similarity networks coupled with their known association relationships. Then, we employ the multi-layer graph convolution to automatically capture the meta-path relations with different lengths in the heterogeneous network and learn the discriminative representations of miRNAs and diseases. After that, MGCNSS establishes a highly reliable negative sample set from the unlabeled sample set with the negative distance-based sample selection strategy. Finally, we train MGCNSS under an unsupervised learning manner and predict the potential associations between miRNAs and diseases. The experimental results fully demonstrate that MGCNSS outperforms all baseline methods on both balanced and imbalanced datasets. More importantly, we conduct case studies on colon neoplasms and esophageal neoplasms, further confirming the ability of MGCNSS to detect potential candidate miRNAs. The source code is publicly available on GitHub https://github.com/15136943622/MGCNSS/tree/master.
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Affiliation(s)
- Zhen Tian
- School of Computer and Artificial Intelligence, Zhengzhou University, Zhengzhou 450000, China
- Yangtze Delta Region Institute (Quzhou), University of Electronic Science and Technology of China, Quzhou 324000, China
| | - Chenguang Han
- School of Computer and Artificial Intelligence, Zhengzhou University, Zhengzhou 450000, China
| | - Lewen Xu
- School of Computer and Artificial Intelligence, Zhengzhou University, Zhengzhou 450000, China
| | - Zhixia Teng
- College of Computer and Control Engineering, Northeast Forestry University, Harbin 150040, China
| | - Wei Song
- School of Computer and Artificial Intelligence, Zhengzhou University, Zhengzhou 450000, China
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Liu J, Zhu L, Huang X, Lu Z, Wang Y, Yang Y, Ye J, Gu C, Lv W, Zhang C, Hu J. Does the time interval from neoadjuvant camrelizumab combined with chemotherapy to surgery affect outcomes for locally advanced esophageal squamous cell carcinoma? J Cancer Res Clin Oncol 2024; 150:161. [PMID: 38536527 PMCID: PMC10972911 DOI: 10.1007/s00432-024-05696-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2024] [Accepted: 03/11/2024] [Indexed: 04/14/2024]
Abstract
BACKGROUND There is currently no consensus on the optimal interval time between neoadjuvant therapy and surgery, and whether prolonged time interval from neoadjuvant therapy to surgery results in bad outcomes for locally advanced esophageal squamous cell carcinoma (ESCC). In this study, we aim to evaluate outcomes of time intervals ≤ 8 weeks and > 8 weeks in locally advanced ESCC. METHODS This retrospective study consecutively included ESCC patients who received esophagectomy after neoadjuvant camrelizumab combined with chemotherapy at the Department of Thoracic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine. The primary endpoints were disease-free survival (DFS) and overall survival (OS), while the secondary endpoints were pathological response, surgical outcomes, and postoperative complications. RESULTS From 2019 to 2021, a total of 80 patients were included in our study and were divided into two groups according to the time interval from neoadjuvant immunochemotherapy to surgery: ≤ 8 weeks group (n = 44) and > 8 weeks group (n = 36). The rate of MPR in the ≤ 8 weeks group was 25.0% and 27.8% in the > 8 weeks group (P = 0.779). The rate of pCR in the ≤ 8 weeks group was 11.4%, with 16.7% in the > 8 weeks group (P = 0.493). The incidence of postoperative complications in the ≤ 8 weeks group was 27.3% and 19.4% in the > 8 weeks group (P = 0.413). The median DFS in the two groups had not yet reached (hazard ratio [HR], 3.153; 95% confidence interval [CI] 1.383 to 6.851; P = 0.004). The median OS of ≤ 8 weeks group was not achieved (HR, 3.703; 95% CI 1.584 to 8.657; P = 0.0012), with the > 8 weeks group 31.6 months (95% CI 21.1 to 42.1). In multivariable analysis, inferior DFS and OS were observed in patients with interval time > 8 weeks (HR, 2.992; 95% CI 1.306 to 6.851; and HR, 3.478; 95% CI 1.481 to 8.170, respectively). CONCLUSIONS Locally advanced ESCC patients with time interval from neoadjuvant camrelizumab combined with chemotherapy to surgery > 8 weeks were associated with worse long-term survival.
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Affiliation(s)
- Jiacong Liu
- Department of Thoracic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, No. 79 Qingchun Road, Hangzhou, 310003, China
| | - Linhai Zhu
- Department of Thoracic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, No. 79 Qingchun Road, Hangzhou, 310003, China.
| | - Xuhua Huang
- Department of Thoracic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, No. 79 Qingchun Road, Hangzhou, 310003, China
| | - Zhongjie Lu
- Department of Thoracic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, No. 79 Qingchun Road, Hangzhou, 310003, China
| | - Yanye Wang
- Department of Thoracic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, No. 79 Qingchun Road, Hangzhou, 310003, China
| | - Yuhong Yang
- Department of Thoracic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, No. 79 Qingchun Road, Hangzhou, 310003, China
| | - Jiayue Ye
- Department of Thoracic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, No. 79 Qingchun Road, Hangzhou, 310003, China
| | - Chen Gu
- Department of Thoracic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, No. 79 Qingchun Road, Hangzhou, 310003, China
| | - Wang Lv
- Department of Thoracic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, No. 79 Qingchun Road, Hangzhou, 310003, China
| | - Chong Zhang
- Department of Thoracic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, No. 79 Qingchun Road, Hangzhou, 310003, China.
| | - Jian Hu
- Department of Thoracic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, No. 79 Qingchun Road, Hangzhou, 310003, China.
- Key Laboratory of Clinical Evaluation Technology for Medical Device of Zhejiang Province, Hangzhou, 310003, China.
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Pan J, Jia Y, Shi J, Yao R, Guo J. The efficacy and safety of compound kushen injection for adults with esophageal cancer: A meta-analysis of randomized controlled trials. JOURNAL OF ETHNOPHARMACOLOGY 2024; 322:117604. [PMID: 38113988 DOI: 10.1016/j.jep.2023.117604] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/08/2023] [Revised: 11/03/2023] [Accepted: 12/13/2023] [Indexed: 12/21/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Compound Kushen injection (CKI), derived from the traditional Chinese medicine Sophora flavescens, has been widely prescribed to treat a variety of cancers including esophageal cancer (ESCA) in China. AIM OF THE STUDY This study aimed to evaluate the efficacy and safety of CKI for ESCA systematically. METHODS The protocol was registered in the PROSPERO database with No. CRD42022320503. PubMed, Embase, the Cochrane Library, Web of Science, CNKI, Wanfang Database, Clinicaltrials, and Chi-CTR were searched to select RCTs that compared CKI with other interventions for ESCA with outcome measures including clinical efficacy, complete response, quality of life (QoL), adverse events (AEs), and serious AEs (SAEs). The Cochrane Risk of Bias 2 (RoB2) tool was used to assess the quality of RCT. The overall effect sizes were estimated with odds ratios (ORs) and 95% confidence intervals (CIs) on binary outcome data. Meta-analyses were conducted to estimate effect sizes. Subgroup and sensitivity analyses on characteristics of RCTs were performed to test the robustness. Publication bias was also detected with different methods. The evidence strength was assessed with the Grading of Recommendation, Assessment, Development, and Evaluation method. RESULTS This study finally included 35 RCTs with 2491 ESCA patients. The RoB of RCTs was some concern. The effect size of OR was 2.92 (95% CI [2.39, 3.57]) on clinical efficacy, 2.27 (95% CI [1.84, 2.81]) on complete response, 3.71 (95% CI [2.86, 4.80]) on QoL, 0.39 (95% CI [0.30, 0.50]) on AEs, and 0.13 (95% CI [0.07, 0.27]) on SAEs where the statistical significances (P < 0.00001) were found for all outcome measures. These overall effect sizes showed that CKI was more efficacious and safety for ESCA. Moreover, subgroup and sensitivity analyses found consistent results. Most publication bias analyses showed insignificant differences. The evidence strengths were moderate. CONCLUSION The moderate evidence from this comprehensive PRISMA-compliant meta-analysis suggested that CKI may be a valuable alternative for adult patients with ESCA on its significant efficacy and safety. However, more RCTs of high quality with low RoB, large sample sizes, and long follow-up periods are still warranted to update the ESCA clinical guideline for physicians and policymakers in further study.
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Affiliation(s)
- Jiangpeng Pan
- The Research and Application Center of Precision Medicine, The Second Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, PR China; Academy of Medical Sciences, Zhengzhou University, Zhengzhou, Henan, PR China.
| | - Yongliang Jia
- BGI College & Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan, PR China.
| | - Jianxiang Shi
- BGI College & Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan, PR China.
| | - Ruinan Yao
- Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, PR China.
| | - Jiancheng Guo
- The Research and Application Center of Precision Medicine, The Second Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, PR China.
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Milone M, Bianchi PP, Cianchi F, Coratti A, D'Amore A, De Manzoni G, De Pasqual CA, Formisano G, Jovine E, Morelli L, Offi M, Peri A, Pietrabissa A, Staderini F, Tribuzi A, Giacopuzzi S. Fashioning esophagogastric anastomosis in robotic Ivor-Lewis esophagectomy: a multicenter experience. Langenbecks Arch Surg 2024; 409:103. [PMID: 38517543 PMCID: PMC10959816 DOI: 10.1007/s00423-024-03290-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2023] [Accepted: 03/15/2024] [Indexed: 03/24/2024]
Abstract
BACKGROUND The aim of the present study is to compare outcomes of the robotic hand-sewn, linear- and circular-stapled techniques performed to create an intrathoracic esophagogastric anastomosis in patients who underwent Ivor-Lewis esophagectomy. METHODS Patients who underwent a planned Ivor-Lewis esophagectomy were retrospectively analysed from prospectively maintained databases. Only patients who underwent a robotic thoracic approach with the creation of an intrathoracic esophagogastric anastomosis were included in the study. Patients were divided into three groups: hand-sewn-, circular stapled-, and linear-stapled anastomosis group. Demographic information and surgery-related data were extracted. The primary outcome was the rate of anastomotic leakages (AL) in the three groups. Moreover, the rate of grade A, B and C anastomotic leakage were evaluated. In addition, patients of each group were divided in subgroups according to the characteristics of anastomotic fashioning technique. RESULTS Two hundred and thirty patients were enrolled in the study. No significant differences were found between the three groups about AL rate (p = 0.137). Considering the management of the AL for each of the three groups, no significant differences were found. Evaluating the correlation between AL rate and the characteristics of anastomotic fashioning technique, no significant differences were found. CONCLUSIONS No standardized anastomotic fashioning technique has yet been generally accepted. This study could be considered a call to perform ad hoc high-quality studies involving high-volume centers for upper gastrointestinal surgery to evaluate what is the most advantageous anastomotic technique.
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Affiliation(s)
- Marco Milone
- Department of Clinical Medicine and Surgery, ″Federico II″ University of Naples, Via Sergio Pansini, 5, 80131, Naples, Italy
| | | | - Fabio Cianchi
- Chirurgia Dell'Apparato Digerente Azienda Ospedaliero-Universitaria Careggi, Florence, Italy
| | | | - Anna D'Amore
- Department of Clinical Medicine and Surgery, ″Federico II″ University of Naples, Via Sergio Pansini, 5, 80131, Naples, Italy.
| | - Giovanni De Manzoni
- General and Upper GI Surgery Division, Department of Surgery, University of Verona, Verona, Italy
| | - Carlo Alberto De Pasqual
- General and Upper GI Surgery Division, Department of Surgery, University of Verona, Verona, Italy
| | | | - Elio Jovine
- Department of General Surgery, IRCCS, Azienda Ospedaliero-Universitaria Di Bologna, Maggiore Hospital, 40133, Bologna, Italy
| | - Luca Morelli
- General Surgery Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Mariafortuna Offi
- Department of General Surgery, IRCCS, Azienda Ospedaliero-Universitaria Di Bologna, Maggiore Hospital, 40133, Bologna, Italy
| | - Andrea Peri
- Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
- Department of Surgery, University of Pavia, Pavia, Italy
| | | | - Fabio Staderini
- Chirurgia Dell'Apparato Digerente Azienda Ospedaliero-Universitaria Careggi, Florence, Italy
| | | | - Simone Giacopuzzi
- General and Upper GI Surgery Division, Department of Surgery, University of Verona, Verona, Italy
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Sharip A, Rakhimova S, Molkenov A, Ashenova A, Kozhamkulov U, Akhmetollayev I, Zinovyev A, Zhukov Y, Omarov M, Tuleutaev M, Rakhmetova V, Terwilliger JD, Lee JH, Zhumadilov Z, Akilzhanova A, Kairov U. Transcriptome profiling and analysis of patients with esophageal squamous cell carcinoma from Kazakhstan. Front Genet 2024; 15:1249751. [PMID: 38562378 PMCID: PMC10982404 DOI: 10.3389/fgene.2024.1249751] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2023] [Accepted: 03/06/2024] [Indexed: 04/04/2024] Open
Abstract
Esophageal squamous cell carcinoma (ESCC) is the predominant subtype of esophageal cancer in Central Asia, often diagnosed at advanced stages. Understanding population-specific patterns of ESCC is crucial for tailored treatments. This study aimed to unravel ESCC's genetic basis in Kazakhstani patients and identify potential biomarkers for early diagnosis and targeted therapies. ESCC patients from Kazakhstan were studied. We analyzed histological subtypes and conducted in-depth transcriptome sequencing. Differential gene expression analysis was performed, and significantly dysregulated pathways were identified using KEGG pathway analysis (p-value < 0.05). Protein-protein interaction networks were constructed to elucidate key modules and their functions. Among Kazakhstani patients, ESCC with moderate dysplasia was the most prevalent subtype. We identified 42 significantly upregulated and two significantly downregulated KEGG pathways, highlighting molecular mechanisms driving ESCC pathogenesis. Immune-related pathways, such as viral protein interaction with cytokines, rheumatoid arthritis, and oxidative phosphorylation, were elevated, suggesting immune system involvement. Conversely, downregulated pathways were associated with extracellular matrix degradation, crucial in cancer invasion and metastasis. Protein-protein interaction network analysis revealed four distinct modules with specific functions, implicating pathways in esophageal cancer development. High-throughput transcriptome sequencing elucidated critical molecular pathways underlying esophageal carcinogenesis in Kazakhstani patients. Insights into dysregulated pathways offer potential for early diagnosis and precision treatment strategies for ESCC. Understanding population-specific patterns is essential for personalized approaches to ESCC management.
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Affiliation(s)
- Aigul Sharip
- Center for Life Sciences, National Laboratory Astana, Nazarbayev University, Astana, Kazakhstan
| | - Saule Rakhimova
- Center for Life Sciences, National Laboratory Astana, Nazarbayev University, Astana, Kazakhstan
| | - Askhat Molkenov
- Center for Life Sciences, National Laboratory Astana, Nazarbayev University, Astana, Kazakhstan
| | - Ainur Ashenova
- Center for Life Sciences, National Laboratory Astana, Nazarbayev University, Astana, Kazakhstan
| | - Ulan Kozhamkulov
- Center for Life Sciences, National Laboratory Astana, Nazarbayev University, Astana, Kazakhstan
| | | | | | - Yuri Zhukov
- Multidisciplinary Medical Center, Astana, Kazakhstan
| | - Marat Omarov
- Multidisciplinary Medical Center, Astana, Kazakhstan
| | | | - Venera Rakhmetova
- Department of Internal Diseases, Astana Medical University, Astana, Kazakhstan
| | - Joseph D. Terwilliger
- Sergiеvsky Center, Columbia University, New York, NY, United States
- Division of Medical Genetics, New York State Psychiatric Institute, New York, NY, United States
- Department of Psychiatry and Department of Genetics and Development, Columbia University, New York, NY, United States
| | - Joseph H. Lee
- Sergiеvsky Center, Columbia University, New York, NY, United States
- Departments of Epidemiology and Neurology, Columbia University, New York, NY, United States
| | - Zhaxybay Zhumadilov
- Center for Life Sciences, National Laboratory Astana, Nazarbayev University, Astana, Kazakhstan
- School of Medicine, Nazarbayev University, Astana, Kazakhstan
| | - Ainur Akilzhanova
- Center for Life Sciences, National Laboratory Astana, Nazarbayev University, Astana, Kazakhstan
| | - Ulykbek Kairov
- Center for Life Sciences, National Laboratory Astana, Nazarbayev University, Astana, Kazakhstan
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Chang Z, Jia Y, Gao M, Song L, Zhang W, Zhao R, Yu D, Liu X, Li J, Qin Y. PHF5A promotes esophageal squamous cell carcinoma progression via stabilizing VEGFA. Biol Direct 2024; 19:19. [PMID: 38429756 PMCID: PMC10905922 DOI: 10.1186/s13062-023-00440-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2023] [Accepted: 11/23/2023] [Indexed: 03/03/2024] Open
Abstract
BACKGROUND Esophageal squamous cell carcinoma (ESCC) is the main subtype of esophageal cancer. Current therapeutic effect is far from satisfaction. Hence, identifying susceptible genes and potential targets is necessary for therapy of ESCC patients. METHODS Plant homeodomain (PHD)-finger domain protein 5 A (PHF5A) expression in ESCC tissues was examined by immunohistochemistry. RNA interference was used for in vitro loss-of-function experiments. In vivo assay was performed using xenograft mice model by subcutaneous injection. Besides, microarray assay and co-immunoprecipitation experiments were used to study the potential downstream molecules of PHF5A in ESCC. The molecular mechanism between PHF5A and vascular endothelial growth factor A (VEGFA) was explored by a series of ubiquitination related assays. RESULTS We found that PHF5A was highly expressed in ESCC tissues compared to normal tissues and that was correlated with poor prognosis of ESCC. Loss-of-function experiments revealed that PHF5A silence remarkably inhibited cell proliferation, migration, and induced apoptosis as well as cell cycle arrest. Consistently, in vivo assay demonstrated that PHF5A deficiency was able to attenuate tumor growth. Furthermore, molecular studies showed that PHF5A silencing promoted VEGFA ubiquitination by interacting with MDM2, thereby regulating VEGFA protein expression. Subsequently, in rescue experiments, our data suggested that ESCC cell viability and migration promoted by PHF5A were dependent on intact VEGFA. Finally, PI3K/AKT signaling rescue was able to alleviate shPHF5A-mediated cell apoptosis and cell cycle arrest. CONCLUSION PHF5A is a tumor promoter in ESCC, which is dependent on VEGFA and PI3K/AKT signaling. PHF5A might serve as a potential therapeutic target for ESCC treatment.
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Affiliation(s)
- Zhiwei Chang
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, P.R. China
- State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, Henan, 450052, P.R. China
| | - Yongxu Jia
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, P.R. China
- State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, Henan, 450052, P.R. China
| | - Ming Gao
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, P.R. China
- State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, Henan, 450052, P.R. China
| | - Lijie Song
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, P.R. China
- State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, Henan, 450052, P.R. China
| | - Weijie Zhang
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, P.R. China
- State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, Henan, 450052, P.R. China
| | - Ruihua Zhao
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, P.R. China
- State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, Henan, 450052, P.R. China
| | - Dandan Yu
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, P.R. China
- State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, Henan, 450052, P.R. China
| | - Xiaolei Liu
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, P.R. China
- State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, Henan, 450052, P.R. China
| | - Jing Li
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, P.R. China
- State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, Henan, 450052, P.R. China
| | - Yanru Qin
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, P.R. China.
- State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, Henan, 450052, P.R. China.
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Mehta A, Stanger BZ. Lineage Plasticity: The New Cancer Hallmark on the Block. Cancer Res 2024; 84:184-191. [PMID: 37963209 PMCID: PMC10841583 DOI: 10.1158/0008-5472.can-23-1067] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2023] [Revised: 09/12/2023] [Accepted: 11/07/2023] [Indexed: 11/16/2023]
Abstract
Plasticity refers to the ability of cells to adopt a spectrum of states or phenotypes. In cancer, it is a critical contributor to tumor initiation, progression, invasiveness, and therapy resistance, and it has recently been recognized as an emerging cancer hallmark. Plasticity can occur as a result of cell-intrinsic factors (e.g., genetic, transcriptional, or epigenetic fluctuations), or through cell-extrinsic cues (e.g., signaling from components of the tumor microenvironment or selective pressure from therapy). Over the past decade, technological advances, analysis of patient samples, and studies in mouse model systems have led to a deeper understanding of how such plastic states come about. In this review, we discuss: (i) the definition of plasticity; (ii) methods to measure and quantify plasticity; (iii) the clinical relevance of plasticity; and (iv) therapeutic hypotheses to modulate plasticity in the clinic.
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Affiliation(s)
- Arnav Mehta
- Department of Medicine, Massachusetts General Hospital, Boston, MA
- Massachusetts General Hospital Cancer Center, Massachusetts General Hospital, Boston, MA
- Harvard Medical School, Boston, MA
- Broad Institute of MIT and Harvard, Cambridge, MA
| | - Ben Z. Stanger
- Abramson Family Cancer Research Institute, Perelman School of Medicine at University of Pennsylvania, Philadelphia, PA
- Department of Medicine, Perelman School of Medicine at University of Pennsylvania, Philadelphia, PA
- Department of Cell and Developmental Biology, Perelman School of Medicine at University of Pennsylvania, Philadelphia, PA
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Mahmoud W, Hassoun L, Kerbage A, Mukherji D, Shamseddine A, Tamraz S, Hakim A, Barada K. Esophageal cancer: a twenty-four-year experience at a tertiary care center with an evaluation of the prognostic significance of the neutrophil-lymphocyte ratio. BMC Gastroenterol 2024; 24:27. [PMID: 38195445 PMCID: PMC10775605 DOI: 10.1186/s12876-023-03115-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2023] [Accepted: 12/29/2023] [Indexed: 01/11/2024] Open
Abstract
BACKGROUND A high neutrophil-lymphocyte ratio (NLR) may be associated with worse survival in esophageal cancer (EC). Our aims were to describe the demographic and clinical data of EC in a tertiary referral center in Lebanon and to determine the prognostic value of NLR. METHODS A retrospective cohort study based on chart review of patients diagnosed with EC was conducted at the American University of Beirut Medical Center (AUBMC). The demographic characteristics, clinical presentation and outcomes were described and compared between squamous cell carcinomas (ESCC) and adenocarcinomas (EAC). Data about esophageal cancer incidence were obtained from the National Cancer Registry, the Ministry of Public Health and GLOBOCAN 2020. Cox regression analysis was performed to determine whether the NLR is an independent predictor of survival, using variables based on clinical knowledge and previously established data. RESULTS 110 patients were diagnosed with EC, which was the least common among other gastrointestinal malignancies. Our follow up rates reached 86.4%. The median survival was 9 months (IQR 3-25.5.) and was comparable between ESCC (median of 7 months, IQR 2-25) and EAC (median of 9 months, IQR 3-26.3), p = 0.803. Advanced stage was associated with a worse prognosis (p = 0.037). The mean NLR(±SD) was 5.20 ± 6.8, with no significant difference between EAC and ESCC (4.5 ± 3.4 vs. 5.9 ± 9.2, p = 0.420) or between early or advanced stages (5.4 ± 8.1 vs. 4.7 ± 6.8, p = 0.732). The area under the curve for the NLR was 0.560 (95% CI: 0.374-0.746, p = 0.488). After adjusting for age, gender, TNM staging and grading, cox regression analysis showed that an increased NLR was a significant predictor of mortality, with an adjusted hazard ratio of 1.095 (p = 0.011). CONCLUSION EC is quite uncommon in Lebanon despite a high prevalence of smoking and obesity. Advanced stage and high NLR were associated with a negative prognostic value.
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Affiliation(s)
- Walaa Mahmoud
- Division of Gastroenterology and Hepatology, American University of Beirut Medical Center, Beirut, Lebanon
| | - Lara Hassoun
- Division of Gastroenterology and Hepatology, American University of Beirut Medical Center, Beirut, Lebanon
| | - Anthony Kerbage
- Division of Gastroenterology and Hepatology, American University of Beirut Medical Center, Beirut, Lebanon
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, United States of America
| | - Deborah Mukherji
- Division of Gastroenterology and Hepatology, American University of Beirut Medical Center, Beirut, Lebanon
| | - Ali Shamseddine
- Division of Gastroenterology and Hepatology, American University of Beirut Medical Center, Beirut, Lebanon
| | - Sally Tamraz
- Division of Gastroenterology and Hepatology, American University of Beirut Medical Center, Beirut, Lebanon
| | - Ayman Hakim
- Division of Gastroenterology and Hepatology, American University of Beirut Medical Center, Beirut, Lebanon
| | - Kassem Barada
- Division of Gastroenterology and Hepatology, American University of Beirut Medical Center, Beirut, Lebanon.
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Beyen TK, Seife E, Gurara AM, McCormack V, Taye G, Addissie A. Spatiotemporal Distribution, Time to Treatment Outcome Clustering and Determinants of Esophageal Cancer in Ethiopia, a Scoping Study. Cancer Control 2024; 31:10732748241251712. [PMID: 38716644 PMCID: PMC11080749 DOI: 10.1177/10732748241251712] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2023] [Revised: 03/12/2024] [Accepted: 04/09/2024] [Indexed: 05/12/2024] Open
Abstract
INTRODUCTION Esophageal cancer was the eighth and sixth leading cause of morbidity of all cancers in the world, and the 15th and 12th in Ethiopia, respectively. There is a lack of comprehensive data regarding Ethiopia's esophageal cancer hotspot, treatment outcome clustering, and other factors. OBJECTIVE This scoping review was designed to understand the extent and type of existing evidence regarding spatiotemporal distribution, time to treatment outcome clustering, and determinants of esophageal cancer in Ethiopia up to March 28, 2023. METHODS Three-step search strategies were employed for the scoping review from March 15 to 28, 2023. Targeted databases included PubMed/Medline, PubMed Central (PMC), Google Scholar, Hinari, and Cochrane for published studies and different websites for unpublished studies for evidence synthesis. Data were extracted using the Joanna Briggs Institute (JBI) manual format. RESULTS Our final analysis comprised 17 (16 quantitative and 1 qualitative) studies. Three studies attempted to depict the country's temporal distribution, whereas 12 studies showed the spatial distribution of esophageal cancer by proportion. The regional state of Oromia recorded a high percentage of cases. Numerous risk factors linked to the tumor have been identified in 8 investigations. Similarly, 5 studies went into detail regarding the likelihood of survival and the factors that contribute to malignancy, while 2 studies covered the results of disease-related treatments. CONCLUSIONS The substantial body of data that underpins this finding supports the fact that esophageal cancer has several risk factors and that its prevalence varies greatly across the country and among regions. Surgery, radiotherapy, or chemotherapy helped the patient live longer. However, no research has investigated which treatment is best for boosting patient survival and survival clustering. Therefore, research with robust models for regional distribution, clustering of time to treatment outcomes, and drivers of esophageal cancer will be needed.
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Affiliation(s)
- Teresa Kisi Beyen
- Department of Public Health, College of Health Science Arsi University, Asella, Ethiopia
- PhD student at School of Public Health, College of Health Science, Addis Ababa University, Addis Ababa, Ethiopia
| | - Edom Seife
- Clinical Oncologist, College of Health Science, Addis Ababa University, Addis Ababa, Ethiopia
| | - Abenet M. Gurara
- Department of Nursing, College of Health Science Arsi University, Asella, Ethiopia
| | - Valerie McCormack
- Environment and Lifestyle Epidemiology, Branch International Agency for Research on Cancer, Lyon, France
| | - Girma Taye
- Department of preventive Medicine, School of Public Health Addis Ababa University, Ethiopia
| | - Adamu Addissie
- Department of preventive Medicine, School of Public Health Addis Ababa University, Ethiopia
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Zhao S, Hu X, Zhou P, Li A, Chen L, Wang D, He J, Jiang Y. Molecular profiles of different PD-L1 expression in patients with esophageal squamous cell carcinoma. Cancer Biol Ther 2023; 24:2256927. [PMID: 38032149 PMCID: PMC10515684 DOI: 10.1080/15384047.2023.2256927] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2023] [Accepted: 09/05/2023] [Indexed: 12/01/2023] Open
Abstract
BACKGROUND PD-1/PD-L1 inhibitors are approved treatments for patients with esophageal squamous cell carcinoma (ESCC). The present investigation aspired to explore the interrelation between molecular phenotype and PD-L1 expression in ESCC. METHODS PD-L1 testing and targeted next-generation sequencing (NGS) were performed on tumoral tissues from 139 ESCC patients. Tumor-infiltrating lymphocytes (TILs) were scrutinized using a tyramide signal amplification system combined with immunohistochemistry. RESULTS Among enrolled patients, 36.7% displayed high PD-L1 expression (combined positive score [CPS] ≥10). BRCA1 and NF1 gene mutations were significantly associated with high PD-L1 expression (p < .05) while TGFβ pathway alterations were linked to low PD-L1 expression (p = .02). High copy number instability (CNI) and copy number alterations (CNA) were correlated with low PD-L1 expression. Patients with CDKN2A deletion exhibited higher PD-L1 expression. Varying types of TILs were observed across different PD-L1 expression groups. The ratio of CD8+PD-L1+ T cells and CD8+PD-1+ T cells to CD8+ T cells remained comparable in both tumoral and stromal regions, but the ratio of CD68+PD-L1+ macrophages to CD68+ macrophages was higher than the ratio of CD68+PD-1+ macrophages to CD68+ macrophages. CPS was significantly correlated with PD-L1+ lymphocytes and CD68+ macrophages in the tumoral region. CD8+ T cell infiltration was positively correlated with PD-1+ cells in both tumoral and stromal regions. CONCLUSION In this study, we presented the prevalence rates of PD-L1 expression in Chinese ESCC patients. The association of genetic profiles with PD-L1 expression levels also provide the clue that genomic phenotype may interact with the immunologic phenotype in ESCC.
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Affiliation(s)
- Songchen Zhao
- Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
| | - Xintong Hu
- Key Laboratory of Organ Regeneration & Transplantation of the Ministry of Education, Genetic Diagnosis Center, The First Hospital of Jilin University, Changchun, China
| | - Peiwen Zhou
- Key Laboratory of Organ Regeneration & Transplantation of the Ministry of Education, Genetic Diagnosis Center, The First Hospital of Jilin University, Changchun, China
| | - Ang Li
- Key Laboratory of Organ Regeneration & Transplantation of the Ministry of Education, Genetic Diagnosis Center, The First Hospital of Jilin University, Changchun, China
| | - Liguo Chen
- Key Laboratory of Organ Regeneration & Transplantation of the Ministry of Education, Genetic Diagnosis Center, The First Hospital of Jilin University, Changchun, China
| | - Duo Wang
- Key Laboratory of Organ Regeneration & Transplantation of the Ministry of Education, Genetic Diagnosis Center, The First Hospital of Jilin University, Changchun, China
| | - Jiaxue He
- Key Laboratory of Organ Regeneration & Transplantation of the Ministry of Education, Genetic Diagnosis Center, The First Hospital of Jilin University, Changchun, China
| | - Yanfang Jiang
- Key Laboratory of Organ Regeneration & Transplantation of the Ministry of Education, Genetic Diagnosis Center, The First Hospital of Jilin University, Changchun, China
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Tan B, Wang N, Yang S, Liu H, Cheng Y. Irradiation Induces Gasdermin E-Triggered Tumor Immunity to Inhibit Esophageal Carcinoma Cell Survival. ACS OMEGA 2023; 8:46438-46449. [PMID: 38107880 PMCID: PMC10720026 DOI: 10.1021/acsomega.3c03791] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Revised: 09/21/2023] [Accepted: 11/15/2023] [Indexed: 12/19/2023]
Abstract
Gasdermin E (GSDME), an executor of pyroptosis, can be activated by caspase-3 and has been recognized as a tumor suppressor in various human cancers. In addition, caspase-3/GSDME signal-induced pyroptosis is a form of immunogenic cell death (ICD). In this study, we aimed to understand the association between radiotherapy and caspase-3/GSDME signal-related ICD in esophageal carcinoma (EC) cells. The expression of caspase-3 and GSDME in two EC cell lines, ECA-109 and KYSE-150, was silenced or overexpressed by transfection with specific siRNAs or overexpression vectors. Cells were subjected to 0-8 Gy irradiation, and cell death was evaluated by CCK-8 assay, annexin V-FITC staining, lactate dehydrogenase (LDH) detection kit, Western blotting, and immunofluorescence. Irradiation in both EC cell lines promoted dose-dependent viability loss and apoptosis. More specifically, 8 Gy X-ray increased the apoptosis rate from 4.1 to 12.8% in ECA-109 cells and from 4.6 to 21.1% in KYSE-150 cells. In irradiated EC cells, the levels of LDH release and caspase-3/GSDME cleavage were increased. Caspase-3 silencing inhibited irradiation-induced GSDME cleavage and EC cell death. Furthermore, we identified the death of EC cells suppressed by caspase-3 siRNA, and the levels of CRT, HMGB1, HSP70, and HSP90 were also markedly downregulated by caspase-3 siRNA. Similarly, GSDME silencing diminished irradiation-induced EC cell death and the levels of ICD markers. Overexpression of caspase-3 and GSDME accelerated irradiation-induced ICD. In summary, irradiation in EC cells induces GSDME-mediated pyroptosis and activates ICD to inhibit esophageal carcinoma cell survival.
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Affiliation(s)
- Bingxu Tan
- Department
of Radiation Oncology, Qilu Hospital of
Shandong University, Jinan 250012, Shandong, People’s Republic of China
| | - Nana Wang
- Department
of Radiation Oncology, Qilu Hospital of
Shandong University, Jinan 250012, Shandong, People’s Republic of China
| | - Shengsi Yang
- Department
of Radiation Oncology, Qilu Hospital of
Shandong University, Jinan 250012, Shandong, People’s Republic of China
| | - Hui Liu
- Department
of Radiation Oncology, Qilu Hospital of
Shandong University, Jinan 250012, Shandong, People’s Republic of China
| | - Yufeng Cheng
- Department
of Radiation Oncology, Qilu Hospital of
Shandong University, Jinan 250012, Shandong, People’s Republic of China
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Ghiglieri C, Dempster M, Wright S, Graham-Wisener L. Psychosocial functioning in individuals with advanced oesophago-gastric cancer: a mixed methods systematic review. BMC Palliat Care 2023; 22:164. [PMID: 37891568 PMCID: PMC10612179 DOI: 10.1186/s12904-023-01288-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2022] [Accepted: 10/16/2023] [Indexed: 10/29/2023] Open
Abstract
BACKGROUND Oesophago-gastric cancer is an aggressive disease with a high rate of recurrence and mortality across the disease trajectory. Reduced psychosocial functioning has been evidenced amongst those with advanced disease, however little is known about the contributing factors. Determining these factors is an important clinical consideration to inform assessment and intervention. This review aimed to synthesise the available evidence on the psychosocial functioning of individuals with advanced oesophago-gastric cancer and their carers. METHODS A JBI mixed-methods systematic review. Four bibliographic databases, MEDLINE, Embase, PsycINFO, and CINAHL, were searched. Quantitative and qualitative studies were screened for inclusion and critically appraised for methodological quality. Both types of data were extracted using JBI tools for mixed-methods systematic reviews. A convergent segregated approach to synthesis and integration was used. The findings of the synthesis have been configured according to JBI methodology. RESULTS A total of 12 studies were included in this review, including 6 quantitative studies and 6 qualitative studies. The quantitative results provide preliminary indication of several physical, biological, psychological and macro-level contextual factors associated with psychosocial functioning in this clinical population. The qualitative findings shed light on a range of physical, psychosocial, and existential challenges faced by advanced oesophago-gastric cancer patients. These multiple and often persistent challenges appear to cause considerable distress; however, patients describe the importance of maintaining a sense of normality and control over their illness and its effects. Patients value continuity and structure, however many report shortcomings when accessing care. No findings reporting the experiences from the perspective of carers were found, therefore all findings represent the perspective of the patient. CONCLUSIONS Further high-quality research is needed to understand how best to support and manage the palliative care needs of individuals living with advanced oesophago-gastric cancer. Implications for practice are discussed, suggesting that psychosocial interventions, complex symptom management and continuity of care could improve the psychosocial functioning of individuals in this setting. PRE-REGISTRATION The systematic review was pre-registered at the International Prospective Register of Systematic Reviews (PROSPERO; CRD42020181273) and the protocol can be viewed on the OSF ( http://osf.io/exuzf ).
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Affiliation(s)
- Cara Ghiglieri
- Centre for Improving Health-Related Quality of Life, School of Psychology, Queen's University Belfast, Belfast, BT7 1NN, Northern Ireland.
| | - Martin Dempster
- Centre for Improving Health-Related Quality of Life, School of Psychology, Queen's University Belfast, Belfast, BT7 1NN, Northern Ireland
| | - Sam Wright
- Centre for Improving Health-Related Quality of Life, School of Psychology, Queen's University Belfast, Belfast, BT7 1NN, Northern Ireland
| | - Lisa Graham-Wisener
- Centre for Improving Health-Related Quality of Life, School of Psychology, Queen's University Belfast, Belfast, BT7 1NN, Northern Ireland
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Qi X, Su X, Wang C, Yao Q, Fan Y. Risk of second cancer in esophageal squamous cell carcinoma and adenocarcinoma survivors: a population-based analysis in SEER dataset. Transl Gastroenterol Hepatol 2023; 8:33. [PMID: 38021360 PMCID: PMC10643214 DOI: 10.21037/tgh-23-29] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2023] [Accepted: 09/01/2023] [Indexed: 12/01/2023] Open
Abstract
Background Previous studies have reported increased risk of second cancer in both esophageal squamous cell cancer (ESCC) and esophageal adenocarcinoma (EAC) survivors. This study aimed to examine the risk and influential factors of second cancer in ESCC and EAC patients. Methods This population-based cohort study included 7,297 ESCC patients and 11,812 EAC patients who were in 1992-2019 from the Surveillance, Epidemiology, and End Results (SEER) program in the United States. These patients were followed up until diagnosis of second cancer, death, or end of the study (December 31, 2019). We calculated standard incidence ratio (SIR) and 95% confidence interval (CI) of second cancer and performed competing-risk regression to estimate the subdistribution hazard ratios (sHR) comparing categories of patients' characteristics. Results After a total of 49,509.38 person-years of follow-up, 431 (5.9%) ESCC patients and 636 (5.9%) EAC patients developed a second cancer. An overall increased risk of second cancer was observed in both ESCC patients (SIR: 1.66, 95% CI: 1.51-1.83) and EAC patients (SIR: 1.11, 95% CI: 1.02-1.20). ESCC patients were at increased risk of second malignancy in oral cavity and pharynx (SIR: 12.57, 95% CI: 9.87-15.79), stomach (SIR: 3.03, 95% CI: 1.77-4.85), nose and larynx (SIR: 4.79, 95% CI: 2.47-8.37), and lung and bronchus (SIR: 2.44, 95% CI: 1.96-2.99), but decreased risk of prostate cancer (SIR: 0.73, 95% CI: 0.52-0.99). EAC patients had increased risk of second malignancies in stomach (SIR: 4.41, 95% CI: 3.23-5.89), lung and bronchus (SIR: 1.26, 95% CI: 1.02-1.54), and kidney (SIR: 1.57, 95% CI: 1.05-2.25). The risk of second cancer was higher in female ESCC patients than in males (sHR: 1.34, 95% CI: 1.11-1.63) and decreased with more advanced tumor stage in both ESCC patients (sHR: 0.62, 95% CI: 0.50-0.76 for regional stage; sHR: 0.27, 95% CI: 0.20-0.36 for distant stage) and EAC patients (sHR: 0.47, 95% CI: 0.40-0.56 for regional stage; sHR: 0.10, 95% CI: 0.07-0.13 for distant stage). Conclusions Both ESCC and EAC patients are at considerable risk of certain types of second cancer.
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Affiliation(s)
- Xiaona Qi
- Department of Nursing, Harbin Medical University Cancer Hospital, Harbin, China
- School of Nursing, Harbin Medical University, Harbin, China
| | - Xiaoying Su
- School of Public Health, Fujian Medical University, Fuzhou, China
| | - Changhong Wang
- Department of Thoracic Surgery, Harbin Medical University Cancer Hospital, Harbin, China
| | - Qiang Yao
- Department of Colorectal Surgery, Harbin Medical University Cancer Hospital, Harbin, China
| | - Yuying Fan
- School of Nursing, Harbin Medical University, Harbin, China
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Li Y, Wei B, Xue X, Li H, Li J. Microbiome changes in esophageal cancer: implications for pathogenesis and prognosis. Cancer Biol Med 2023; 21:j.issn.2095-3941.2023.0177. [PMID: 37817487 PMCID: PMC10884538 DOI: 10.20892/j.issn.2095-3941.2023.0177] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2023] [Accepted: 09/06/2023] [Indexed: 10/12/2023] Open
Abstract
Esophageal cancer (EC) is an aggressive malignancy with a poor prognosis. Various factors, including dietary habits, and antacid and antibiotic use, have been shown to influence the esophageal microbiome. Conversely, enrichment and diversity of the esophageal microbiome can also impact its function. Recent studies have revealed prevalent changes in the esophageal microbiome among patients with EC, thus suggesting the potential contribution of the esophageal microbiome to EC development. Additionally, distinct microbiome compositions have been observed in patients with different responses to radiotherapy and chemotherapy, indicating the role of the esophageal microbiome in modulating treatment outcomes. In this review, we have examined previous studies on the esophageal microbiome in healthy individuals and patients with EC or other esophageal diseases, with a focus on identifying microbial communities associated with EC pathogenesis and prognosis. Understanding the role of the microbiome in EC may aid in early detection and optimized treatment strategies, ultimately leading to better outcomes for patients.
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Affiliation(s)
- Yi Li
- Department of Molecular Pathology, Clinical Pathology Center, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou 450003, China
| | - Bing Wei
- Department of Molecular Pathology, Clinical Pathology Center, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou 450003, China
- Henan Key Laboratory of Molecular Pathology, Zhengzhou 450003, China
| | - Xia Xue
- Henan Key Laboratory of Helicobacter pylori & Microbiota and Gastrointestinal Cancer, Marshall Medical Research Center, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
| | - Hongle Li
- Department of Molecular Pathology, Clinical Pathology Center, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou 450003, China
- Henan Key Laboratory of Molecular Pathology, Zhengzhou 450003, China
| | - Jun Li
- Department of Molecular Pathology, Clinical Pathology Center, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou 450003, China
- Henan Key Laboratory of Molecular Pathology, Zhengzhou 450003, China
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Li R, Chai L, Lei L, Guo R, Wen X. MiR-671-5p sponging activity of circMMP1 promotes esophageal squamous cancer progression. Thorac Cancer 2023; 14:2924-2933. [PMID: 37635445 PMCID: PMC10569906 DOI: 10.1111/1759-7714.15078] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2023] [Revised: 08/01/2023] [Accepted: 08/05/2023] [Indexed: 08/29/2023] Open
Abstract
BACKGROUND The aim of this study was to explore the function and mechanism of circular RNA (circRNA) matrix metallopeptidase 1 (circMMP1) in the progression of esophageal squamous cell carcinoma (ESCC). METHODS CircMMP1 expression was detected by quantitative real-time PCR (qRT-PCR), and its relationship with the prognosis of ESCC patients was evaluated by Kaplan-Meier analysis. Cells were transfected using corresponding plasmids, and the cell proliferation activity, migration and invasion capabilities in vitro were assessed. The protein level in tissues and cells was analyzed using western blotting. RNA pulldown, dual-luciferase reporter assay and RNA immunoprecipitation assay were performed in ESCC cells to detect the interaction between circMMP1 and miR-671-5p, or the correlation between miR-671-5p and ANO1. Xenograft tumor experiment was carried out to uncover the function of circMMP1 in vivo. RESULTS The high level of circMMP1 in tumor tissues was associated with poor prognoses of ESCC patients. Knockdown of circMMP1 suppressed ESCC cell proliferation, migration and invasion in vitro. MiR-671-5p was the target of circMMP1 and mediated the inhibition effect of circMMP1 on ESCC cells. CircMMP1 targeted miR-671-5p to regulate ANO1 expression, which was downstream of miR-671-5p. Overexpression of ANO1 weakened tumor-repressive function of circMMP1 knockdown in ESCC cells. Moreover, silencing of circMMP1 impeded ESCC tumor growth in vivo. CONCLUSION Our study provided novel evidence that circMMP1 accelerated ESCC progression by acting as a miR-671-5p sponge to enhance ANO1 expression.
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Affiliation(s)
- Rong Li
- Department of RadiotherapyThe First Affiliated Hospital of Xi'an Jiaotong UniversityXi'anChina
| | - Linyan Chai
- Department of RadiotherapyThe First Affiliated Hospital of Xi'an Jiaotong UniversityXi'anChina
| | - Lei Lei
- Department of CardiologyThe Second Affiliated Hospital of Xi'an Jiaotong UniversityXi'anChina
| | - Rong Guo
- Department of Nuclear MedicineThe Second Affiliated Hospital of Xi'an Jiaotong UniversityXi'anChina
| | - Xiulin Wen
- Department of NursingThe First Affiliated Hospital of Xi'an Jiaotong UniversityXi'anChina
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Qureshi MM, Lin Y, Moeller AR, Yan SX, Dyer MA, Suzuki K, Everett P, Litle V, Truong MT, Mak KS. Change in stage after neoadjuvant chemoradiation is associated with survival in patients with esophageal cancer. J Surg Oncol 2023; 128:781-789. [PMID: 37288789 DOI: 10.1002/jso.27367] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2022] [Revised: 05/17/2023] [Accepted: 05/27/2023] [Indexed: 06/09/2023]
Abstract
BACKGROUND The aim of this study was to determine if change in stage after neoadjuvant chemoradiation (CRT) was associated with improved survival in esophageal cancer using a national database. METHODS Using the National Cancer Database, patients with non-metastatic, resectable esophageal cancer who received neoadjuvant CRT and surgery were identified. Comparing clinical to the pathologic stage, change in stage was classified as pathologic complete response (pCR), downstaged, same-staged, or upstaged. Univariable and multivariable Cox regression models were used to identify factors associated with survival. RESULTS A total of 7745 patients were identified. The median overall survival (OS) was 34.9 months. Median OS was 60.3 months if pCR, 39.1 months if downstaged, 28.3 months if same-staged, and 23.4 months if upstaged (p < 0.0001). On multivariable analysis, pCR was associated with improved OS compared to the other groups (downstaged: hazard ratio [HR]: 1.32 [95% confidence interval [CI]: 1.18-1.46]; same-staged: HR: 1.89 [95% CI: 1.68-2.13]; upstaged: HR: 2.54 [95% CI: 2.25-2.86]; all p < 0.0001). CONCLUSIONS In this large database study, change in stage after neoadjuvant CRT was strongly associated with survival for patients with non-metastatic, resectable esophageal cancer. There was a significant stepwise decline in survival, in descending order of pCR, downstaged tumor, same-staged tumor, and upstaged tumor.
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Affiliation(s)
- Muhammad M Qureshi
- Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts, USA
- Department of Radiation Oncology, Boston Medical Center, Boston, Massachusetts, USA
| | - Yue Lin
- Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts, USA
| | - Alexander R Moeller
- Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts, USA
| | - Sherry X Yan
- Department of Radiation Oncology, Boston Medical Center, Boston, Massachusetts, USA
| | - Michael A Dyer
- Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts, USA
- Department of Radiation Oncology, Boston Medical Center, Boston, Massachusetts, USA
| | - Kei Suzuki
- Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts, USA
- Department of Surgery, Boston Medical Center, Boston, Massachusetts, USA
| | - Peter Everett
- Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts, USA
- Department of Medicine, Boston Medical Center, Boston, Massachusetts, USA
| | - Virginia Litle
- Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts, USA
- Department of Surgery, Boston Medical Center, Boston, Massachusetts, USA
| | - Minh-Tam Truong
- Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts, USA
- Department of Radiation Oncology, Boston Medical Center, Boston, Massachusetts, USA
| | - Kimberley S Mak
- Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts, USA
- Department of Radiation Oncology, Boston Medical Center, Boston, Massachusetts, USA
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Xue Y, Cheng Z, Liao Y, Chen X. Role of exosome-mediated molecules SNORD91A and SLC40A1 in M2 macrophage polarization and prognosis of ESCC. Discov Oncol 2023; 14:177. [PMID: 37740815 PMCID: PMC10517911 DOI: 10.1007/s12672-023-00797-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2023] [Accepted: 09/20/2023] [Indexed: 09/25/2023] Open
Abstract
BACKGROUND Exosome-mediated interaction serves as a significant regulatory factor for M2 macrophage polarization in cancer. METHODS All accessible data were acquired from The Cancer Genome Atlas (TCGA) database and analyzed using R software. Molecules implicated in exocrine secretion were amassed from the ExoCarta database. Our research initially quantified the immune microenvironment in Esophageal Squamous Cell Carcinoma (ESCC) patients based on the expression profile sourced from the TCGA database. Additionally, we delved into the biological role of M2 macrophages in ESCC via Gene Set Enrichment Analysis (GSEA). RESULTS We observed that patients with high M2 macrophage infiltration typically have a poorer prognosis. Subsequently, a total of 1457 molecules were identified, with 103 of these molecules believed to function through exocrine mechanisms, as supported by data from the ExoCarta database. SNORD91A and SLC40A1 were ultimately pinpointed due to their correlation with patient prognosis. Moreover, we investigated their potential roles in ESCC, including biological enrichment, immune infiltration, and genomic instability analysis. CONCLUSIONS Our study identified exosome-associated molecules, namely SNORD91A and SLC40A1, which notably impact ESCC prognosis and local M2 macrophage recruitment, thereby presenting potential therapeutic targets for ESCC.
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Affiliation(s)
- Yang Xue
- Department of Thoracic Surgery, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, China
| | - Zhengyan Cheng
- Department of Pathology, Sichuan Academy of Medical Science & Sichuan Provincial People's Hospital, Chengdu, China
| | - Yida Liao
- Department of Thoracic Surgery, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, China
| | - Xing Chen
- Department of Thoracic Surgery, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, China.
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