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Su YC, Wu CC, Chen YH, Su CC, Chang YC, Hsieh MC, Kao Yang YH. Assessing the effectiveness of targeted agents in adjuvant therapy for patients with metastatic colorectal cancer undergoing surgical resection: a retrospective cohort study. Ther Adv Med Oncol 2024; 16:17588359241246427. [PMID: 38655393 PMCID: PMC11036930 DOI: 10.1177/17588359241246427] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2023] [Accepted: 03/22/2024] [Indexed: 04/26/2024] Open
Abstract
Background Primary tumor resection and metastasectomy may be beneficial for many patients with metastatic colorectal cancer (mCRC). Objective To assess the differences in postoperative survival outcomes between adjuvant therapy with chemotherapy alone and chemotherapy plus targeted agents (TAs). Design Retrospective cohort study. Methods Patients with mCRC who underwent surgical resection for primary colorectal tumor and distant metastases and received adjuvant therapy from 1 January 2010 to 31 December 2017 were enrolled in the Taiwan Cancer Registry. We analyzed the overall survival of patients with resectable or initially unresectable mCRC who received adjuvant chemotherapy alone and chemotherapy plus TAs. Results We enrolled 1124 and 542 patients with resectable and initially unresectable mCRC, respectively. Adjuvant chemotherapy plus TAs and chemotherapy alone resulted in similar mortality rates among patients with resectable mCRC [adjusted hazard ratio (aHR) = 1.13; 95% confidence interval (CI), 0.93-1.36]; however, it marginally reduced the mortality rate among patients with initially unresectable mCRC who underwent conversion surgery after neoadjuvant therapy (aHR = 0.81; 95% CI, 0.62-1.06). The subgroup analysis of patients who received more than nine cycles of TAs preoperatively and anti-epidermal growth factor receptor agents revealed aHRs of 0.48 (95% CI, 0.27-0.87) and 0.33 (95% CI, 0.18-0.60), respectively. Conclusion Adjuvant chemotherapy plus TAs may improve survival in patients with initially unresectable tumors who underwent conversion surgery following neoadjuvant therapy with TAs, especially in those who respond well to the targeted therapy. Our study underscores the importance of stratifying patients with mCRC based on tumor resectability when selecting the adjuvant therapy regimen.
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Affiliation(s)
- Yi-Chia Su
- Department of Pharmacy, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- Department of Pharmacy, Chia-Nan University of Pharmacy and Science, Tainan, Taiwan
- Department of Nursing, Shu-Zen Junior College of Medicine and Management, Kaohsiung, Taiwan
| | - Chih-Chien Wu
- Division of Colorectal Surgery, Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- Department of Surgery, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Yu-Hsun Chen
- Division of Colorectal Surgery, Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Chien-Chou Su
- Clinical Innovation Center, National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan
- Department of Pharmacy, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Yu-Ching Chang
- Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Meng-Che Hsieh
- Department of Hematology and Oncology, E-Da Cancer Hospital, Kaohsiung, Taiwan
- College of Medicine, I-Shou University, Kaohsiung, Taiwan
| | - Yea-Huei Kao Yang
- Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, No. 1, University Road, Tainan 701, Taiwan
- Health Outcome Research Center, National Cheng Kung University, Tainan, Taiwan
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Lee JM, Han YD, Cho MS, Hur H, Lee KY, Kim NK, Min BS. Neoadjuvant chemotherapy versus upfront surgery as the initial treatment for patients with resectable, synchronous colorectal cancer liver metastases. J Surg Oncol 2023; 128:549-559. [PMID: 37288777 DOI: 10.1002/jso.27308] [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: 11/11/2022] [Revised: 03/27/2023] [Accepted: 04/21/2023] [Indexed: 06/09/2023]
Abstract
BACKGROUND Although perioperative chemotherapy has been the standard treatment for colorectal cancer with resectable liver metastases (CRLM), studies that have compared neoadjuvant chemotherapy (NAC) and upfront surgery, especially in the setting of synchronous metastases are rare. METHODS We compared perioperative outcomes, overall survival (OS) and overall survival after recurrence (rOS) in a retrospective study of 281 total and 104 propensity score-matched (PSM) patients who underwent curative resection, with or without NAC, for synchronous CRLM, from 2006 to 2017. A Cox regression model was developed for OS. RESULTS After PSM, 52 NAC and 52 upfront surgery patients with similar baseline characteristics were compared. Postoperative morbidity, mortality, and 5-year OS rate (NAC: 78.9%, surgery: 64.0%; p = 0.102) were similar between groups; however, the NAC group had better rOS (NAC: 67.3%, surgery: 31.5%; p = 0.049). Initial cancer stage (T4, N1-2), poorly differentiated histology, and >1 hepatic metastases were independent predictors of worse OS. Based on these factors, patients were divided into low-risk (≤1 risk factor, n = 115) and high-risk (≥2 risk factors, n = 166) groups. For high-risk patients, NAC yielded better OS than upfront surgery (NAC: 74.5%, surgery: 53.2%; p = 0.024). CONCLUSIONS Although NAC and upfront surgery-treated patients had similar perioperative outcomes and OS, better postrecurrence survival was shown in patients with NAC. In addition, NAC may benefit patients with worse prognoses; therefore, physicians should consider patient disease risk before initiating treatment to identify patients who are most likely to benefit from chemotherapy.
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Affiliation(s)
- Jong Min Lee
- Department of Surgery, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, Korea
| | - Yoon Dae Han
- Department of Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Min Soo Cho
- Department of Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Hyuk Hur
- Department of Surgery, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, Korea
| | - Kang Young Lee
- Department of Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Nam Kyu Kim
- Department of Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Byung Soh Min
- Department of Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
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Georgilis E, Gavriatopoulou M, Tsilimigras DI, Malandrakis P, Theodosopoulos T, Ntanasis-Stathopoulos I. Optimizing Adjuvant Therapy after Surgery for Colorectal Cancer Liver Metastases: A Systematic Review. J Clin Med 2023; 12:jcm12062401. [PMID: 36983401 PMCID: PMC10051548 DOI: 10.3390/jcm12062401] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2022] [Revised: 03/09/2023] [Accepted: 03/19/2023] [Indexed: 03/30/2023] Open
Abstract
The liver is the most common site of colorectal cancer metastatic spread. Although metastasectomy is the gold standard for fit patients with resectable colorectal cancer liver metastases (CRLMs), their management after surgical treatment remains controversial. The objective of this systematic review was to collate the currently available data of the agents used in the adjuvant setting in order to define the most optimal therapeutic strategy. A systematic review of the literature was conducted by searching PubMed/Medline and Cochrane library databases. We included studies that evaluated the efficacy, the tolerability and the safety profile of various chemotherapeutic agents that are used as adjuvant treatment after surgical resection of CRLMs. The outcomes of interest were regression-free survival (RFS), disease-free survival (DFS), overall survival (OS) and severe toxicities. From 543 initial articles, 29 publications with 7028 patients were finally included. In general, the results of the eligible studies indicated that adjuvant therapy after resection of CRLMs led to improved RFS/DFS rates, but this benefit did not contribute to a statistically significant prolongation of OS. Moreover, the choice of the therapeutic strategy, namely systematic or regional chemotherapy or the combination of both, did not seem to have a differential impact on patient outcomes. However, these results should be interpreted with caution since the majority of the chosen studies are of low or moderate quality. In this context, further high-quality clinical trials conducted on patient sub-populations with modern therapies are required in order to reduce in-study and between-study heterogeneity and determine which patients are expected to derive the maximum benefit from adjuvant therapy after surgery for CRLMs.
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Affiliation(s)
- Emmanouil Georgilis
- Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece
| | - Maria Gavriatopoulou
- Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece
| | - Diamantis I Tsilimigras
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH 43210, USA
| | - Panagiotis Malandrakis
- Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece
| | - Theodosios Theodosopoulos
- Second Department of Surgery, Aretaieion University Hospital, National and Kapodistrian University of Athens, 11528 Athens, Greece
| | - Ioannis Ntanasis-Stathopoulos
- Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece
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Lee HY, Woo IS. Perioperative Systemic Chemotherapy for Colorectal Liver Metastasis: Recent Updates. Cancers (Basel) 2021; 13:cancers13184590. [PMID: 34572817 PMCID: PMC8464667 DOI: 10.3390/cancers13184590] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2021] [Accepted: 09/10/2021] [Indexed: 12/29/2022] Open
Abstract
Simple Summary The development of cytotoxic chemotherapy, targeted agents and immune check point inhibitors has improved survival outcomes and quality of life in patients diagnosed with metastatic colorectal cancer (CRC). Long-term survival and cure are possible in well-selected CRC patients with liver metastases (LM). The criteria for resectable LM and the eligibility of patients should be evaluated at the time of diagnosis or during the clinical course via a multidisciplinary team approach. The advantages of adjuvant chemotherapy after curative resection of LM are uncertain currently. Systemic preoperative chemotherapy may convert unresectable LM to a resectable type. However, the optimal combination of systemic drugs and treatment strategy has yet to be established. This article summarizes recent reports of perioperative systemic treatment for patients with colorectal liver metastases (CLM). This review provides an update for physicians involved in managing patients with CLM. Abstract The liver is the most common site of metastases for colorectal cancer. Complete resection in some patients with resectable liver metastases (LM) can lead to long-term survival and cure. Adjuvant systemic chemotherapy after complete resection of LM improves recurrence-free survival; however, the overall survival benefit is not clear. In selected patients, preoperative systemic treatment for metastatic colorectal cancer can convert unresectable to resectable cancer. This review will focus on patient selection, and integration of perioperative and postoperative systemic treatment to surgery in resectable and initially unresectable LM. Additionally, new drugs and biomarkers will be discussed.
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Bang YH, Hong YS, Lee JS, Lee KW, Han HS, Kim SY, Kim JW, Kim HK, Kim JW, Eun CK, Kim TW, Kim JE. Effectiveness of Combining Bevacizumab With First-Line Chemotherapy Regimens for Metastatic Colorectal Cancer in Real-World Practice. Clin Colorectal Cancer 2020; 20:101-112.e6. [PMID: 33223477 DOI: 10.1016/j.clcc.2020.10.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2020] [Revised: 10/04/2020] [Accepted: 10/21/2020] [Indexed: 11/29/2022]
Abstract
BACKGROUND Anti-vascular endothelial growth factor (VEGF) agents have shown clinical benefits against metastatic colorectal cancer (mCRC) when combined with cytotoxic chemotherapeutic drugs. Because randomized controlled trials have restrictive enrollment criteria, and because the participants typically do not resemble actual patients, we here investigated the efficacy of bevacizumab as part of a combination therapy for mCRC in a Korean real-world practice setting. PATIENTS AND METHODS We retrospectively evaluated 3748 patients with an initial diagnosis of mCRC or recurrent colorectal cancer with distant metastasis who received first-line chemotherapy in a tertiary cancer center. The primary study endpoint was overall survival. We used multivariate analysis using the Cox regression hazard model and propensity score matching (PSM) methods to adjust for any confounding clinicopathologic factors. Subgroup analysis was also performed for patients who did not receive local treatments for metastatic lesions before receipt of first-line chemotherapy. RESULTS In an initial crude analysis, patients who received first-line FOLFOX or FOLFIRI showed better survival outcomes if these regimens were combined with bevacizumab (median overall survival, 3.5 vs. 2.3 years; hazard ratio [HR] = 0.66; 95% confidence interval [CI], 0.59-0.73; P < .001). However, Cox regression hazard model adjusted analysis using PSM methods revealed no significant survival differences between these groups (3.0 vs. 2.6 years; HR = 0.92; 95% CI, 0.79-1.07; P = .2612). We performed further survival analysis of 2814 patients with unresectable disease without metastasectomy who received metastatic radiofrequency ablation before chemotherapy. Cox regression and PSM analysis indicated that bevacizumab group showed better survival (HR = 0.82; 95% CI, 0.71-0.94; P = .005; and HR = 0.84; 95% CI, 0.71-0.99; P = .018). CONCLUSION The addition of bevacizumab to a first-line chemotherapeutic regimen provides survival benefits in a real-world setting for mCRC patients who cannot undergo curative-intent local treatment for metastatic lesions.
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Affiliation(s)
- Yeong Hak Bang
- Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea; Department of Digital Health, Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University, Seoul, Korea
| | - Yong Sang Hong
- Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Ji Sung Lee
- Clinical Research Center, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Keun-Wook Lee
- Division of Hematology and Medical Oncology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Hye Sook Han
- Department of Internal Medicine, Chungbuk National University Hospital, Cheongju, Korea; Department of Internal Medicine, Chungbuk National University College of Medicine, Cheongju, Korea
| | - Sun Young Kim
- Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Ji-Won Kim
- Division of Hematology and Medical Oncology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Hee Kyung Kim
- Department of Internal Medicine, Chungbuk National University College of Medicine, Cheongju, Korea
| | - Jin Won Kim
- Division of Hematology and Medical Oncology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Choi Ki Eun
- Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Tae Won Kim
- Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
| | - Jeong Eun Kim
- Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
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Rada M, Lazaris A, Kapelanski-Lamoureux A, Mayer TZ, Metrakos P. Tumor microenvironment conditions that favor vessel co-option in colorectal cancer liver metastases: A theoretical model. Semin Cancer Biol 2020; 71:52-64. [PMID: 32920126 DOI: 10.1016/j.semcancer.2020.09.001] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2020] [Revised: 09/03/2020] [Accepted: 09/03/2020] [Indexed: 02/07/2023]
Abstract
Vessel co-option is an alternative strategy by which tumour cells vascularize and gain access to nutrients to support tumour growth, survival and metastasis. In vessel co-option, the cancer cells move towards the pre-existing vasculature and hijack them. Vessel co-option is adopted by a wide range of human tumours including colorectal cancer liver metastases (CRCLM) and is responsible for the effectiveness of treatment in CRCLM. Furthermore, vessel co-option is an intrinsic feature and an acquired mechanism of resistance to anti-angiogenic treatment. In this review, we describe the microenvironment, the molecular players, discovered thus far of co-opting CRCLM lesions and propose a theoretical model. We also highlight key unanswered questions that are critical to improving our understanding of CRCLM vessel co-option and for the development of effective approaches for the treatment of co-opting tumours.
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Affiliation(s)
- Miran Rada
- Cancer Research Program, McGill University Health Centre Research Institute, Montreal, Quebec, H4A3J1, Canada
| | - Anthoula Lazaris
- Cancer Research Program, McGill University Health Centre Research Institute, Montreal, Quebec, H4A3J1, Canada
| | - Audrey Kapelanski-Lamoureux
- Cancer Research Program, McGill University Health Centre Research Institute, Montreal, Quebec, H4A3J1, Canada
| | - Thomas Z Mayer
- Cancer Research Program, McGill University Health Centre Research Institute, Montreal, Quebec, H4A3J1, Canada
| | - Peter Metrakos
- Cancer Research Program, McGill University Health Centre Research Institute, Montreal, Quebec, H4A3J1, Canada.
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Filip S, Vymetalkova V, Petera J, Vodickova L, Kubecek O, John S, Cecka F, Krupova M, Manethova M, Cervena K, Vodicka P. Distant Metastasis in Colorectal Cancer Patients-Do We Have New Predicting Clinicopathological and Molecular Biomarkers? A Comprehensive Review. Int J Mol Sci 2020; 21:E5255. [PMID: 32722130 PMCID: PMC7432613 DOI: 10.3390/ijms21155255] [Citation(s) in RCA: 49] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2020] [Revised: 07/21/2020] [Accepted: 07/22/2020] [Indexed: 02/06/2023] Open
Abstract
Colorectal cancer (CRC) remains a serious health problem worldwide. Approximately half of patients will develop distant metastasis after CRC resection, usually with very poor prognosis afterwards. Because patient performance after distant metastasis surgery remains very heterogeneous, ranging from death within 2 years to a long-term cure, there is a clinical need for a precise risk stratification of patients to aid pre- and post-operative decisions. Furthermore, around 20% of identified CRC cases are at IV stage disease, known as a metastatic CRC (mCRC). In this review, we overview possible molecular and clinicopathological biomarkers that may provide prognostic and predictive information for patients with distant metastasis. These may comprise sidedness of the tumor, molecular profile and epigenetic characteristics of the primary tumor and arising metastatic CRC, and early markers reflecting cancer cell resistance in mCRC and biomarkers identified from transcriptome. This review discusses current stage in employment of these biomarkers in clinical practice as well as summarizes current experience in identifying predictive biomarkers in mCRC treatment.
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Affiliation(s)
- Stanislav Filip
- Department of Oncology and Radiotherapy, Charles University, Faculty of Medicine in Hradec Kralove, Šimkova 870, 50001 Hradec Králové, Czech Republic; (J.P.); (O.K.); (S.J.)
| | - Veronika Vymetalkova
- Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Videnska 1083, 14220 Prague, Czech Republic; (V.V.); (L.V.); (K.C.)
- Biomedical Centre, Faculty of Medicine in Pilsen, Charles University, Alej Svobody 1655, 32300 Pilsen, Czech Republic
- Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Albertov 4, 12800 Prague, Czech Republic
| | - Jiri Petera
- Department of Oncology and Radiotherapy, Charles University, Faculty of Medicine in Hradec Kralove, Šimkova 870, 50001 Hradec Králové, Czech Republic; (J.P.); (O.K.); (S.J.)
| | - Ludmila Vodickova
- Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Videnska 1083, 14220 Prague, Czech Republic; (V.V.); (L.V.); (K.C.)
- Biomedical Centre, Faculty of Medicine in Pilsen, Charles University, Alej Svobody 1655, 32300 Pilsen, Czech Republic
- Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Albertov 4, 12800 Prague, Czech Republic
| | - Ondrej Kubecek
- Department of Oncology and Radiotherapy, Charles University, Faculty of Medicine in Hradec Kralove, Šimkova 870, 50001 Hradec Králové, Czech Republic; (J.P.); (O.K.); (S.J.)
| | - Stanislav John
- Department of Oncology and Radiotherapy, Charles University, Faculty of Medicine in Hradec Kralove, Šimkova 870, 50001 Hradec Králové, Czech Republic; (J.P.); (O.K.); (S.J.)
| | - Filip Cecka
- Department of Surgery, University Hospital in Hradec Kralove, Sokolská 581, 50005 Hradec Králové, Czech Republic;
| | - Marketa Krupova
- The Fingerland Department of Pathology, University Hospital in Hradec Kralove, Sokolská 581, 50005 Hradec Králové, Czech Republic; (M.K.); (M.M.)
| | - Monika Manethova
- The Fingerland Department of Pathology, University Hospital in Hradec Kralove, Sokolská 581, 50005 Hradec Králové, Czech Republic; (M.K.); (M.M.)
| | - Klara Cervena
- Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Videnska 1083, 14220 Prague, Czech Republic; (V.V.); (L.V.); (K.C.)
- Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Albertov 4, 12800 Prague, Czech Republic
| | - Pavel Vodicka
- Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Videnska 1083, 14220 Prague, Czech Republic; (V.V.); (L.V.); (K.C.)
- Biomedical Centre, Faculty of Medicine in Pilsen, Charles University, Alej Svobody 1655, 32300 Pilsen, Czech Republic
- Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Albertov 4, 12800 Prague, Czech Republic
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Chiang JM, Hung HY, You JF, Chiang SF, Lee CF, Chou HS, Lee WC, Chan KM. Applicability of postoperative carcinoembryonic antigen levels in determining post-liver-resection adjuvant chemotherapy regimens for colorectal cancer hepatic metastasis. Medicine (Baltimore) 2019; 98:e17696. [PMID: 31689796 PMCID: PMC6946275 DOI: 10.1097/md.0000000000017696] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2019] [Revised: 09/09/2019] [Accepted: 09/26/2019] [Indexed: 12/31/2022] Open
Abstract
Liver resection (LR) is the standard procedure for treating colorectal cancer (CRC) hepatic metastasis; however, LR associated with a high recurrence incidence. This study aimed to determine an optimal post-LR adjuvant chemotherapeutic strategy to improve overall long-term patient outcomes. A retrospective study of 490 patients who had undergone curative LR for CRC hepatic metastasis was performed. Patients who underwent post-LR adjuvant chemotherapy demonstrated high overall survival (OS) rates (hazard ratio [HR] = 0.58, P = .002) but not high recurrence-free survival (RFS) rates (HR = 1.02, P = .885). Moreover, OS was significantly longer in patients who underwent 5-fluorouracil + leucovorin (5-FU/LV; HR = 0.63, P = .039), oxaliplatin-based chemotherapy (HR = 0.45, P < .001), or irinotecan-based chemotherapy with bevacizumab (HR = 0.64, P = .040) than in those who did not. Among patients with carcinoembryonic antigen (CEA) levels of <5 ng/mL at 1 month after LR, significant differences were noted only in those who underwent 5-FU/LV (HR = 0.58, P = .035) and oxaliplatin-based chemotherapy (HR = 0.38, P < .001). In conclusion, perioperative CEA levels are crucial in prognosis and treatment of patients with CRC hepatic metastasis after LR. Additionally, certain regimens of adjuvant chemotherapy alongside post-LR CEA levels may provide beneficial results.
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Affiliation(s)
| | | | | | | | - Chen-Fang Lee
- Department of General Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Kwei-Shan District, Taoyuan City, Taiwan
| | - Hong-Shiue Chou
- Department of General Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Kwei-Shan District, Taoyuan City, Taiwan
| | - Wei-Chen Lee
- Department of General Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Kwei-Shan District, Taoyuan City, Taiwan
| | - Kun-Ming Chan
- Department of General Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Kwei-Shan District, Taoyuan City, Taiwan
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Chow FCL, Chok KSH. Colorectal liver metastases: An update on multidisciplinary approach. World J Hepatol 2019; 11:150-172. [PMID: 30820266 PMCID: PMC6393711 DOI: 10.4254/wjh.v11.i2.150] [Citation(s) in RCA: 149] [Impact Index Per Article: 24.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2018] [Revised: 11/24/2018] [Accepted: 12/04/2018] [Indexed: 02/06/2023] Open
Abstract
Liver metastasis is the commonest form of distant metastasis in colorectal cancer. Selection criteria for surgery and liver-directed therapies have recently been extended. However, resectability remains poorly defined. Tumour biology is increasingly recognized as an important prognostic factor; hence molecular profiling has a growing role in risk stratification and management planning. Surgical resection is the only treatment modality for curative intent. The most appropriate surgical approach is yet to be established. The primary cancer and the hepatic metastasis can be removed simultaneously or in a two-step approach; these two strategies have comparable long-term outcomes. For patients with a limited future liver remnant, portal vein embolization, combined ablation and resection, and associating liver partition and portal vein ligation for staged hepatectomy have been advocated, and each has their pros and cons. The role of neoadjuvant and adjuvant chemotherapy is still debated. Targeted biological agents and loco-regional therapies (thermal ablation, intra-arterial chemo- or radio-embolization, and stereotactic radiotherapy) further improve the already favourable results. The recent debate about offering liver transplantation to highly selected patients needs validation from large clinical trials. Evidence-based protocols are missing, and therefore optimal management of hepatic metastasis should be personalized and determined by a multi-disciplinary team.
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Affiliation(s)
| | - Kenneth Siu-Ho Chok
- Department of Surgery and State Key Laboratory for Liver Research, the University of Hong Kong, Hong Kong, China.
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10
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Type of adjuvant chemotherapy and treatment frequency in survival outcome of patients with colorectal liver metastases who underwent liver metastasectomy: an 8-year cohort study in Taiwan. Int J Colorectal Dis 2018; 33:985-989. [PMID: 29619561 DOI: 10.1007/s00384-018-3034-6] [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] [Accepted: 03/25/2018] [Indexed: 02/04/2023]
Abstract
PURPOSE The role of adjuvant chemotherapy (ACT) in treating patients who have colorectal liver metastases (CLM) and undergo liver metastasectomy (LMS) is unclear in this patient population. We aimed to compare the mortality of patients receiving different ACT (i.e., oxaliplatin-based, irinotecan-based, and 5-fluorouracil-only (5FU)) and different treatment frequencies. METHODS We included 2583 patients with CLM who underwent LMS (including synchronous LMS [SLMS] and metachronous LMS [MLMS]) in this retrospective cohort study. We used Cox proportional hazard model to obtain hazard ratios (HRs) for mortality. The reference group was 5FU-only ACT when comparing ACT type and the reference group was treatment for ≤ 3 times when comparing ACT frequency. RESULTS In SLMS patients, oxaliplatin-based ACT (HR = 0.78) and receiving ACT for ≥ 4 times (4-6 times, HR = 0.61; 7-9 times, HR = 0.69; 10-12 times, HR = 0.66) were associated with lower risk of mortality. In MLMS patients, oxaliplatin-based ACT (HR = 0.52), irinotecan-based ACT (HR = 0.64), and receiving ACT for 10-12 times (HR = 0.65) were associated with lower risk of mortality. CONCLUSIONS In SLMS and MLMS patients, patients who received oxaliplatin-based ACT were more likely to survive than patients who received 5FU-only ACT. In MLMS patients, patients who received irinotecan-based ACT were also more likely to survive than those who received 5FU-only ACT. We recommend a course of at least four to six times of ACT after LMS in this patient population.
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Lazaris A, Amri A, Petrillo SK, Zoroquiain P, Ibrahim N, Salman A, Gao Z, Vermeulen PB, Metrakos P. Vascularization of colorectal carcinoma liver metastasis: insight into stratification of patients for anti-angiogenic therapies. J Pathol Clin Res 2018; 4:184-192. [PMID: 29654716 PMCID: PMC6065118 DOI: 10.1002/cjp2.100] [Citation(s) in RCA: 50] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2017] [Revised: 02/21/2018] [Accepted: 03/01/2018] [Indexed: 12/30/2022]
Abstract
Current treatment for metastatic disease targets angiogenesis. With the increasing data demonstrating that cancer cells do not entirely rely on angiogenesis but hijack the existing vasculature through mechanisms such as co-option of existing blood vessels, identification of targets has become of utmost importance. Our study looks at the vasculature of chemonaïve and treated colorectal carcinoma liver metastases (CRCLMs) to obtain a basic understanding of the microvessel density, type of vasculature (mature versus immature), and correlation with histopathological growth patterns that demonstrate unique patterns of angiogenesis. We performed immunohistochemistry on chemonaïve sections of desmoplastic histopathological growth pattern (DHGP) and replacement histopathological growth patterns (RHGP) lesions with CD31 [endothelial cell (EC) marker] and CD34/Ki67 double staining, which denotes proliferating ECs. The CD31 stains demonstrated a lower microvascular CD31 +ve capillary density in the DHGP versus RHGP lesions; and integrating both immunostains with CD34/Ki67 staining on serial sections revealed proliferating vessels in DHGP lesions and co-option of mature existing blood vessels in RHGP lesions. Interestingly, upon treatment with chemotherapy and bevacizumab, the RHGP lesions showed no necrosis whereas the DHGP lesions had almost 100% necrosis of the cancer cells and in most cases there was a single layer of viable cancer cells, just under or within the desmoplastic ring. The survival of these cells may be directly related to spatial location and possibly a different microenvironment, which may involve adhesion to different extracellular matrix components and/or different oxygen/nutrient availability. This remains to be elucidated. We provide evidence that DHGP CRCLMs obtain their blood supply via sprouting angiogenesis whereas RHGP lesions obtain their blood supply via co-option of existing vasculature. Furthermore current treatment regimens do not affect RHGP lesions and although they kill the majority of the cancer cells in DHGP lesions, there are cells surviving within or adjacent to the desmoplastic ring which could potentially give rise to a growing lesion.
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Affiliation(s)
- Anthoula Lazaris
- Department of SurgeryMcGill University Health Center Research Institute, Cancer Research ProgramQuebecCanada
| | - Abdellatif Amri
- Department of SurgeryMcGill University Health Center Research Institute, Cancer Research ProgramQuebecCanada
| | - Stephanie K Petrillo
- Department of SurgeryMcGill University Health Center Research Institute, Cancer Research ProgramQuebecCanada
| | - Paublo Zoroquiain
- Department of SurgeryMcGill University Health Center Research Institute, Cancer Research ProgramQuebecCanada
| | - Nisreen Ibrahim
- Department of Anatomy and Cell BiologyMcGill UniversityQuebecCanada
| | - Ayat Salman
- Department of SurgeryMcGill University Health Center Research Institute, Cancer Research ProgramQuebecCanada
| | - Zu‐Hua Gao
- Department of PathologyMcGill University Health CenterQuebecCanada
| | - Peter B Vermeulen
- Translational Cancer Research UnitGZA Hospitals St.‐AugustinusWilrijkBelgium
| | - Peter Metrakos
- Department of SurgeryMcGill University Health Center Research Institute, Cancer Research ProgramQuebecCanada
- Department of Anatomy and Cell BiologyMcGill UniversityQuebecCanada
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Brandi G, De Lorenzo S, Nannini M, Curti S, Ottone M, Dall’Olio FG, Barbera MA, Pantaleo MA, Biasco G. Adjuvant chemotherapy for resected colorectal cancer metastases: Literature review and meta-analysis. World J Gastroenterol 2016; 22:519-533. [PMID: 26811604 PMCID: PMC4716056 DOI: 10.3748/wjg.v22.i2.519] [Citation(s) in RCA: 72] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2015] [Revised: 10/06/2015] [Accepted: 11/13/2015] [Indexed: 02/06/2023] Open
Abstract
Surgical resection is the only option of cure for patients with metastatic colorectal cancer (CRC). However, the risk of recurrence within 18 mo after metastasectomy is around 75% and the liver is the most frequent site of relapse. The current international guidelines recommend an adjuvant therapy after surgical resection of CRC metastases despite the lower level of evidence (based on the quality of studies in this setting). However, there is still no standard treatment and the effective role of an adjuvant therapy remains controversial. The aim of this review is to report the state-of-art of systemic chemotherapy and regional chemotherapy with hepatic arterial infusion in the management of patients after resection of metastases from CRC, with a literature review and meta-analysis of the relevant randomized controlled trials.
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Konda B, Shum H, Rajdev L. Anti-angiogenic agents in metastatic colorectal cancer. World J Gastrointest Oncol 2015; 7:71-86. [PMID: 26191351 PMCID: PMC4501927 DOI: 10.4251/wjgo.v7.i7.71] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2015] [Revised: 05/13/2015] [Accepted: 06/01/2015] [Indexed: 02/05/2023] Open
Abstract
Colorectal cancer (CRC) is a major public health concern being the third leading cause of cancer mortality in the United States. The availability of better therapeutic options has led to a decline in cancer mortality in these patients. Surgical resection should be considered in all stages of the disease. The use of conversion therapy has made surgery a potentially curative option even in patients with initially unresectable metastatic disease. In this review we discuss the role of various anti-angiogenic agents in patients with metastatic CRC (mCRC). We describe the mechanism of action of these agents, and the rationale for their use in combination with chemotherapy. We also review important clinical studies that have evaluated the safety and efficacy of these agents in mCRC patients. Despite the discovery of several promising anti-angiogenic agents, mCRC remains an incurable disease with a median overall survival of just over 2 years in patients exposed to all available treatment regimens. Further insights into tumor biology and tumor microenvironment may help improve outcomes in these patients.
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Abstract
The role of antiangiogenic and anti-epidermal growth factor receptor (EGFR) agents has been investigated extensively in colorectal cancer in the palliative, adjuvant, and neoadjuvant settings. Although the role of biologic agents has become well-defined in the first, second, and subsequent lines of treatment of metastatic colorectal cancer (mCRC), considerable debate continues around the optimal sequencing and around optimal patient selection. The benefits from integrating bevacizumab or cetuximab in the adjuvant setting have been investigated in several randomized phase III clinical trials in stage II/III disease, all with disappointing results. Neoadjuvant approaches incorporating biologic therapy in patients with liver metastatic disease have led to mixed results. Although the current evidence does suggest increased down-staging and increased resectability with the addition of cetuximab in patients with initially unresectable or borderline resectable liver metastases, a positive effect of anti-EGFR therapy on the overall survival (OS) in this setting is not conclusive. Patients with resectable liver metastases derive no benefit and may experience potential harm from the addition of cetuximab to neoadjuvant chemotherapy. Similarly, there is neither rationale nor adequate data to support the addition of bevacizumab to neoadjuvant chemotherapy in patients with resectable liver metastases. In this review, we examine the role of antiangiogenesis and anti-EGFR therapies across the spectrum of adjuvant, neoadjuvant, and metastatic disease.
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Affiliation(s)
- Marwan Fakih
- From the City of Hope Comprehensive Cancer Center, Duarte, CA
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16
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Turan N, Benekli M, Dane F, Unal OU, Kara HV, Koca D, Balvan O, Eren T, Tastekin D, Helvaci K, Berk V, Demirci U, Ozturk SC, Dogan E, Cetin B, Kucukoner M, Tonyali O, Tufan G, Oztop I, Gumus M, Coskun U, Uner A, Ozet A, Buyukberber S. Adjuvant systemic chemotherapy with or without bevacizumab in patients with resected pulmonary metastases from colorectal cancer. Thorac Cancer 2014; 5:398-404. [PMID: 26763794 DOI: 10.1111/1759-7714.12107] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2014] [Accepted: 03/03/2014] [Indexed: 01/29/2023] Open
Abstract
INTRODUCTION We investigated the impact of modern chemotherapy regimens and bevacizumab following pulmonary metastasectomy (PM) from metastatic colorectal cancer (CRC). METHODS A total of 122 consecutive patients who were curatively resected for pulmonary metastases of CRC in twelve oncology centers were retrospectively analysed between January 2000 and April 2012. RESULTS Of 122 patients, 14 did not receive any treatment following PM. The remaining 108 patients received fluoropyrimidine-based (n = 12), irinotecan-based (n = 56) and oxaliplatin-based (n = 40) chemotherapy combinations. Among these, 52 patients received bevacizumab (BEV) while 56 did not (NoBEV). Median recurrence-free survival (RFS) was 17 months and median overall survival (OS) has not been reached at a median follow-up of 25 months after PM. Three and five-year OS rates were 66% and 53%, respectively. RFS and OS were similar, irrespective of the chemotherapy regimen or BEV use. Positive pulmonary margin, KRAS mutation status, and previous liver metastasectomy were negative independent prognostic factors for RFS, while pathologically confirmed thoracic lymph node involvement was the only negative independent prognostic for OS in multivariate analysis. CONCLUSIONS No significant RFS or OS difference was observed in respect to chemotherapy regimens with or without BEV in patients with pulmonary metastases of CRC following curative resection.
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Affiliation(s)
- Nedim Turan
- Department of Medical Oncology, Malatya State Hospital Malatya, Turkey
| | - Mustafa Benekli
- Department of Medical Oncology, Gazi University Faculty of Medicine Ankara, Turkey
| | - Faysal Dane
- Department of Medical Oncology, Marmara University Faculty of Medicine Istanbul, Turkey
| | - Olcun Umit Unal
- Department of Medical Oncology, Dokuz Eylül University Faculty of Medicine Izmir, Turkey
| | - Hasan Volkan Kara
- Department of Thoracic Surgery, Marmara University Faculty of Medicine Istanbul, Turkey
| | - Dogan Koca
- Department of Medical Oncology, Regional Training and Research Hospital Van, Turkey
| | - Ozlem Balvan
- Department of Medical Oncology, Dr Lutfi Kirdar Kartal Education and Research Hospital Istanbul, Turkey
| | - Tulay Eren
- Department of Medical Oncology, Numune Education and Research Hospital Ankara, Turkey
| | - Didem Tastekin
- Department of Medical Oncology, Necmettin Erbakan University Faculty of Medicine Konya, Turkey
| | - Kaan Helvaci
- Department of Medical Oncology, Dr Abdurrahman Yurtaslan Education and Research Hospital Ankara, Turkey
| | - Veli Berk
- Department of Medical Oncology, Erciyes University Faculty of Medicine Kayseri, Turkey
| | - Umut Demirci
- Department of Medical Oncology, Dr Abdurrahman Yurtaslan Education and Research Hospital Ankara, Turkey
| | - Selcuk Cemil Ozturk
- Department of Medical Oncology, Adıyaman University Education and Research Hospital Adıyaman, Turkey
| | - Erkan Dogan
- Department of Medical Oncology, Regional Training and Research Hospital Van, Turkey
| | - Bulent Cetin
- Department of Medical Oncology, Regional Training and Research Hospital Van, Turkey
| | - Mehmet Kucukoner
- Department of Medical Oncology, Dicle University Faculty of Medicine Diyarbakir, Turkey
| | - Onder Tonyali
- Department of Medical Oncology, Antakya State Hospital Hatay, Turkey
| | - Gulnihal Tufan
- Department of Medical Oncology, Rize Education and Research Hospital Rize, Turkey
| | - Ilhan Oztop
- Department of Medical Oncology, Dokuz Eylül University Faculty of Medicine Izmir, Turkey
| | - Mahmut Gumus
- Department of Medical Oncology, Dr Lutfi Kirdar Kartal Education and Research Hospital Istanbul, Turkey
| | - Ugur Coskun
- Department of Medical Oncology, Gazi University Faculty of Medicine Ankara, Turkey
| | - Aytug Uner
- Department of Medical Oncology, Gazi University Faculty of Medicine Ankara, Turkey
| | - Ahmet Ozet
- Department of Medical Oncology, Gazi University Faculty of Medicine Ankara, Turkey
| | - Suleyman Buyukberber
- Department of Medical Oncology, Gazi University Faculty of Medicine Ankara, Turkey
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Connor AA, Burkes R, Gallinger S. Strategies in the Multidisciplinary Management of Synchronous Colorectal Cancer and Resectable Liver Metastases. CURRENT COLORECTAL CANCER REPORTS 2014. [DOI: 10.1007/s11888-014-0222-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Rong Z, Martel G, Vandenbroucke-Menu F, Adam R, Lapointe R. Impact of peri-operative bevacizumab on survival in patients with resected colorectal liver metastases: an analysis of the LiverMetSurvey. HPB (Oxford) 2014; 16:342-9. [PMID: 24641317 PMCID: PMC3967886 DOI: 10.1111/hpb.12138] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2013] [Accepted: 05/12/2013] [Indexed: 12/12/2022]
Abstract
BACKGROUND Peri-operative chemotherapy is recommended for the management of colorectal liver metastases (CRLM). The aim of this study was to examine the impact of peri-operative bevacizumab on survival in patients with resected CRLM. METHODS A multicentre retrospective cohort of patients with resected CRLM was analysed from the LiverMetSurvey Registry. Patients who received peri-operative FOLFOX (group A) were compared with those who received peri-operative FOLFOX and bevacizumab (group B). RESULTS In total, 501 patients were compared (A, n = 384; B, n = 117). Group A was older (68.3 versus 62.5 years, P < 0.01), had more rectal cancers (30.7 versus 18.8%, P < 0.01) and higher carcinoembryonic antigen (CEA) levels at diagnosis (17.0 versus 9.7 ng/ml, P = 0.043). No difference was observed regarding primary tumour stage, synchronicity and the number or size of metastases. Post-operative infections were more frequent in group B (4.7% versus 12.8%, P < 0.01). Peri-operative bevacizumab had no effect on 3-year overall survival (OS) (76.4% versus 79.8%, P = 0.334), or disease-free survival (DFS) (7.4% versus 7.9%, P = 0.082). DFS was negatively associated with primary tumour node positivity (P = 0.011) and synchronicity (P = 0.041). CONCLUSIONS The addition of bevacizumab to standard peri-operative chemotherapy does not appear to be associated with improved OS or DFS in patients with resected CRLM.
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Affiliation(s)
- Zhixia Rong
- Service de chirurgie hépatobiliaire, pancréatique et de transplantation hépatique, Centre Hospitalier de l'Université de Montréal (CHUM), Université de MontréalMontréal, QC, Canada
| | - Guillaume Martel
- Service de chirurgie hépatobiliaire, pancréatique et de transplantation hépatique, Centre Hospitalier de l'Université de Montréal (CHUM), Université de MontréalMontréal, QC, Canada
| | - Franck Vandenbroucke-Menu
- Service de chirurgie hépatobiliaire, pancréatique et de transplantation hépatique, Centre Hospitalier de l'Université de Montréal (CHUM), Université de MontréalMontréal, QC, Canada
| | - René Adam
- Centre Hépato-Biliaire, Hôpital Paul Brousse, Université Paris-SudVillejuif, France
| | - Réal Lapointe
- Service de chirurgie hépatobiliaire, pancréatique et de transplantation hépatique, Centre Hospitalier de l'Université de Montréal (CHUM), Université de MontréalMontréal, QC, Canada,Correspondence Réal Lapointe, Service de chirurgie hépatobiliaire, pancréatique et de transplantation hépatique, Centre Hospitalier de l'Université de Montréal (CHUM), 1058 rue Saint-Denis, Montréal, Québec, H2X 3J4, Canada. Tel: +1-514-890-8000. Fax: +1514 412 7380. E-mail:
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Zhang DH, Dong M, Zhou JP. Dysregulation of microRNA-320 expression in colorectal cancer. Shijie Huaren Xiaohua Zazhi 2013; 21:3592-3597. [DOI: 10.11569/wcjd.v21.i32.3592] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To detect the expression of miR-320 in colorectal cancer to reveal its relationship with clinical and pathological characteristics of colorectal cancer, and to investigate the effect of miR-320 overexpression on chemosensitivity of colorectal cancer cell lines.
METHODS: The expression of miR-34a was detected by real-time PCR in CRC tissues and tumor-adjacent non-tumorous tissues. HCT-116 and ClonA1 cell lines were transfected with either a LV-miR-320 or a negative control (NC). C-Jun N-terminal kinase (JNK) expression was measured by Western blot after up-regulation of miR-320. The chemosensitivity of cell lines was tested by MTT assay.
RESULTS: MiR-320 expression was significantly down-regulated in CRC cancer tissues compared with tumor-adjacent tissues (P = 0.012). The expression of miR-320 was correlated with degree of differentiation, local invasion and TNM stage (P = 0.045, 0.012, 0.04). Overexpression of miR-320 significantly suppressed the expression of JNK, and the IC50 values for the LV-miR-320 group were significantly lower than those for the negative control group (11.34 vs 24.73, 12.56 vs 25.34, P = 0.023, 0.018).
CONCLUSION: MiR-320 is frequently down-regulated in CRC, which can repress the expression of JNK and modulate chemosensitivity of colorectal cancer cell lines. MiR-320 may play an important role in carcinogenesis and therapy of colorectal cancer.
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