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Sharafi Monfared M, Nazmi S, Parhizkar F, Jafari D. Soluble B7 and TNF family in colorectal cancer: Serum level, prognostic and treatment value. Hum Immunol 2025; 86:111232. [PMID: 39793378 DOI: 10.1016/j.humimm.2025.111232] [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: 10/24/2024] [Revised: 12/25/2024] [Accepted: 01/02/2025] [Indexed: 01/13/2025]
Abstract
Soluble immune checkpoints (sIC) are crucial factors in the immune system. They regulate immune responses by transforming intercellular signals via binding to their membrane-bound receptor or ligand. Moreover, soluble ICs are vital in immune regulation, cancer development, and prognosis. They can be identified and measured in various tumor microenvironments. Recently, sICs have become increasingly important in clinically assessing malignancies like colorectal cancer (CRC) patients. This review explores the evolving role of the soluble B7 family and soluble tumor necrosis factor (TNF) superfamily members in predicting disease progression, treatment response, and overall patient outcomes in CRC. We comprehensively analyze the diagnostic and prognostic potential of soluble immune checkpoints in CRC. Understanding the role of these soluble immune checkpoints in CRC management and their potential as targets for precision medicine approaches can be critical for improving outcomes for patients with colorectal cancer.
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Affiliation(s)
- Mohanna Sharafi Monfared
- Student's Research Committee, Zanjan University of Medical Sciences, Zanjan, Iran; School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Sina Nazmi
- Student's Research Committee, Zanjan University of Medical Sciences, Zanjan, Iran; School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Forough Parhizkar
- Department of Immunology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Davood Jafari
- Department of Immunology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.
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Wang Y, Hu C, Du T, Li J, Hui K, Jiang X. Combination of potassium oxonate with anti-PD-1 for the treatment of colorectal cancer. Front Oncol 2025; 15:1528004. [PMID: 39990679 PMCID: PMC11842225 DOI: 10.3389/fonc.2025.1528004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2024] [Accepted: 01/20/2025] [Indexed: 02/25/2025] Open
Abstract
Introduction Identification of effective therapies for colorectal cancer (CRC) remains an urgent medical need, especially for the microsatellite stable (MSS) phenotype. In our previous study, potassium oxonate (PO), a uricase inhibitor commonly used for elevating uric acid in mice, unexpectedly showed remarkable inhibition of tumor growth when combined with anti-programmed death-1 (PD-1). Further research demonstrated that the combination of potassium oxonate and anti-PD-1 could reprogram the immune microenvironment. This study aimed to explore the anti-tumor effect of PO combined with anti-PD-1, and investigate the impact on the immunosuppressive tumor microenvironment (TME). Methods We established a syngeneic mouse model of CRC and divided into groups of control group, single drugs group of PO and anti-PD-1, and the combination group. Use the HE staining, immunohistochemistry (IHC) and TUNEL staining of tumor issues to verify the anti-neoplasm of each group. We also tested the changes of TME through flow cytometry of spleen of mice in each group, as well as the IHC of cytokines. Results The co-therapy of PO and anti-PD-1 showed admirable anti-tumor effect compared with the control group and the single drug groups. The TME were tended to an environment beneficial for killing tumors by enhancing chemotactic factor release, increasing CD8+ T cell infiltration and activation, and decreasing the amount of regulatory T cells. Moreover, IFN-γ and IL-2 secretion were found to be enriched in the tumor TME. Conclusion Our study indicated that combination of PO and anti-PD-1 could synergistically suppress CRC progression and altered the tumor microenvironment in favor of antitumor immune responses.
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Affiliation(s)
- Yuanyuan Wang
- Department of Oncology, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang, Jiangsu, China
| | - Chenxi Hu
- Department of Oncology, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang, Jiangsu, China
| | - Tianpeng Du
- Department of Urology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Jiawen Li
- Department of Oncology, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang, Jiangsu, China
| | - Kaiyuan Hui
- Department of Oncology, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang, Jiangsu, China
| | - Xiaodong Jiang
- Department of Oncology, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang, Jiangsu, China
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Liu X. Effects of Shenmai Injection on proliferation, migration, invasion and angiogenesis of colorectal carcinoma vascular endothelial cells. Medicine (Baltimore) 2025; 104:e41307. [PMID: 39833060 PMCID: PMC11749673 DOI: 10.1097/md.0000000000041307] [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: 11/29/2023] [Accepted: 10/24/2024] [Indexed: 01/22/2025] Open
Abstract
BACKGROUND Colorectal cancer, being 1 of the most significant malignant tumors globally, poses a substantial risk to human health. Unfortunately, its 5-year survival rate stands at a mere 65%. There remains an urgent need for the development of novel treatments to combat this detrimental malignancy effectively. The Shenmai Injection (SMI) is a Chinese medicine that has been proven to have significant clinical efficacy in the treatment of cardiovascular diseases. This study aimed to examine the impact of SMI on the proliferation, migration, invasion, and angiogenesis of tumor-derived endothelial cells (Td-EC). METHODS Human umbilical vein endothelial cells (HUVEC) induced Td-EC, and HUVEC were treated with conditioned media from the human colorectal carcinoma cells (HCT116). The effects of HCT116 on the proliferation, migration, and invasion of hepatocellular carcinoma cells after treatment of SMI were observed by MTS assay and Transwell techniques. Additionally, an angiogenesis experiment was used to investigate Td-EC tube formation capacity. RESULTS SMI had a significant inhibiting effect on the proliferation, migration, and invasion of HCT116. SMI was also able to inhibit the angiogenesis of Td-EC. Notably, SMI did not have any effect on the normal endothelium. CONCLUSION SMI has obvious antiproliferation, migration, infiltration, and neogenesis effects on HCT116.
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Affiliation(s)
- Xiangyu Liu
- Lanzhou University Second Hospital, Chengguan District, Lanzhou, China
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Heitmann F, Christ SM, March C, Pech M, Thormann M, Damm R. Lesion Volume Divided by ADC Measures Is an Independent Prognostic Marker in Colorectal Liver Metastasis Treated by Y90-radioembolization. In Vivo 2025; 39:292-301. [PMID: 39740889 PMCID: PMC11705130 DOI: 10.21873/invivo.13827] [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: 08/25/2024] [Revised: 09/12/2024] [Accepted: 09/13/2024] [Indexed: 01/02/2025]
Abstract
BACKGROUND/AIM To assess the ability of apparent diffusion coefficient (ADC) at baseline in predicting overall survival in patients who undergo Y90-radioembolization (Y90-RE) for liver-dominant metastatic colorectal cancer (mCRC) in the salvage situation. PATIENTS AND METHODS A retrospective review of 411 lesions in 63 patients with refractory mCRC treated with Y90-RE was conducted. Manual region of interest (ROI) measurements were applied using a whole lesion and volume method. Minimum and mean ADC values were measured, and averages were calculated per patient. Ratios combining tumor volume and ADC were correlated with OS, and a receiver-operating characteristic (ROC) analysis defined a cut-off value. Cox regression analysis was performed, and the log-rank test confirmed prognostic cut-off levels for survival. RESULTS The median survival was 6.4 months. Multivariate Cox regression identified tumor volume divided by minimum ADC (ADCtumor volume, min) as an independent predictor of OS (HR=1.814, 95%CI=1.188-2.770, p=0.006). Neither ADCmin nor ADCmean were significantly associated with survival. Optimal prediction was identified with a ADCtumor volume, min cut-off of 0.3673 arbitrary units (AU) yielding 76.0% sensitivity and 70.3% specificity. Patients with ADCtumor volume min <0.3673 had a median OS of 10.4 months, compared to 4.7 months for those above the cut-off (p<0.001). CONCLUSION Tumor volume divided by minimum ADC at baseline (ADCtumor volume, min) was identified as an independent predictor of OS in mCRC scheduled for Y90-radioembolization in the salvage situation and may improve future patient selection.
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Affiliation(s)
- Franziska Heitmann
- Department of Radiology and Nuclear Medicine, University Hospital Magdeburg, University of Magdeburg, Magdeburg, Germany
| | - Sebastian M Christ
- Department of Radiation Oncology, University Hospital Zurich, Zurich, Switzerland
- Department of Radiation Oncology, Charité Berlin, Berlin, Germany
| | - Christine March
- Department of Radiology and Nuclear Medicine, University Hospital Magdeburg, University of Magdeburg, Magdeburg, Germany
| | - Maciej Pech
- Department of Radiology and Nuclear Medicine, University Hospital Magdeburg, University of Magdeburg, Magdeburg, Germany
| | - Maximilian Thormann
- Department of Radiology and Nuclear Medicine, University Hospital Magdeburg, University of Magdeburg, Magdeburg, Germany;
- Department of Nuclear Medicine, Charité Berlin, Berlin, Germany
| | - Robert Damm
- Department of Radiology and Nuclear Medicine, University Hospital Magdeburg, University of Magdeburg, Magdeburg, Germany
- Practice of Radiology, Dessau, Germany
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Karami R, Fathi M, Jalali P, Hassannia H, Zarei A, Hojjat-Farsangi M, Jadidi F. The emerging role of TIM-3 in colorectal cancer: a promising target for immunotherapy. Expert Opin Ther Targets 2024; 28:1093-1115. [PMID: 39670788 DOI: 10.1080/14728222.2024.2442437] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Revised: 11/30/2024] [Accepted: 12/10/2024] [Indexed: 12/14/2024]
Abstract
INTRODUCTION Colorectal cancer (CRC) imposes a substantial worldwide health burden, necessitating innovative strategies to enhance therapeutic outcomes. T cell immunoglobulin-3 (Tim-3), an immune checkpoint, enhances immunological tolerance. Tim-3's role in CRC surpasses its conventional function as an indicator of dysfunction in T lymphocytes. AREAS COVERED This review provides an all-inclusive summary of the structural and functional attributes of Tim-3's involvement in the case of CRC. It explores the implications of Tim-3 expression in CRC with regard to tumor progression, clinical characteristics, and therapeutic approaches. Furthermore, it delves into the intricate signaling pathways and molecular mechanisms through which Tim-3 exerts its dual function in both immunity against tumors and immune evasion. EXPERT OPINION Understanding Tim-3's complicated network of interactions in CRC has significant consequences for the development of novel immunotherapeutic strategies targeted toward restoring anti-tumor immune responses and improving patient survival. Tim-3 is an important and valuable target for CRC patient risk classification and treatment because it regulates a complex network of strategies for suppressing immune responses, including causing T cell exhaustion, increasing Treg (regulatory T-cell) proliferation, and altering antigen-presenting cell activity.
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Affiliation(s)
- Reza Karami
- Immunology Research Centre, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mehrdad Fathi
- Immunology Research Centre, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Pooya Jalali
- Immunology Research Centre, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hadi Hassannia
- Department of Paramedicine, Amol School of Paramedical Sciences, Mazandaran University of Medical Sciences, Sari, Iran
| | - Asieh Zarei
- Department of Biochemistry, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
| | | | - Farhad Jadidi
- Immunology Research Centre, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
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Nayl AA, El-Fakharany EM, Abd-Elhamid AI, Arafa WAA, Alanazi AH, Ahmed IM, Abdelgawad MA, Aly AA, Bräse S. Alginate-modified graphene oxide anchored with lactoperoxidase as a novel bioactive nanocombination for colorectal cancer therapy. Sci Rep 2024; 14:24804. [PMID: 39438495 PMCID: PMC11496692 DOI: 10.1038/s41598-024-74604-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2024] [Accepted: 09/27/2024] [Indexed: 10/25/2024] Open
Abstract
It is imperative to explore new biocompatible drugs with low toxicity for use in medicinal fields such as fighting tumors. Bovine lactoperoxidase (BLPO) stems from the most important enzymes in the bovine whey that provide a proper pattern for nano-formulation with nanomaterials. LPO is a suitable protein to be coated or adsorbed to alginate modified graphene oxide (GO-SA), which forms the modified GO-SA-LPO hybrid structure. This novel combination provides LPO stability with strong anticancer effects and boosts immunity response. The characterization results obtained from different techniques confirmed a successful LPO adsorption on the GO-SA composite surface. Moreover, nano-formulation of LPO with GO-SA composite exhibited a reduction in its size and overall charge. In addition, the experimental results showed greater LPO activity stability in the modified GO-SA-LPO nanocombination than free LPO after storage for 10 weeks at 4 °C. The in vitro study, a crucial step in the validation of our approach, demonstrated that the modified GO-SA-LPO nanocombination showed a potent anticancer selectivity toward colon cancer cell lines more than GO-SA composite or free form of LPO, which enhanced in a dose-dependent manner with high safety manner against normal cells. The apoptotic effect of this novel nanocombination was confirmed by the greatest variations in the expression of both well-known apoptosis genes (p53 and Bcl-2), severe changes in the cellular morphology, DNA fragmentation, and nuclear staining with fluorescence yellow and orange of the target cancer cells. Also, this superior efficacy of the modified GO-SA-LPO nanocombination was induced by suppressing some pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin (IL-6), and necrosis factor-kappa B (NF-ĸB). Our observations presented that the modified nanocombination of LPO may offer a novel remedy for treating colon tumors via induced apoptosis pathway, inflammation reduction, and immune response improvement.
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Affiliation(s)
- AbdElAziz A Nayl
- Department of Chemistry, College of Science, Jouf University, Sakaka, Aljouf, 72341, Saudi Arabia.
| | - Esmail M El-Fakharany
- Protein Research Department, Genetic Engineering and Biotechnology Research Institute GEBRI, City of Scientific Research and Technological Applications (SRTA city), New Borg El-Arab, Alexandria, 21934, Egypt
- Pharmaceutical and Fermentation Industries Development Centre (PFIDC), City of Scientific Research and Technological Applications (SRTA-City), New Borg El-Arab, Alexandria, Egypt
- Pharos University in Alexandria, Canal El Mahmoudia Street, Beside Green Plaza Complex, Alexandria, 21648, Egypt
| | - Ahmed I Abd-Elhamid
- Composites and Nanostructured Materials Research Department, Advanced Technology and New Materials Research Institute, City of Scientific Research and Technological Applications (SRTA-City), New Borg Al-Arab, Alexandria, 21934, Egypt
| | - Wael A A Arafa
- Department of Chemistry, College of Science, Jouf University, Sakaka, Aljouf, 72341, Saudi Arabia
| | - Ahmed H Alanazi
- Department of Chemistry, College of Science, Jouf University, Sakaka, Aljouf, 72341, Saudi Arabia
| | - Ismail M Ahmed
- Department of Chemistry, College of Science, Jouf University, Sakaka, Aljouf, 72341, Saudi Arabia
| | - Mohamed A Abdelgawad
- Department of Pharmaceutical Chemistry, College of Pharmacy, Jouf University, Sakaka, 72341, Al Jouf, Saudi Arabia
| | - Ashraf A Aly
- Chemistry Department, Faculty of Science, Organic Division, Minia University, El-Minia, 61519, Egypt
| | - Stefan Bräse
- Institute of Biological and Chemical Systems - Functional Molecular Systems (IBCS-FMS), Kaiserstrasse 12, Karlsruhe, 76131, Germany.
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Yu J, Deng X, Lin X, Xie L, Guo S, Lin X, Lin D. DST regulates cisplatin resistance in colorectal cancer via PI3K/Akt pathway. J Pharm Pharmacol 2024:rgae104. [PMID: 39419785 DOI: 10.1093/jpp/rgae104] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2024] [Accepted: 07/26/2024] [Indexed: 10/19/2024]
Abstract
OBJECTIVES Dystonin (DST), a potential tumor suppressor gene, plays a crucial role in regulating cancer cell proliferation and resistance to chemotherapy. However, DST's specific role in colorectal cancer (CRC) has not been thoroughly investigated, and this study aims to elucidate its molecular role in modulating cisplatin (DDP) resistance in CRC. METHODS DST expression was analyzed in CRC tumors, DDP-resistant CRC tissues, paracancer tissues, and normal tissues. Lentiviral overexpression and shRNA knockdown were conducted in advanced CRC and DDP-resistant cell lines to assess cell viability, apoptosis, invasion, migration, proliferation, and angiogenesis. Xenograft mouse models studied DST's impact on CRC tumor growth and DDP resistance in vivo. RESULTS DST expression was significantly reduced in CRC tumor and DDP-resistant CRC tissues compared to paracancer and normal tissues (P < .001). Upregulating DST inhibited CRC and DDP-resistant cell viability, proliferation, invasion, and migration while promoting apoptosis. DST overexpression also reduced angiogenesis and attenuated DDP-induced cytotoxicity in CRC cells. Mechanistically, DST upregulation suppressed DDP resistance in CRC cells via the PI3K/Akt signaling pathway. DST upregulation reduced CRC tumor growth and mitigated DDP resistance, in vivo. CONCLUSION DST plays a crucial role in limiting CRC progression and overcoming DDP resistance, suggesting potential for targeted CRC therapies.
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Affiliation(s)
- Jianwei Yu
- Department of Gastroenterology, Longyan First Affiliated Hospital of Fujian Medical University, Longyan 364000, Fujian Province, China
| | - Xueqiong Deng
- Department of Gastroenterology, Longyan First Affiliated Hospital of Fujian Medical University, Longyan 364000, Fujian Province, China
| | - Xueqin Lin
- Department of Gastroenterology, Longyan First Affiliated Hospital of Fujian Medical University, Longyan 364000, Fujian Province, China
| | - Li Xie
- Department of Gastroenterology, Longyan First Affiliated Hospital of Fujian Medical University, Longyan 364000, Fujian Province, China
| | - Sisi Guo
- Department of Gastroenterology, Longyan First Affiliated Hospital of Fujian Medical University, Longyan 364000, Fujian Province, China
| | - Xiaoliang Lin
- Department of Gastroenterology, Longyan First Affiliated Hospital of Fujian Medical University, Longyan 364000, Fujian Province, China
| | - Dong Lin
- Department of Gastroenterology, Longyan First Affiliated Hospital of Fujian Medical University, Longyan 364000, Fujian Province, China
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Cao W, Xie Y, Cai L, Wang M, Chen Z, Wang Z, Xv J, Wang Y, Li R, Liu X, Wang W. Pan‑cancer analysis on the role of KMT2C expression in tumor progression and immunotherapy. Oncol Lett 2024; 28:444. [PMID: 39091583 PMCID: PMC11292467 DOI: 10.3892/ol.2024.14577] [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: 12/04/2023] [Accepted: 05/10/2024] [Indexed: 08/04/2024] Open
Abstract
Histone lysine N-methyltransferase 2C (KMT2C) is involved in transcriptional regulation and DNA damage repair. Mutations in KMT2C have been implicated in the progression, metastasis, and drug resistance of multiple cancer types. However, the roles of KMT2C in the regulation of tumor prognosis, immune cell infiltration and the immune microenvironment in these multiple cancer types remain unclear. Therefore, in the present study, data from The Cancer Genome Atlas and Genotype-Tissue Expression databases were used for KMT2C expression analyses. Kaplan-Meier and univariate Cox regression analyses were also performed to investigate the prognostic role of KMT2C. In addition, Gene Set Enrichment Analysis (GSEA) was conducted to study the KMT2C-related signaling pathways. Tumor immune estimation resource 2 and single-sample GSEA were conducted to investigate the correlation between KMT2C expression and immune cell infiltrations, and Spearman's analysis was conducted to study the correlations among KMT2C, tumor mutational burden, microsatellite instability, immune regulators, chemokines and immune receptors. Immunohistochemistry of patient kidney tumor samples was performed to verify the correlation between KMT2C and programmed death-ligand 1 (PD-L1) expression. Finally, RNA interference, wound healing and colony formation assays were conducted to evaluate the effects of KMT2C expression on cell proliferation and metastasis. The results of the present study demonstrated that KMT2C was highly expressed in multiple cancer types, was a protective factor in kidney renal clear cell carcinoma and ovarian serous cystadenocarcinoma, and a risk factor for lung squamous cell carcinoma and uveal melanoma. In addition, KMT2C levels were negatively correlated with immune-activated pathways and the infiltration of immune cells, and positively correlated with inhibitory immune factors and tumor angiogenesis. Patients with low KMT2C expression had higher objective response rates to immunotherapy, and drug sensitivity analysis indicated that topoisomerase, histone deacetylase, DOT1-like histone H3K79 methyltransferase and G9A nuclear histone lysine methyltransferase inhibitors could potentially be used to treat tumors with high KMT2C expression levels. Finally, the KMT2C and PD-L1 expression levels were shown to be positively correlated, and KMT2C knockdown markedly promoted the proliferation and invasion capacities of A549 cells. In conclusion, the present study revealed that low KMT2C expression may be a promising biomarker for predicting the response of patients with cancer to immunotherapy. Conversely, high KMT2C expression was shown to promote tumor angiogenesis, which may contribute to the formation of the immunosuppressive tumor microenvironment.
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Affiliation(s)
- Wei Cao
- Department of Thoracic Surgery, Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230601, P.R. China
| | - Yawen Xie
- Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, School of Pharmacy, Anhui Medical University, Hefei, Anhui 230032, P.R. China
| | - Li Cai
- Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, School of Pharmacy, Anhui Medical University, Hefei, Anhui 230032, P.R. China
- Department of Pathology, School of Basic Medicine, Anhui Medical University, Hefei, Anhui 230032, P.R. China
| | - Mengqing Wang
- Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, School of Pharmacy, Anhui Medical University, Hefei, Anhui 230032, P.R. China
| | - Zhuoying Chen
- Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, School of Pharmacy, Anhui Medical University, Hefei, Anhui 230032, P.R. China
| | - Ziteng Wang
- Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, School of Pharmacy, Anhui Medical University, Hefei, Anhui 230032, P.R. China
| | - Jiajia Xv
- Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, School of Pharmacy, Anhui Medical University, Hefei, Anhui 230032, P.R. China
| | - Yuqing Wang
- Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, School of Pharmacy, Anhui Medical University, Hefei, Anhui 230032, P.R. China
| | - Rong Li
- Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, School of Pharmacy, Anhui Medical University, Hefei, Anhui 230032, P.R. China
| | - Xuesong Liu
- Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, School of Pharmacy, Anhui Medical University, Hefei, Anhui 230032, P.R. China
| | - Wenliang Wang
- Institute of Clinical Immunology, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China
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Jafari A, Hosseini FA, Jalali FS. A systematic review of the economic burden of colorectal cancer. Health Sci Rep 2024; 7:e70002. [PMID: 39170890 PMCID: PMC11336656 DOI: 10.1002/hsr2.70002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2023] [Revised: 04/08/2024] [Accepted: 08/01/2024] [Indexed: 08/23/2024] Open
Abstract
Background Colorectal cancer is the third most common cancer in the Western Hemisphere. It is the third most common cancer in men after prostate and lung cancers and the second most common cancer in women after breast cancer. According to some studies, the incidence and prevalence of colorectal cancer is increasing rapidly. Main Body In the present study, a systematic review of the articles related to the economic burden of colorectal cancer was carried out. The articles were taken from the following databases: SID, Medline/Pubmed, Embase, Scopus, Web of Science, NHS Economic Evaluation Database (EED), Econlit, and Google Scholar. Furthermore, the PICOTS model was used to select the inclusion criteria. The quality of the articles' methodologies was evaluated using Drummond's checklist. Then, some data were extracted from relevant articles, in terms of year, place of research, sample size, costing approach, type of measured costs, average direct medical costs, average direct nonmedical costs, and average indirect costs. The data from 37 studies dealing with the costs of patients with colorectal cancer were extracted. Most of the studies were conducted in the United States, and the social perspective was the most common perspective to measure the costs. According to the majority of the studies, direct medical costs were considered the greatest driver in causing the economic burden of colorectal cancer. The costs of hospitalization, medicine, surgery, chemotherapy, and radiotherapy accounted for the largest share of direct medical costs, and the costs of transportation, accommodation, and home care were the greatest share of direct nonmedical costs. Furthermore, the costs associated with disability, absenteeism, and premature death were identified as the main drivers of indirect costs. Conclusion The findings of this study showed that colorectal cancer imposes great direct and indirect costs on families, the health system, and society. The best way to deal with this disease and, hence, to reduce its economic burden is to take comprehensive preventive measures and modify the lifestyle. In addition, health policymakers can limit the costs of this disease by expanding the screening program.
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Affiliation(s)
- Abdosaleh Jafari
- School of Health Management and Information Sciences, Health Human Resources Research CenterShiraz University of Medical SciencesShirazIran
| | | | - Faride S. Jalali
- School of Health Management and Information Sciences, Health Human Resources Research CenterShiraz University of Medical SciencesShirazIran
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Abedizadeh R, Majidi F, Khorasani HR, Abedi H, Sabour D. Colorectal cancer: a comprehensive review of carcinogenesis, diagnosis, and novel strategies for classified treatments. Cancer Metastasis Rev 2024; 43:729-753. [PMID: 38112903 DOI: 10.1007/s10555-023-10158-3] [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: 08/08/2023] [Accepted: 11/27/2023] [Indexed: 12/21/2023]
Abstract
Colorectal cancer is the third most common and the second deadliest cancer worldwide. To date, colorectal cancer becomes one of the most important challenges of the health system in many countries. Since the clinical symptoms of this cancer appear in the final stages of the disease and there is a significant golden time between the formation of polyps and the onset of cancer, early diagnosis can play a significant role in reducing mortality. Today, in addition to colonoscopy, minimally invasive methods such as liquid biopsy have received much attention. The treatment of this complex disease has been mostly based on traditional treatments including surgery, radiotherapy, and chemotherapy; the high mortality rate indicates a lack of success for current treatment methods. Moreover, disease recurrence is another problem of traditional treatments. Recently, new approaches such as targeted therapy, immunotherapy, and nanomedicine have opened new doors for cancer treatment, some of which have already entered the market, and many methods have shown promising results in clinical trials. The success of immunotherapy in the treatment of refractory disease, the introduction of these methods into neoadjuvant therapy, and the successful results in tumor shrinkage without surgery have made immunotherapy a tough competitor for conventional treatments. It seems that the combination of those methods with such targeted therapies will go through promising changes in the future of colorectal cancer treatment.
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Affiliation(s)
- Roya Abedizadeh
- Department of Cancer Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Isar 11, Babol, 47138-18983, Iran
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Bani-Hashem Square, Tehran, 16635-148, Iran
| | - Fateme Majidi
- Department of Cancer Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Isar 11, Babol, 47138-18983, Iran
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Bani-Hashem Square, Tehran, 16635-148, Iran
| | - Hamid Reza Khorasani
- Department of Cancer Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Isar 11, Babol, 47138-18983, Iran
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Bani-Hashem Square, Tehran, 16635-148, Iran
| | - Hassan Abedi
- Department of Internal Medicine, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran.
| | - Davood Sabour
- Department of Cancer Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Isar 11, Babol, 47138-18983, Iran.
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Bani-Hashem Square, Tehran, 16635-148, Iran.
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11
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Monahan BV, Patel T, Poggio JL. Stage IV Colorectal Cancer at Initial Presentation versus Progression during and after Treatment, Differences in Management: Management Differences for Initial Presentation versus Progression of Disease after Initial Treatment. Clin Colon Rectal Surg 2024; 37:108-113. [PMID: 38322603 PMCID: PMC10843884 DOI: 10.1055/s-0043-1761626] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2024]
Abstract
Stage IV colorectal cancer is a prevalent disease and understanding the appropriate treatment options is important. Medical oncologic treatment remains the mainstay of treatment in cases where curative resection is not possible. Surgical intervention is indicated if the primary tumor and associated metastases are amenable to curative resection or if obstructive, bleeding, or perforative complications arise from the tumor. New endoscopic techniques can provide palliation and benefit for patients who cannot undergo surgery and may speed time to chemotherapy initiation. Recently, immunotherapy has shown promise at managing, controlling, and regressing advanced disease, in some cases converting it to curative with resection. For patients that progress while on treatment, continued medical therapy remains the mainstay of treatment. Further research into the benefits of asymptomatic primary tumor resection without curative intent needs to be performed. Colorectal cancer, and more specifically metastatic colorectal cancer, continues to have improved 1- and 5-year survival rates and likely will continue to do so over the coming months and years.
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Affiliation(s)
- Brian V. Monahan
- Department of Surgery, Temple University Hospital, Philadelphia, Pennsylvania
| | - Takshaka Patel
- Department of Surgery, Temple University Hospital, Philadelphia, Pennsylvania
| | - Juan Lucas Poggio
- Department of Surgery, Temple University Hospital, Philadelphia, Pennsylvania
- Division of Colorectal Surgery, Temple University Hospital, Philadelphia, Pennsylvania
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Luo X, Zhang N, Guo L, Zhou L, Jiang H, Cui RS. Comprehensive needs, social support, and disease perception in lung cancer patients treated with immune checkpoint inhibitors: a cross-sectional study. Support Care Cancer 2024; 32:166. [PMID: 38372773 DOI: 10.1007/s00520-024-08348-y] [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: 07/19/2023] [Accepted: 01/30/2024] [Indexed: 02/20/2024]
Abstract
PURPOSE The aim of this study was to investigate the comprehensive needs of lung cancer patients treated with immune checkpoint inhibitors and to explore the relationships between comprehensive needs and social support and disease perception, moreover, to analyse associated factors of comprehensive needs. METHODS The study was conducted in a teaching hospital in Jiaxing Province, China. A total of 141 patients with lung cancer completed a battery of self-report questionnaires, including the Comprehensive Needs Assessment Tool in Cancer for Patients (CNAT), Social Supportive Rating Scale (SSRS), Brief Illness Perception Questionnaire (BIPQ), and demographic and clinical characteristics questionnaire. RESULTS The level of comprehensive needs was highest in the domain "medical demand" (42.17 ± 26.57), and the item with the highest level of comprehensive needs was "I need information about the financial support for my medical expenses" (2.00 ± 1.07). Statistically significant correlations were identified between the comprehensive needs score, social support, and disease perception. The multiple regression analysis showed that immunotherapy course, whether irAEs occur, social support, and disease perception were factors influencing patients' comprehensive needs. CONCLUSIONS The most prevalent needs in lung cancer patients were found in the "medical needs" domain. Additionally, immunotherapy course, whether irAEs occur, disease perception, and social support were associated with comprehensive needs among lung cancer patients. It is essential to combine the associated factors to accurately evaluate patient needs. We should pay more attention to proposing the comprehensive measures for these patients and providing more individualized supportive care during the lengthy treatment period.
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Affiliation(s)
- Xiaoyan Luo
- Department of Nursing, Medical College, Jiaxing College, No.899, Guangdome Road, Nanhu District, Jiaxing, Zhejiang Province, China
| | - Ningning Zhang
- Department of Medical Oncology, The First Hospital of Jiaxing, South Zhonghuan Road, Jiaxing, 1882314001, Zhejiang Province, China
| | - Lingru Guo
- Department of Nursing, Medical College, Jiaxing College, No.899, Guangdome Road, Nanhu District, Jiaxing, Zhejiang Province, China
| | - Li Zhou
- Department of Nursing, Medical College, Jiaxing College, No.899, Guangdome Road, Nanhu District, Jiaxing, Zhejiang Province, China
| | - Haiying Jiang
- Department of Nursing, Medical College, Jiaxing College, No.899, Guangdome Road, Nanhu District, Jiaxing, Zhejiang Province, China
| | - Ren-Shan Cui
- Department of Nursing, Medical College, Jiaxing College, No.899, Guangdome Road, Nanhu District, Jiaxing, Zhejiang Province, China.
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Xu S, Zhong F, jiang J, Yao F, Li M, Tang M, Cheng Y, Yang Y, Wen W, Zhang X, Huang B, Wang X. High Expression of SRSF10 Promotes Colorectal Cancer Progression by Aberrant Alternative Splicing of RFC5. Technol Cancer Res Treat 2024; 23:15330338241271906. [PMID: 39110418 PMCID: PMC11307364 DOI: 10.1177/15330338241271906] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2024] [Revised: 05/21/2024] [Accepted: 06/03/2024] [Indexed: 08/10/2024] Open
Abstract
BACKGROUND Colorectal cancer (CRC) remains a global health concern with persistently high incidence and mortality rates. However, the specific pathogenesis of CRC remains poorly understood. This study aims to investigate the role and pathogenesis of serine and arginine rich splicing factor 10 (SRSF10) in colorectal cancer. METHODS Bioinformatics analysis was employed to predict SRSF10 gene expression in CRC patients. Functional experiments involving SRSF10 knockdown and overexpression were conducted using CCK8, transwell, scratch assay, and flow cytometry. Additionally, the PRIdictor website was utilized to predict the SRSF10 interaction site with RFC5. The identification of different transcripts of SRSF10-acting RFC5 pre-mRNA was achieved through agarose gel electrophoresis. RESULT The knockdown of SRSF10 inhibited the proliferation and migration ability of CRC cells, while promoting apoptosis and altering the DNA replication of CRC cells. Conversely, when SRSF10 was highly expressed, it enhanced the proliferation and migration ability of CRC cells and caused changes in the cell cycle of colorectal cancer cells. This study revealed a change in the replicating factor C subunit 5 (RFC5) gene in colorectal cancer cells following SRSF10 knockdown. Furthermore, it was confirmed that SRSF10 increased RFC5 exon2-AS1(S) transcription variants, thereby promoting the development of colorectal cancer through AS1 exclusion to exon 2 of RFC5. CONCLUSION In summary, this study demonstrates that SRSF10 promotes the progression of colorectal cancer by generating an aberrantly spliced exclusion isoform of AS1 within RFC5 exon 2. These findings suggest that SRSF10 could serve as a crucial target for the clinical diagnosis and treatment of CRC.
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Affiliation(s)
- Shuai Xu
- Department of Clinical Laboratory, Jiangxi Province Key Laboratory of Laboratory Medicine, Nanchang, China
- The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Fangmin Zhong
- Department of Clinical Laboratory, Jiangxi Province Key Laboratory of Laboratory Medicine, Nanchang, China
- The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Junyao jiang
- Department of Clinical Laboratory, Jiangxi Province Key Laboratory of Laboratory Medicine, Nanchang, China
- The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Fangyi Yao
- Department of Clinical Laboratory, Jiangxi Province Key Laboratory of Laboratory Medicine, Nanchang, China
- The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Meiyong Li
- Department of Clinical Laboratory, Jiangxi Province Key Laboratory of Laboratory Medicine, Nanchang, China
- The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Mengxin Tang
- The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Ying Cheng
- Department of Clinical Laboratory, Jiangxi Province Key Laboratory of Laboratory Medicine, Nanchang, China
- The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Yulin Yang
- Department of Clinical Laboratory, Jiangxi Province Key Laboratory of Laboratory Medicine, Nanchang, China
- The Second Affiliated Hospital of Nanchang University, Nanchang, China
- School of Public Health, Nanchang University, No. 461 BaYi Boulevard, Nanchang 330006, Jiangxi, China
| | - Wen Wen
- Department of Clinical Laboratory, Jiangxi Province Key Laboratory of Laboratory Medicine, Nanchang, China
- The Second Affiliated Hospital of Nanchang University, Nanchang, China
- School of Public Health, Nanchang University, No. 461 BaYi Boulevard, Nanchang 330006, Jiangxi, China
| | - Xueru Zhang
- Department of Clinical Laboratory, Jiangxi Province Key Laboratory of Laboratory Medicine, Nanchang, China
- The Second Affiliated Hospital of Nanchang University, Nanchang, China
- School of Public Health, Nanchang University, No. 461 BaYi Boulevard, Nanchang 330006, Jiangxi, China
| | - Bo Huang
- Department of Clinical Laboratory, Jiangxi Province Key Laboratory of Laboratory Medicine, Nanchang, China
- The Second Affiliated Hospital of Nanchang University, Nanchang, China
- School of Public Health, Nanchang University, No. 461 BaYi Boulevard, Nanchang 330006, Jiangxi, China
| | - Xiaozhong Wang
- Department of Clinical Laboratory, Jiangxi Province Key Laboratory of Laboratory Medicine, Nanchang, China
- The Second Affiliated Hospital of Nanchang University, Nanchang, China
- School of Public Health, Nanchang University, No. 461 BaYi Boulevard, Nanchang 330006, Jiangxi, China
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14
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Shu Y, Zheng S. The current status and prospect of immunotherapy in colorectal cancer. Clin Transl Oncol 2024; 26:39-51. [PMID: 37301804 DOI: 10.1007/s12094-023-03235-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2023] [Accepted: 05/24/2023] [Indexed: 06/12/2023]
Abstract
Metastatic colorectal cancer (mCRC) is a heterogeneous disease. We reviewed the current clinical trials on immunotherapy in metastatic colorectal cancer with high microsatellite instability and microsatellite stability. Owing to the advances in immunotherapy, its use has gradually expanded from second- and third-line therapies to first-line, early neoadjuvant, and adjuvant therapies. Based on current research results, immunotherapy has shown very good results in dMMR/MSI-H patients, whether it is neoadjuvant therapy for operable patients or first-line or multi-line therapy for advanced patients. KEYNOTE 016 study also showed that patients with MSS were basically ineffective in single immunotherapy. Moreover, immunotherapy for colorectal cancer may also require identification of new biomarkers.
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Affiliation(s)
- Yefei Shu
- Department of Medical Oncology, Affiliated Hangzhou Cancer Hospital, Zhejiang University School of Medicine, Hangzhou, China.
| | - Song Zheng
- Department of Medical Oncology, Affiliated Hangzhou Cancer Hospital, Zhejiang University School of Medicine, Hangzhou, China.
- Department of Medical Oncology, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
- The Fourth Clinical School of Zhejiang Chinese Medical University, Hangzhou, China.
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Chakraborty B, Agarwal S, Kori S, Das R, Kashaw V, Iyer AK, Kashaw SK. Multiple Protein Biomarkers and Different Treatment Strategies for Colorectal Carcinoma: A Comprehensive Prospective. Curr Med Chem 2024; 31:3286-3326. [PMID: 37151060 DOI: 10.2174/0929867330666230505165031] [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: 11/12/2022] [Revised: 02/20/2023] [Accepted: 02/24/2023] [Indexed: 05/09/2023]
Abstract
In this review, we emphasized important biomarkers, pathogenesis, and newly developed therapeutic approaches in the treatment of colorectal cancer (CRC). This includes a complete description of small-molecule inhibitors, phytopharmaceuticals with antiproliferative potential, monoclonal antibodies for targeted therapy, vaccinations as immunotherapeutic agents, and many innovative strategies to intervene in the interaction of oncogenic proteins. Many factors combine to determine the clinical behavior of colorectal cancer and it is still difficult to comprehend the molecular causes of a person's vulnerability to CRC. It is also challenging to identify the causes of the tumor's onset, progression, and responsiveness or resistance to antitumor treatment. Current recommendations for targeted medications are being updated by guidelines throughout the world in light of the growing number of high-quality clinical studies. So, being concerned about the aforementioned aspects, we have tried to present a summarized pathogenic view, including a brief description of biomarkers and an update of compounds with their underlying mechanisms that are currently under various stages of clinical testing. This will help to identify gaps or shortfalls that can be addressed in upcoming colorectal cancer research.
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Affiliation(s)
- Biswadip Chakraborty
- Integrated Drug Discovery Research Laboratory, Department of Pharmaceutical Sciences, Dr. Harisingh Gour University (A Central University), Sagar (MP), India
| | - Shivangi Agarwal
- Integrated Drug Discovery Research Laboratory, Department of Pharmaceutical Sciences, Dr. Harisingh Gour University (A Central University), Sagar (MP), India
| | - Shivam Kori
- Integrated Drug Discovery Research Laboratory, Department of Pharmaceutical Sciences, Dr. Harisingh Gour University (A Central University), Sagar (MP), India
| | - Ratnesh Das
- Department of Chemistry, ISF College of Pharmacy, Moga-Punjab, India
| | - Varsha Kashaw
- Sagar Institute of Pharmaceutical Sciences, Sagar (M.P.), India
| | - Arun K Iyer
- Use-inspired Biomaterials & Integrated Nano Delivery (U-BiND) Systems Laboratory, Department of Pharmaceutical Sciences, Wayne State University, Detroit, Michigan, USA
- Molecular Imaging Program, Karmanos Cancer Institute, Detroit, Michigan, USA
| | - Sushil Kumar Kashaw
- Integrated Drug Discovery Research Laboratory, Department of Pharmaceutical Sciences, Dr. Harisingh Gour University (A Central University), Sagar (MP), India
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16
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Chen C, Jiang X, Zhao Z. Inhibition or promotion, the potential role of arginine metabolism in immunotherapy for colorectal cancer. ALL LIFE 2023. [DOI: 10.1080/26895293.2022.2163306] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
Affiliation(s)
- Chengyang Chen
- Department of General Surgery, Hebei Key Laboratory of Colorectal Cancer Precision Diagnosis and Treatment, The First Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China
| | - Xia Jiang
- Department of General Surgery, Hebei Key Laboratory of Colorectal Cancer Precision Diagnosis and Treatment, The First Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China
| | - Zengren Zhao
- Department of General Surgery, Hebei Key Laboratory of Colorectal Cancer Precision Diagnosis and Treatment, The First Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China
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17
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Liu X, Chen L, Wen F, Zheng S, Ge W. The high expression of FOXE1 in colorectal cancer predicts a promising prognosis: a retrospective study. Clin Exp Med 2023; 23:3995-4001. [PMID: 37278933 DOI: 10.1007/s10238-023-01096-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: 03/20/2023] [Accepted: 05/18/2023] [Indexed: 06/07/2023]
Abstract
Purpose Forkhead box (FOX) family proteins regulate transcription and DNA repair and are involved in cell growth, differentiation, embryogenesis, and lifespan. The transcription factor FOXE1 is a member of the FOX family. The relationship between the expression level of FOXE1 and colorectal cancer (CRC) prognosis remains controversial. It is vital to verify the relationship between FOXE1 expression and the prognosis of patients with CRC. Methods We constructed a tissue microarray containing 879 primary colorectal cancer tissues and 203 normal mucosa samples. The tumor and normal mucosa tissues were stained with FOXE1 by immunohistochemistry, and the staining results were divided into two groups: high expression group and low expression group. Chi-square test was performed for the classification variable of the difference between FOXE1 expression levels and clinicopathological parameters. The survival curve was calculated according to the Kaplan-Meier method and the logarithmic rank test. The Cox proportional risk regression model was used for multivariate analysis of prognostic factors in patients with CRC.Results The expression level of FOXE1 in colorectal cancer was higher than that in the normal mucosa adjacent to cancer, although the difference was not significant. However, the expression of FOXE1 was correlated with tumor size, T stage, N stage, M stage, and pTNM stage. Univariate and multivariate analyses suggested that FOXE1 could be used as an independent prognostic factor in patients with CRC. Conclusions FOXE1 may be a potential independent prognostic factor for colorectal cancer patients.
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Affiliation(s)
- Xibo Liu
- Department of Pathology, Shaoxing People's Hospital, No. 568, Zhongxing North Road, Shaoxing, 312000, Zhejiang Province, China
| | - Lirong Chen
- Department of Pathology, The Second Affiliated Hospital of Zhejiang University School of Medicine, No.88 Jiefang Road, Hangzhou, 310009, China
| | - Fei Wen
- Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, Zhejiang, China
| | - Shu Zheng
- Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, Zhejiang, China
| | - Weiting Ge
- Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, Zhejiang, China.
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Chitkara A, Bakhtiar M, Sahin IH, Hsu D, Zhang J, Anamika FNU, Mahnoor M, Ahmed R, Gholami S, Saeed A. A Meta-Analysis to Assess the Efficacy of HER2-Targeted Treatment Regimens in HER2-Positive Metastatic Colorectal Cancer (mCRC). Curr Oncol 2023; 30:8266-8277. [PMID: 37754515 PMCID: PMC10528053 DOI: 10.3390/curroncol30090600] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2023] [Revised: 08/28/2023] [Accepted: 08/30/2023] [Indexed: 09/28/2023] Open
Abstract
Recent trials provide evidence that HER2 is a potential new target for patients with colorectal cancer. While HER2-positive tumors do not show a very encouraging response to anti-HER2-positive agents like trastuzumab alone, promising results have been observed when combined with other synergistically acting tyrosine kinase inhibitors (TKIs). Our meta-analysis was conducted following the Cochrane Handbook and written following the PRISMA guidelines. The protocol was registered on PROSPERO with the registration number CRD42022338935. After a comprehensive search for relevant articles, 14 CTs were identified and uploaded to Rayyan, and six trials were ultimately selected for inclusion. The meta-analysis revealed that a median of three prior lines of therapy was used before enrolling in the six trials comprising 238 patients with HER2-positive metastatic colorectal cancer (mCRC). The pooled objective response rate (ORR) and disease control rate (DCR) were 31.33% (95% confidence interval [CI] 24.27-38.39) and 74.37% (95% CI 64.57-84.17), respectively. The pooled weighted progression-free survival (PFS) was 6.2 months. The pooled ORR and DCR meta-analysis indicate a significant response to HER2-targeted therapy in this patient in HER2-positive mCRC. Additionally, a pooled PFS of 6.2 months suggests that HER2-targeted treatment regimens are associated with a meaningful improvement in survival outcomes in this population.
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Affiliation(s)
- Akshit Chitkara
- Department of Internal Medicine, University of California, Riverside, CA 92521, USA;
| | - Muhammad Bakhtiar
- School of Medicine, King Edward Medical University/Mayo Hospital, Lahore 54000, Pakistan; (M.B.); (R.A.)
| | - Ibrahim Halil Sahin
- Department of Medicine, Division of Hematology-Oncology, University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA 15232, USA; (I.H.S.); (D.H.); (J.Z.)
| | - Dennis Hsu
- Department of Medicine, Division of Hematology-Oncology, University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA 15232, USA; (I.H.S.); (D.H.); (J.Z.)
| | - Janie Zhang
- Department of Medicine, Division of Hematology-Oncology, University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA 15232, USA; (I.H.S.); (D.H.); (J.Z.)
| | - FNU Anamika
- Department of Internal Medicine, Hackensack Meridian Ocean University Medical Center, Brick, NJ 08724, USA;
| | - Mahnoor Mahnoor
- School of Medicine, Mohtarma Benazir Bhutto Shaheed Medical College, Mirpur 10230, Pakistan;
| | - Rabeea Ahmed
- School of Medicine, King Edward Medical University/Mayo Hospital, Lahore 54000, Pakistan; (M.B.); (R.A.)
| | - Sepideh Gholami
- Department of Hematology-Oncology, Northwell Health Cancer Institute, New Hyde Park, NY 11042, USA;
| | - Anwaar Saeed
- Department of Medicine, Division of Hematology-Oncology, University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA 15232, USA; (I.H.S.); (D.H.); (J.Z.)
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Luo X, Cui R, Zhang N, Jiang H, Zhou L, Wang X. Investigation and analysis of the comprehensive unmet needs of cancer patients treated with immune checkpoint inhibitors: a cross-sectional study. Support Care Cancer 2023; 31:460. [PMID: 37436492 DOI: 10.1007/s00520-023-07911-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2022] [Accepted: 06/27/2023] [Indexed: 07/13/2023]
Abstract
PURPOSE This study aimed to describe the level of comprehensive needs among cancer patients treated with immune checkpoint inhibitors, to explore the relationship between comprehensive needs and demographic factors, and to examine the relationship between comprehensive needs and treatment variables. METHOD A cross-sectional descriptive study design was adopted. From September 2021 to July 2022, 194 cancer patients treated with immune checkpoint inhibitors were recruited using a convenience sampling method in tertiary teaching hospitals in Zhejiang Province, China. The Comprehensive Needs Assessment Tool for Cancer Patients (CNAT) and questionnaires to assess demographic and clinical characteristics were used to collect data. RESULTS The average comprehensive needs score for cancer patients treated with immune checkpoint inhibitors was 39.2 ± 17.2. Patients reported high levels of medical care needs, knowledge information needs, hospital facilities needs and nursing needs but low levels of religious spiritual support needs, psychoemotional needs, actual support needs, and physical symptom needs. Multiple stepwise linear regression showed that age, primary caregivers, cancer type, number of immunotherapy courses and the occurrence of immune-related adverse events (irAEs) were the main factors affecting the comprehensive needs of cancer patients treated with ICIs (p < 0.05). CONCLUSIONS Age, primary caregivers, cancer type, number of immunotherapy treatment courses and the occurrence of irAEs are important factors affecting the comprehensive unmet needs of cancer patients treated with immune checkpoint inhibitors. Nurses should perform targeted interventions according to the different situations of patients to improve the quality of care.
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Affiliation(s)
- Xiaoyan Luo
- Department of Nursing, Medical College, Jiaxing University, No.899, Guangdome Road, Nanhu District, Jiaxing, 314001, Zhejiang Province, China
| | - Renshan Cui
- Department of Nursing, Medical College, Jiaxing University, No.899, Guangdome Road, Nanhu District, Jiaxing, 314001, Zhejiang Province, China.
| | - Ningning Zhang
- Department of Medical Oncology, The First Hospital of Jiaxing, Jiaxing, China
| | - Haiying Jiang
- Department of Nursing, Medical College, Jiaxing University, No.899, Guangdome Road, Nanhu District, Jiaxing, 314001, Zhejiang Province, China
| | - Li Zhou
- Department of Nursing, Medical College, Jiaxing University, No.899, Guangdome Road, Nanhu District, Jiaxing, 314001, Zhejiang Province, China
| | - Xue Wang
- School of Nursing, Liaoning University of Traditional Chinese Medicine, Shenyang, China
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Xue WH, Li XW, Ding YQ, Wu N, Pei BB, Ma XY, Xie J, Yang WH. Efficacy and safety of third-line or later-line targeted treatment for patients with metastatic colorectal cancer: a meta-analysis. Front Oncol 2023; 13:1165040. [PMID: 37324019 PMCID: PMC10265471 DOI: 10.3389/fonc.2023.1165040] [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: 02/20/2023] [Accepted: 05/17/2023] [Indexed: 06/17/2023] Open
Abstract
Targeted therapy has been standardized in front-line therapies for metastatic colorectal cancer (mCRC), while explicit recommendations for third- or later-line are still lacking. This study evaluated the efficacy and safety of combining targeted therapy with chemotherapy in the third- or later-line treatment for mCRC via meta-analysis, providing evidence-based guidance for clinical or research practice. Comprehensive retrieval of related studies was conducted according to the PRISMA guideline. Studies were stratified with patient characteristics and pharmacological classification of the drugs. For the data available for quantitative analysis, pooled overall response rate, disease control rate, hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), and adverse events rate with respective 95% confidence intervals (CIs) were calculated. A total of 22 studies (1,866 patients) were included in this meta-analysis. Data from 17 studies (1,769 patients) involving targets of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) were extracted for meta-analyses. The overall response rates for monotherapy and combined therapy were 4% (95% CI: 3%, 5%) and 20% (95% CI: 11%, 29%). The pooled HRs (combined therapy vs. mono) for OS and PFS were 0.72 (95% CI: 0.53, 0.99) and 0.34 (95% CI: 0.26, 0.45). Another five studies were included in narrative depiction, involving targets of BRAF, HER-2, ROS1, and NTRK. The findings of this meta-analysis indicate that VEGF and EGFR inhibitors manifest promising clinical response rates and prolonged survival in the treatment of mCRC with acceptable adverse events.
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Affiliation(s)
- Wen-Hui Xue
- Department of Digestive Oncology, Cancer Center, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
| | - Xue-Wei Li
- Department of Biochemistry and Molecular Biology, Shanxi Key Laboratory of Birth Defect and Cell Regeneration, Shanxi Medical University, Taiyuan, Shanxi, China
| | - Ya-Qian Ding
- Department of Digestive Oncology, Cancer Center, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
| | - Na Wu
- Department of Digestive Oncology, Cancer Center, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
| | - Bei-Bei Pei
- Department of Digestive Oncology, Cancer Center, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
| | - Xiao-Yan Ma
- Department of Digestive Oncology, Cancer Center, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
| | - Jun Xie
- Department of Biochemistry and Molecular Biology, Shanxi Key Laboratory of Birth Defect and Cell Regeneration, Shanxi Medical University, Taiyuan, Shanxi, China
| | - Wen-Hui Yang
- Department of Gastroenterology, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi, China
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Jiang YL, Fu XY, Yin ZH. Retrospective efficacy analysis of olaparib combined with bevacizumab in the treatment of advanced colorectal cancer. World J Gastrointest Surg 2023; 15:906-916. [PMID: 37342840 PMCID: PMC10277937 DOI: 10.4240/wjgs.v15.i5.906] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2023] [Revised: 03/11/2023] [Accepted: 04/07/2023] [Indexed: 05/26/2023] Open
Abstract
BACKGROUND Colorectal cancer (CRC) is a highly prevalent malignancy of the digestive tract worldwide, characterized by a significant morbidity and mortality rate and subtle initial symptoms. Diarrhea, local abdominal pain, and hematochezia occur with the development of cancer, while systemic symptoms such as anemia and weight loss occur in patients with advanced CRC. Without timely interventions, the disease can have fatal consequences within a short span. The current therapeutic options for colon cancer include olaparib and bevacizumab, which are widely utilized. This study intends to evaluate the clinical efficacy of olaparib combined with bevacizumab in the treatment of advanced CRC, hoping to provide insights into advanced CRC treatment.
AIM To investigate the retrospective efficacy of olaparib combined with bevacizumab in the treatment of advanced CRC.
METHODS A retrospective analysis was conducted on a cohort of 82 patients with advanced colon cancer who were admitted to the First Affiliated Hospital of the University of South China between January 2018 and October 2019. Among them, 43 patients subjected to the classical FOLFOX chemotherapy regimen were selected as the control group, and 39 patients undergoing treatment with olaparib combined with bevacizumab were selected as the observation group. Subsequent to different treatment regimens, the short-term efficacy, time to progression (TTP), and incidence rate of adverse reactions between the two groups were compared. Changes in serum-related indicators [vascular endothelial growth factor (VEGF), matrix metalloprotein-9 (MMP-9), cyclooxygenase-2 (COX-2)] and tumor markers [human epididymis protein 4 (HE4), carbohydrate antigen 125 (CA125), carbohydrate antigen 199 (CA199)] levels before and after treatment were compared between the two groups at the same time.
RESULTS The objective response rate was discovered to be 82.05%, and the disease control rate was 97.44% in the observation group, which were significantly higher than the respective rates of 58.14% and 83.72% in the control group (P < 0.05). The median TTP was 24 mo (95%CI: 19.987-28.005) in the control group and 37 mo (95%CI: 30.854-43.870) in the observation group. The TTP in the observation group was significantly better than that in the control group, and the difference held statistical significance (log-rank test value = 5.009, P = 0.025). Before treatment, no substantial difference was detected in serum VEGF, MMP-9, and COX-2 levels and tumor markers HE4, CA125, and CA199 levels between the two groups (P > 0.05). Following treatment with different regimens, the above indicators in the two groups were remarkably promoted (P < 0.05), VEGF, MMP-9, and COX-2 in the observation group were lower than those in the control group (P < 0.05), and HE4, CA125, and CA199 levels were also lower than those in the control group (P < 0.05). Vis-à-vis the control group, the total incidence of gastrointestinal reactions, thrombosis, bone marrow suppression, liver and kidney function injury, and other adverse reactions in the observation group was notably lowered, with the difference considered statistically significant (P < 0.05).
CONCLUSION Olaparib combined with bevacizumab in the treatment of advanced CRC demonstrates a strong clinical effect of delaying disease progression and reducing the serum levels of VEGF, MMP-9, COX-2 and tumor markers HE4, CA125 and CA199. Moreover, given its fewer adverse reactions, it can be regarded as a safe and reliable treatment option.
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Affiliation(s)
- Yi-Ling Jiang
- Department of Oncology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang 421001, Hunan Province, China
| | - Xue-Yuan Fu
- Department of Anorectal, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang 421001, Hunan Province, China
| | - Zhi-Hui Yin
- Department of Anorectal, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang 421001, Hunan Province, China
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22
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Wu R, Tong S, Yin J, Zhu Z, Mao Z, Xu L. Oncolytic vaccinia virus acts synergistically with anti-PD-L1 antibody to enhance the killing of colon cancer cells by CD8 + T cells. Pathol Res Pract 2023; 247:154535. [PMID: 37257241 DOI: 10.1016/j.prp.2023.154535] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Revised: 04/11/2023] [Accepted: 05/11/2023] [Indexed: 06/02/2023]
Abstract
Both oncolytic vaccinia virus (OVV) and anti-PD-L1 antibody hold promise in cancer immunotherapy. Herein, we aimed to explore the possible synergistic effects of OVV and anti-PD-L1 on the growth and metastasis of colon cancer (CC) in mouse models. Microarray profiling of CC-related genes was first conducted. Expression of PD-L1 in CC tissues was predicted by TCGA and verified by flow cytometry and RT-qPCR. Then, mouse CC cell lines stably carrying luciferase MC38-luc and CT26-luc were infected with recombinant double-deleted vaccinia virus (vvDD) to evaluate the effect of vvDD on cell viability. The data indicated that PD-L1 was highly expressed in CC tissues and cells following vvDD infection. MC38-luc cells were inoculated into mice to construct CC-bearing mouse models, which were treated with vvDD or combined with anti-PD-L1, with tumor growth, metastasis, survival, and the immune environment analyzed. It was found that OVV combined with anti-PD-L1 antibody led to lower tumor burden and growth and higher survival rates than individual treatment in CC-bearing mice. In addition, this combination exerted a remote effect on the untreated subcutaneous tumors in the lateral abdomen, thus suppressing the tumor metastasis. Furthermore, combined therapy of OVV with anti-PD-L1 antibody activated CD8+ T cells, reduced exhaustion of CD8+ T cells, and enhanced their immune response, strengthening the killing of CC cells and inhibiting tumor growth and metastasis. In conclusion, our findings provide mechanistic insights into the action and efficacy of OVV as an immunomodulatory agent combined with the anti-PD-L1 antibody for the treatment of CC.
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Affiliation(s)
- Runda Wu
- Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215000, PR China
| | - Shan Tong
- Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215000, PR China
| | - Jun Yin
- Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215000, PR China
| | - Zheng Zhu
- Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215000, PR China
| | - Zhongqi Mao
- Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215000, PR China.
| | - Lu Xu
- Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215000, PR China.
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23
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Huang F, Wang Z, Zhu L, Lin C, Wang JX. Comprehensive Analysis of the Expression, Prognostic Value, and Immune Infiltration Activities of GABRD in Colon Adenocarcinoma. Mediators Inflamm 2023; 2023:8709458. [PMID: 37181811 PMCID: PMC10169248 DOI: 10.1155/2023/8709458] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2023] [Revised: 04/03/2023] [Accepted: 04/16/2023] [Indexed: 05/16/2023] Open
Abstract
Colon adenocarcinoma (COAD) is one of the tumors with the highest mortality rates. It is of the utmost significance to make an accurate prognostic assessment and to tailor one's treatment to the specific needs of the patient. Multiple lines of evidence point to the possibility that genetic variables and clinicopathological traits are connected to the onset and development of cancer. In the past, a number of studies have revealed that gamma-aminobutyric acid type A receptor subunit delta (GABRD) plays a role in the advancement of a number of different cancers. However, its function in COAD was rarely reported. In this study, we analyzed TCGA datasets and identified 29 survival-related differentially expressed genes (DEGs) in COAD patients. In particular, GABRD expression was noticeably elevated in COAD specimens. There was a correlation between high GABRD expression and an advanced clinical stage. According to the results of the survival tests, patients whose GABRD expression was high had a lower overall survival time and progression-free survival time than those whose GABRD expression was low. GABRD expression was found to be an independent predictive predictor for overall survival, as determined by multivariate COX regression analysis. Additionally, the predictive nomogram model can accurately predict the fate of individuals with COAD. In addition, we observed that GABRD expressions were positively associated with the expression of T cells regulatory (Tregs), macrophages M0, while negatively associated with the expression of T cells CD8, T cells follicular helper, macrophages M1, dendritic cells activated, eosinophils, and T cells CD4 memory activated. The IC50 of BI-2536, bleomycin, embelin, FR-180204, GW843682X, LY317615, NSC-207895, rTRAIL, and VX-11e was higher in the GABRD high-expression group. In conclusion, we have shown evidence that GABRD is a novel biomarker that is connected with immune cell infiltration in COAD and may be utilized to predict the prognosis of COAD patients.
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Affiliation(s)
- Fakun Huang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Fujian Medical University, Fujian, China
| | | | - Liyue Zhu
- Fujian Medical University, Fuzhou, Fujian, China
| | | | - Jia-xing Wang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Fujian Medical University, Fujian, China
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24
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Yu J, Sun Q, Hui Y, Xu J, Shi P, Chen Y, Chen Y. Vitamin D receptor prevents tumour development by regulating the Wnt/β-catenin signalling pathway in human colorectal cancer. BMC Cancer 2023; 23:336. [PMID: 37046222 PMCID: PMC10091620 DOI: 10.1186/s12885-023-10690-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2022] [Accepted: 02/28/2023] [Indexed: 04/14/2023] Open
Abstract
BACKGROUND Colorectal cancer (CRC) is a common disease threatening human lives worldwide, and vitamin D receptor (VDR) contributes protective roles in this disease. However, the molecular mechanisms underlying VDR protection in CRC progression require further investigation. METHODS In this study, we statistically analyzed the relationship between VDR expression and CRC development in patients and detected invasion and apoptosis in CRC cells with VDR overexpression and interference. We also detected the expression of key genes involved in Wnt/β-catenin signalling (β-catenin, lymphoid enhancer factor (LEF)-1 and cyclin D1) in SW480 cells and nude mice injected with VDR-overexpressing SW480 cells and observed tumour development. Additionally, we performed Co-immunoprecipitation (Co-IP) and glutathione-S-transferase (GST) pull-down assays to identify the protein interactions of VDR with β-catenin, dual luciferase (LUC) and chromatin immunoprecipitation (ChIP) to detect the activation of LEF-1 by VDR. RESULTS The VDR level was closely related to the development and prognosis of CRC patients. VDR overexpression inhibited invasion but promoted apoptosis in cancer cells. β-catenin shRNA contributed oppositely to cancer cell activity with VDR shRNA. Additionally, VDR interacted with β-catenin at the protein level and blocked its nuclear accumulation. VDR regulated the expression of β-catenin, cyclin D1 and LEF-1 and directly activated LEF-1 transcription in vitro. Furthermore, nude mice injected with VDR-overexpressing SW480 cells revealed suppression of tumour growth and decreased expression of β-catenin, cyclin D1 and LEF-1. CONCLUSIONS This study indicated that VDR protected against CRC disease in humans by inhibiting Wnt/β-catenin signalling to control cancer cell invasion and apoptosis, providing new evidence to explore VDR biomarkers or agonists for CRC patient diagnosis and treatment.
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Affiliation(s)
- Jie Yu
- Department of Pathology, The People's Hospital of Suzhou New District, No. 95, Huashan Road, High Tech Zone, Suzhou, Jiangsu Prov, China
| | - Qi Sun
- Department of Pathology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Yi Hui
- Department of Pathology, The People's Hospital of Suzhou New District, No. 95, Huashan Road, High Tech Zone, Suzhou, Jiangsu Prov, China
| | - Jinping Xu
- Department of Pathology, The People's Hospital of Suzhou New District, No. 95, Huashan Road, High Tech Zone, Suzhou, Jiangsu Prov, China
| | - Pancheng Shi
- Department of Pathology, The People's Hospital of Suzhou New District, No. 95, Huashan Road, High Tech Zone, Suzhou, Jiangsu Prov, China
| | - Yu Chen
- Department of Pathology, The People's Hospital of Suzhou New District, No. 95, Huashan Road, High Tech Zone, Suzhou, Jiangsu Prov, China
| | - Yunzhao Chen
- Department of Pathology, The People's Hospital of Suzhou New District, No. 95, Huashan Road, High Tech Zone, Suzhou, Jiangsu Prov, China.
- Department of Pathology, Zhejiang Provincial People's Hospital, Hangzhou, China.
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25
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Ochman B, Mielcarska S, Kula A, Dawidowicz M, Robotycka J, Piecuch J, Szrot M, Dzięgielewska-Gęsiak S, Muc-Wierzgoń M, Waniczek D, Świętochowska E. Do Elevated YKL-40 Levels Drive the Immunosuppressive Tumor Microenvironment in Colorectal Cancer? Assessment of the Association of the Expression of YKL-40, MMP-8, IL17A, and PD-L1 with Coexisting Type 2 Diabetes, Obesity, and Active Smoking. Curr Issues Mol Biol 2023; 45:2781-2797. [PMID: 37185706 PMCID: PMC10136442 DOI: 10.3390/cimb45040182] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2023] [Revised: 03/23/2023] [Accepted: 03/24/2023] [Indexed: 03/29/2023] Open
Abstract
The influence of chitinase-3-like protein 1 (YKL-40 or CHI3L1) expression on the immunological properties of the tumor microenvironment, which may affect the effectiveness of immunotherapy, is currently not sufficiently understood in colorectal cancer (CRC). The aim of this study was to investigate the relationship between YKL-40 expression and the immunological properties of the tumor microenvironment in CRC. We performed in silico analysis, including analysis of immune cell infiltration scores and the immune landscape depending on YKL-40 expression, gene set enrichment analysis (GSEA), and analysis of three Gene Expression Omnibus (GEO) datasets. In 48 CRC tissue homogenates and the surgical margin, we analyzed the expression of YKL-40, MMP8, IL17A, and PD-L1. Moreover, we analyzed the expression of YKL-40 in tissue homogenates retrieved from patients with coexisting diabetes, obesity, and smoking. The expression of YKL-40 was significantly higher in CRC tumor tissue compared to healthy tissue and correlated with MMP-8, IL17A, and PD-L1 expression. In silico analysis revealed an association of YKL-40 with disease recurrence, and GSEA revealed a potential link between elevated YKL-40 expression and immunosuppressive properties of the tumor microenvironment in CRC.
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26
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Wu R, Tang S, Wang Q, Kong P, Liu F. Hsa_circ_0003602 Contributes to the Progression of Colorectal Cancer by Mediating the miR-149-5p/SLC38A1 Axis. Gut Liver 2023; 17:267-279. [PMID: 36148577 PMCID: PMC10018293 DOI: 10.5009/gnl210542] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Revised: 02/27/2022] [Accepted: 03/02/2022] [Indexed: 11/04/2022] Open
Abstract
Background/Aims We aimed to investigate the role and working mechanism of Homo sapiens circular RNA_0003602 (hsa_circ_0003602) in colorectal cancer (CRC) development. Methods The expression of circ_0003602, miR-149-5p, and solute carrier family 38 member 1 (SLC38A1) was detected by quantitative real-time polymerase chain reaction. RNase R assays were conducted to determine the characteristics of circ_0003602. CCK-8 assays, flow cytometry analysis, transwell invasion assays, wound healing assays and tube formation assays were employed to evaluate cell viability, apoptosis, invasion, migration, and angiogenesis. All protein levels were examined by Western blot or immunohistochemistry assay. The glutamine metabolism was monitored by corresponding glutamine, α-ketoglutarate and glutamate assay kits. Dual-luciferase reporter assay was utilized to confirm the targeted combination between miR-149-5p and circ_0003602 or SLC38A1. A xenograft tumor model was established to analyze the role of circ_0003602 in CRC tumor growth in vivo. Results Circ_0003602 was upregulated in CRC tissues and cell lines. Circ_0003602 silencing suppressed CRC cell viability, migration, invasion, angiogenesis, and glutaminolysis; induced cell apoptosis in vitro; and blocked tumor growth in vivo. Moreover, circ_0003602 directly interacted with miR-149-5p to negatively regulate its expression, and circ_0003602 knockdown suppressed the malignant behaviors of CRC cells largely by upregulating miR-149-5p. MiR-149-5p directly bound to the 3' untranslated region of SLC38A1 to induce its degradation, and miR-149-5p overexpression reduced the malignant potential of CRC cells largely by downregulating SLC38A1. Circ_0003602 positively regulated SLC38A1 expression by sponging miR-149-5p in CRC cells. Conclusions Circ_0003602 knockdown impedes CRC development by targeting the miR-149-5p/SLC38A1 axis, which provides a novel theoretical basis and new insights for CRC treatment.
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Affiliation(s)
- Rong Wu
- Clinical Medicine College, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Shiyu Tang
- Department of Clinical Medicine, North Sichuan Medical College, Nanchong, China
| | - Qiuxiao Wang
- Department of Clinical Medicine of Combination of Chinese and Western Medicine, North Sichuan Medical College, Nanchong, China
| | - Pengfei Kong
- Division of Anorectal, Department of Integrated Traditional Chinese and Western Medicine, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
| | - Fang Liu
- Department of Clinical Medicine of Combination of Chinese and Western Medicine, North Sichuan Medical College, Nanchong, China
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27
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Zhang ZY, Sun JH, Liang MJ, Wang XP, Guan J, Zhou ZQ. The E3 ubiquitin ligase SCF (FBXW10)-mediated LATS2 degradation regulates angiogenesis and liver metastasis in colorectal cancer. Int J Biochem Cell Biol 2023; 158:106408. [PMID: 36990424 DOI: 10.1016/j.biocel.2023.106408] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Revised: 03/20/2023] [Accepted: 03/24/2023] [Indexed: 03/29/2023]
Abstract
F-box and WD repeat domain containing 10 (FBXW10) is a member of the FBXW subgroup that contains the WD40 domain. FBXW10 has been rarely reported in colorectal cancer (CRC) and its mechanism is unclear. To investigate the role of FBXW10 in CRC, we conducted in vitro and in vivo experiments. Through the database and our clinical samples, we found that FBXW10 expression was up-regulated in CRC, and it was positively correlated with CD31 expression. CRC patients with high FBXW10 expression levels had a poor prognosis. Overexpression of FBXW10 up-regulated cell proliferation, migration and vascular formation, while knockdown of FBXW10 had the opposite effects. Studies on the mechanism of FBXW10 in CRC showed that FBXW10 could ubiquitinate large tumor suppressor kinase 2 (LATS2) and promote its degradation with the Fbox region of FBXW10 played an essential role in this process. In vivo studies demonstrated that knockout of FBXW10 inhibited tumor proliferation and reduced liver metastasis. In conclusion, our study proved that FBXW10 was significantly overexpressed in CRC and was involved in the pathogenesis of CRC by affecting angiogenesis and liver metastasis. Mechanistically, FBXW10 degraded LATS2 through ubiquitination. Therefore, FBXW10-LATS2 can be used as a therapeutic target for CRC in subsequent studies.
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28
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Chen M, Tan AH, Li J. Curcumin Represses Colorectal Cancer Cell Proliferation by Triggering Ferroptosis via PI3K/Akt/mTOR Signaling. Nutr Cancer 2023; 75:726-733. [PMID: 36346025 DOI: 10.1080/01635581.2022.2139398] [Citation(s) in RCA: 37] [Impact Index Per Article: 18.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
Curcumin is known to suppress the progression of colorectal cancer by inhibiting cancer cell proliferation. In this study, we explored the role of ferroptosis in the antiproliferative properties of curcumin. The effect of curcumin on ferroptosis In Vitro was evaluated in HCT-8 cells. Ferroptosis was first blocked by ferrostatin-1 (Fer-1) and the antiproliferative effect of curcumin was evaluated by determining the levels of ferroptotic markers, including glutathione (GSH), SLC7A11, GPX4, iron, malondialdehyde (MDA), and reactive oxygen species (ROS). An agonist and an inhibitor of PI3K were also used to verify the signaling pathway involved in the antiproliferative effects. Curcumin repressed HCT-8 cell proliferation in a dose-dependent manner. Treating HCT-8 cells with curcumin significantly downregulated GSH, SLC7A11, and GPX4, while significantly increasing levels of iron, MDA, and ROS. In addition, curcumin promoted ferroptosis and reduced proliferation of HCT-8 cells by suppressing the PI3K/Akt/mTOR pathway, and these effects were antagonized by Fer-1. The effects of curcumin were antagonized by a PI3K agonist and reinforced by a PI3K inhibitor. Curcumin triggers ferroptosis and suppresses proliferation of colorectal cancer cells by inhibiting the PI3K/Akt/mTOR signaling pathway. These results indicate its potential as a treatment against colorectal cancer.
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Affiliation(s)
- Mei Chen
- Anorectal Department, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, P.R. China
| | - An-Hui Tan
- Anorectal Department, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, P.R. China
| | - Jing Li
- Anorectal Department, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, P.R. China
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29
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Niu L, Liu L, Cai J. A novel strategy for precise prognosis management and treatment option in colon adenocarcinoma with TP53 mutations. Front Surg 2023; 10:1079129. [PMID: 36843983 PMCID: PMC9947352 DOI: 10.3389/fsurg.2023.1079129] [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: 10/25/2022] [Accepted: 01/10/2023] [Indexed: 02/11/2023] Open
Abstract
Background TP53 is one of the most frequent mutated genes in colon cancer. Although colon cancer with TP53 mutations has a high risk of metastasis and worse prognosis generally, it showed high heterogeneity clinically. Methods A total of 1,412 colon adenocarcinoma (COAD) samples were obtained from two RNA-seq cohorts and three microarray cohorts, including the TCGA-COAD (N = 408), the CPTAC-COAD (N = 106), GSE39582 (N = 541), GSE17536 (N = 171) and GSE41258 (N = 186). The LASSO-Cox method was used to establish the prognostic signature based on the expression data. The patients were divided into high-risk and low-risk groups based on the median risk score. The efficiency of the prognostic signature was validated in various cohorts, including TP53-mutant and TP53 wild-type. The exploration of potential therapeutic targets and agents was performed by using the expression data of TP53-mutant COAD cell lines obtained from the CCLE database and the corresponding drug sensitivity data obtained from the GDSC database. Results A 16-gene prognostic signature was established in TP53-mutant COAD. The high-risk group had significantly inferior survival time compared to the low-risk group in all TP53-mutant datasets, while the prognostic signature failed to classify the prognosis of COAD with TP53 wild-type properly. Besides, the risk score was the independent poor factor for the prognosis in TP53-mutant COAD and the nomogram based on the risk score was also shown good predictive efficiency in TP53-mutant COAD. Moreover, we identified SGPP1, RHOQ, and PDGFRB as potential targets for TP53-mutant COAD, and illuminated that the high-risk patients might benefit from IGFR-3801, Staurosporine, and Sabutoclax. Conclusion A novel prognostic signature with great efficiency was established especially for COAD patients with TP53 mutations. Besides, we identified novel therapeutic targets and potential sensitive agents for TP53-mutant COAD with high risk. Our findings provided not only a new strategy for prognosis management but also new clues for drug application and precision treatment in COAD with TP53 mutations.
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Marritt KL, Hildebrand KM, Hildebrand KN, Singla AK, Zemp FJ, Mahoney DJ, Jirik FR, Monument MJ. Intratumoral STING activation causes durable immunogenic tumor eradication in the KP soft tissue sarcoma model. Front Immunol 2023; 13:1087991. [PMID: 36700206 PMCID: PMC9868147 DOI: 10.3389/fimmu.2022.1087991] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2022] [Accepted: 12/15/2022] [Indexed: 01/11/2023] Open
Abstract
Introduction Soft tissue sarcomas (STS) are highly metastatic, connective-tissue lineage solid cancers. Immunologically, sarcomas are frequently characterized by a paucity of tumor infiltrating lymphocytes and an immune suppressive microenvironment. Activation of the STING pathway can induce potent immune-driven anti-tumor responses within immunogenic solid tumors; however, this strategy has not been evaluated in immunologically cold sarcomas. Herein, we assessed the therapeutic response of intratumoral STING activation in an immunologically cold murine model of undifferentiated pleomorphic sarcoma (UPS). Materials and Results A single intratumoral injection of the murine STING agonist, DMXAA resulted in durable cure in up to 60% of UPS-bearing mice. In mice with synchronous lung metastases, STING activation within hindlimb tumors resulted in 50% cure in both anatomic sites. Surviving mice all rejected UPS re-challenge in the hindlimb and lung. Therapeutic efficacy of STING was inhibited by lymphocyte deficiency but unaffected by macrophage deficiency. Immune phenotyping demonstrated enrichment of lymphocytic responses in tumors at multiple timepoints following treatment. Immune checkpoint blockade enhanced survival following STING activation. Discussion These data suggest intratumoral activation of the STING pathway elicits local and systemic anti-tumor immune responses in a lymphocyte poor sarcoma model and deserves further evaluation as an adjunctive local and systemic treatment for sarcomas.
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Affiliation(s)
- Kayla L. Marritt
- Department of Surgery, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada,McCaig Bone and Joint Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada,Arnie Charbonneau Cancer Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
| | - Karys M. Hildebrand
- Department of Surgery, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada,McCaig Bone and Joint Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada,Arnie Charbonneau Cancer Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
| | - Kurt N. Hildebrand
- Department of Surgery, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada,McCaig Bone and Joint Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada,Arnie Charbonneau Cancer Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
| | - Arvind K. Singla
- Department of Surgery, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada,McCaig Bone and Joint Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada,Arnie Charbonneau Cancer Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
| | - Franz J. Zemp
- Arnie Charbonneau Cancer Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada,Department of Microbiology, Immunology and Infectious Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada,Alberta Children’s Hospital Research Institute, University of Calgary, Calgary, AB, Canada
| | - Douglas J. Mahoney
- Arnie Charbonneau Cancer Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada,Department of Microbiology, Immunology and Infectious Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada,Alberta Children’s Hospital Research Institute, University of Calgary, Calgary, AB, Canada
| | - Frank R. Jirik
- McCaig Bone and Joint Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada,Alberta Children’s Hospital Research Institute, University of Calgary, Calgary, AB, Canada,Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
| | - Michael J. Monument
- Department of Surgery, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada,McCaig Bone and Joint Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada,Arnie Charbonneau Cancer Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada,*Correspondence: Michael J. Monument,
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31
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Miao Z, Zhao X, Liu X. Hypoxia induced β-catenin lactylation promotes the cell proliferation and stemness of colorectal cancer through the wnt signaling pathway. Exp Cell Res 2023; 422:113439. [PMID: 36464122 DOI: 10.1016/j.yexcr.2022.113439] [Citation(s) in RCA: 34] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2022] [Revised: 10/21/2022] [Accepted: 11/27/2022] [Indexed: 12/03/2022]
Abstract
Colorectal cancer (CRC) is a common malignant tumor of digestive system. Its incidence rate and mortality rate ranks the third among all the malignant tumors. The objective of this study was to explore the role of β-catenin in the CRC progression. The CRC tissues were collected to analyze the β-catenin levels. The CRC cells (SW620 and RRKO) were treated with hypoxia to simulate the hypoxic microenvironment of tumor in vitro. The β-catenin levels in the CRC cells were assessed with RT-qPCR, Western blot and Immunofluorescence. The cell biological behaviors were determined with CCK-8, flow cytometry and sphere formation assays. Besides, the glucose uptake, lactate production, ECAR and OCR was detected by seahorse. For the β-catenin lactylation determination, the IP and Western blot assay was performed. Then the protein stability of β-catenin was measured after cycloheximide treatment. The results showed that β-catenin was highly expressed in the CRC tissues and cells. Hypoxia treatment dramatically increased the protein levels and lactylation of β-catenin in the CRC cells. In addition, β-catenin knockdown dramatically inhibited the cell growth and stemness of the CRC cells. Besides, activation of Wnt signaling pathway neutralized the role of sh-β-catenin in the hypoxia treated CRC cells. In conclusion, this study confirmed that hypoxia induced the glycolysis promoted the β-catenin lactylation, which further enhanced the protein stability and expression of β-catenin, thus aggravating the malignant behaviors of CRC cells.
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Affiliation(s)
- Zhi Miao
- Frontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University, Tianjin, 300072, China; Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300072, China.
| | - Xiaomeng Zhao
- Frontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University, Tianjin, 300072, China; Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300072, China
| | - Xiang Liu
- Department of Laboratory Medicine, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430016, China; The Key Laboratory for Biomedical Photonics of MOE at Wuhan National Laboratory for Optoelectronics-Hubei Bioinformatics & Molecular Imaging Key Laboratory, Systems Biology Theme, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, China
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Current progress in the development of prophylactic and therapeutic vaccines. SCIENCE CHINA. LIFE SCIENCES 2022; 66:679-710. [PMID: 36469218 PMCID: PMC9734355 DOI: 10.1007/s11427-022-2230-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Accepted: 10/21/2022] [Indexed: 12/12/2022]
Abstract
Vaccines are essential public health tools and play an important role in reducing the burden of infectious diseases in the population. Emerging infectious diseases and outbreaks pose new challenges for vaccine development, requiring the rapid design and production of safe and effective vaccines against diseases with limited resources. Here, we focus on the development of vaccines in broad fields ranging from conventional prophylactic vaccines against infectious diseases to therapeutic vaccines against chronic diseases and cancer providing a comprehensive overview of recent advances in eight different vaccine forms (live attenuated vaccines, inactivated vaccines, polysaccharide and polysaccharide conjugate vaccines, recombinant subunit vaccines, virus-like particle and nanoparticle vaccines, polypeptide vaccines, DNA vaccines, and mRNA vaccines) and the therapeutic vaccines against five solid tumors (lung cancer breast cancer colorectal cancer liver cancer and gastric cancer), three infectious diseases (human immunodeficiency virus, hepatitis B virus and human papillomavirus-induced diseases) and three common chronic diseases (hypertension, diabetes mellitus and dyslipidemia). We aim to provide new insights into vaccine technologies, platforms, applications and understanding of potential next-generation preventive and therapeutic vaccine technologies paving the way for the vaccines design in the future.
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Hwang IJ, Park J, Seo SB. Non-canonical transcriptional regulation of INHAT subunit SET/TAF-Iβ by EZH2. Biochem Biophys Res Commun 2022; 635:136-143. [DOI: 10.1016/j.bbrc.2022.10.041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2022] [Accepted: 10/10/2022] [Indexed: 11/26/2022]
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Chen L, Ma X, Dong H, Qu B, Yang T, Xu M, Sheng G, Hu J, Liu A. Construction and assessment of a joint prediction model and nomogram for colorectal cancer. J Gastrointest Oncol 2022; 13:2406-2414. [PMID: 36388680 PMCID: PMC9660088 DOI: 10.21037/jgo-22-917] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Accepted: 10/18/2022] [Indexed: 01/24/2023] Open
Abstract
BACKGROUND Colorectal cancer (CRC) is one of the most common tumors in the digestive system, and all its risk factors are not yet known. It is important to identify valuable clinical indicators to predict the risk of CRC. METHODS A total of 227 participants, comprising 162 healthy adults and 65 patients diagnosed with CRC at Tianjin Hospital from January 2017 to March 2022, were included in this study. Electrochemiluminescence was adopted to test the expression levels of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA199). Univariate and multivariate logistic regression analyses were performed to identify independent risk factors for CRC, and a joint prediction model was then constructed. A nomogram was prepared, and the model was later assessed using the receiver operating characteristic curve and calibration curve. RESULTS The univariate analysis showed that there were statistically significant differences between the two groups in terms of smoking (χ2=8.67), fecal occult blood (χ2=119.41), Helicobacter pylori (H. pylori) infection (χ2=30.87), a history of appendectomy (χ2=5.47), serum total bile acid levels (t=19.80), serum CEA levels (t=37.82), serum CA199 levels (t=6.82), and serum ferritin levels (t=54.31) (all P<0.05). The multiple logistic regression analysis showed that smoking, fecal occult blood, H. pylori infection, a history of appendectomy, serum CEA levels, and serum CA199 levels were independent risk factors for CRC (all P<0.05). Based on the above findings, a joint prediction model was constructed, and the area under the receiver operator characteristic (ROC) curve of the model was 0.842. A nomogram and calibration curve was drawn, and the internal validation results indicated that the model had good diagnostic value. CONCLUSIONS Smoking, fecal occult blood, H. pylori infection, a history of appendectomy, serum CEA levels, and serum CA199 levels are independent risk factors for CRC, and the prediction model based on these factors had good predictive ability.
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Affiliation(s)
- Liming Chen
- Department of Anorectal Surgery, Tianjin Hospital, Tianjin, China
| | - Xi Ma
- Department of Anorectal Surgery, Tianjin Hospital, Tianjin, China
| | - Huajiang Dong
- Logistics University of the Chinese People’s Armed Police Force, Tianjin, China
| | - Bo Qu
- Institute of Disaster and Emergency Medicine, Tianjin University, Tianjin, China
| | - Tao Yang
- Department of General Surgery, Tianjin First Central Hospital, Tianjin, China
| | - Min Xu
- Department of General Surgery, Tianjin First Central Hospital, Tianjin, China
| | - Guannan Sheng
- Department of General Surgery, Tianjin First Central Hospital, Tianjin, China
| | - Jun Hu
- Department of Colorectal Cancer Surgery, Tianjin Medical University Cancer Institute and Hospital, the National Clinical Research Center of Cancer and Key Laboratory of Cancer Prevention and Therapy, Tianjin, China
| | - Aidong Liu
- Department of Pathology, Tianjin Hospital, Tianjin, China
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Prognostic Analysis of LncRNA MCM3AP-AS1 in Colorectal Cancer and the Mechanism of Its Effect on Tumor Cell Activity. BIOMED RESEARCH INTERNATIONAL 2022; 2022:1616370. [PMID: 36172487 PMCID: PMC9512606 DOI: 10.1155/2022/1616370] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/18/2022] [Revised: 08/29/2022] [Accepted: 09/07/2022] [Indexed: 11/18/2022]
Abstract
To determine the clinical prognostic significance of lncRNA MCM3AP-AS1 in colorectal cancer (CRC) and its preliminary mechanism, 43 CRC patients and 48 healthy individuals were analyzed. Peripheral blood MCM3AP-AS1 was quantified via qRT–PCR in CRC patients at admission and 2 h after surgery and in healthy individuals. Human colon cancer cells (HCT116 and SW480) were transfected with shRNAs targeting upregulation of MCM3AP-AS1 expression (named as sh-MCM3AP-AS1 group) and corresponding negative RNAs (named as sh-MCM3AP-AS1 group). Additionally, the cells were then treated either with 50 mM of the VEGF-specific inhibitor PTK787 (Selleck, USA) (named as inhibition group) or normal saline as a control (named as control group). Before therapy, CRC patients presented a higher MCM3AP-AS1 level than healthy individuals (P < 0.05), and the sensitivity and specificity of MCM3AP-AS1 in predicting the occurrence of CRC were 65.12% and 83.33%, respectively (P < 0.001). After therapy, CRC patients presented a decrease in MCM3AP-AS1 levels, and recurrence was higher in patients who died (P < 0.05). Additionally, the high MCM3AP-AS1 expression group presented a higher mortality than the low MCM3AP-AS1 expression group (P < 0.05). In an in vitro assay, CRC cells showed a higher MCM3AP-AS1 level than CCD-18Co cells, and the sh-MCM3AP-AS1 group presented decreased cell proliferation and invasiveness, whereas the levels apoptosis-associated proteins were increased (P < 0.05). Moreover, the VEGF and VEGFR2 mRNA levels were increased in CRC cells, and VEGF/VEGFR2 pathway-associated proteins were inhibited in the sh-MCM3AP-AS1 group (P < 0.05). Moreover, treatment with PTK787 decreased cell proliferation and invasivness but increased the levels of apoptosis-associated proteins (P < 0.05).
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Chen F, Chen S, Luo Y, Si A, Yang Y, Li Y, Hu W, Zhang Y. Long-Time Trend of Colorectal Cancer Mortality Attributable to High Processed Meat Intake in China and a Bayesian Projection from 2020 to 2030: A Model-Based Study. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:10603. [PMID: 36078321 PMCID: PMC9517814 DOI: 10.3390/ijerph191710603] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/04/2022] [Revised: 08/20/2022] [Accepted: 08/23/2022] [Indexed: 06/15/2023]
Abstract
Colorectal cancer is among the leading causes of cancer worldwide. Processed meat was known to be positively associated with a higher risk of gastrointestinal cancer. This study focused on the long-time trends of colorectal cancer mortality attributable to high processed meat intake in China from 1990 to 2019 and the projection for the next decade based on data obtained from the Global Burden of Disease 2019 study. We used an age-period-cohort model to fit the long-time trend. The joinpoint model was conducted to estimate the average and annual change of the attributable mortality. The Bayesian age-period-cohort model was used to project the crude attributable mortality from 2020 to 2030. An upward trend in colorectal cancer mortality attributable to high processed meat intake was observed for both sexes in China from 1990 to 2019, with an overall net drift of 4.009% for males and 2.491% for females per year. Projection analysis suggested that the burden of colorectal cancer incidence and mortality would still be high. Our findings suggested that colorectal cancer death attributable to high processed meat intake is still high in China, and elderly males were at higher risk. Gradually decreasing the intake of processed meat could be an effective way to reduce colorectal cancer mortality.
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Affiliation(s)
- Fangyao Chen
- Department of Epidemiology and Biostatistics, School of Public Health, Xi’an Jiaotong University Health Science Center, Xi’an 710061, China
- Department of Radiology, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, China
| | - Shiyu Chen
- Department of Epidemiology and Biostatistics, School of Public Health, Xi’an Jiaotong University Health Science Center, Xi’an 710061, China
| | - Yaqi Luo
- Department of Epidemiology and Biostatistics, School of Public Health, Xi’an Jiaotong University Health Science Center, Xi’an 710061, China
- Department of Nursing, Xi’an Jiaotong University Health Science Center, Xi’an 710061, China
| | - Aima Si
- Department of Epidemiology and Biostatistics, School of Public Health, Xi’an Jiaotong University Health Science Center, Xi’an 710061, China
| | - Yuhui Yang
- Department of Epidemiology and Biostatistics, School of Public Health, Xi’an Jiaotong University Health Science Center, Xi’an 710061, China
| | - Yemian Li
- Department of Epidemiology and Biostatistics, School of Public Health, Xi’an Jiaotong University Health Science Center, Xi’an 710061, China
| | - Weiwei Hu
- Department of Epidemiology and Biostatistics, School of Public Health, Xi’an Jiaotong University Health Science Center, Xi’an 710061, China
| | - Yuxiang Zhang
- Department of Epidemiology and Biostatistics, School of Public Health, Xi’an Jiaotong University Health Science Center, Xi’an 710061, China
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Talaat IM, Elemam NM, Zaher S, Saber-Ayad M. Checkpoint molecules on infiltrating immune cells in colorectal tumor microenvironment. Front Med (Lausanne) 2022; 9:955599. [PMID: 36072957 PMCID: PMC9441912 DOI: 10.3389/fmed.2022.955599] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2022] [Accepted: 07/29/2022] [Indexed: 11/19/2022] Open
Abstract
Colorectal cancer (CRC) is one of the most prevalent cancer types worldwide, with a high mortality rate due to metastasis. The tumor microenvironment (TME) contains multiple interactions between the tumor and the host, thus determining CRC initiation and progression. Various immune cells exist within the TME, such as tumor-infiltrating lymphocytes (TILs), tumor-associated macrophages (TAMs), and tumor-associated neutrophils (TANs). The immunotherapy approach provides novel opportunities to treat solid tumors, especially toward immune checkpoints. Despite the advances in the immunotherapy of CRC, there are still obstacles to successful treatment. In this review, we highlighted the role of these immune cells in CRC, with a particular emphasis on immune checkpoint molecules involved in CRC pathogenesis.
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Affiliation(s)
- Iman M. Talaat
- Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates
- Sharjah Institute for Medical Research, University of Sharjah, Sharjah, United Arab Emirates
- Pathology Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Noha M. Elemam
- Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates
- Sharjah Institute for Medical Research, University of Sharjah, Sharjah, United Arab Emirates
- *Correspondence: Noha M. Elemam,
| | - Shroque Zaher
- College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates
| | - Maha Saber-Ayad
- Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates
- Sharjah Institute for Medical Research, University of Sharjah, Sharjah, United Arab Emirates
- Department of Pharmacology, Faculty of Medicine, Cairo University, Cairo, Egypt
- Maha Saber-Ayad,
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Zhong Y, Huang S, Feng Z, Fu Y, Mo A. Recent advances and trends in the applications of MXene nanomaterials for tissue engineering and regeneration. J Biomed Mater Res A 2022; 110:1840-1859. [PMID: 35975580 DOI: 10.1002/jbm.a.37438] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2022] [Revised: 07/14/2022] [Accepted: 08/03/2022] [Indexed: 11/08/2022]
Abstract
MXene, as a new two-dimensional nanomaterial, is endowed with lots of particular properties, such as large surface area, excellent conductivity, biocompatibility, biodegradability, hydrophilicity, antibacterial activity, and so on. In the past few years, MXene nanomaterials have become a rising star in biomedical fields including biological imaging, tumor diagnosis, biosensor, and tissue engineering. In this review, we sum up the recent applications of MXene nanomaterials in the field of tissue engineering and regeneration. First, we briefly introduced the synthesis and surface modification engineering of MXene. Then we focused on the application and development of MXene and MXene-based composites in skin, bone, nerve and heart tissue engineering. Uniquely, we also paid attention to some research on MXene with few achievements at present but might become a new trend in tissue engineering and regeneration in the future. Finally, this paper will also discuss several challenges faced by MXene nanomaterials in the clinical application of tissue engineering.
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Affiliation(s)
- Yongjin Zhong
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Implantology, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Si Huang
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Implantology, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Zeru Feng
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Implantology, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Yu Fu
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Implantology, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Anchun Mo
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Implantology, West China Hospital of Stomatology, Sichuan University, Chengdu, China
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NAV3 Is a Novel Prognostic Biomarker Affecting the Immune Status of the Tumor Microenvironment in Colorectal Cancer. J Immunol Res 2022; 2022:8337048. [PMID: 35812247 PMCID: PMC9262578 DOI: 10.1155/2022/8337048] [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: 05/15/2022] [Revised: 06/08/2022] [Accepted: 06/14/2022] [Indexed: 11/17/2022] Open
Abstract
Colorectal cancer (CRC) is one of the most common malignant tumors in the world. Tumor microenvironment (TME) plays a crucial role in the development of CRC. With the deep understanding of TME function, growing studies have demonstrated that alteration in tumor-infiltrating immune cells (TICs) and gene expressions are associated with clinical outcomes of various tumors. In this study, we aimed to recognize critical prognostic genes involved in immune states in TME of CRC. Hence, the proportion of TICs and the number of immune and stromal components in CRC samples from TCGA datasets were calculated by the use of CIBERSORT and ESTIMATE calculation methods. Different assays were applied to collect differential expression genes (DEGs) shared by the ImmuneScore and StromalScore. DEGs were further analyzed by the use of univariate Cox regression. Our attention focused on neuron navigator 3 (NAV3) which was highly expressed in CRC specimens and associated with an advanced clinical stage and poor prognosis of CRC patients. KEGG assays revealed that NAV3 may be involved in Alzheimer disease, amyotrophic lateral sclerosis, Huntington disease, FoxO signaling pathway, and human papillomavirus infection. Correlation assays showed that macrophage M0 and B cells memory, NK cells activated, dendritic cells resting, T cells CD4 memory activated, and T cells CD8 were correlated with NAV3 expression, indicating that NAV3 may represent the immune status of TME. Finally, RT-PCR confirmed that NAV3 expression was distinctly increased in CRC cells, and its knockdown suppressed the proliferation of CRC cells. Overall, NAV3 could be used as a novel predictor for TME of CRC and might be a novel prognostic biomarker. In the future, drugs targeting NAV3 might be developed as a potential immunotherapy for CRC patients.
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Influence of Early Predictive Nursing on Complications and Quality of Life in Patients after Colorectal Cancer Surgery. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:8410664. [PMID: 35722144 PMCID: PMC9200512 DOI: 10.1155/2022/8410664] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/09/2022] [Revised: 04/10/2022] [Accepted: 05/19/2022] [Indexed: 11/17/2022]
Abstract
Objective To analyze the effect of early predictive nursing on complications and quality of life in patients after colorectal cancer surgery. Methods A total of 130 patients with colorectal cancer who were diagnosed and underwent surgical resection in our hospital from 2019 to 2021 were recruited and assigned via the random number table method (1 : 1) to receive either conventional nursing (routine group) or predictive nursing (study group). Outcome measures included the incidence of complications and the quality of life. Results Predictive nursing was associated with shorter operation time and hospital stay and less blood loss (2.35 ± 0.41, 9.32 ± 1.86, and 70.52 ± 16.52) versus conventional nursing (3.02 ± 0.78, 11.20 ± 2.14, and 81.51 ± 17.74) (all P < 0.05). Patients in the study group showed a lower incidence of complications than the control group (10.76% vs 35.38%) (all P < 0.05). Predictive nursing resulted in better anxiety relief than conventional nursing (P < 0.05). Predictive nursing was associated with higher emotional function, cognitive function, role function, and physical function scores (83.51 ± 12.56, 82.45 ± 9.15, 82.48 ± 10.46, 84.43 ± 13.48, and 82.73 ± 9.67) than conventional nursing (73.85 ± 13.54, 72.54 ± 12.74, 72.48 ± 10.45, 73.99 ± 14.51, and 72.45 ± 11.69) (all P < 0.05). Patients receiving predictive nursing showed a significantly higher nursing satisfaction versus conventional nursing (P < 0.05). Conclusion Early predictive nursing for patients receiving colorectal cancer surgery can lower the incidence of complications, effectively improve the quality of life of patients, shorten the hospital stay, reduce the amount of bleeding, and enhance the satisfaction of patients.
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Wu Z, Yin B, You F. Molecular Mechanism of Anti-Colorectal Cancer Effect of Hedyotis diffusa Willd and Its Extracts. Front Pharmacol 2022; 13:820474. [PMID: 35721163 PMCID: PMC9201484 DOI: 10.3389/fphar.2022.820474] [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: 11/23/2021] [Accepted: 04/06/2022] [Indexed: 11/13/2022] Open
Abstract
With the sharp change in our diet and lifestyle, the incidence of colorectal cancer (CRC) is increasing among young people and has become the second most common malignant tumor worldwide. Although the current treatment of CRC is getting updated rapidly, recurrence and metastasis are still inevitable. Therefore, new anticancer drugs are needed to break existing limitations. In recent years, Hedyotis diffusa Willd (HDW) extracts have been proved to demonstrate excellent anti-colorectal cancer effects and have been widely used in clinical practices. In this review, we aim to explore the advantages, potential signaling pathways, and representative active ingredients of HDW in the treatment of CRC from the perspective of molecular mechanism, in order to provide new ideas for the future treatment of CRC.
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Affiliation(s)
- Zihong Wu
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Bei Yin
- School of Second Clinical Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Fengming You
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
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Han W, Xing W, Wang K, Wang B, Bai K. Alisol A attenuates malignant phenotypes of colorectal cancer cells by inactivating PI3K/Akt signaling. Oncol Lett 2022; 24:249. [PMID: 35761944 PMCID: PMC9214697 DOI: 10.3892/ol.2022.13369] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Accepted: 02/02/2022] [Indexed: 12/03/2022] Open
Abstract
Despite the advancement in the diagnosis and therapeutic strategies for colorectal cancer, the outcomes of patients with colorectal cancer remain unsatisfactory. Alisol A is a natural constituent of Alismatis rhizoma (zexie) and has demonstrated anti-cancer properties; however, the function of Alisol A in colorectal cancer is still unknown. In the present study, the effect of Alisol A on colorectal cancer progression was investigated. MTT and colony formation assays showed that treatment with Alisol A repressed colorectal cancer cell proliferation in a dose-dependent manner. Similarly, western blot analysis demonstrated that Alisol A upregulated E-cadherin protein expression levels, but downregulated N-cadherin and Vimentin protein expression levels in colorectal cancer cells. In addition, the number of cells in G0/G1 phase was enhanced, while that of S phase was reduced in Alisol A-treated colorectal cancer cells. Apoptosis and pyroptosis of colorectal cancer cells were stimulated following treatment with Alisol A. Alisol A suppressed the migration ability of colorectal cancer cells in a dose-dependent manner. Moreover, Alisol A increased the chemotherapeutic sensitivity of colorectal cancer cells to cisplatin. Mechanically, western blot analysis confirmed that Alisol A repressed the phosphorylation levels of PI3K, Akt and mTOR in colorectal cancer cells. The Akt activator, SC79 reversed the effect of Alisol A on colorectal cancer cell proliferation and apoptosis. In conclusion, Alisol A induced an inhibitory effect on colorectal cancer progression by inactivating PI3K/Akt signaling.
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Affiliation(s)
- Weiwei Han
- Department of Anorectal, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250014, P.R. China
| | - Wenjing Xing
- Department of Traditional Chinese Medicine, Zibo Central Hospital, Zibo, Shandong 255000, P.R. China
| | - Kechao Wang
- Department of Traditional Chinese Medicine, Zibo Central Hospital, Zibo, Shandong 255000, P.R. China
| | - Benjun Wang
- Department of Anorectal, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250014, P.R. China
| | - Keyun Bai
- Department of Anorectal, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250014, P.R. China
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Fan H, Ai R, Mu S, Niu X, Guo Z, Liu L. MiR-19a suppresses ferroptosis of colorectal cancer cells by targeting IREB2. Bioengineered 2022; 13:12021-12029. [PMID: 35599631 PMCID: PMC9275930 DOI: 10.1080/21655979.2022.2054194] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Colorectal cancer (CRC) is the most common malignant tumor occurred in digestive system. However, the prognosis of CRC patients is poor. Therefore, it is urgent to illuminate the mechanism suppressing CRC and explore novel targets or therapies for CRC treatment. MicroRNAs (miRNAs) are a class of non-coding RNAs with a length of 20–23 nucleotides encoded by endogenous genes, which are associated with the development of a variety of cancers, including CRC. Studies have shown that miR-19a is identified as oncogenic miRNA and promotes the proliferation, migration and invasion of CRC cells. However, the relationship between miR-19a and ferroptosis in CRC remains unknown. Here, we reported that iron-responsive element-binding protein 2 (IREB2), as an inducer of ferroptosis, was negatively regulated by miR-19a. IREB2 is a direct target of miR-19a. In addition, ferroptosis was suppressed by miR-19a through inhibiting IREB2. Thus, we proposed a novel mechanism of ferroptosis mediated by miR-19a in CRC cells, which could give rise to a new strategy for the therapy of CRC.
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Affiliation(s)
- Hongwei Fan
- Department of Gastroenterology, Shijiazhuang People’s Hospital, Shijiazhuang, Hebei, China
| | - Rong Ai
- Department of Gastroenterology, Shijiazhuang People’s Hospital, Shijiazhuang, Hebei, China
| | - Suen Mu
- Department of Gastroenterology, Shijiazhuang People’s Hospital, Shijiazhuang, Hebei, China
| | - Xuemin Niu
- Department of Gastroenterology, Shijiazhuang People’s Hospital, Shijiazhuang, Hebei, China
| | - Zhengrong Guo
- Department of Gastroenterology, Shijiazhuang People’s Hospital, Shijiazhuang, Hebei, China
| | - Lin Liu
- Department of Pathology, Shijiazhuang People’s Hospital, Shijiazhuang, Hebei, China
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Current Role of Immunotherapy in Gastric, Esophageal and Gastro-Esophageal Junction Cancers—A Report from the Western Canadian Gastrointestinal Cancer Consensus Conference. Curr Oncol 2022; 29:3160-3170. [PMID: 35621647 PMCID: PMC9139288 DOI: 10.3390/curroncol29050257] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2022] [Revised: 04/20/2022] [Accepted: 04/28/2022] [Indexed: 12/24/2022] Open
Abstract
Gastric, esophageal and gastro-esophageal junction cancers are associated with inferior outcomes. For early-stage disease, perioperative chemotherapy or chemoradiation followed by surgery is the standard treatment. For most patients with advanced upper gastrointestinal tract cancers, platinum-based chemotherapy remains a standard treatment. Recently, several randomized clinical trials have demonstrated the benefit of immunotherapy involving checkpoint inhibitors alone or in combination with chemotherapy in patients with gastro-esophageal cancer and have changed the treatment landscape. The Western Canadian Gastrointestinal Cancer Consensus Conference (WCGCCC), involving experts from four Western Canadian provinces, convened virtually on 16 June 2021 and developed the recommendations on the role of immunotherapy in patients with gastro-esophageal cancer.
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Ren H, Wang Y, Guo Y, Wang M, Ma X, Li W, Guo Y, Li Y. Matrine impedes colorectal cancer proliferation and migration by downregulating endoplasmic reticulum lipid raft associated protein 1 expression. Bioengineered 2022; 13:9780-9791. [PMID: 35412433 PMCID: PMC9161898 DOI: 10.1080/21655979.2022.2060777] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022] Open
Abstract
Matrine exhibits anti-tumor effect on the proliferation and invasion of colorectal cancer (CRC) cells by reducing the activity of the p38 signaling pathway. However, these studies were limited because the underlying mechanism by which matrine inhibited CRC progression remained unclear. In this study, we provided for the first time that endoplasmic reticulum lipid raft associated protein 1 (Erlin1) is a novel target of matrine. Erlin1 was significantly upregulated in tumors and its knockdown suppressed the proliferation and migration of CRC cells, while its overexpression promoted CRC cell growth and migration. Furthermore, Erlin1 overexpression promoted inhibited apoptosis. Importantly, matrine treatment could reverse the oncogenic function of Erlin1 on CRC cell proliferation and migration. When Erlin1 was knocked down, matrine exhibited a more obvious anti-tumor effect in CRC cells. Partly due to this, matrine functions as an important anti-tumor drug and the results discovered here may clarify the mechanisms of matrine application for CRC treatment. CRC patients with low expression of Erlin1 might be more suitable for the treatment of matrine. This study could promote the application of matrine to be a promising therapeutic strategy for CRC patients.
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Affiliation(s)
- Hongtao Ren
- Department of Radiotherapy, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Yali Wang
- Department of Radiotherapy, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Ya Guo
- Department of Radiotherapy, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Mincong Wang
- Department of Radiotherapy, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Xiulong Ma
- Department of Radiotherapy, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Wen Li
- Department of Radiotherapy, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Yuyan Guo
- Department of Radiotherapy, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Yiming Li
- Department of General Surgery, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
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Chen C, Hou S, Zhao F, Wu B, Liu T, Zhang Z, Li Y, Li H. Application of Bevacizumab Combined With Chemotherapy in Patients With Colorectal Cancer and Its Effects on Brain-Gut Peptides, Intestinal Flora, and Oxidative Stress. Front Surg 2022; 9:872112. [PMID: 35478726 PMCID: PMC9035672 DOI: 10.3389/fsurg.2022.872112] [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: 02/09/2022] [Accepted: 02/24/2022] [Indexed: 11/26/2022] Open
Abstract
Objective To investigate the efficacy of bevacizumab combined with chemotherapy in the treatment of colorectal cancer (CRC) and to analyze the effects on brain peptides, intestinal flora, and oxidative stress in CRC patients. Methods Eighty two patients with CRC who were admitted to our hospital from March 2018 to June 2021 were selected as the research subjects and divided into the control group (n = 41) and the observation group (n = 41). The control group was treated with XELOX chemotherapy, and the observation group was additionally treated with bevacizumab, which was repeated every 3 weeks for a total of two treatments. The therapeutic effects of the two groups were evaluated after treatment. The brain-gut peptide index, intestinal flora index and oxidative stress index were detected, and the adverse reactions of the two groups were recorded. Results In the control group, ER was 36.59% (15/41) and DCR was 73.17% (30/41). In the observation group, ER was 63.41% (26/41) and DCR was 90.24% (37/41). ER and DCR in the observation group were higher than those in the control group (P < 0.05). After treatment, the levels of motilin and gastrin in the observation group were lower than those in the control group, and ghrelin was higher than that in the control group (P < 0.05). After treatment, the levels of Bifidobacterium, Lactobacilli and Enterococcus in the observation group were higher than those in the control group, and the level of Escherichia coli was lower than that in the control group (P < 0.05). After treatment, the SOD level of the observation group was lower than that of the control group, and the MDA level was higher than that of the control group. Conclusion Bevacizumab combined with chemotherapy has good efficacy in the treatment of colorectal cancer patients, which can effectively improve the gastrointestinal motility of patients, regulate the intestinal flora of the body, rebuild the microecological balance, effectively reduce the oxidative stress response of patients, and reduce the incidence of adverse reactions.
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Affiliation(s)
- Chao Chen
- Department of Colorectal Surgery, Nankai University Affiliated Hospital, Tianjin, China
| | - Songtao Hou
- Department of Anorectal Surgery, Tianjin Binhai New Area Traditional Chinese Medicine Hospital, Tianjin, China
| | - Fei Zhao
- Department of Anorectal Surgery, Tianjin Binhai New Area Traditional Chinese Medicine Hospital, Tianjin, China
| | - Bin Wu
- Department of General Surgery, Shandong Ningjin People's Hospital, Dezhou, China
| | - Tingting Liu
- Department of Colorectal Surgery, Nankai University Affiliated Hospital, Tianjin, China
| | - Zhao Zhang
- Department of Colorectal Surgery, Nankai University Affiliated Hospital, Tianjin, China
| | - Yuwei Li
- Department of Colorectal Surgery, Nankai University Affiliated Hospital, Tianjin, China
- *Correspondence: Yuwei Li
| | - Hongchao Li
- Department of Colorectal Surgery, Hebei Province Hospital of Chinese Medicine, Shijiazhuang, China
- Hongchao Li
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Tang M, Zheng Z, Shang J, Zhang S. Risk Analysis of Positive PD-L1 Expression and Clinicopathological Features and Survival Prognosis in Patients with Colorectal Cancer: Systematic Review and Meta-Analysis. JOURNAL OF HEALTHCARE ENGINEERING 2022; 2022:8212486. [PMID: 35449848 PMCID: PMC9017426 DOI: 10.1155/2022/8212486] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Revised: 03/01/2022] [Accepted: 03/16/2022] [Indexed: 11/18/2022]
Abstract
In order to explore the significance of PD-L1 expression in the prognosis and clinicopathological characteristics of colorectal cancer (CRC), the PubMed, Embase, Web of Science, Cochrane Library, CNKI, and multisquare databases are systematically searched for the relevant relationship between PD-L1 expression and CRC prognosis. The search time is completed until June 2021. Literature is filtered and data extracted by inclusion exclusion criteria, and Meta-analysis is performed with Stata SE12.0 software. 16 documents are included, and a total of 1997 CRC patients are included. The results show that recurrence-free survival (RFS) [OR = 2.69, 95%CI (2.07,3.48), P < 0.00001, I2 = 0%, Z = 7.50), and disease-free survival (DFS) (OR = 3.71, 95% CI (2.32,5.93), P < 0.00001, I2 = 37%, Z = 5.48) and PD-L1 expression and tumor differentiation (OR = 4.00, 95%CI (2.97,5.38), P < 0.00001, I2 = 0%, Z = 9.11) and lymphatic action metastasis (OR = 2.69,95% CI (2.07,3.48), P < 0.00001, I2 = 0%, Z = 7.50) is significantly associated.PD-L1 expression in tumor tissue suggests a poor prognosis in colorectal cancer, and the predictive significance of PD-L1 expression and PD-L1 expression in tumor cells in tumor-infiltrating immune cells may be inconsistent.
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Affiliation(s)
- Maocai Tang
- Department of Gastrointestinal Surgery, Chongqing University Cancer Hospital, Chongqing 400044, China
| | - Ziling Zheng
- Department of Gastrointestinal Surgery, Chongqing University Cancer Hospital, Chongqing 400044, China
| | - Jingkun Shang
- Department of Gastrointestinal Surgery, Chongqing University Cancer Hospital, Chongqing 400044, China
| | - Shouru Zhang
- Department of Gastrointestinal Surgery, Chongqing University Cancer Hospital, Chongqing 400044, China
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Lin Y, Kong DX, Zhang YN. Does the Microbiota Composition Influence the Efficacy of Colorectal Cancer Immunotherapy? Front Oncol 2022; 12:852194. [PMID: 35463305 PMCID: PMC9023803 DOI: 10.3389/fonc.2022.852194] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2022] [Accepted: 03/07/2022] [Indexed: 12/12/2022] Open
Abstract
Colorectal cancer (CRC) is the second most common malignancy globally, and many people with CRC suffer the fate of death. Due to the importance of CRC and its negative impact on communities, treatment strategies to control it or increase patient survival are being studied. Traditional therapies, including surgery and chemotherapy, have treated CRC patients. However, with the advancement of science, we are witnessing the emergence of novel therapeutic approaches such as immunotherapy for CRC treatment, which have had relatively satisfactory clinical outcomes. Evidence shows that gastrointestinal (GI) microbiota, including various bacterial species, viruses, and fungi, can affect various biological events, regulate the immune system, and even treat diseases like human malignancies. CRC has recently shown that the gut microorganism pattern can alter both antitumor and pro-tumor responses, as well as cancer immunotherapy. Of course, this is also true of traditional therapies because it has been revealed that gut microbiota can also reduce the side effects of chemotherapy. Therefore, this review summarized the effects of gut microbiota on CRC immunotherapy.
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Affiliation(s)
- Yan Lin
- Health Management Center, Department of General Practice, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, China
- *Correspondence: Yan Lin, ; You-Ni Zhang,
| | - De-Xia Kong
- Health Management Center, Department of General Practice, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, China
| | - You-Ni Zhang
- Department of Laboratory Medicine, Tiantai People’s Hospital, Taizhou, China
- *Correspondence: Yan Lin, ; You-Ni Zhang,
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Guan Y, Jiang SR, Liu JG, Shi JR, Liu ZB. USP20 regulates the stability of EMT transcription factor SOX4 and influences colorectal cancer metastasis. Pathol Res Pract 2022; 233:153879. [PMID: 35405623 DOI: 10.1016/j.prp.2022.153879] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2021] [Revised: 12/28/2021] [Accepted: 04/01/2022] [Indexed: 10/18/2022]
Abstract
BACKGROUND Colorectal cancer (CRC) is a familiar malignancy accompanied by higher morbidity and mortality. The deubiquitination enzyme USP20 has been discovered to be one key factor in several cancers progression. SOX4 is a critical transcription factor to regulate the expression of various genes, and participates into the occurrence and progression of cancers. In this study, it was aimed to illustrate the role of USP20 and the regulatory relationship between USP20 and SOX4 in CRC. METHODS The protein expressions of USP20, SOX4, E-cadherin, N-cadherin, Snail and slug were tested through western blot. The cell proliferation ability was verified through CCK-8 assay. The migration and invasion abilities were detected through Transwell assay. The mRNA expression of SOX4 was confirmed through RT-qPCR. The interaction between USP20 and SOX4 was notarized through Co-IP assay. RESULT Our study demonstrated that USP20 displayed higher expression, and facilitated CRC progression through regulating cell proliferation, migration, invasion and EMT process markers. USP20 was found to modulate SOX4 protein expression. Next, it was verified that USP20 regulated SOX4 degradation through deubiquitination. Finally, through rescue assays, we revealed that USP20 mediated SOX4 expression to accelerate CRC progression. CONCLUSIONS In this study, USP20 regulated the stability of EMT transcription factor SOX4 and aggravated colorectal cancer metastasis. This finding might highlight the function of USP20 in the treatment of CRC.
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Affiliation(s)
- Yu Guan
- Department of General Surgery, Peking University First Hospital, Beijing 100034, China
| | - Shi-Ru Jiang
- Department of General Surgery, Peking University First Hospital, Beijing 100034, China
| | - Jun-Guang Liu
- Department of General Surgery, Peking University First Hospital, Beijing 100034, China
| | - Ji-Rong Shi
- Department of General Surgery, Peking University First Hospital, Beijing 100034, China
| | - Zhan-Bing Liu
- Department of General Surgery, Peking University First Hospital, Beijing 100034, China.
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Guo S, Sun Y. OTOP2, Inversely Modulated by miR-3148, Inhibits CRC Cell Migration, Proliferation and Epithelial–Mesenchymal Transition: Evidence from Bioinformatics Data Mining and Experimental Verification. Cancer Manag Res 2022; 14:1371-1384. [PMID: 35418782 PMCID: PMC9000554 DOI: 10.2147/cmar.s345299] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2021] [Accepted: 03/04/2022] [Indexed: 01/22/2023] Open
Abstract
Introduction Colorectal cancer (CRC) represents one of the most frequent human malignancies with its underlying pathogenesis still unclear. The prevalence of multi-omics in screening biomarkers associated with CRC has largely accelerated our understanding into the pathophysiology of CRC. The present work aimed to mine the Gene Expression Omnibus (GEO) datasets associated with CRC studies and identify potential targets correlated with CRC pathogenesis. Methods We screened the DEGs in GSE50760 and GSE104178 and performed functional Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Furthermore, the overlapped DEGs were subjected to functional GO enrichment and KEGG pathway enrichment analysis. The protein–protein interaction (PPI) network and miRNA-mRNA network were constructed based on the overlapped DEGs. The in vitro functional assays including qRT-PCR, caspase-3 and -9 activity assay, wound healing assay, CCK-8 assay and luciferase reporter assay were performed to determine the role of OTOP2/miR-3148 axis in regulating CRC cell progression. Results Fifty-three overlapped genes were screened over GSE50760 and GSE104178 and ten hub genes were identified by PPI network analysis. Expression levels of GCG, SST, NPY, GUCA2B, PYY, UCN3, GUCA2A, TMEM82 and BEST4 were not correlated with the overall survival of patients with CRC. However, the high expression of otopetrin 2 (OTOP2) in the CRC tissues was significantly correlated with better overall survival of patients with CRC. The expression of OTOP2 in CRC tissues was significantly lowever than that in normal ones. The in vitro functional assays demonstrated that OTOP2 silence reduced caspase-3/-9 activities, promoted cell migration, proliferation and epithelial–mesenchymal transition in HT29 and SW620 cells. Furthermore, miR-3148 could inversely regulate OTOP2 expression in CRC cell lines. Conclusion Collectively, the work suggested the potential role of the OTOP2/miR-3148 axis in the pathophysiology of CRC by mining the GEO database.
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Affiliation(s)
- Shuai Guo
- Division of No.2 Gastrointestinal Surgery, Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, People’s Republic of China
| | - Yang Sun
- Division of No.2 Gastrointestinal Surgery, Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, People’s Republic of China
- Correspondence: Yang Sun, Tel +86-17709872003, Email
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