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Sun L, Ni X, Liu Y, Jiang Y, Wang PP, Gao J. A Neutral Glucan Extracted from Dried Ginger (Zingiberis Rhizoma): Preparation, Structure Characterization, and Immunomodulatory Activity. PLANTA MEDICA 2025. [PMID: 40228537 DOI: 10.1055/a-2574-2730] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/16/2025]
Abstract
A neutral glucan, GJ0D, was obtained from dried ginger (Zingiberis rhizoma) by enzymatic extraction and purification with column chromatography. The fine structure of GJ0D was assessed through monosaccharide composition analysis, methylation, and two-dimensional nuclear magnetic resonance. GJ0D has a relative molecular weight of 4.0 KDa and possesses a backbone consisting of 1,4-linked α-Glcp with substitution at C-6 of Glcp by T-Glcp. Immunoactivity assessment showed that GJ0D significantly upregulates the expression of IL-6, IL-1β, and TNF-α in RAW264.7 cells. The reactive oxygen species (ROS) production was also increased in RAW264.7 cells. In addition, the expression of several proteins associated with immune activation signaling pathways including TLR4, the phosphorylation of IKKβ, and NF-κB (p100 and p52) were significantly upregulated by GJ0D. These results suggest that GJ0D could promote inflammation through the TLR4/IKKβ/P100 signaling pathway, suggesting a potential application as an immunomodulating agent.
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Affiliation(s)
- Long Sun
- Department of Marine Pharmacology, College of Food Science and Technology, Shanghai Ocean University, Shanghai, China
| | - Xing Ni
- Oncology Department, Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, Jiangsu, China
| | - Yulin Liu
- Department of Marine Pharmacology, College of Food Science and Technology, Shanghai Ocean University, Shanghai, China
| | - Yantao Jiang
- Oncology Department, Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, Jiangsu, China
| | - Pei-Pei Wang
- Department of Marine Pharmacology, College of Food Science and Technology, Shanghai Ocean University, Shanghai, China
- Marine Biomedical Science and Technology Innovation Platform of Lin-Gang Special Area, Shanghai, China
| | - Jingdong Gao
- Oncology Department, Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, Jiangsu, China
- Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
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Nishida A, Andoh A. The Role of Inflammation in Cancer: Mechanisms of Tumor Initiation, Progression, and Metastasis. Cells 2025; 14:488. [PMID: 40214442 PMCID: PMC11987742 DOI: 10.3390/cells14070488] [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: 01/27/2025] [Revised: 03/14/2025] [Accepted: 03/20/2025] [Indexed: 04/14/2025] Open
Abstract
Inflammation is an essential component of the immune response that protects the host against pathogens and facilitates tissue repair. Chronic inflammation is a critical factor in cancer development and progression. It affects every stage of tumor development, from initiation and promotion to invasion and metastasis. Tumors often create an inflammatory microenvironment that induces angiogenesis, immune suppression, and malignant growth. Immune cells within the tumor microenvironment interact actively with cancer cells, which drives progression through complex molecular mechanisms. Chronic inflammation is triggered by factors such as infections, obesity, and environmental toxins and is strongly linked to increased cancer risk. However, acute inflammatory responses can sometimes boost antitumor immunity; thus, inflammation presents both challenges and opportunities for therapeutic intervention. This review examines how inflammation contributes to tumor biology, emphasizing its dual role as a critical factor in tumorigenesis and as a potential therapeutic target.
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Affiliation(s)
- Atsushi Nishida
- Department of Medicine, Shiga University of Medical Science, Seta-Tsukinowa, Otsu 520-2192, Shiga, Japan;
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Liu Y, Cui S, Wang J, Hu B, Chen S. Perioperative inflammatory index differences between pulmonary squamous cell carcinoma and adenocarcinoma and their prognostic implications. Front Oncol 2025; 15:1554699. [PMID: 40052128 PMCID: PMC11882399 DOI: 10.3389/fonc.2025.1554699] [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: 01/02/2025] [Accepted: 02/05/2025] [Indexed: 03/09/2025] Open
Abstract
Background Perioperative inflammatory indices reflect systemic inflammatory responses and have been linked to cancer progression and prognosis. This study aims to explore the differences in perioperative inflammatory indices between lung squamous cell carcinoma (LSCC) and adenocarcinoma (LUAD) and their association with long-term outcomes. Methods This study included 287 lung cancer patients who underwent curative resection between June 2016 and December 2017, comprising 61 cases of LSCC and 226 cases of LUAD. Perioperative baseline information and inflammatory cell counts were collected. Patients were followed up for a median duration of 76 months, during which disease-free survival (DFS) and overall survival (OS) were recorded. Cox regression analysis was used to evaluate the prognostic significance of inflammatory factor levels. Results Significant differences were observed in white blood cell count and systemic inflammation response index (SIRI) between LSCC and LUAD (P < 0.05). Regression analysis identified age (OR=2.096, P=0.004), postoperative day 1 D-dimer level (OR=1.550, P<0.001), and Platelet-to-lymphocyte ratio (PLR) (OR=1.901, P=0.031) as independent risk factors for perioperative venous thromboembolism (VTE). Furthermore, open surgical approach (HR=2.437, P=0.016), tumor type (LSCC; HR=2.437, P=0.016), and PLR (HR=1.534, P=0.019) were independent risk factors for DFS. Conclusion Inflammatory index is key predictors of perioperative VTE and DFS in lung cancer, emphasizing their critical role in prognosis.
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Affiliation(s)
- Yi Liu
- Department of Thoracic Surgery, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
| | - Songping Cui
- Department of Thoracic Surgery, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
| | - Jing Wang
- Department of Thoracic Surgery, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
- Mass General Cancer Center, Mass General Brigham, Harvard Medical School, Boston, MA, United States
| | - Bin Hu
- Department of Thoracic Surgery, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
| | - Shuo Chen
- Department of Thoracic Surgery, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
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Yücer R, Schröder A, Topçu G, Efferth T. Identification of anti-inflammatory and anti-cancer compounds targeting the NF-κB-NLRP3 inflammasome pathway from a phytochemical library of the Sideritis genus. JOURNAL OF ETHNOPHARMACOLOGY 2025; 338:119074. [PMID: 39522840 DOI: 10.1016/j.jep.2024.119074] [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: 03/06/2024] [Revised: 10/09/2024] [Accepted: 11/08/2024] [Indexed: 11/16/2024]
Abstract
ETHNOBOTANICAL RELEVANCE For centuries, the aerial parts of Sideritis species have been known for their medicinal properties as herbal teas. Although the antioxidant and anti-inflammatory properties of the genus have been widely documented, the underlying mechanisms are yet to be sufficiently clarified. AIM OF THE STUDY We investigated the anti-inflammatory and anticancer activities of phytochemicals of the Sideritis genus. MATERIAL AND METHODS Through literature mining, a chemical library containing 657 components of the Sideritis genus was formed. We studied these compounds for binding to NLRP3 and NF-κB proteins in silico by virtual drug screening and molecular docking, and in vitro by microscale thermophoresis (MST). Liquid chromatography-high-resolution mass spectrometry analysis (LC-HRMS) was performed in the Sideritis extracts. One of the identified compounds, verbascoside, was investigated for its cytotoxic activity by mining a panel of 49 tumor cell lines in the data repository of the National Cancer Institute (NCI, USA). RESULTS Virtual screening and molecular docking results highlighted two compounds targeting both proteins of interest, i.e., verbascoside (acteoside) and apigenin 7,4'-bis(trans-p-coumarate), as both had lowest binding energies of less than -10 kcal/mol. Using MST, we then verified that both compounds bound to the target proteins. Verbascoside bound to NLRP3 and NF-κB with Kd values of 0.67 ± 0.18 μM and 0.01 ± 0.08 μM, while apigenin 7,4'-bis(trans-p-coumarate) had Kd values of 4.60 ± 1.66 μM and 0.27 ± 0.75 μM, respectively. Verbascoside was abundant in the Sideritis extracts, according to LC-HRMS analysis. Since inflammation is strongly related to carcinogenesis, we investigated the anticancer activity of verbascoside in the second part of this study. We investigated the activity of verbascoside in 49 tumor cell lines of the NCI. Comparing its activity with 81 standard anticancer drugs revealed numerous interactions with DNA-damaging agents (alkylators, topoisomerase I/II inhibitors, antimetabolites), indicating that verbascoside may also affect the DNA of tumor cells. We further investigated the involvement of verbascoside in several main drug resistance mechanisms, i.e., ABC transporters, oncogenes, tumor suppressors, cellular proliferation rates, and other parameters. Except for the correlation to the mutational status of NRAS, no other significant relationships were found, indicating that verbascoside is not involved in most of the common drug resistance mechanisms. Two-dimensional cluster analysis-based heatmap generation of a proteomic profile from 40 out of 3171 proteins revealed a significant correlation between the expression of these proteins in 49 tumor cell lines, and the cellular response to verbascoside. This indicates that the presence of these proteins is a determinant for sensitivity or resistance to this natural product. CONCLUSION The database established here represents a valuable resource for the screening of bioactivites of the Sideritis genus. The experimental validation of the anti-inflammatory and cytotoxic activities of selected compounds proved that virtual drug screening and molecular docking are suitable tools for the identification of putative drug candidates. Verbascoside was among the top 10 compounds binding to two key anti-inflammatory proteins, NLRP3 and NF-kB. Additionally, data from the NCI indicate that verbascoside is not linked to main drug resistance mechanisms.
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Affiliation(s)
- Rümeysa Yücer
- Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Staudinger Weg 5, 55128, Mainz, Germany.
| | - Angela Schröder
- Theophrastus Paracelsus Foundation, 64367, Mühltal, Germany.
| | - Gülaçtı Topçu
- Department of Pharmacognosy and Phytochemistry, Faculty of Pharmacy, Bezmialem Vakif University, 34093, Fatih, Istanbul, Turkiye; Drug Application & Research Center (DARC), Bezmialem Vakif University, 34093, Fatih, Istanbul, Turkiye.
| | - Thomas Efferth
- Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Staudinger Weg 5, 55128, Mainz, Germany.
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Tang X, He M, Ren Y, Ji M, Yan X, Zeng W, Lv Y, Li Y, He Y. Traditional Chinese Medicine formulas-based interventions on colorectal carcinoma prevention: The efficacies, mechanisms and advantages. JOURNAL OF ETHNOPHARMACOLOGY 2025; 337:119008. [PMID: 39471879 DOI: 10.1016/j.jep.2024.119008] [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: 07/30/2024] [Revised: 10/08/2024] [Accepted: 10/26/2024] [Indexed: 11/01/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE The Traditional Chinese Medicine Formulas (TCMFs) represent a distinctive medical approach to disease treatment and have been utilized in clinical practice for treating intestinal diseases for thousands of years. Recently, TCMFs have received increasing attention due to their advantages of high efficiency, safety, as well as low toxicity, providing promising strategies for preventing colorectal carcinoma (CRC). Nonetheless, the potential mechanism of TCMFs in preventing CRC has not been fully elucidated. AIM OF THE STUDY The literature from the past three years was reviewed to highlight the therapeutic effects and underlying mechanisms of TCMFs in preventing CRC. MATERIALS AND METHODS The keywords have been searched, including "traditional Chinese medicine formulas," "herb pairs," "Herbal plant-derived nanoparticles," et al. in "PubMed" and "China National Knowledge Infrastructure (CNKI)," and screened published articles related to the treatment of intestinal precancerous lesions. This review primarily examined the effectiveness and mechanisms of TCMFs in treating intestinal precancerous lesions, highlighting their significant potential in preventing CRC. RESULTS Gegen Qinlian decoction, Shaoyao decoction, Wu Wei Wan, etc., exert substantial therapeutic effects on intestinal precancerous lesions. These therapeutic effects are demonstrated by a reduction in disease activity index scores, suppression of intestinal inflammation, and preservation of body weight and intestinal function, all of which contribute to the effective prevention of CRC. Besides, the classic Chinese herbal pairs and the extracellular vesicle-like nanoparticles of herbaceous plants have demonstrated superior efficacy in the treatment of intestinal precancerous lesions. Mechanistically, protecting the epithelial barrier, regulating gut microbiota as well as related metabolism, modulating macrophage polarization, and maintaining immune balance contribute to the role of TCMFs in CRC prevention. CONCLUSIONS This review demonstrates the great potential and mechanism of TCMFs in CRC prevention and provides a scientific basis for their utilization in CRC prevention.
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Affiliation(s)
- Xiaojuan Tang
- School of biomedical sciences, Hunan University, Changsha, 410012, Hunan, China; Hunan Provincial Hospital of Integrated Traditional Chinese and Western Medicine (The Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine), Changsha, 410006, Hunan, China; Hunan Academy of Chinese Medicine, Changsha, 410006, Hunan, China.
| | - Min He
- Hunan University of Chinese Medicine, Changsha, 410208, Hunan, China
| | - Yuan Ren
- Hunan University of Chinese Medicine, Changsha, 410208, Hunan, China
| | - Meng Ji
- Hunan University of Chinese Medicine, Changsha, 410208, Hunan, China
| | - Xiaoqi Yan
- Hunan Provincial Hospital of Integrated Traditional Chinese and Western Medicine (The Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine), Changsha, 410006, Hunan, China
| | - Wen Zeng
- Hunan University of Chinese Medicine, Changsha, 410208, Hunan, China
| | - Yuan Lv
- Hunan Provincial Hospital of Integrated Traditional Chinese and Western Medicine (The Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine), Changsha, 410006, Hunan, China; Hunan Academy of Chinese Medicine, Changsha, 410006, Hunan, China
| | - Yongmin Li
- Hunan Provincial Hospital of Integrated Traditional Chinese and Western Medicine (The Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine), Changsha, 410006, Hunan, China; Hunan Academy of Chinese Medicine, Changsha, 410006, Hunan, China
| | - Yongheng He
- Hunan Provincial Hospital of Integrated Traditional Chinese and Western Medicine (The Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine), Changsha, 410006, Hunan, China; Hunan Academy of Chinese Medicine, Changsha, 410006, Hunan, China; Hunan University of Chinese Medicine, Changsha, 410208, Hunan, China.
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Ebrahimi F, Rasizadeh R, Jafari S, Baghi HB. Prevalence of HPV in anal cancer: exploring the role of infection and inflammation. Infect Agent Cancer 2024; 19:63. [PMID: 39696546 DOI: 10.1186/s13027-024-00624-0] [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: 07/29/2024] [Accepted: 11/27/2024] [Indexed: 12/20/2024] Open
Abstract
Anal cancer incidence is rising globally, driven primarily by human papillomavirus (HPV) infection. HPV, especially high-risk types 16 and 18, is considered a necessary cause of anal squamous cell carcinoma. Certain populations like people living with HIV, men who have sex with men, inflammatory bowel disease patients, smokers, and those with compromised immunity face elevated risk. Chronic inflammation facilitates viral persistence, cell transformation, and immune evasion through pathways involving the PD-1/PD-L1 axis. HIV coinfection further increases risk by impairing immune surveillance and epithelial integrity while promoting HPV oncogene expression. Understanding these inflammatory processes, including roles of CD8 + T cells and PD-1/PD-L1, could guide development of immunotherapies against anal cancer. This review summarizes current knowledge on inflammation's role in anal cancer pathogenesis and the interplay between HPV, HIV, and host immune factors.
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Affiliation(s)
- Fatemeh Ebrahimi
- Immunology Research Centre, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Reyhaneh Rasizadeh
- Immunology Research Centre, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Virology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran
| | - Sajjad Jafari
- Department of Medical Microbiology and Virology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Hossein Bannazadeh Baghi
- Immunology Research Centre, Tabriz University of Medical Sciences, Tabriz, Iran.
- Department of Virology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
- Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, PO Box 5165665931, Tabriz, Iran.
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Pakfetrat A, Dalirsani Z, Saghravanian N, Anvari K, Asalian S, Salehi A, Taherizadeh M. Tumor Metastasis to the Oral Soft Tissues and Jaw Bones: A Retrospective Study and Review of the Literature. Clin Exp Dent Res 2024; 10:e70011. [PMID: 39420710 PMCID: PMC11486913 DOI: 10.1002/cre2.70011] [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: 03/16/2024] [Revised: 08/26/2024] [Accepted: 08/29/2024] [Indexed: 10/19/2024] Open
Abstract
OBJECTIVES Metastasis to the oral soft tissues and jaw is rare and accounts for 1%-3% of maxillofacial malignancies. These lesions usually occur in the context of an extensive malignant tumor with a poor prognosis. MATERIALS AND METHODS Archived cases from the Oral and Maxillofacial Pathology Department of the Faculty of Dentistry and two hospital centers of Mashhad University of Medical Sciences were examined. Inclusion criteria were cases with available records of pathologically confirmed metastatic lesions of the oral cavity with or without diagnosed primary malignancy. RESULTS Metastatic lesions in the oral cavity and jaw were found in 18 patients, including seven women and 11 men, with a mean age of 49.5 years. Metastatic lesions were more common in the jaw (66%) and particularly in the mandible (38%) than elsewhere. In the case of soft tissue metastases, the gingiva was more affected than other sites. The primary tumor was most commonly in the kidney in men and in the breast in women (36%-28%). In addition, the diagnosis of a metastatic lesion led to the detection of the primary tumor elsewhere in six out of 18 cases (33.3%). CONCLUSIONS Early diagnosis of the lesions is challenging, given the absence of specific signs or symptoms, which, in some cases, nonetheless resemble inflammatory, benign, reactive lesions. Therefore, dentists play a crucial role in diagnosing such lesions, as they lead to the discovery of hidden distant primary tumors. Biopsy should always be considered for suspicious lesions, even if the probability is very low.
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Affiliation(s)
- Atessa Pakfetrat
- Oral and Maxillofacial Diseases Research CenterMashhad University of Medical SciencesMashhadIran
| | - Zohreh Dalirsani
- Oral and Maxillofacial Diseases Research CenterMashhad University of Medical SciencesMashhadIran
| | - Nasrollah Saghravanian
- Oral and Maxillofacial Diseases Research CenterMashhad University of Medical SciencesMashhadIran
| | - Kazem Anvari
- Department of Radiotherapy Oncology and Cancer Research CenterMashhad University of Medical SciencesMashhadIran
| | | | - Armaghan Salehi
- Student Research Committee, Faculty of DentistryMashhad University of Medical SciencesMashhadIran
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Yu D, Liu J, Meng C, Liu B, Liao J. Pan-immune-inflammation value as a novel prognostic biomarker for digestive system cancers: a meta-analysis. World J Surg Oncol 2024; 22:306. [PMID: 39563378 PMCID: PMC11577901 DOI: 10.1186/s12957-024-03595-z] [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: 07/23/2024] [Accepted: 11/17/2024] [Indexed: 11/21/2024] Open
Abstract
BACKGROUND Digestive system cancers pose a significant global health challenge with high incidence and mortality rates. Inflammation is a key factor in cancer progression, necessitating reliable prognostic indicators. The pan-immune-inflammation value (PIV), as a new biomarker of immune-inflammatory response, has emerged as a potential prognostic biomarker for cancers. METHODS We performed a meta-analysis to evaluate the prognostic significance of PIV in digestive system cancers. Our search, up to June 2024, included 20 studies from 19 articles with 5037 patients. We extracted and analyzed data on PIV levels and assessed hazard ratios (HRs) for overall survival (OS), progression-free survival (PFS), disease-free survival (DFS), recurrence-free survival (RFS), and cancer-specific survival (CSS) using STATA 14.0. RESULTS Our analysis found that high PIV levels were significantly associated with poor prognosis in patients with digestive system cancers. Specifically, high PIV was linked to shorter OS (HR = 2.039, P < 0.001), PFS (HR = 1.877, P = 0.028), DFS (HR = 1.624, P = 0.005), RFS (HR = 2.393, P = 0.037), and CSS (HR = 2.053, P < 0.001). Additionally, the adverse prognostic impact of high PIV on OS was consistent across different cancer types, including digestive tract, colorectal, esophageal, and hepatobiliary pancreatic cancers. Although some heterogeneity was observed, sensitivity and bias analyses confirmed the reliability of these findings. CONCLUSIONS PIV was a valuable and practical prognostic marker for digestive system cancers, providing significant predictive value across multiple survival metrics. Its simplicity and minimal invasiveness nature support its potential integration into routine clinical practice.
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Affiliation(s)
- Dongli Yu
- Department of Surgery, Zhejiang Hospital, 12 Lingyin Road, Zhejiang, 310013, China
| | - Jingting Liu
- Department of Health management, Sir Run Run Shaw International Medical Centre, 9 Jingtan Road, Hangzhou, 310000, Zhejiang, China
| | - Chunyan Meng
- Department of Surgery, Zhejiang Hospital, 12 Lingyin Road, Zhejiang, 310013, China
| | - Baoqing Liu
- Department of Surgery, Zhejiang Hospital, 12 Lingyin Road, Zhejiang, 310013, China
| | - Jianhua Liao
- Department of Surgery, Zhejiang Hospital, 12 Lingyin Road, Zhejiang, 310013, China.
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Hasibuan PAZ, Simanjuntak Y, Hey-Hawkins E, Lubis MF, Rohani AS, Park MN, Kim B, Syahputra RA. Unlocking the potential of flavonoids: Natural solutions in the fight against colon cancer. Biomed Pharmacother 2024; 176:116827. [PMID: 38850646 DOI: 10.1016/j.biopha.2024.116827] [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: 02/29/2024] [Revised: 05/21/2024] [Accepted: 05/26/2024] [Indexed: 06/10/2024] Open
Abstract
Colorectal cancer (CRC) is a major cause of cancer-related deaths worldwide, underscoring the importance of understanding the diverse molecular and genetic underpinnings of CRC to improve its diagnosis, prognosis, and treatment. This review delves into the adenoma-carcinoma-metastasis model, emphasizing the "APC-KRAS-TP53" signature events in CRC development. CRC is categorized into four consensus molecular subtypes, each characterized by unique genetic alterations and responses to therapy, illustrating its complexity and heterogeneity. Furthermore, we explore the role of chronic inflammation and the gut microbiome in CRC progression, emphasizing the potential of targeting these factors for prevention and treatment. This review discusses the impact of dietary carcinogens and lifestyle factors and the critical role of early detection in improving outcomes, and also examines conventional chemotherapy options for CRC and associated challenges. There is significant focus on the therapeutic potential of flavonoids for CRC management, discussing various types of flavonoids, their sources, and mechanisms of action, including their antioxidant properties, modulation of cell signaling pathways, and effects on cell cycle and apoptosis. This article presents evidence of the synergistic effects of flavonoids with conventional cancer therapies and their role in modulating the gut microbiome and immune response, thereby offering new avenues for CRC treatment. We conclude by emphasizing the importance of a multidisciplinary approach to CRC research and treatment, incorporating insights from genetic, molecular, and lifestyle factors. Further research is needed on the preventive and therapeutic potential of natural compounds, such as flavonoids, in CRC, underscoring the need for personalized and targeted treatment strategies.
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Affiliation(s)
| | - Yogi Simanjuntak
- Department of Pharmacology, Faculty of Pharmacy, Universitas Sumatera Utara, Sumatera Utara, Indonesia
| | - Evamarie Hey-Hawkins
- Leipzig University, Faculty of Chemistry and Mineralogy, Centre for Biotechnology and Biomedicine (BBZ), Institute of Bioanalytical Chemistry, Deutscher Platz 5, Leipzig 04103, Germany
| | - Muhammad Fauzan Lubis
- Department of Pharmaceutical Biology, Faculty of Pharmacy, Universitas Sumatera Utara, Sumatera Utara, Indonesia
| | - Ade Sri Rohani
- Department of Pharmacology, Faculty of Pharmacy, Universitas Sumatera Utara, Sumatera Utara, Indonesia
| | - Moon Nyeo Park
- Department of Internal Medicine, College of Korean Medicine, Kyung Hee University, Seoul, 02447, Republic of Korea; College of Korean Medicine, Kyung Hee University, Hoegidong Dongdaemungu, Seoul 05253, Republic of Korea
| | - Bonglee Kim
- Department of Internal Medicine, College of Korean Medicine, Kyung Hee University, Seoul, 02447, Republic of Korea; College of Korean Medicine, Kyung Hee University, Hoegidong Dongdaemungu, Seoul 05253, Republic of Korea
| | - Rony Abdi Syahputra
- Department of Pharmacology, Faculty of Pharmacy, Universitas Sumatera Utara, Sumatera Utara, Indonesia
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Wang H, Li W. Prognostic significance of SIRI in patients with late-stage lung adenocarcinoma receiving EGFR-TKI treatment. Curr Probl Cancer 2024; 50:101099. [PMID: 38723294 DOI: 10.1016/j.currproblcancer.2024.101099] [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: 11/08/2023] [Revised: 03/10/2024] [Accepted: 04/25/2024] [Indexed: 06/16/2024]
Abstract
OBJECTIVE In this study, we examined the relationship between the Systemic Inflammatory Response Index (SIRI) and the overall prognosis of patients with late-stage lung adenocarcinoma who harbor epidermal growth factor receptor (EGFR) mutations and are undergoing first-line treatment with EGFR-tyrosine kinase inhibitors (EGFR-TKIs). METHODS A cohort comprising 52 patients with late-stage lung adenocarcinoma, who received treatment at Jinzhou Central Hospital between January 2018 and December 2022, were carefully selected. Patient data spanning from pre-treatment assessments through follow-up periods were meticulously collected from electronic medical records and subsequently subjected to a comprehensive retrospective analysis. The collected data was subjected to in-depth processing and analyzed using SPSS 27.0 statistical software. To determine the optimal cut-off value of the pre-treatment SIRI, a receiver operating characteristic (ROC) curve was employed. Survival analysis was performed using the Kaplan-Meier method, and both univariate and multivariate prognostic analyses were conducted using Cox regression. RESULTS The optimal SIRI cut-off value was determined to be 1.659 (with a specificity of 0.964 and sensitivity of 0.652, P = 0.000). Based on this value, patients were categorized into high and low SIRI groups. Chi-squared tests demonstrated that SIRI exhibited statistically significant correlations with patient age and smoking history (P < 0.05). Survival analysis revealed that the group with a lower SIRI had a significantly extended progression-free survival (PFS) (P < 0.001). Cox univariate analysis identified hypertension, pleural metastasis, liver metastasis, and SIRI as factors associated with PFS (P < 0.05). In the subsequent multivariate analysis, liver metastasis and SIRI ≥ 1.659 (P < 0.001) were identified as independent risk factors for patients. CONCLUSION Pre-treatment SIRI holds predictive significance for the prognosis of patients with late-stage lung adenocarcinoma with EGFR mutations undergoing first-line treatment EGFR-TKI treatment.
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Affiliation(s)
- Herong Wang
- Graduate Student Training Base of Jinzhou Medical University (Central Hospital of Jinzhou), Jinzhou 121000, China
| | - Wei Li
- Department of Oncology, Central Hospital of Jinzhou, Jinzhou 121000, China.
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Yildirim S, Dogan A, Akdag G, Yüksel Yasar Z, Bal H, Kinikoglu O, Oksuz S, Ozkerim U, Tunbekici S, Yildiz HS, Alan O, Coban Kokten S, Isik D, Surmeli H, Basoglu T, Sever ON, Odabas H, Yildirim ME, Turan N. The role of laboratory indices on treatment response and survival in breast cancer receiving neoadjuvant chemotherapy. Sci Rep 2024; 14:12123. [PMID: 38802494 PMCID: PMC11130235 DOI: 10.1038/s41598-024-63096-7] [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: 01/31/2024] [Accepted: 05/24/2024] [Indexed: 05/29/2024] Open
Abstract
Neoadjuvant chemotherapy (NACT) is the standard treatment for locally advanced, high-risk breast cancer. Pathological complete response (pCR) improves survival. Peripheral blood-derived indices reflecting systemic inflammation and nutritional status have long been used as predictive and prognostic markers in solid malignancies. This retrospective study investigates whether eight commonly used indices in patients receiving NACT affect pCR and survival. This study includes 624 locally advanced breast cancer patients who received NACT. The biomarker indices were calculated from peripheral blood samples taken two weeks before starting chemotherapy. The indices' optimal cut-off values were determined using ROC Curve analysis. During a median follow-up period of 42 months, recurrence was detected in 146 patients, and 75 patients died. pCR was observed in 166 patients (26.6%). In univariate analysis, NLR, PLR, SII, PNI, HALP, and HRR were statistically significantly associated (p = 0.00; p = 0.03; p = 0.03; p = 0.02; p = 0.00; p = 0.02 respectively), but in multivariate analysis, only NLR was significantly predictive for pCR(p = 0.04). In multivariate analysis, the HGB/RDW score significantly predicted DFS(p = 0.04). The PNI score was identified as a marker predicting survival for both OS and PFS (p = 0.01, p = 0.01, respectively). In conclusion, peripheral blood-derived indices have prognostic and predictive values on pCR and survival. However, further studies are needed to validate our findings.
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Affiliation(s)
- Sedat Yildirim
- Department of Medical Oncology, Kartal Dr. Lütfi Kirdar City Hospital, Health Science University, Cevizli, D-100 Güney Yanyol, Cevizli Mevkii No:47, 34865, Kartal, Istanbul, Turkey.
| | - Akif Dogan
- Department of Medical Oncology, Kartal Dr. Lütfi Kirdar City Hospital, Health Science University, Cevizli, D-100 Güney Yanyol, Cevizli Mevkii No:47, 34865, Kartal, Istanbul, Turkey
| | - Goncagul Akdag
- Department of Medical Oncology, Kartal Dr. Lütfi Kirdar City Hospital, Health Science University, Cevizli, D-100 Güney Yanyol, Cevizli Mevkii No:47, 34865, Kartal, Istanbul, Turkey
| | - Zeynep Yüksel Yasar
- Department of Medical Oncology, Kartal Dr. Lütfi Kirdar City Hospital, Health Science University, Cevizli, D-100 Güney Yanyol, Cevizli Mevkii No:47, 34865, Kartal, Istanbul, Turkey
| | - Hamit Bal
- Department of Medical Oncology, Kartal Dr. Lütfi Kirdar City Hospital, Health Science University, Cevizli, D-100 Güney Yanyol, Cevizli Mevkii No:47, 34865, Kartal, Istanbul, Turkey
| | - Oguzcan Kinikoglu
- Department of Medical Oncology, Kartal Dr. Lütfi Kirdar City Hospital, Health Science University, Cevizli, D-100 Güney Yanyol, Cevizli Mevkii No:47, 34865, Kartal, Istanbul, Turkey
| | - Sila Oksuz
- Department of Medical Oncology, Kartal Dr. Lütfi Kirdar City Hospital, Health Science University, Cevizli, D-100 Güney Yanyol, Cevizli Mevkii No:47, 34865, Kartal, Istanbul, Turkey
| | - Ugur Ozkerim
- Department of Medical Oncology, Kartal Dr. Lütfi Kirdar City Hospital, Health Science University, Cevizli, D-100 Güney Yanyol, Cevizli Mevkii No:47, 34865, Kartal, Istanbul, Turkey
| | - Salih Tunbekici
- Department of Medical Oncology, Kartal Dr. Lütfi Kirdar City Hospital, Health Science University, Cevizli, D-100 Güney Yanyol, Cevizli Mevkii No:47, 34865, Kartal, Istanbul, Turkey
| | - Hacer Sahika Yildiz
- Department of Medical Oncology, Kartal Dr. Lütfi Kirdar City Hospital, Health Science University, Cevizli, D-100 Güney Yanyol, Cevizli Mevkii No:47, 34865, Kartal, Istanbul, Turkey
| | - Ozkan Alan
- Division of Medical Oncology, School of Medicine, Koç University, Istanbul, Turkey
| | - Sermin Coban Kokten
- Department of Pathology, Kartal Dr. Lütfi Kirdar City Hospital, Health Science University, Istanbul, Turkey
| | - Deniz Isik
- Department of Medical Oncology, Kartal Dr. Lütfi Kirdar City Hospital, Health Science University, Cevizli, D-100 Güney Yanyol, Cevizli Mevkii No:47, 34865, Kartal, Istanbul, Turkey
| | - Heves Surmeli
- Department of Medical Oncology, Kartal Dr. Lütfi Kirdar City Hospital, Health Science University, Cevizli, D-100 Güney Yanyol, Cevizli Mevkii No:47, 34865, Kartal, Istanbul, Turkey
| | - Tugba Basoglu
- Department of Medical Oncology, Kartal Dr. Lütfi Kirdar City Hospital, Health Science University, Cevizli, D-100 Güney Yanyol, Cevizli Mevkii No:47, 34865, Kartal, Istanbul, Turkey
| | - Ozlem Nuray Sever
- Department of Medical Oncology, Kartal Dr. Lütfi Kirdar City Hospital, Health Science University, Cevizli, D-100 Güney Yanyol, Cevizli Mevkii No:47, 34865, Kartal, Istanbul, Turkey
| | - Hatice Odabas
- Department of Medical Oncology, Kartal Dr. Lütfi Kirdar City Hospital, Health Science University, Cevizli, D-100 Güney Yanyol, Cevizli Mevkii No:47, 34865, Kartal, Istanbul, Turkey
| | - Mahmut Emre Yildirim
- Department of Medical Oncology, Kartal Dr. Lütfi Kirdar City Hospital, Health Science University, Cevizli, D-100 Güney Yanyol, Cevizli Mevkii No:47, 34865, Kartal, Istanbul, Turkey
| | - Nedim Turan
- Department of Medical Oncology, Kartal Dr. Lütfi Kirdar City Hospital, Health Science University, Cevizli, D-100 Güney Yanyol, Cevizli Mevkii No:47, 34865, Kartal, Istanbul, Turkey
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12
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Mao KY, Cao YC, Si MY, Rao DY, Gu L, Tang ZX, Zhu SY. Advances in systemic immune inflammatory indices in non-small cell lung cancer: A review. Medicine (Baltimore) 2024; 103:e37967. [PMID: 38701309 PMCID: PMC11062741 DOI: 10.1097/md.0000000000037967] [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: 08/10/2023] [Accepted: 03/29/2024] [Indexed: 05/05/2024] Open
Abstract
Lung cancer is one of the most prevalent cancers globally, with non-small cell lung cancers constituting the majority. These cancers have a high incidence and mortality rate. In recent years, a growing body of research has demonstrated the intricate link between inflammation and cancer, highlighting that inflammation and cancer are inextricably linked and that inflammation plays a pivotal role in cancer development, progression, and prognosis of cancer. The Systemic Immunoinflammatory Index (SII), comprising neutrophil, lymphocyte, and platelet counts, is a more comprehensive indicator of the host's systemic inflammation and immune status than a single inflammatory index. It is widely used in clinical practice due to its cost-effectiveness, simplicity, noninvasiveness, and ease of acquisition. This paper reviews the impact of SII on the development, progression, and prognosis of non-small cell lung cancer.
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Affiliation(s)
- Kai-Yun Mao
- First Clinical Medical College, Gannan Medical University, Ganzhou, China
| | - Yuan-Chao Cao
- First Clinical Medical College, Gannan Medical University, Ganzhou, China
| | - Mao-Yan Si
- Department of Cardiothoracic Surgery, The First Affiliated Hospital of Gannan Medical University, Ganzhou, China
| | - Ding-yu Rao
- Department of Cardiothoracic Surgery, The First Affiliated Hospital of Gannan Medical University, Ganzhou, China
| | - Liang Gu
- Department of Cardiothoracic Surgery, The First Affiliated Hospital of Gannan Medical University, Ganzhou, China
| | - Zhi-Xian Tang
- Department of Cardiothoracic Surgery, The First Affiliated Hospital of Gannan Medical University, Ganzhou, China
| | - Shen-yu Zhu
- Department of Cardiothoracic Surgery, The First Affiliated Hospital of Gannan Medical University, Ganzhou, China
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13
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Tang M, Yin Y, Wang W, Gong K, Dong J, Gao X, Li J, Fang L, Ma J, Hong Y, Li Z, Bi T, Zhang W, Liu W. Exploring the multifaceted effects of Interleukin-1 in lung cancer: From tumor development to immune modulation. Life Sci 2024; 342:122539. [PMID: 38423172 DOI: 10.1016/j.lfs.2024.122539] [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: 11/27/2023] [Revised: 02/21/2024] [Accepted: 02/25/2024] [Indexed: 03/02/2024]
Abstract
Lung cancer, acknowledged as one of the most fatal cancers globally, faces limited treatment options on an international scale. The success of clinical treatment is impeded by challenges such as late diagnosis, restricted treatment alternatives, relapse, and the emergence of drug resistance. This predicament has led to a saturation point in lung cancer treatment, prompting a rapid shift in focus towards the tumor microenvironment (TME) as a pivotal area in cancer research. Within the TME, Interleukin-1 (IL-1) is abundantly present, originating from immune cells, tissue stromal cells, and tumor cells. IL-1's induction of pro-inflammatory mediators and chemokines establishes an inflammatory milieu influencing tumor occurrence, development, and the interaction between tumors and the host immune system. Notably, IL-1 expression in the TME exhibits characteristics such as staging, tissue specificity, and functional pluripotency. This comprehensive review aims to delve into the impact of IL-1 on lung cancer, encompassing aspects of occurrence, invasion, metastasis, immunosuppression, and immune surveillance. The ultimate goal is to propose a novel treatment approach, considering the intricate dynamics of IL-1 within the TME.
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Affiliation(s)
- Mingbo Tang
- Department of Thoracic Surgery, The First Hospital of Jilin University, Changchun, Jilin, 130021, China
| | - Yipeng Yin
- Department of Thoracic Surgery, The First Hospital of Jilin University, Changchun, Jilin, 130021, China
| | - Wei Wang
- Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education, Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China; Shandong Key Laboratory of Endocrinology and Lipid Metabolism, Jinan, Shandong 250021, China; Shandong Institute of Endocrine and Metabolic Diseases, Jinan, Shandong 250021, China; "Chuangxin China" Innovation Base of stem cell and Gene Therapy for endocrine Metabolic diseases, Jinan, Shandong 250021, China; Shandong Engineering Laboratory of Prevention and Control for Endocrine and Metabolic Diseases, Jinan, Shandong 250021, China; Shandong Engineering Research Center of Stem Cell and Gene Therapy for Endocrine and Metabolic Diseases, Jinan, Shandong 250021, China
| | - Kejian Gong
- Department of Thoracic Surgery, The First Hospital of Jilin University, Changchun, Jilin, 130021, China
| | - Junxue Dong
- Laboratory of Infection Oncology, Institute of Clinical Molecular Biology, Universitätsklinikum Schleswig-Holstein (UKSH), Christian Albrechts University of Kiel, Kiel, Germany
| | - Xinliang Gao
- Department of Thoracic Surgery, The First Hospital of Jilin University, Changchun, Jilin, 130021, China
| | - Jialin Li
- Department of Thoracic Surgery, The First Hospital of Jilin University, Changchun, Jilin, 130021, China
| | - Linan Fang
- Department of Thoracic Surgery, The First Hospital of Jilin University, Changchun, Jilin, 130021, China
| | - Jianzun Ma
- Department of Thoracic Surgery, The First Hospital of Jilin University, Changchun, Jilin, 130021, China
| | - Yang Hong
- Department of Thoracic Surgery, The First Hospital of Jilin University, Changchun, Jilin, 130021, China
| | - Zhiqin Li
- Department of Thoracic Surgery, The First Hospital of Jilin University, Changchun, Jilin, 130021, China
| | - Taiyu Bi
- Department of Thoracic Surgery, The First Hospital of Jilin University, Changchun, Jilin, 130021, China
| | - Wenyu Zhang
- Department of Thoracic Surgery, The First Hospital of Jilin University, Changchun, Jilin, 130021, China
| | - Wei Liu
- Department of Thoracic Surgery, The First Hospital of Jilin University, Changchun, Jilin, 130021, China.
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14
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Zaoui M, Louadj L, Ferrand N, Nehme R, Sabbah M, Abdennebi-Najar L. Carcinogenic effect of low doses of polycyclic and heterocyclic aromatic hydrocarbons and amines and lack of protection by inulin supplementation. Food Chem Toxicol 2024; 185:114454. [PMID: 38237855 DOI: 10.1016/j.fct.2024.114454] [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: 07/02/2023] [Revised: 12/29/2023] [Accepted: 01/12/2024] [Indexed: 02/05/2024]
Abstract
Evidence suggests that meat processing and heat treatment may increase cancer risk through exposure to potentially carcinogenic compounds, polycyclic aromatic hydrocarbons (PAHs), and heterocyclic aromatic amines (HAAs). This study aims to investigate the effect of low concentrations of PAHs and HAAs (from 1 to 100 μmol/L/24h and 48h) in colorectal tumor cells (HT-29, HCT116, and LS174T) and to evaluate the effect of PAHs in the presence of inulin in mice. In vitro, the 4-PAHs have no effect on healthy colon cells but decreased the viability of the colorectal tumor cells and activated the mRNA and protein expressions of CYP1A1 and CYP1B1. In vivo, in mice with colitis induced by 3% DSS, the 4-PAHs (equimolar mix at 50,100, 150 mg/kg.bw, orally 3 times a week for 3 weeks) induced a loss of body weight and tumor formation. Inulin (10 g/L) had no effect on colon length and tumor formation. A significant decrease in the loss of b.w was observed in inulin group as compared to the fiber free group. These results underscore the importance of considering the biological association between low-dose exposure to 4-HAPs and diet-related colon tumors.
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Affiliation(s)
- Maurice Zaoui
- Sorbonne Université-INSERM UMR 938, Centre de Recherche Saint-Antoine (CRSA), Institut Universitaire de Cancérologie (IUC), Paris, France
| | - Lila Louadj
- Sorbonne Université-INSERM UMR 938, Centre de Recherche Saint-Antoine (CRSA), Institut Universitaire de Cancérologie (IUC), Paris, France
| | - Nathalie Ferrand
- Sorbonne Université-INSERM UMR 938, Centre de Recherche Saint-Antoine (CRSA), Institut Universitaire de Cancérologie (IUC), Paris, France
| | - Ralph Nehme
- Quality and Health Department, IDELE Institute, 149 Rue de Bercy, 75012 Paris, France
| | - Michele Sabbah
- Sorbonne Université-INSERM UMR 938, Centre de Recherche Saint-Antoine (CRSA), Institut Universitaire de Cancérologie (IUC), Paris, France
| | - Latifa Abdennebi-Najar
- Quality and Health Department, IDELE Institute, 149 Rue de Bercy, 75012 Paris, France; Sorbonne Université-INSERM UMR 938, Centre de Recherche Saint-Antoine (CRSA), Institut Universitaire de Cancérologie (IUC), Paris, France.
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15
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Khiji MN, Arghidash F, Tanha GK, Zadeh RH, Ghorbani E, Khazaei M, Hassanian SM, Gataa IS, Lam AKY, Giovannetti E, Ferns GA, Nazari E, Avan A. The Therapeutic Application of Hydrogen in Cancer: The Potential and Challenges. Curr Pharm Des 2024; 30:1295-1306. [PMID: 38638053 DOI: 10.2174/0113816128296710240404040232] [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: 01/01/2024] [Revised: 03/09/2024] [Accepted: 03/12/2024] [Indexed: 04/20/2024]
Abstract
Hydrogen therapy has emerged as a possible approach for both preventing and treating cancer. Cancers are often associated with oxidative stress and chronic inflammation. Hydrogen, with its unique physiological functions and characteristics, exhibits antioxidant, anti-inflammatory, and anti-apoptotic properties, making it an attractive candidate for cancer treatment. Through its ability to mitigate oxidative damage, modulate inflammatory responses, and sustain cellular viability, hydrogen demonstrates significant potential in preventing cancer recurrence and improving treatment outcomes. Preclinical studies have shown the efficacy of hydrogen therapy in several cancer types, highlighting its ability to enhance the effectiveness of conventional treatments while reducing associated side effects. Furthermore, hydrogen therapy has been found to be safe and well-tolerated in clinical settings. Nonetheless, additional investigations are necessary to improve a comprehensive understanding of the mechanisms underlying hydrogen's therapeutic potential and refine the administration and dosage protocols. However, further clinical trials are still needed to explore its safety profile and capacity. In aggregate, hydrogen therapy represents an innovative and promising treatment for several malignancies.
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Affiliation(s)
- Morteza Nazari Khiji
- Student Research Committee, Sabzevar University of Medical Sciences, Sabzevar, Iran
| | - Faezeh Arghidash
- Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Ghazaleh Khalili Tanha
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Rasoul Hossein Zadeh
- Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Elnaz Ghorbani
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Majid Khazaei
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Seyed Mahdi Hassanian
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | | | - Alfred King-Yin Lam
- Department of Pathology, School of Medicine and Dentistry, Griffith University, Gold Coast Campus, Gold Coast, QLD 4222, Australia
| | - Elisa Giovannetti
- Cancer Pharmacology Lab, AIRC Start Up Unit, Fondazione Pisana per La Scienza, Pisa, Italy
- Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam U.M.C., VU University Medical Center [VUMC], Amsterdam, The Netherlands
| | - Gordon A Ferns
- Division of Medical Education, Brighton & Sussex Medical School, Falmer, Brighton, Sussex BN1 9PH, UK
| | - Elham Nazari
- Department of Health Information, Technology and Management, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Amir Avan
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Faculty of Health, School of Biomedical Sciences, Queensland University of Technology, Brisbane, Australia
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16
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Karaoğlan BB, Savaş B, Utkan G, Ürün Y. Exploring the connection between microsatellite instability and inflammatory indicators in cancers. Future Oncol 2024; 20:95-105. [PMID: 38318682 DOI: 10.2217/fon-2023-0695] [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] [Indexed: 02/07/2024] Open
Abstract
Aim: This study aimed to investigate the association between microsatellite instability (MSI) status and inflammatory indicators in patients with cancer. Patients & methods: A total of 204 patients with various cancer diagnoses, including 102 with MSI-high (MSI-H) and 102 with microsatellite stable tumors, were enrolled. Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), C-reactive protein (CRP)-to-albumin ratio and systemic immune-inflammation index were evaluated. Results: In microsatellite stable patients, NLR, LMR, PLR and systemic immune-inflammation index were significantly linked to worse survival in univariate analysis, and having a LMR ≤2.6 negatively affected survival in multivariate analysis, although these indicators did not affect the survival of MSI-H patients. Conclusion: The impact of chronic inflammation on survival varies with MSI status. Further research is needed for targeted therapies in different tumors.
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Affiliation(s)
| | - Berna Savaş
- Ankara University School of Medicine, Department of Pathology, 06230
| | - Güngör Utkan
- Ankara University School of Medicine, Department of Medical Oncology, 06620
| | - Yüksel Ürün
- Ankara University School of Medicine, Department of Medical Oncology, 06620
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17
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Li M, Gui J, Wang H, An J, Wu R, Liu X, Wu B, Xiao H. Prognostic Value of Platelet Aggregation Function in Patients with laryngeal Carcinoma. Int J Gen Med 2023; 16:5559-5566. [PMID: 38034899 PMCID: PMC10683666 DOI: 10.2147/ijgm.s428122] [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: 07/23/2023] [Accepted: 10/18/2023] [Indexed: 12/02/2023] Open
Abstract
Background Laryngeal cancer was one of the most common malignancies of the head in those years. It has become one of the most common causes of death due to its high recurrence rate and high metastasis rate. It was well known that platelets, especially activated platelets, promote the proliferation, division, and invasion of tumor cells. Activated platelets promote cancer progression and metastasis. However, the prognostic value of platelet aggregation function in laryngeal cancer remains poorly understood. The purpose of this study was to investigate the predictive significance of platelet aggregation function in laryngeal cancer. Materials and Methods Between January 2015 and December 2016, we conducted a retrospective analysis of 203 patients who were diagnosed with laryngeal cancer consecutively. The patients were stratified by platelet aggregation function into two groups: low "adenosine diphosphate induced light transmittance aggregometry (ADP-induced LTA) ≤15.1" and high (ADP-induced LTA >15.1). Pathological tissues from different parts of the operation were collected and the pathologist determined the pathological type. We assessed the prognostic significance of platelet aggregation function using Kaplan-Meier curves and Cox regression. Results The low cohort had a significantly higher lymphocyte count than the high cohort. Compared with the high cohort, the low cohort had significantly lower levels of platelet-to-lymphocyte ratio (PLR), ADP-induced LTA, and Interleukins (IL)-6. The ADP-induced LTA (hazard ratio, 1.212; P <0.001) was independently related with 5-year overall survival rate. Conclusion Patients with ADP-induced LTA >15.1 experience poor outcomes. Platelet aggregation function, when elevated, could be a new prognostic indicator for laryngeal cancer.
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Affiliation(s)
- Minghua Li
- Department of Otolaryngology-Head and Neck Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, People’s Republic of China
| | - Jiawei Gui
- Department of Otolaryngology-Head and Neck Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, People’s Republic of China
| | - Hao Wang
- Department of Otolaryngology-Head and Neck Surgery, The Affiliated BenQ Hospital of Nanjing Medical University, Nanjing, 210019, People’s Republic of China
| | - Jun An
- Department of Otolaryngology-Head and Neck Surgery, Xuzhou Central Hospital, Xuzhou, 221009, People’s Republic of China
| | - Ruoqing Wu
- Department of Otolaryngology-Head and Neck Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, People’s Republic of China
| | - Xiaotong Liu
- Department of Otolaryngology-Head and Neck Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, People’s Republic of China
| | - Bo Wu
- Department of Otolaryngology-Head and Neck Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, People’s Republic of China
| | - Hui Xiao
- Department of Otolaryngology-Head and Neck Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, People’s Republic of China
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18
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Mishra S, Persons PA, Lorenzo AM, Chaliki SS, Bersoux S. Time-Restricted Eating and Its Metabolic Benefits. J Clin Med 2023; 12:7007. [PMID: 38002621 PMCID: PMC10672223 DOI: 10.3390/jcm12227007] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2023] [Revised: 10/26/2023] [Accepted: 11/04/2023] [Indexed: 11/26/2023] Open
Abstract
Newer management strategies are being evaluated to treat obesity, which continues to increase worldwide. After 12 h of fasting, the body switches from glucose to fat metabolism, regulating protein synthesis and autophagy. These cellular responses are central to the metabolic benefits of time-restricted eating (TRE), independent of calorie restriction and weight loss, and they have heightened interest in TRE regimens. Controversy remains, however, regarding the benefits of TRE regimens. We reviewed the current literature and concluded that TRE is equivalent to calorie restriction for weight loss and has positive effects for patients with diseases such as nonalcoholic fatty liver disease, cancer, and cardiovascular disease.
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Affiliation(s)
- Sneha Mishra
- Division of Community Internal Medicine Mayo Clinic, Scottsdale, AZ 85259, USA; (P.A.P.); (A.M.L.); (S.S.C.); (S.B.)
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19
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Qi X, Qiao B, Song T, Huang D, Zhang H, Liu Y, Jin Q, Yang M, Liu D. Clinical utility of the pan-immune-inflammation value in breast cancer patients. Front Oncol 2023; 13:1223786. [PMID: 37711203 PMCID: PMC10499041 DOI: 10.3389/fonc.2023.1223786] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Accepted: 08/14/2023] [Indexed: 09/16/2023] Open
Abstract
Background The newly discovered pan-immune-inflammation value (PIV) has been illustrated to have good prognostic value for cancer patient prognosis. However, the prognostic usefulness of PIV in breast cancer patients is unknown. As a result, to aid the clinic in providing a distinctive and trustworthy biomarker to better assess breast cancer patient's prognosis, we conducted this meta-analysis to investigate the relationship between PIV and the survival of breast cancer patients. Methods We conducted a systematic search of Pubmed, Embase, the Cochrane Library, and the CNKI databases to screen for eligible studies published up to April 2023. Outcomes included overall survival (OS), progression-free survival (PFS), and pathological complete response (pCR). The hazard ratio (HR) and the corresponding 95% confidence interval (CI) were used as the indicators. STATA 15.0 software was used to perform meta-analysis, sensitivity analysis, and publication bias analysis. Results A total of eight articles, involving 2953 patients, met the inclusion criteria and were included in this meta-analysis. The results showed that patients with higher PIV levels had a significantly shorter OS (HR: 2.045, 95% CI: 1.355-3.086, P = 0.001) and PFS (HR: 1.466, 95% CI: 1.163-1.848, P = 0.001). Besides, the PIV value was negatively correlated with the efficacy of neoadjuvant chemotherapy. Sensitivity analysis showed that the results of this study were reliable and stable. Conclusions PIV has a good prognostic value in breast cancer patients and is expected to be a prognostic biomarker for breast cancer.
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Affiliation(s)
- Xiaoyan Qi
- Department of Breast Surgery, Liaoning Cancer Hospital & Institution, Shenyang, Liaoning, China
- Department of Breast Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun, China
| | - Boyang Qiao
- School of Pharmaceutical Sciences, Wuhan University, Wuhan, China
| | - Tingting Song
- Department of Breast Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun, China
| | - Dan Huang
- Department of Breast Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun, China
| | - Hui Zhang
- Department of Breast Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun, China
| | - Yang Liu
- Department of Breast Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun, China
| | - Qi Jin
- Department of Neurology and Neuroscience Center, The First Hospital of Jilin University, Changchun, China
| | - Ming Yang
- Department of Breast Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun, China
| | - Delong Liu
- Department of Thoracic Surgery, Liaoning Cancer Hospital & Institution, Shenyang, Liaoning, China
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Liu HL, Feng X, Tang MM, Zhou HY, Peng H, Ge J, Liu T. Prognostic significance of preoperative lymphocyte to monocyte ratio in patients with signet ring gastric cancer. World J Gastrointest Surg 2023; 15:1673-1683. [PMID: 37701703 PMCID: PMC10494583 DOI: 10.4240/wjgs.v15.i8.1673] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2023] [Revised: 05/31/2023] [Accepted: 06/21/2023] [Indexed: 08/25/2023] Open
Abstract
BACKGROUND The ratio of lymphocytes to monocytes (LMR) has been shown to be an effective predictor of gastric cancer prognosis. However, its predictive accuracy for signet ring gastric cancer is currently not well understood. AIM To evaluate the prognosis predictive accuracy of preoperative LMR in signet ring gastric cancer. METHODS A total of 212 signet ring gastric cancer patients admitted at the Xiangya Hospital of Central South University, Department of Gastrointestinal Surgery, from January 2012 to December 2016 were enrolled in the study. The prognosis predictive accuracy of preoperative LMR was explored based on the area under the receiver operating characteristic. Factors that significantly affect the survival of patients were identified using single factor analysis, and those that were independently associated with signet ring gastric cancer were identified through multivariate analysis. RESULTS The results of the single factor analysis revealed a strong correlation between the survival of signet ring gastric cancer patients and several factors, including tumor invasion (χ2 = 49.726; P < 0.001), lymph node metastasis (χ2 = 30.269; P < 0.001), pTNM stage (χ2 = 49.322; P < 0.001), surgical approach (χ2 = 8.489; P = 0.004), age (t = -2.213; P < 0.028), carcinoembryonic antigen (CEA) (Z = -3.265; P = 0.001), platelet-to-lymphocyte ratio (Z = -2.196; P = 0.028), LMR (Z = -2.226; P = 0.026), ALB (t = 3.284; P = 0.001), prognostic nutritional index (t = -3.789; P < 0.001) and FIB (Z = -3.065; P = 0.002). Furthermore, the multivariate analysis further demonstrated that age (HR: 0.563, 95%CI: 0.363-0.873), tumor invasion depth (HR: 0.226, 95%CI: 0.098-0.520), pTNM stage (HR: 0.444, 95%CI: 0.255-0.771), preoperative CEA level (HR: 0.597, 95%CI: 0.386-8.790), and preoperative LMR level (HR: 1.776, 95%CI: 1.150-2.741) were independent factors influencing the prognosis of signet ring gastric cancer. CONCLUSION In signet ring gastric cancer patients, a low preoperative LMR level predicts poor prognosis. The death risk ratio of the low LMR group compared to the high LMR group is 1.776.
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Affiliation(s)
- He-Li Liu
- Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
- The Hunan Provincial Key Laboratory of Precision Diagnosis and Treatment for Gastrointestinal Tumor, The Hunan Provincial Key Laboratory of Precision Diagnosis and Treatment for Gastrointestinal Tumor, Changsha 410008, Hunan Province, China
| | - Xiang Feng
- Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
| | - Mi-Mi Tang
- Institute for Rational and Safe Medication Practices National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
| | - Hai-Yan Zhou
- Department of Pathology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
| | - Huan Peng
- Clinical Nursing Teaching and Research Section, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
| | - Jie Ge
- Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
| | - Ting Liu
- Institute for Rational and Safe Medication Practices National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
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Sharma A, Choi HK, Lee HJ. Carbon Dots for the Treatment of Inflammatory Diseases: An Appraisal of In Vitro and In Vivo Studies. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2023; 2023:3076119. [PMID: 37273553 PMCID: PMC10234732 DOI: 10.1155/2023/3076119] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/03/2022] [Revised: 02/16/2023] [Accepted: 04/25/2023] [Indexed: 06/06/2023]
Abstract
In recent decades, several studies demonstrating various applications of carbon dots (C-dots), including metal sensing, bioimaging, pH sensing, and antimicrobial activities, have been published. Recent developments have shifted this trend toward biomedical applications that target various biomarkers relevant to chronic diseases. However, relevant developments and research results regarding the anti-inflammatory properties of C-dots against inflammation-associated diseases have not been systematically reviewed. Hence, this review discusses the anti-inflammatory effects of C-dots in in vivo and in vitro models of LPS-induced inflammation, gout, cartilage tissue engineering, drug-induced inflammation, spinal cord injury, wound healing, liver diseases, stomach cancer, gastric ulcers, acute kidney and lung injury, psoriasis, fever or hypothermia, and bone tissue regeneration. The compiled studies demonstrate the promising potential of C-dots as anti-inflammatory agents for the development of new drugs.
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Affiliation(s)
- Anshul Sharma
- College of Bionanotechnology, Department of Food and Nutrition, Gachon University, Gyeonggi-do 13120, Republic of Korea
| | - Hyo-Kyoung Choi
- Korea Food Research Institute, 245, Nongsaengmyeong-ro, Iseo-myeon, Wanju-gun, Jeollabuk-do, Republic of Korea 55365
| | - Hae-Jeung Lee
- College of Bionanotechnology, Department of Food and Nutrition, Gachon University, Gyeonggi-do 13120, Republic of Korea
- Institute for Aging and Clinical Nutrition Research, Gachon University, Gyeonggi-do 13120, Republic of Korea
- Department of Health Sciences and Technology, GAIHST, Gachon University, Incheon 21999, Republic of Korea
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Myriagkou M, Papakonstantinou E, Deligiannidou GE, Patsilinakos A, Kontogiorgis C, Pontiki E. Novel Pyrimidine Derivatives as Antioxidant and Anticancer Agents: Design, Synthesis and Molecular Modeling Studies. Molecules 2023; 28:molecules28093913. [PMID: 37175322 PMCID: PMC10180197 DOI: 10.3390/molecules28093913] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2023] [Revised: 04/28/2023] [Accepted: 05/02/2023] [Indexed: 05/15/2023] Open
Abstract
The heterocyclic ring system of pyrido [2,3-d]pyrimidines is a privileged scaffold in medicinal chemistry, possessing several biological activities. The synthesis of the pyrimidine derivatives was performed via the condensation of a suitable α,β-unsaturated ketone with 4-amino-6-hydroxy-2-mercaptopyrimidine monohydrate in glacial acetic acid. Chalcones were synthesized, as starting materials, via the Claisen-Schmidt condensation of an appropriately substituted ketone and an appropriately substituted aldehyde in the presence of aqueous KOH 40% w/v in ethanol. All the synthesized compounds were characterized using IR, 1H-NMR, 13C-NMR, LC-MS and elemental analysis. The synthesized compounds were evaluated for their antioxidant (DPPH assay), anti-lipid peroxidation (AAPH), anti-LOX activities and ability to interact with glutathione. The compounds do not interact significantly with DPPH but strongly inhibit lipid peroxidation. Pyrimidine derivatives 2a (IC50 = 42 μΜ), 2f (IC50 = 47.5 μΜ) and chalcone 1g (IC50 = 17 μM) were the most potent lipoxygenase inhibitors. All the tested compounds were found to interact with glutathione, apart from 1h. Cell viability and cytotoxicity assays were performed with the HaCaT and A549 cell lines, respectively. In the MTT assay towards the HaCaT cell line, none of the compounds presented viability at 100 μM. On the contrary, in the MTT assay towards the A549 cell line, the tested compounds showed strong cytotoxicity at 100 μM, with derivative 2d presenting the strongest cytotoxic effects at the concentration of 50 μΜ.
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Affiliation(s)
- Malama Myriagkou
- Department of Pharmaceutical Chemistry, School of Pharmacy, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
| | - Evangelia Papakonstantinou
- Laboratory of Hygiene and Environmental Protection, School of Medicine, Democritus University of Thrace, 25510 Alexandroupoli, Greece
| | - Georgia-Eirini Deligiannidou
- Laboratory of Hygiene and Environmental Protection, School of Medicine, Democritus University of Thrace, 25510 Alexandroupoli, Greece
| | | | - Christos Kontogiorgis
- Laboratory of Hygiene and Environmental Protection, School of Medicine, Democritus University of Thrace, 25510 Alexandroupoli, Greece
| | - Eleni Pontiki
- Department of Pharmaceutical Chemistry, School of Pharmacy, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
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de Almeida Lança ML, Carvalho YR, Almeida JD, Kaminagakura E. Hidden colon adenocarcinoma diagnosed from mouth metastasis: case report and literature review. World J Surg Oncol 2023; 21:88. [PMID: 36899349 PMCID: PMC9999513 DOI: 10.1186/s12957-023-02978-y] [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: 11/28/2022] [Accepted: 02/27/2023] [Indexed: 03/12/2023] Open
Abstract
BACKGROUND We report an unusual case of metastatic colon adenocarcinoma to the maxilla as an initial clinical sign of the disease, this being the second case reported in the palate. In addition, we show an extensive review of the literature, with clinical cases of adenocarcinoma with metastasis to the mouth. CASE PRESENTATION An 80-year-old man complained of "swelling on the palate" with a 3-week evolution time. He reported suffering from constipation and high blood pressure. The intraoral examination revealed a pedunculated, red, and painless nodule on the maxillary gingiva. Under the diagnostic hypotheses of squamous cell carcinoma and malignant neoplasm of the salivary gland, an incisional biopsy was performed. Microscopically, the columnar epithelium was observed forming papillary areas, neoplastic cells with prominent nucleoli, hyperchromatic nuclei, atypical mitotic figures, and mucous cells, being positive for CK 20, suggesting the provisional diagnosis of metastatic adenocarcinoma, probably of gastrointestinal origin. The patient was submitted to endoscopy and colonoscopy exams, and a lesion in the sigmoid region of the colon was observed. After a colon biopsy, a moderately differentiated adenocarcinoma was confirmed, establishing the final diagnosis of metastatic neoplasia of colon adenocarcinoma to the oral lesion. The literature review revealed 45 clinical cases of colon adenocarcinoma with metastasis to the oral cavity. To the best of our knowledge, it is the second case on the palate. CONCLUSIONS Colon adenocarcinoma with metastasis to the oral cavity is rare but should be included in the differential diagnosis of neoplasms of the oral cavity, even when there are no known primary tumors in some cases, and this may be the first indication of the presence of a tumor.
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Affiliation(s)
- Maria Leticia de Almeida Lança
- Department of Bioscience and Oral Diagnosis, Institute of Science and Technology, São Paulo State University (UNESP), Avenue: Engenheiro Francisco José Longo, 777, São José dos Campos, 1245-000, Brazil
| | - Yasmin Rodarte Carvalho
- Department of Bioscience and Oral Diagnosis, Institute of Science and Technology, São Paulo State University (UNESP), Avenue: Engenheiro Francisco José Longo, 777, São José dos Campos, 1245-000, Brazil
| | - Janete Dias Almeida
- Department of Bioscience and Oral Diagnosis, Institute of Science and Technology, São Paulo State University (UNESP), Avenue: Engenheiro Francisco José Longo, 777, São José dos Campos, 1245-000, Brazil
| | - Estela Kaminagakura
- Department of Bioscience and Oral Diagnosis, Institute of Science and Technology, São Paulo State University (UNESP), Avenue: Engenheiro Francisco José Longo, 777, São José dos Campos, 1245-000, Brazil.
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Discovering the Clinical and Prognostic Role of Pan-Immune-Inflammation Values on Oral Cavity Squamous Cell Carcinoma. Cancers (Basel) 2023; 15:cancers15010322. [PMID: 36612318 PMCID: PMC9818418 DOI: 10.3390/cancers15010322] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2022] [Revised: 12/24/2022] [Accepted: 12/26/2022] [Indexed: 01/06/2023] Open
Abstract
A newly introduced pan-immune-inflammation value (PIV) was not evaluated for its role in oral cavity squamous cell carcinoma (OSCC). In this study, the PIV was calculated with the following equation (neutrophil count × platelet count × monocyte count)/lymphocyte count from the results of the automated hematology analyzers in 853 OSCC patients from 2005 to 2017. The optimal cutoff for the preoperative PIV was 268, as determined by a receiver operating characteristic curve. Significant differences were observed for alcohol consumption, smoking, pT status, pN status, overall pathological status, extranodal extension, cell differentiation, depth of invasion, and perineural invasion between higher and lower PIV patients (all p values < 0.05). Kaplan-Meier and univariate regression analyses indicated that higher PIV was associated with worse overall survival, disease-free survival, locoregional recurrence-free survival, and distant metastasis-free survival (all p values < 0.001). Multivariate analyses adjusted by various factors further demonstrated that PIV was an independent prognostic factor for overall and distant metastasis-free survival (p = 0.027, HR: 1.281 and p = 0.031, HR: 1.274, respectively). In conclusion, a higher PIV level was associated with poor clinicopathological factors in OSCC patients and could be used to predict poor posttreatment outcomes, especially for overall and distant metastasis-free survival.
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25
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Devoy C, Flores Bueso Y, Tangney M. Understanding and harnessing triple-negative breast cancer-related microbiota in oncology. Front Oncol 2022; 12:1020121. [PMID: 36505861 PMCID: PMC9730816 DOI: 10.3389/fonc.2022.1020121] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2022] [Accepted: 10/31/2022] [Indexed: 11/27/2022] Open
Abstract
Bacterial inhabitants of the body have the potential to play a role in various stages of cancer initiation, progression, and treatment. These bacteria may be distal to the primary tumour, such as gut microbiota, or local to the tissue, before or after tumour growth. Breast cancer is well studied in this context. Amongst breast cancer types, Triple Negative Breast Cancer (TNBC) is more aggressive, has fewer treatment options than receptor-positive breast cancers, has an overall worse prognosis and higher rates of reoccurrence. Thus, an in-depth understanding of the bacterial influence on TNBC progression and treatment is of high value. In this regard, the Gut Microbiota (GM) can be involved in various stages of tumour progression. It may suppress or promote carcinogenesis through the release of carcinogenic metabolites, sustenance of proinflammatory environments and/or the promotion of epigenetic changes in our genome. It can also mediate metastasis and reoccurrence through interactions with the immune system and has been recently shown to influence chemo-, radio-, and immune-therapies. Furthermore, bacteria have also been found to reside in normal and malignant breast tissue. Several studies have now described the breast and breast tumour microbiome, with the tumour microbiota of TNBC having the least taxonomic diversity among all breast cancer types. Here, specific conditions of the tumour microenvironment (TME) - low O2, leaky vasculature and immune suppression - are supportive of tumour selective bacterial growth. This innate bacterial ability could enable their use as delivery agents for various therapeutics or as diagnostics. This review aims to examine the current knowledge on bacterial relevance to TNBC and potential uses while examining some of the remaining unanswered questions regarding mechanisms underpinning observed effects.
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Affiliation(s)
- Ciaran Devoy
- Cancer Research@UCC, College of Medicine and Health, University College Cork, Cork, Ireland,SynBio Center, University College Cork, Cork, Ireland,APC Microbiome Ireland, University College Cork, Cork, Ireland
| | - Yensi Flores Bueso
- Cancer Research@UCC, College of Medicine and Health, University College Cork, Cork, Ireland,SynBio Center, University College Cork, Cork, Ireland,APC Microbiome Ireland, University College Cork, Cork, Ireland
| | - Mark Tangney
- Cancer Research@UCC, College of Medicine and Health, University College Cork, Cork, Ireland,SynBio Center, University College Cork, Cork, Ireland,APC Microbiome Ireland, University College Cork, Cork, Ireland,School of Pharmacy, College of Medicine and Health, University College Cork, Cork, Ireland,*Correspondence: Mark Tangney,
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26
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Ramírez-Patiño R, Avalos-Navarro G, Figuera LE, Varela-Hernández JJ, Bautista-Herrera LA, Muñoz-Valle JF, Gallegos-Arreola MP. Influence of nitric oxide signaling mechanisms in cancer. Int J Immunopathol Pharmacol 2022; 36:3946320221135454. [PMID: 36260949 PMCID: PMC9585559 DOI: 10.1177/03946320221135454] [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] [Indexed: 11/06/2022] Open
Abstract
Nitric oxide (NO) is a molecule with multiple biological functions that is involved in various pathophysiological processes such as neurotransmission and blood vessel relaxation as well as the endocrine system, immune system, growth factors, and cancer. However, in the carcinogenesis process, it has a dual behavior; at low doses, NO regulates homeostatic functions, while at high concentrations, it promotes tissue damage or acts as an agent for immune defense against microorganisms. Thus, its participation in the carcinogenic process is controversial. Cancer is a multifactorial disease that presents complex behavior. A better understanding of the molecular mechanisms associated with the initiation, promotion, and progression of neoplastic processes is required. Some hypotheses have been proposed regarding the influence of NO in activating oncogenic pathways that trigger carcinogenic processes, because NO might regulate some signaling pathways thought to promote cancer development and more aggressive tumor growth. Additionally, NO inhibits apoptosis of tumor cells, together with the deregulation of proteins that are involved in tissue homeostasis, promoting spreading to other organs and initiating metastatic processes. This paper describes the signaling pathways that are associated with cancer, and how the concentration of NO can serve a beneficial or pathological function in the initiation and promotion of neoplastic events.
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Affiliation(s)
- R Ramírez-Patiño
- Departamento de Ciencias Médicas y de la Vida, Centro Universitario de la Ciénega (CUCIÉNEGA), Universidad de Guadalajara, Ocotlán Jalisco, México
| | - G Avalos-Navarro
- Departamento de Ciencias Médicas y de la Vida, Centro Universitario de la Ciénega (CUCIÉNEGA), Universidad de Guadalajara, Ocotlán Jalisco, México
| | - LE Figuera
- División de Génetica, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS), Guadalajara Jalisco, México,Doctorado en Genética Humana, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, Guadalajara Jalisco, México
| | - JJ Varela-Hernández
- Departamento de Ciencias Médicas y de la Vida, Centro Universitario de la Ciénega (CUCIÉNEGA), Universidad de Guadalajara, Ocotlán Jalisco, México
| | - LA Bautista-Herrera
- Departamento de Farmacobiología, Centro Universitario de Ciencias Exactas e Ingeniería (CUCEI), Universidad de Guadalajara, Guadalajara Jalisco, México
| | - JF Muñoz-Valle
- Instituto de Investigación en Ciencias Biomédicas (IICB), Centro Universitario de Ciencias de la Salud (CUCS) Universidad de Guadalajara, Guadalajara Jalisco, México
| | - MP Gallegos-Arreola
- División de Génetica, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS), Guadalajara Jalisco, México,Martha Patricia Gallegos-Arreola, División de Genética CIBO, IMSS, Sierra Mojada 800, Col, Independencia, Guadalajara, Jalisco 44340, México.
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Islam MS, Morshed MR, Babu G, Khan MA. The role of inflammations and EMT in carcinogenesis. ADVANCES IN CANCER BIOLOGY - METASTASIS 2022; 5:100055. [DOI: 10.1016/j.adcanc.2022.100055] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/28/2024]
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Król M, Kupnicka P, Bosiacki M, Chlubek D. Mechanisms Underlying Anti-Inflammatory and Anti-Cancer Properties of Stretching-A Review. Int J Mol Sci 2022; 23:ijms231710127. [PMID: 36077525 PMCID: PMC9456560 DOI: 10.3390/ijms231710127] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Revised: 08/25/2022] [Accepted: 08/31/2022] [Indexed: 02/07/2023] Open
Abstract
Stretching is one of the popular elements in physiotherapy and rehabilitation. When correctly guided, it can help minimize or slow down the disabling effects of chronic health conditions. Most likely, the benefits are associated with reducing inflammation; recent studies demonstrate that this effect from stretching is not just systemic but also local. In this review, we present the current body of knowledge on the anti-inflammatory properties of stretching at a molecular level. A total of 22 papers, focusing on anti-inflammatory and anti-cancer properties of stretching, have been selected and reviewed. We show the regulation of oxidative stress, the expression of pro- and anti-inflammatory genes and mediators, and remodeling of the extracellular matrix, expressed by changes in collagen and matrix metalloproteinases levels, in tissues subjected to stretching. We point out that a better understanding of the anti-inflammatory properties of stretching may result in increasing its importance in treatment and recovery from diseases such as osteoarthritis, systemic sclerosis, and cancer.
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Affiliation(s)
- Małgorzata Król
- Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Powstańców Wlkp. 72, 70-111 Szczecin, Poland
| | - Patrycja Kupnicka
- Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Powstańców Wlkp. 72, 70-111 Szczecin, Poland
- Correspondence:
| | - Mateusz Bosiacki
- Chair and Department of Functional Diagnostics and Physical Medicine, Pomeranian Medical University, Żołnierska 54, 71-210 Szczecin, Poland
| | - Dariusz Chlubek
- Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Powstańców Wlkp. 72, 70-111 Szczecin, Poland
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Kumari S, Sharma S, Advani D, Khosla A, Kumar P, Ambasta RK. Unboxing the molecular modalities of mutagens in cancer. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2022; 29:62111-62159. [PMID: 34611806 PMCID: PMC8492102 DOI: 10.1007/s11356-021-16726-w] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/24/2021] [Accepted: 09/22/2021] [Indexed: 04/16/2023]
Abstract
The etiology of the majority of human cancers is associated with a myriad of environmental causes, including physical, chemical, and biological factors. DNA damage induced by such mutagens is the initial step in the process of carcinogenesis resulting in the accumulation of mutations. Mutational events are considered the major triggers for introducing genetic and epigenetic insults such as DNA crosslinks, single- and double-strand DNA breaks, formation of DNA adducts, mismatched bases, modification in histones, DNA methylation, and microRNA alterations. However, DNA repair mechanisms are devoted to protect the DNA to ensure genetic stability, any aberrations in these calibrated mechanisms provoke cancer occurrence. Comprehensive knowledge of the type of mutagens and carcinogens and the influence of these agents in DNA damage and cancer induction is crucial to develop rational anticancer strategies. This review delineated the molecular mechanism of DNA damage and the repair pathways to provide a deep understanding of the molecular basis of mutagenicity and carcinogenicity. A relationship between DNA adduct formation and cancer incidence has also been summarized. The mechanistic basis of inflammatory response and oxidative damage triggered by mutagens in tumorigenesis has also been highlighted. We elucidated the interesting interplay between DNA damage response and immune system mechanisms. We addressed the current understanding of DNA repair targeted therapies and DNA damaging chemotherapeutic agents for cancer treatment and discussed how antiviral agents, anti-inflammatory drugs, and immunotherapeutic agents combined with traditional approaches lay the foundations for future cancer therapies.
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Affiliation(s)
- Smita Kumari
- Molecular Neuroscience and Functional Genomics Laboratory, Department of Biotechnology, Delhi Technological University, Shahbad Daulatpur, Bawana Road, Delhi, 110042, India
| | - Sudhanshu Sharma
- Molecular Neuroscience and Functional Genomics Laboratory, Department of Biotechnology, Delhi Technological University, Shahbad Daulatpur, Bawana Road, Delhi, 110042, India
| | - Dia Advani
- Molecular Neuroscience and Functional Genomics Laboratory, Department of Biotechnology, Delhi Technological University, Shahbad Daulatpur, Bawana Road, Delhi, 110042, India
| | - Akanksha Khosla
- Molecular Neuroscience and Functional Genomics Laboratory, Department of Biotechnology, Delhi Technological University, Shahbad Daulatpur, Bawana Road, Delhi, 110042, India
| | - Pravir Kumar
- Molecular Neuroscience and Functional Genomics Laboratory, Department of Biotechnology, Delhi Technological University, Shahbad Daulatpur, Bawana Road, Delhi, 110042, India
| | - Rashmi K Ambasta
- Molecular Neuroscience and Functional Genomics Laboratory, Department of Biotechnology, Delhi Technological University, Shahbad Daulatpur, Bawana Road, Delhi, 110042, India.
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30
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Han R, Tian Z, Jiang Y, Guan G, Wang X, Sun X, Yu Y, Jing X. Prognostic significance of the systemic immune inflammation index in patients with metastatic and unresectable pancreatic cancer. Front Surg 2022; 9:915599. [PMID: 36111233 PMCID: PMC9468225 DOI: 10.3389/fsurg.2022.915599] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Accepted: 08/08/2022] [Indexed: 11/13/2022] Open
Abstract
PurposeSystemic inflammatory markers may be predictors of the survival rate of patients with pancreatic cancer (PC). The aim of this work was to investigate the prognostic value of markers, mainly the systemic immune inflammation index (SII), in patients with metastatic and unresectable PC and to explore the relationship between markers and liver metastasis.MethodsRecords of patients with metastatic and unresectable PC at the Affiliated Hospital of Qingdao University from January 2000 to December 2019 and who were followed until December 2020 were retrospectively analyzed. Clinical data and laboratory indexes were collected, and cut-off values for inflammatory markers were determined using median values. The Cox proportional hazard model was used to analyze the prognostic value of the markers through univariate and multivariate survival analysis.ResultsAll 253 patients met the inclusion criteria, and 102 (42.0%) patients had liver metastasis. The patients were divided into a high SII group and a low SII group, and the cut-off value was 533. In the multivariate analysis, high SII (HR = 2.151; p < 0.001), chemotherapy (HR = 0.546; p < 0.001), lymph node metastasis (HR = 4.053; p < 0.001), and distant metastasis (HR = 1.725; p = 0.001) were independent risk markers of overall survival (OS). The level of markers, mainly SII, PLR and NLR, were higher in patients with liver metastasis.ConclusionsA high level of SII is an independent risk factor for short overall survival of patients with metastatic and unresectable PC. Patients with a high level of the inflammatory markers SII, PLR, and NLR, may be more prone to early liver metastasis.
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Affiliation(s)
- Rongshuang Han
- Gastroenterology Department, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Zibin Tian
- Gastroenterology Department, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Yueping Jiang
- Gastroenterology Department, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Ge Guan
- Liver Disease Center Department, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Xiaowei Wang
- Gastroenterology Department, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Xueguo Sun
- Gastroenterology Department, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Yanan Yu
- Gastroenterology Department, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Xue Jing
- Gastroenterology Department, The Affiliated Hospital of Qingdao University, Qingdao, China
- Correspondence: Xue Jing
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Abstract
Obesity and the associated metabolic syndrome is considered a pandemic whose prevalence is steadily increasing in many countries worldwide. It is a complex, dynamic, and multifactorial disorder that presages the development of several metabolic, cardiovascular, and neurodegenerative diseases, and increases the risk of cancer. In patients with newly diagnosed cancer, obesity worsens prognosis, increasing the risk of recurrence and decreasing survival. The multiple negative effects of obesity on cancer outcomes are substantial, and of great clinical importance. Strategies for weight control have potential utility for both prevention efforts and enhancing cancer outcomes. Presently, time-restricted eating (TRE) is a popular dietary intervention that involves limiting the consumption of calories to a specific window of time without any proscribed caloric restriction or alteration in dietary composition. As such, TRE is a sustainable long-term behavioral modification, when compared to other dietary interventions, and has shown many health benefits in animals and humans. The preliminary data regarding the effects of time-restricted feeding on cancer development and growth in animal models are promising but studies in humans are lacking. Interestingly, several short-term randomized clinical trials of TRE have shown favorable effects to reduce cancer risk factors; however, long-term trials of TRE have yet to investigate reductions in cancer incidence or outcomes in the general population. Few studies have been conducted in cancer populations, but a number are underway to examine the effect of TRE on cancer biology and recurrence. Given the simplicity, feasibility, and favorable metabolic improvements elicited by TRE in obese men and women, TRE may be useful in obese cancer patients and cancer survivors; however, the clinical implementation of TRE in the cancer setting will require greater in-depth investigation.
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Affiliation(s)
- Manasi Das
- VA San Diego Healthcare System, San Diego, CA, USA.,Department of Medicine, Division of Endocrinology and Metabolism, University of California, La Jolla, San Diego, CA, USA
| | - Nicholas J G Webster
- VA San Diego Healthcare System, San Diego, CA, USA. .,Department of Medicine, Division of Endocrinology and Metabolism, University of California, La Jolla, San Diego, CA, USA. .,Moores Cancer Center, University of California, La Jolla, San Diego, CA, USA.
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Кузнецов КО, Сафина ЭР, Гаймакова ДВ, Фролова ЯС, Оганесян ИЮ, Садертдинова АГ, Назмиева КА, Исламгулов АХ, Каримова АР, Галимова АМ, Ризванова ЭВ. [Metformin and malignant neoplasms: a possible mechanism of antitumor action and prospects for use in practice]. PROBLEMY ENDOKRINOLOGII 2022; 68:45-55. [PMID: 36337018 PMCID: PMC9762452 DOI: 10.14341/probl13097] [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: 04/08/2022] [Revised: 07/13/2022] [Accepted: 07/14/2022] [Indexed: 06/16/2023]
Abstract
Metformin is a first-line antidiabetic drug for the treatment of type 2 diabetes mellitus (DM2); its molecular target is AMP-activated protein kinase (AMPK), which is involved in many metabolic processes. Metformin not only reduces blood glucose levels and improves insulin sensitivity, but also inhibits lipolysis and reduces cardiovascular risk in patients with DM2. In recent years, it has been proven that metformin slows down the aging process, stimulates hair growth, eliminates cognitive impairment, and also has an antitumor effect. Most basic studies have shown that metformin inhibits the growth of tumor cells and promotes cellular apoptosis, while clinical studies show contradictory results. This discrepancy can be explained by the difference in the concentration of metformin between basic and clinical studies. The maximum daily dose of metformin for patients with DM2 is 2500 mg / day, and the dose used in basic research was much higher. Metformin directly activates the AMPK signaling pathway, inhibits the production of reactive oxygen species, induces the activation of mTORC1, inhibits cyclin D1, which leads to a reduction in the risk of the occurrence and development of malignant neoplasms. In addition, metformin indirectly inhibits tumor growth, proliferation, invasion and metastasis by reducing the concentration of glucose in the blood, insulin resistance, as well as by reducing inflammation and affecting the tumor microenvironment. Glycolysis plays an important role in the energy metabolism of tumors, and metformin is able to have an inhibitory effect on it. Currently, studies of the mechanism of antitumor effects of metformin are becoming more extensive and in-depth, but there are still some contradictions.
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Affiliation(s)
- К. О. Кузнецов
- Российский национальный исследовательский медицинский университет им. Н.И. Пирогова
| | - Э. Р. Сафина
- Башкирский государственный медицинский университет
| | | | - Я. С. Фролова
- Первый Московский государственный медицинский университет им. И.М. Сеченова
| | - И. Ю. Оганесян
- Первый Московский государственный медицинский университет им. И.М. Сеченова
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Liu XC, Jiang YP, Sun XG, Zhao JJ, Zhang LY, Jing X. Prognostic Significance of the Systemic Immune-Inflammation Index in Patients With Cholangiocarcinoma: A Meta-Analysis. Front Oncol 2022; 12:938549. [PMID: 35875153 PMCID: PMC9300870 DOI: 10.3389/fonc.2022.938549] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2022] [Accepted: 06/13/2022] [Indexed: 11/30/2022] Open
Abstract
Background The systemic immune-inflammation index (SII) is a significant prognostic factor for neoplastic diseases. However, the prognostic value of SII in patients with cholangiocarcinoma (CCA) remains unclear. This meta-analysis aimed to investigate the prognostic value of preoperative SII in patients with CCA. Method We systematically searched for relevant studies in PubMed, Scopus, EMBASE, Web of Science, PROSPERO, and Cochrane Library databases up to March 22, 2022. Hazard ratios (HRs) and 95% confidence intervals (CIs) were used to estimate the association between SII and survival outcomes, including overall survival (OS) and recurrence-free survival. Results Five studies with 1402 patients were included in this meta-analysis to determine the prognostic value of preoperative SII. The results showed that a higher SII was associated with poor OS in patients with CCA who underwent invasive surgery (HR=1.916; 95% CI, 1.566–2.343; Z=6.329; P<0.001). The results were reliable in the subgroup analysis according to country, age, sample size, SII cutoff values, and treatment methods. Conclusions A high preoperative SII appears to be an effective and practical method for monitoring survival in patients with CCA. Systematic Review Registration International Platform of Registered Systematic. Review and Meta-Analysis Protocols (INPLASY), identifier INPLASY202240015.
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Ekwueme DU, Halpern MT, Chesson HW, Ashok M, Drope J, Hong YR, Maciosek M, Pesko MF, Kenkel DS. Health Economics Research in Primary Prevention of Cancer: Assessment, Current Challenges, and Future Directions. J Natl Cancer Inst Monogr 2022; 2022:28-41. [PMID: 35788376 PMCID: PMC9609253 DOI: 10.1093/jncimonographs/lgac014] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2021] [Accepted: 04/07/2022] [Indexed: 11/13/2022] Open
Abstract
In the past 2 decades, the demand for information on health economics research to guide health care decision making has substantially increased. Studies have provided evidence that eliminating or reducing tobacco use; eating a healthy diet, including fruit and vegetables; being physically active; reducing alcohol consumption; avoiding ultraviolet radiation; and minimizing exposure to environmental and occupational carcinogenic agents should substantially reduce cancer incidence in the population. The benefits of these primary prevention measures in reducing cancer incidence are not instantaneous. Therefore, health economics research has an important role to play in providing credible information to decision makers on the health and economic benefits of primary prevention. This article provides an overview of health economics research related to primary prevention of cancer. We addressed the following questions: 1) What are the gaps and unmet needs for performing health economics research focused on primary prevention of cancer? 2) What are the challenges and opportunities to conducting health economics research to evaluate primary prevention of cancer? and 3) What are the future directions for enhancing health economics research on primary prevention of cancer? Modeling primary prevention of cancer is often difficult given data limitations, long delays before the policy or intervention is effective, possible unintended effects of the policy or intervention, and the necessity of outside expertise to understand key inputs or outputs to the modeling. Despite these challenges, health economics research has an important role to play in providing credible information to decision makers on the health and economic benefits of primary prevention of cancer.
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Affiliation(s)
- Donatus U Ekwueme
- Division of Cancer Prevention and Control, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Michael T Halpern
- Healthcare Delivery Research Program, National Cancer Institute, Bethesda, MD, USA
| | - Harrell W Chesson
- Division of STD Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Mahima Ashok
- Health Transformation & Network Management, Blue Shield of California, Oakland, CA, USA
| | - Jeffrey Drope
- Health Policy and Administration Division of the School of Public Health at University of Illinois, Chicago, Chicago, IL, USA
| | - Young-Rock Hong
- Department of Health Service Research, Management and Policy, University of Florida, Gainesville, FL, USA
| | | | - Michael F Pesko
- Department of Economics, Georgia State University, Atlanta, GA, USA
| | - Donald S Kenkel
- Department of Economics, Cornell University, Ithaca, NY, USA
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Wang W, Xu Y, Wang X, Chu Y, Zhang H, Zhou L, Zhu H, Li J, Kuai R, Zhou F, Yang D, Peng H. Swimming Impedes Intestinal Microbiota and Lipid Metabolites of Tumorigenesis in Colitis-Associated Cancer. Front Oncol 2022; 12:929092. [PMID: 35847876 PMCID: PMC9285133 DOI: 10.3389/fonc.2022.929092] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2022] [Accepted: 06/03/2022] [Indexed: 12/09/2022] Open
Abstract
Background Accumulating data support that regular physical activity potentially inhibits chronic colitis, a risk factor for colitis-associated cancer (CAC). However, possible effects of physical activity on CAC and the underlying mechanisms remain poorly understood. Methods A pretreatment of swimming on azoxymethane/dextran sodium sulfate (AOM/DSS)-induced CAC mice was implemented to determine its protective effect. Inflammation and tumorigenesis were assessed using colorectums from C57BL/6 mice. In order to determine how swimming alters colonic lipid metabolism and gene expression, a comparative analysis was conducted. Meanwhile, alterations in intestinal microbiota and short-chain fatty acids (SCFAs) were detected and analyzed. Finally, an integration analysis of colonic lipid metabolism with gene expression and intestinal microbiota was performed respectively. Result Swimming pretreatment relieved bowel inflammation and minimized tumor formation. We demonstrated that prostaglandin E2 (PGE2)/PGE2 receptor 2 subtype (EP2) signaling as a potential regulatory target for swimming induces colonic lipid metabolites. Swimming-induced genera, Erysipelatoclostridium, Parabacteroides, Bacteroides, and Rikenellaceae_RC9_gut_group, induced intestinal SCFAs and affected the function of colonic lipid metabolites enriched in glycerophospholipid metabolism and choline metabolism in cancer. Conclusion According to our experiments, swimming pretreatment can protect mice from CAC by intervention in the possible link between colonic lipid metabolites and PGE2/EP2 signaling. Further, swimming-induced genera and probiotics promoted glycerophospholipid metabolism and choline metabolism in cancer, the major constituents of colonic lipid metabolites, and increased SCFAs, which were also important mechanisms for the anti-inflammatory and anti-tumorigenic effects of swimming.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | - Daming Yang
- *Correspondence: Haixia Peng, ; Daming Yang,
| | - Haixia Peng
- *Correspondence: Haixia Peng, ; Daming Yang,
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Risk of Anorectal Cancer Associated with Benign Anal Inflammatory Diseases: A Retrospective Matched Cohort Study. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:ijerph19127467. [PMID: 35742716 PMCID: PMC9223752 DOI: 10.3390/ijerph19127467] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Revised: 06/16/2022] [Accepted: 06/16/2022] [Indexed: 02/04/2023]
Abstract
Purpose: The purpose of our study was to evaluate the relationship between benign anal inflammatory diseases and anorectal cancer and assess its risk factors. Methods: A retrospective matched cohort study was conducted that included data from 2002 to 2013. The National Health Insurance Service National Sample Cohort data from 2002 to 2013 was used for the study. Of a total study population of 143,884 individuals, 28,110 individuals with anal fissures were assigned to the case group, while 115,774 individuals without anal fissures were assigned to the control group based on the 1:4 propensity score matching age, sex, and year (case: diagnosed year, control: health service received year). Results: The risk of anorectal cancer was higher in the case group (hazard ratio [HR]: 1.95, 95% confidence interval [CI]: 1.51–2.53) compared to the control group. After grouping anorectal cancers into anal cancer and rectal cancer, the risk remained higher in the case group (anal cancer HR: 2.79, 95% CI: 1.48–5.27; rectal cancer HR: 1.82, 95% CI; 1.37–2.42). The case group was further categorized into patients with fissures and patients with fistulas; patients with fissures showed a higher risk of developing anorectal cancer than patients with fistulas (HR: 2.05, 95% CI: 1.53–2.73 vs. HR: 1.73, 95% CI: 1.13–2.66). Study participants in their 30s and 40s had a 4.19- and 7.39-times higher risk of anorectal cancer compared to those in the higher age groups (0.64–1.84), while patients who did not have inflammatory bowel disease (IBD) had a higher risk of developing anorectal cancer (HR: 2.09, 95% CI: 1.56–2.80). Conclusions and Relevance: Patients with anal fistulas or fissures have an increased risk of being diagnosed with anorectal cancer, especially at a young age and even without IBD.
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Guven DC, Sahin TK, Erul E, Kilickap S, Gambichler T, Aksoy S. The Association between the Pan-Immune-Inflammation Value and Cancer Prognosis: A Systematic Review and Meta-Analysis. Cancers (Basel) 2022; 14:2675. [PMID: 35681656 PMCID: PMC9179577 DOI: 10.3390/cancers14112675] [Citation(s) in RCA: 77] [Impact Index Per Article: 25.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2022] [Revised: 05/25/2022] [Accepted: 05/27/2022] [Indexed: 01/27/2023] Open
Abstract
Background: Prognostic scores derived from the blood count have garnered significant interest as an indirect measure of the inflammatory pressure in cancer. The recently developed pan-immune-inflammation value (PIV), an equation including the neutrophil, platelet, monocyte, and lymphocyte levels, has been evaluated in several cohorts, although with variations in the tumor types, disease stages, cut-offs, and treatments. Therefore, we evaluated the association between survival and PIV in cancer, performing a systematic review and meta-analysis. Methods: We conducted a systematic review from the Pubmed, Medline, and Embase databases to filter the published studies until 17 May 2022. The meta-analyses were performed with the generic inverse-variance method with a random-effects model. Results: Fifteen studies encompassing 4942 patients were included. In the pooled analysis of fifteen studies, the patients with higher PIV levels had significantly increased risk of death than those with lower PIV levels (HR: 2.00, 95% CI: 1.51−2.64, p < 0.001) and increased risk of progression or death (HR: 1.80, 95% CI: 1.39−2.32, p < 0.001). Analyses were consistent across several clinical scenarios, including non-metastatic or metastatic disease, different cut-offs (500, 400, and 300), and treatment with targeted therapy or immunotherapy (p < 0.001 for each). Conclusion: The available evidence demonstrates that PIV could be a prognostic biomarker in cancer. However, further research is needed to explore the promise of PIV as a prognostic biomarker in patients with non-metastatic disease or patients treated without immunotherapy or targeted therapy.
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Affiliation(s)
- Deniz Can Guven
- Department of Medical Oncology, Hacettepe University Cancer Institute, Ankara 06100, Turkey; (S.K.); (S.A.)
| | - Taha Koray Sahin
- Department of Internal Medicine, Hacettepe University Faculty of Medicine, Ankara 06100, Turkey; (T.K.S.); (E.E.)
| | - Enes Erul
- Department of Internal Medicine, Hacettepe University Faculty of Medicine, Ankara 06100, Turkey; (T.K.S.); (E.E.)
| | - Saadettin Kilickap
- Department of Medical Oncology, Hacettepe University Cancer Institute, Ankara 06100, Turkey; (S.K.); (S.A.)
- Department of Medical Oncology, Istinye University Faculty of Medicine, Istanbul 34010, Turkey
| | - Thilo Gambichler
- Department of Dermatology, Skin Cancer Center, Ruhr-University Bochum, 44791 Bochum, Germany;
| | - Sercan Aksoy
- Department of Medical Oncology, Hacettepe University Cancer Institute, Ankara 06100, Turkey; (S.K.); (S.A.)
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Selimagic A, Dozic A, Husic-Selimovic A, Tucakovic N, Cehajic A, Subo A, Spahic A, Vanis N. The Role of Inflammation in Anal Cancer. Diseases 2022; 10:27. [PMID: 35645248 PMCID: PMC9149845 DOI: 10.3390/diseases10020027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Revised: 05/01/2022] [Accepted: 05/04/2022] [Indexed: 11/16/2022] Open
Abstract
The aim of this article was to present a summary of the current resources available in the literature regarding the role of inflammation in anal cancer development. Anal cancer is relatively uncommon, accounting for about 2.7% of all reported gastrointestinal cancers in the United States. However, the importance of understanding the pathogenesis and risk factors for anal cancer has been recognized over the last several decades due to a noticed increase in incidence worldwide. Infections, autoimmune diseases, and inflammatory diseases of unknown etiology cause chronic inflammation that promotes tumorigenesis. The association between chronic inflammation and cancer development is widely accepted. It is based on different pathophysiological mechanisms that lead to cellular transformation and changes in immunological response, allowing tumor cells to avoid apoptosis and immune surveillance. However, there are still many molecular and cellular mechanisms that remain largely unexplored. Further studies on this topic could be of tremendous significance in elucidating anal cancer pathogenesis and developing immunotherapeutic approaches for its treatment.
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Affiliation(s)
- Amir Selimagic
- Department of Gastroenterohepatology, General Hospital “Prim. dr. Abdulah Nakas”, 71 000 Sarajevo, Bosnia and Herzegovina; (A.H.-S.); (N.T.); (A.C.)
| | - Ada Dozic
- Department of Internal Medicine, General Hospital “Prim. dr. Abdulah Nakas”, 71 000 Sarajevo, Bosnia and Herzegovina; (A.D.); (A.S.); (A.S.); (N.V.)
| | - Azra Husic-Selimovic
- Department of Gastroenterohepatology, General Hospital “Prim. dr. Abdulah Nakas”, 71 000 Sarajevo, Bosnia and Herzegovina; (A.H.-S.); (N.T.); (A.C.)
| | - Nijaz Tucakovic
- Department of Gastroenterohepatology, General Hospital “Prim. dr. Abdulah Nakas”, 71 000 Sarajevo, Bosnia and Herzegovina; (A.H.-S.); (N.T.); (A.C.)
| | - Amir Cehajic
- Department of Gastroenterohepatology, General Hospital “Prim. dr. Abdulah Nakas”, 71 000 Sarajevo, Bosnia and Herzegovina; (A.H.-S.); (N.T.); (A.C.)
| | - Anela Subo
- Department of Internal Medicine, General Hospital “Prim. dr. Abdulah Nakas”, 71 000 Sarajevo, Bosnia and Herzegovina; (A.D.); (A.S.); (A.S.); (N.V.)
| | - Azra Spahic
- Department of Internal Medicine, General Hospital “Prim. dr. Abdulah Nakas”, 71 000 Sarajevo, Bosnia and Herzegovina; (A.D.); (A.S.); (A.S.); (N.V.)
| | - Nedim Vanis
- Department of Internal Medicine, General Hospital “Prim. dr. Abdulah Nakas”, 71 000 Sarajevo, Bosnia and Herzegovina; (A.D.); (A.S.); (A.S.); (N.V.)
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AL-Ishaq RK, Koklesova L, Kubatka P, Büsselberg D. Immunomodulation by Gut Microbiome on Gastrointestinal Cancers: Focusing on Colorectal Cancer. Cancers (Basel) 2022; 14:2140. [PMID: 35565269 PMCID: PMC9101278 DOI: 10.3390/cancers14092140] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2022] [Revised: 04/20/2022] [Accepted: 04/22/2022] [Indexed: 12/14/2022] Open
Abstract
Gastrointestinal cancer (GI) is a global health disease with a huge burden on a patient's physical and psychological aspects of life and on health care providers. It is associated with multiple disease related challenges which can alter the patient's quality of life and well-being. GI cancer development is influenced by multiple factors such as diet, infection, environment, and genetics. Although activating immune pathways and components during cancer is critical for the host's survival, cancerous cells can target those pathways to escape and survive. As the gut microbiome influences the development and function of the immune system, research is conducted to investigate the gut microbiome-immune interactions, the underlying mechanisms, and how they reduce the risk of GI cancer. This review addresses and summarizes the current knowledge on the major immune cells and gut microbiome interactions. Additionally, it highlights the underlying mechanisms of immune dysregulation caused by gut microbiota on four major cancerous pathways, inflammation, cellular proliferation, apoptosis, and metastasis. Overall, gut-immune interactions might be a key to understanding GI cancer development, but further research is needed for more detailed clarification.
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Affiliation(s)
| | - Lenka Koklesova
- Department of Obstetrics and Gynecology, Jessenius Faculty of Medicine, Comenius University in Bratislava, 036 01 Martin, Slovakia;
| | - Peter Kubatka
- Department of Medical Biology, Jessenius Faculty of Medicine, Comenius University in Bratislava, 036 01 Martin, Slovakia;
| | - Dietrich Büsselberg
- Weill Cornell Medicine-Qatar, Education City, Qatar Foundation, Doha 24144, Qatar;
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Contino KF, Yadav H, Shiozawa Y. The gut microbiota can be a potential regulator and treatment target of bone metastasis. Biochem Pharmacol 2022; 197:114916. [PMID: 35041811 PMCID: PMC8858876 DOI: 10.1016/j.bcp.2022.114916] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2021] [Revised: 01/10/2022] [Accepted: 01/10/2022] [Indexed: 02/08/2023]
Abstract
The gut microbiota, an often forgotten organ, have a tremendous impact on human health. It has long been known that the gut microbiota are implicated in cancer development, and more recently, the gut microbiota have been shown to influence cancer metastasis to distant organs. Although one of the most common sites of distant metastasis is the bone, and the skeletal system has been shown to be a subject of interactions with the gut microbiota to regulate bone homeostasis, little research has been done regarding how the gut microbiota control the development of bone metastasis. This review will discuss the mechanisms through which the gut microbiota and derived microbial compounds (i) regulate gastrointestinal cancer disease progression and metastasis, (ii) influence skeletal remodeling and potentially modulate bone metastasis, and (iii) affect and potentially enhance immunotherapeutic treatments for bone metastasis.
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Affiliation(s)
- Kelly F Contino
- Department of Cancer Biology and Comprehensive Cancer Center, Wake Forest University Health Sciences, Winston-Salem, NC 27157, USA
| | - Hariom Yadav
- Department of Neurosurgery and Brain Repair and Institute for Microbiome, University of South Florida, Tampa, FL 33612, USA
| | - Yusuke Shiozawa
- Department of Cancer Biology and Comprehensive Cancer Center, Wake Forest University Health Sciences, Winston-Salem, NC 27157, USA.
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Kong L, Hoshi N, Sui Y, Yamada Y, Yoshida R, Ooi M, Tian Z, Kimura I, Kodama Y. GPR43 Suppresses Intestinal Tumor Growth by Modification of the Mammalian Target of Rapamycin Complex 1 Activity in ApcMin/+ Mice. Med Princ Pract 2022; 31:39-46. [PMID: 34818236 PMCID: PMC8995667 DOI: 10.1159/000518621] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2021] [Accepted: 07/17/2021] [Indexed: 11/19/2022] Open
Abstract
OBJECTIVE G protein-coupled receptor 43 (GPR43), a receptor for short-chain fatty acids, plays a role in suppressing tumor growth; however, the detailed underlying mechanism needs to be comprehensively elucidated. In this study, we investigated the role of GPR43 in inhibiting tumor growth using ApcMin/+, a murine model of intestinal tumors. MATERIALS AND METHODS Using GPR43-/- ApcMin/+ and GPR43+/- ApcMin/+ mice, the number of tumors was analyzed at the end of the experimental period. Immunohistochemistry, quantitative polymerase chain reaction, and Western blotting were performed to analyze cellular proliferation and proliferation-associated signal pathways. RESULTS Our results revealed that GPR43 deficiency resulted in increased tumor numbers in ApcMin/+ mice. Ki67 was highly expressed in GPR43-/- mice (p > 0.05). Increased expression levels of proinflammatory cytokines, including interleukin-6 and tumor necrosis factor-α, and amino acid transporters were not observed in GPR43-deficient mice compared to GPR43-sufficient mice. Furthermore, GPR43-deficient tumor tissues showed enhanced mammalian target of rapamycin-mediated phosphorylated ribosomal protein S6 kinase beta-1 (p > 0.05) and phosphorylated eukaryotic translation initiation factor 4E-binding protein 1 (p > 0.05), but not Akt (protein kinase B) phosphorylation (p = 0.7088). CONCLUSION Collectively, GPR43 affords protection against tumor growth at least partly through inhibition of the mammalian target of rapamycin complex 1 pathway.
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Affiliation(s)
- Lingling Kong
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Namiko Hoshi
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
- *Namiko Hoshi,
| | - Yunlong Sui
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Yasutaka Yamada
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Ryutaro Yoshida
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Makoto Ooi
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Zibin Tian
- Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Ikuo Kimura
- Laboratory of Molecular Neurobiology, Graduate School of Biostudies, Kyoto University, Kyoto, Japan
- Department of Applied Biological Science, Graduate School of Agriculture, Tokyo University of Agriculture and Technology, Tokyo, Japan
| | - Yuzo Kodama
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
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Sun X, Xue Z, Yasin A, He Y, Chai Y, Li J, Zhang K. Colorectal Cancer and Adjacent Normal Mucosa Differ in Apoptotic and Inflammatory Protein Expression. ENGINEERED REGENERATION 2022. [DOI: 10.1016/j.engreg.2022.01.004] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
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Song J, Li A, Qian Y, Liu B, Lv L, Ye D, Sun X, Mao Y. Genetically Predicted Circulating Levels of Cytokines and the Risk of Cancer. Front Immunol 2022; 13:886144. [PMID: 35865545 PMCID: PMC9294168 DOI: 10.3389/fimmu.2022.886144] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Accepted: 06/08/2022] [Indexed: 11/13/2022] Open
Abstract
Background Inflammation plays a pivotal role in the pathogenesis of cancer. Though previous studies have reported a link between several inflammatory biomarkers and risk of certain types of cancer, there is a lack of systematic investigation. Therefore, we aimed to assess the role of circulating cytokines on the risk of cancer using a two-sample Mendelian randomization (MR) approach. Method We used genetic variants associated with circulating levels of cytokines from a meta-analysis of genome-wide association studies (GWASs) of 8,293 Finns as instrumental variables. Summary level data of 20 site-specific cancer were obtained from the UK BioBank including up to 456,348 participants of European ancestry. We performed two-sample MR analyses using inverse-variance weighted (IVW) method as the main method, followed by weighted-median and likelihood-based methods as sensitivity analysis. Pleiotropic and outlier variants were assessed by MR-Egger regression and MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) test. Results 224 genetic variants associated with 27 circulating cytokines achieving genome-wide significance (P<5×10-8) were used as IVs. After Bonferroni correction, genetically predicted high levels of interleukin-18 (IL-18) were associated with a decreased risk of acute myeloid leukemia (odds ratio (OR) per 1 standard deviation (SD) increase = 0.55, 95% confidence interval (CI):0.43-0.69, P=5.39×10-7), and circulating levels of IL-17 were associated with altered stomach cancer risk (OR per 1 SD increase = 0.15, 95% CI: 0.07-0.36, P=1.25×10-5) by IVW. Results were stable across sensitivity analyses, and MR-Egger regression did not suggest the presence of directional pleiotropy. Additionally, we found suggestive evidence for 48 cytokine-cancer associations including tumor necrosis factor related apoptosis-inducing ligand (TRAIL) and cutaneous T-cell attracting chemokine (CTACK) with the risk of several types of cancer (9.26×10-5≤P<0.05). Conclusions By using a genetic epidemiological approach, our study systematically evaluated the role of circulating cytokines on the risk of cancer, and provided clues for potential therapeutic targets. However, the exact underlying biological mechanism warrants further investigation.
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Affiliation(s)
- Jie Song
- School of Public Health, Zhejiang Chinese Medical University, Hangzhou, China
| | - Aole Li
- The Fourth College of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
| | - Yu Qian
- School of Life Sciences, Westlake University, Hangzhou, China
| | - Bin Liu
- School of Public Health, Zhejiang Chinese Medical University, Hangzhou, China
| | - Linshuoshuo Lv
- School of Public Health, Zhejiang Chinese Medical University, Hangzhou, China
| | - Ding Ye
- School of Public Health, Zhejiang Chinese Medical University, Hangzhou, China
| | - Xiaohui Sun
- School of Public Health, Zhejiang Chinese Medical University, Hangzhou, China
| | - Yingying Mao
- School of Public Health, Zhejiang Chinese Medical University, Hangzhou, China
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Maharjan CK, Mo J, Wang L, Kim MC, Wang S, Borcherding N, Vikas P, Zhang W. Natural and Synthetic Estrogens in Chronic Inflammation and Breast Cancer. Cancers (Basel) 2021; 14:cancers14010206. [PMID: 35008370 PMCID: PMC8744660 DOI: 10.3390/cancers14010206] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Revised: 12/17/2021] [Accepted: 12/19/2021] [Indexed: 12/17/2022] Open
Abstract
The oncogenic role of estrogen receptor (ER) signaling in breast cancer has long been established. Interaction of estrogen with estrogen receptor (ER) in the nucleus activates genomic pathways of estrogen signaling. In contrast, estrogen interaction with the cell membrane-bound G-protein-coupled estrogen receptor (GPER) activates the rapid receptor-mediated signaling transduction cascades. Aberrant estrogen signaling enhances mammary epithelial cell proliferation, survival, and angiogenesis, hence is an important step towards breast cancer initiation and progression. Meanwhile, a growing number of studies also provide evidence for estrogen's pro- or anti-inflammatory roles. As other articles in this issue cover classic ER and GPER signaling mediated by estrogen, this review will discuss the crucial mechanisms by which estrogen signaling influences chronic inflammation and how that is involved in breast cancer. Xenoestrogens acquired from plant diet or exposure to industrial products constantly interact with and alter innate estrogen signaling at various levels. As such, they can modulate chronic inflammation and breast cancer development. Natural xenoestrogens generally have anti-inflammatory properties, which is consistent with their chemoprotective role in breast cancer. In contrast, synthetic xenoestrogens are proinflammatory and carcinogenic compounds that can increase the risk of breast cancer. This article also highlights important xenoestrogens with a particular focus on their role in inflammation and breast cancer. Improved understanding of the complex relationship between estrogens, inflammation, and breast cancer will guide clinical research on agents that could advance breast cancer prevention and therapy.
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Affiliation(s)
- Chandra K. Maharjan
- Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL 32610, USA; (C.K.M.); (J.M.); (L.W.); (M.-C.K.)
| | - Jiao Mo
- Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL 32610, USA; (C.K.M.); (J.M.); (L.W.); (M.-C.K.)
| | - Lei Wang
- Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL 32610, USA; (C.K.M.); (J.M.); (L.W.); (M.-C.K.)
| | - Myung-Chul Kim
- Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL 32610, USA; (C.K.M.); (J.M.); (L.W.); (M.-C.K.)
| | - Sameul Wang
- Canyonoak Consulting LLC, San Diego, CA 92127, USA;
| | - Nicholas Borcherding
- Department of Pathology and Immunology, School of Medicine, Washington University, St. Louis, MO 63110, USA;
| | - Praveen Vikas
- Department of Internal Medicine, Carver College of Medicine, Iowa City, IA 52242, USA;
| | - Weizhou Zhang
- Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL 32610, USA; (C.K.M.); (J.M.); (L.W.); (M.-C.K.)
- Mechanism of Oncogenesis Program, University of Florida Health Cancer Center, University of Florida, Gainesville, FL 32610, USA
- Correspondence: to: ; Tel.: +1-352-273-6748
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Das D, Karthik N, Taneja R. Crosstalk Between Inflammatory Signaling and Methylation in Cancer. Front Cell Dev Biol 2021; 9:756458. [PMID: 34901003 PMCID: PMC8652226 DOI: 10.3389/fcell.2021.756458] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Accepted: 10/11/2021] [Indexed: 01/08/2023] Open
Abstract
Inflammation is an intricate immune response against infection and tissue damage. While the initial immune response is important for preventing tumorigenesis, chronic inflammation is implicated in cancer pathogenesis. It has been linked to various stages of tumor development including transformation, proliferation, angiogenesis, and metastasis. Immune cells, through the production of inflammatory mediators such as cytokines, chemokines, transforming growth factors, and adhesion molecules contribute to the survival, growth, and progression of the tumor in its microenvironment. The aberrant expression and secretion of pro-inflammatory and growth factors by the tumor cells result in the recruitment of immune cells, thus creating a mutual crosstalk. The reciprocal signaling between the tumor cells and the immune cells creates and maintains a successful tumor niche. Many inflammatory factors are regulated by epigenetic mechanisms including DNA methylation and histone modifications. In particular, DNA and histone methylation are crucial forms of transcriptional regulation and aberrant methylation has been associated with deregulated gene expression in oncogenesis. Such deregulations have been reported in both solid tumors and hematological malignancies. With technological advancements to study genome-wide epigenetic landscapes, it is now possible to identify molecular mechanisms underlying altered inflammatory profiles in cancer. In this review, we discuss the role of DNA and histone methylation in regulation of inflammatory pathways in human cancers and review the merits and challenges of targeting inflammatory mediators as well as epigenetic regulators in cancer.
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Affiliation(s)
- Dipanwita Das
- Department of Physiology, Healthy Longevity Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Nandini Karthik
- Department of Physiology, Healthy Longevity Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Reshma Taneja
- Department of Physiology, Healthy Longevity Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
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Mukherjee S, Ghosh S, Choudhury S, Gupta P, Adhikary A, Chattopadhyay S. Pomegranate Polyphenols Attenuate Inflammation and Hepatic Damage in Tumor-Bearing Mice: Crucial Role of NF-κB and the Nrf2/GSH Axis. J Nutr Biochem 2021; 97:108812. [PMID: 34224820 DOI: 10.1016/j.jnutbio.2021.108812] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Revised: 05/12/2021] [Accepted: 06/13/2021] [Indexed: 12/27/2022]
Abstract
It has been widely reported that cancer, along with its treatment regimens, cause severe toxicity in the host. A suitable agent having chemopreventive properties as well as capabilities of ameliorating tumor- and drug-induced toxicities is of imminent need. Pomegranate has been projected as an excellent anti-tumor, anti-inflammatory and anti-oxidant agent. In this study, for the first time, we delineated the exact signaling cascade by which dietary supplementation of pomegranate fruit extract (PFE) protects tumor-bearing mice from tumor-induced hepatotoxicity. Increased activities of serum Alanine transaminase, Aspartate transaminase, Lactate dehydrogenase and Alkaline phosphatase, as well as histological studies confirmed the establishment of a state of hepatic dysfunction in tumor-bearers. Further investigations revealed that increased hepatic reactive oxygen species content and glutathione depletion-initiated apoptosis in these hepatocytes as we observed an alteration in the apoptotic proteins. PFE supplementation in tumor-bearing mice, on the other hand, differentially modulated redox-sensitive transcription factors Nrf2 and NF-κB, ultimately decreasing tumor-induced hepatic oxidative damage and cell death. siRNA-mediated inhibition of Nrf2 and NF-κB completely abolished the hepato-protective activities of PFE while pre-treatment of tumor-conditioned hepatocytes with N-acetyl cysteine augmented the cyto-protective properties of PFE. The present study clearly identified Nrf2/NF-κB/glutathione axis as the key factor behind the hepatoprotective potential of PFE. These findings would add to the existing knowledge about cancer chemoprevention by dietary polyphenols and might lead to the application of pomegranate polyphenols as supplement to escalate the effectiveness of cancer therapy by protecting normal cells from cancer related toxicities.
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Affiliation(s)
| | - Sayan Ghosh
- Department of Physiology, University of Calcutta; Kolkata, India
| | | | - Payal Gupta
- Department of Physiology, University of Calcutta; Kolkata, India
| | - Arghya Adhikary
- Centre for Research in Nanoscience and Nanotechnology, University of Calcutta, Kolkata, India
| | - Sreya Chattopadhyay
- Department of Physiology, University of Calcutta; Kolkata, India; Centre for Research in Nanoscience and Nanotechnology, University of Calcutta, Kolkata, India.
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Toll-Like Receptors (TLRs): Structure, Functions, Signaling, and Role of Their Polymorphisms in Colorectal Cancer Susceptibility. BIOMED RESEARCH INTERNATIONAL 2021; 2021:1157023. [PMID: 34552981 PMCID: PMC8452412 DOI: 10.1155/2021/1157023] [Citation(s) in RCA: 163] [Impact Index Per Article: 40.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Revised: 08/04/2021] [Accepted: 08/19/2021] [Indexed: 12/14/2022]
Abstract
Toll-like receptors (TLRs) are the important mediators of inflammatory pathways in the gut which play a major role in mediating the immune responses towards a wide variety of pathogen-derived ligands and link adaptive immunity with the innate immunity. Numerous studies in different populations across the continents have reported on the significant roles of TLR gene polymorphisms in modulating the risk of colorectal cancer (CRC). CRC is one of the major malignancies affecting the worldwide population and is currently ranking the third most common cancer in the world. In this review, we have attempted to discuss the structure, functions, and signaling of TLRs in comprehensive detail together with the role played by various TLR gene SNPs in CRC susceptibility.
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Chang GR, Kuo CY, Tsai MY, Lin WL, Lin TC, Liao HJ, Chen CH, Wang YC. Anti-Cancer Effects of Zotarolimus Combined with 5-Fluorouracil Treatment in HCT-116 Colorectal Cancer-Bearing BALB/c Nude Mice. Molecules 2021; 26:molecules26154683. [PMID: 34361836 PMCID: PMC8347948 DOI: 10.3390/molecules26154683] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2021] [Revised: 07/29/2021] [Accepted: 07/29/2021] [Indexed: 01/05/2023] Open
Abstract
Zotarolimus is a semi-synthetic derivative of rapamycin and an inhibitor of mammalian target of rapamycin (mTOR) signaling. Currently, zotarolimus is used to prolong the survival time of organ grafts, but it is also a novel immunosuppressive agent with potent anti-proliferative activity. Here, we examine the anti-tumor effect of zotarolimus, alone and in combination with 5-fluorouracil, on HCT-116 colorectal adenocarcinoma cells implanted in BALB/c nude mice. Compared with the control mice, mice treated with zotarolimus or zotarolimus combined with 5-FU showed retarded tumor growth; increased tumor apoptosis through the enhanced expression of cleaved caspase 3 and extracellular signal-regulated kinase (ERK) phosphorylation; reduced inflammation-related factors such as IL-1β, TNF-α, and cyclooxygenase-2 (COX-2) protein; and inhibited metastasis-related factors such as CD44, epidermal growth factor receptor (EGFR), transforming growth factor β (TGF-β), and vascular endothelial growth factor (VEGF). Notably, mice treated with a combination of zotarolimus and 5-FU showed significantly retarded tumor growth, reduced tumor size, and increased tumor inhibition compared with mice treated with 5-FU or zotarolimus alone, indicating a strong synergistic effect. This in vivo study confirms that zotarolimus or zotarolimus combined with 5-FU can be used to retard colorectal adenocarcinoma growth and inhibit tumorigenesis. Our results suggest that zotarolimus may increase the chemo-sensitization of tumor cells. Therefore, zotarolimus alone and zotarolimus combined with 5-FU may be potential anti-tumor agents in the treatment of human colon adenocarcinoma. Future research on zotarolimus may lead to the development of new therapeutic strategies.
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Affiliation(s)
- Geng-Ruei Chang
- Department of Veterinary Medicine, National Chiayi University, 580 Xinmin Road, Chiayi 600023, Taiwan; (G.-R.C.); (T.-C.L.); (H.-J.L.)
| | - Chan-Yen Kuo
- Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, 289 Jianguo Road, Xindian District, New Taipei 231405, Taiwan;
- Department of Nursing, Cardinal Tien College of Healthcare and Management, 112 Minzu Road, Sindian District, New Taipei 231038, Taiwan
| | - Ming-Yang Tsai
- Animal Industry Division, Livestock Research Institute, Council of Agriculture, Executive Yuan, 112 Muchang, Xinhua Dist, Tainan 71246, Taiwan;
- Graduate Institute of Bioresources, National Pingtung University of Science and Technology, 1 Shuefu Road, Neipu, Pingtung 91201, Taiwan
| | - Wei-Li Lin
- Bachelor Degree Program in Animal Healthcare, Hungkuang University, 6 Section, 1018 Taiwan Boulevard, Shalu District, Taichung 433304, Taiwan;
- General Education Center, Chaoyang University of Technology, 168 Jifeng Eastern Road, Taichung 413310, Taiwan
| | - Tzu-Chun Lin
- Department of Veterinary Medicine, National Chiayi University, 580 Xinmin Road, Chiayi 600023, Taiwan; (G.-R.C.); (T.-C.L.); (H.-J.L.)
| | - Huei-Jyuan Liao
- Department of Veterinary Medicine, National Chiayi University, 580 Xinmin Road, Chiayi 600023, Taiwan; (G.-R.C.); (T.-C.L.); (H.-J.L.)
| | - Chung-Hung Chen
- Division of Gastroenterology, Department of Internal Medicine, Chang Bing Show Chwan Memorial Hospital, 6 Lugong Road, Lukang Township, Changhua 505029, Taiwan
- Correspondence: (C.-H.C.); (Y.-C.W.); Tel.: +886-975-617357 (C.-H.C.); +886-2332-3456 (Y.-C.W.)
| | - Yu-Chen Wang
- Division of Cardiology, Asia University Hospital, 222 Fuxin Road, Wufeng District, Taichung 413505, Taiwan
- Department of Medical Laboratory Science and Biotechnology, Asia University, 500 Lioufeng Road, Wufeng District, Taichung 413305, Taiwan
- Division of Cardiovascular Medicine, China Medical University Hospital, 2 Yude Road, North District, Taichung 404332, Taiwan
- College of Medicine, China Medical University, 91 Hsueh-Shih Road, North District, Taichung 404333, Taiwan
- Correspondence: (C.-H.C.); (Y.-C.W.); Tel.: +886-975-617357 (C.-H.C.); +886-2332-3456 (Y.-C.W.)
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Jaafar RF, Ibrahim Z, Ataya K, Hassanieh J, Ard N, Faraj W. Receptor-Interacting Serine/Threonine-Protein Kinase-2 as a Potential Prognostic Factor in Colorectal Cancer. ACTA ACUST UNITED AC 2021; 57:medicina57070709. [PMID: 34356990 PMCID: PMC8303330 DOI: 10.3390/medicina57070709] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Revised: 05/25/2021] [Accepted: 06/03/2021] [Indexed: 12/24/2022]
Abstract
Background and objectives: Receptor-interacting serine/threonine-protein kinase-2 (RIPK2) is an important mediator in different pathways in the immune and inflammatory response system. RIPK2 was also shown to play different roles in different cancer types; however, in colorectal cancer (CRC), its role is not well established. This study aims at identifying the role of RIPK2 in CRC progression and survival. Materials and methods: Data of patients and mRNA protein expression level of genes associated with CRC (RIPK2, tumor necrosis factor (TNF), TRAF1, TRAF7, KLF6, interlukin-6 (Il6), interlukin-8 (Il8), vascular-endothelial growth factor A (VEGFA), MKI67, TP53, nuclear factor-kappa B (NFKB), NFKB2, BCL2, XIAP, and RELA) were downloaded from the PrognoScan online public database. Patients were divided between low and high RIPK2 expression and different CRC characteristics were studied between the two groups. Survival curves were evaluated using a Kaplan-Meier estimator. The Pearson correlation was used to study the correlation between RIPK2 and the other factors. Statistical analysis was carried out using SPSS version 25.0. The Human Protein Atlas was also used for the relationship between RIPK2 expression in CRC tissues and survival. Differences were considered statistically significant at p < 0.05. Results: A total of 520 patients were downloaded from the PrognoScan database, and RIPK2 was found to correlate with MKI67, TRAF1, KLF6, TNF, Il6, Il8, VEGFA, NFKB2, BCL2, and RELA. High expression of RIPK2 was associated with high expression of VEGFA (p < 0.01) and increased mortality (p < 0.01). Conclusions: In this study, RIPK2 is shown to be a potential prognostic factor in CRC; however, more studies are needed to assess and verify its potential role as a prognostic marker and in targeted therapy.
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Affiliation(s)
- Rola F. Jaafar
- Department of Surgery, American University of Beirut Medical Center, Beirut 1107 2020, Lebanon; (R.F.J.); (Z.I.); (J.H.)
| | - Zeid Ibrahim
- Department of Surgery, American University of Beirut Medical Center, Beirut 1107 2020, Lebanon; (R.F.J.); (Z.I.); (J.H.)
| | - Karim Ataya
- Division of Liver Transplantation, Hepatobiliary and Pancreatic Surgery, Department of General Surgery, American University of Beirut Medical Centre, Beirut 1107 2020, Lebanon;
| | - Joelle Hassanieh
- Department of Surgery, American University of Beirut Medical Center, Beirut 1107 2020, Lebanon; (R.F.J.); (Z.I.); (J.H.)
| | - Natasha Ard
- Department of General Medicine, Faculty of Medicine, American University of Beirut Medical Center, Beirut 1107 2020, Lebanon;
| | - Walid Faraj
- Department of Surgery, American University of Beirut Medical Center, Beirut 1107 2020, Lebanon; (R.F.J.); (Z.I.); (J.H.)
- Division of Liver Transplantation, Hepatobiliary and Pancreatic Surgery, Department of General Surgery, American University of Beirut Medical Centre, Beirut 1107 2020, Lebanon;
- Correspondence: ; Tel.: +961-350-000 (ext. 5714)
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Zhou C, Duan D, Liu S. Predictive Value of a Prognostic Model Based on Lymphocyte-to-Monocyte Ratio Before Radioiodine Therapy for Recurrence of Papillary Thyroid Carcinoma. Technol Cancer Res Treat 2021; 20:15330338211027910. [PMID: 34191658 PMCID: PMC8252333 DOI: 10.1177/15330338211027910] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND The aim of this study was to investigate the predictive value of a prognostic model based on the lymphocyte-to-monocyte ratio (LMR) before radioiodine treatment for the recurrence of papillary thyroid carcinoma (PTC). METHODS Clinicopathological data of 441 patients with papillary thyroid cancer were collected retrospectively. The Receiver operating characteristic (ROC) was used to determine the optimal cut-off value for predicting PTC recurrence by LMR before radioiodine treatment. Recurrence was the endpoint of the study, and survival was estimated by the Kaplan-Meier method, and any differences in survival were evaluated with a stratified log-rank test. Univariate and multifactorial analyses were performed using Cox proportional-hazards models to identify risk factors associated with PTC recurrence. RESULTS The ROC curve showed that the best cut-off value of LMR before radioiodine treatment to predict recurrence in patients with PTC was 6.61, with a sensitivity of 54.1%, a specificity of 73%, and an area under the curve of 0.628. The recurrence rate was significantly higher in the low LMR group (16%) than in the high LMR group (5%) (P = 0.001, χ2 = 12.005). Multifactorial analysis showed that LMR < 6.61 (P = 0.006; HR = 2.508) and risk stratification (high risk) (P = 0.000; HR = 5.076) before radioiodine treatment were independent risk factors predicting recurrence in patients with PTC. Patients with preoperative LMR < 6.61 and high risk stratification had the lowest recurrence-free survival rate and the shortest recurrence-free survival time. CONCLUSIONS The LMR-based prognostic model before radioactive iodine treatment is valuable for early prediction of PTC recurrence and it can be used in clinical practice as a supplement to risk stratification and applied in combination to help screen out patients with poorer prognosis early.
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Affiliation(s)
- Chunyan Zhou
- Department of Nuclear Medicine, Chongqing Medical University, Yuzhong District, Chongqing, China
| | - Dong Duan
- Department of Nuclear Medicine, Chongqing General Hospital (Chongqing Hospital, University of Chinese Academy of Sciences), Liangjiang New Area, Chongqing, China
| | - Shuang Liu
- Department of Nuclear Medicine, Chongqing Medical University, Yuzhong District, Chongqing, China
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