Search results for "Rectal Neoplasm"
showing 10 items of 605 documents
Pharmacokinetic and metabolism determinants of fluoropyrimidines and oxaliplatin activity in treatment of colorectal patients
2011
Fluoropyrimidines and oxaliplatin continued to be the mainstay of therapeutic regimens in the treatment of colorectal cancer (CRC). For this reason, pharmacokinetic and metabolism of these drugs were analyzed and the identification of accurate and validated predictive, prognostic and toxicity markers became necessary to develop an effective therapy adapted to the patient's molecular profile, while minimizing life-threatening toxicities. In this review, we discuss literature data, defining predictive and prognostic markers actually identified in the treatment of CRC. We analyzed predictive markers of fluoropyrimidines effectiveness, principally for 5-Fluorouracil (5-FU) and also for oral flu…
Retrospective Study of Regorafenib Versus TAS-102 Efficacy and Safety in Chemorefractory Metastatic Colorectal Cancer (mCRC) Patients: A Multi-instit…
2021
INTRODUCTION: There have been significant developments in colorectal cancer (CRC) research over the last few years, with the introduction of new agents that have been prolonged median overall survival of metastatic colorectal cancer (mCRC). These therapies have improved patient outcomes; however, despite significant progress in strategies for cancer treatment, their use is limited by development of resistant mechanism. Almost 30% of patients with refractory mCRC will remain good candidates for further treatment. Regorafenib and TAS-102 are novel antitumor agents for patients with refractory mCRC. However, it is unclear which patients may derive a survival benefit from these drugs in real-li…
KRAS mutations and sensitivity to anti-EGFR monoclonal antibodies in metastatic colorectal carcinoma: an open issue.
2009
Background: Cetuximab and panitumumab, mAbs targeting EGFR, are registered for metastatic colorectal carcinoma (mCRC) patients whose tumors express EGFR as determined by immunohistochemistry. However, this method is not predictive of treatment efficacy. KRAS, the human homolog of the Kirsten rat sarcoma-2 virus oncogene, encodes a small G-protein that functions downstream of EGFR-induced signalling. Objective/Methods: To examine KRAS mutations as predictive factors of response to anti-EGFR mAbs using recently published data. Results/conclusions: Several retrospective studies show that efficacy of these mAbs is confined to patients with wild type KRAS and genotyping of tumors should be consi…
Impact of Postoperative Complications on Survival and Recurrence After Resection of Colorectal Liver Metastases
2019
OBJECTIVE To study the effect of postoperative complications (POC) on overall survival (OS) and disease-free survival (DFS) after surgical resection of colorectal liver metastases (CRLM). SUMMARY BACKGROUND DATA Morbidity rates after liver resection can reach 45%. The negative impact of POC on oncologic outcomes has been reported in various types of cancer, especially colorectal. However, data on the consequences of POC after CRLM resection on long-term survival are scarce. METHODS Eligible studies examining the association between POC after CRLM resection and OS/DFS were sought using the PubMed and Web of Science databases. A random-effects model was used to calculate pooled effect estimat…
Functional categories of TP53 mutation in colorectal cancer: results of an International Collaborative Study.
2006
Item does not contain fulltext BACKGROUND: Loss of TP53 function through gene mutation is a critical event in the development and progression of many tumour types including colorectal cancer (CRC). In vitro studies have found considerable heterogeneity amongst different TP53 mutants in terms of their transactivating abilities. The aim of this work was to evaluate whether TP53 mutations classified as functionally inactive (< or=20% of wildtype transactivation ability) had different prognostic and predictive values in CRC compared with mutations that retained significant activity. MATERIALS AND METHODS: TP53 mutations within a large, international database of CRC (n = 3583) were classified ac…
Phase I/II trial of capecitabine and oxaliplatin in combination with bevacizumab and imatinib in patients with metastatic colorectal cancer: AIO KRK …
2013
Background: Combined inhibition of platelet-derived growth factor receptor beta signalling and vascular endothelial growth factor promotes vascular normalisation in preclinical models and may lead to increased delivery of chemotherapy to tumour tissue. This phase I/II trial assessed the safety and efficacy of capecitabine plus oxaliplatin (XELOX) plus bevacizumab and imatinib in the first-line treatment of patients with metastatic colorectal cancer. Methods: Two dose levels (I/II) were defined: capecitabine 850/1000 mg m−2 twice daily on days 1–14; oxaliplatin 100/130 mg m−2 on day 1; bevacizumab 7.5 mg kg−1 on day 1; imatinib 300 mg day−1 on days 1–21 every 21 days. The primary study endpo…
Bcl-xL and Myeloid cell leukaemia-1 contribute to apoptosis resistance of colorectal cancer cells
2008
AIM: To explore the role of Bcl-x(L) and Myeloid cell leukaemia (Mcl)-1 for the apoptosis resistance of colorectal carcinoma (CRC) cells towards current treatment modalities. METHODS: Bcl-x(L) and Mcl-1 mRNA and protein expression were analyzed in CRC cell lines as well as human CRC tissue by Western blot, quantitative PCR and immunohistochemistry. Bcl-x(L) and Mcl-1 protein expression was knocked down or increased in CRC cell lines by applying specific siRNAs or expression plasmids, respectively. After modulation of protein expression, CRC cells were treated with chemotherapeutic agents, an antagonistic epidermal growth factor receptor (EGFR1) antibody, an EGFR1 tyrosine kinase inhibitor, …
Expression of a mutant HSP110 sensitizes colorectal cancer cells to chemotherapy and improves disease prognosis
2011
Heat shock proteins (HSPs) are necessary for cancer cell survival. We identified a mutant of HSP110 (HSP110ΔE9) in colorectal cancer showing microsatellite instability (MSI CRC), generated from an aberrantly spliced mRNA and lacking the HSP110 substrate-binding domain. This mutant was expressed at variable levels in almost all MSI CRC cell lines and primary tumors tested. HSP110ΔE9 impaired both the normal cellular localization of HSP110 and its interaction with other HSPs, thus abrogating the chaperone activity and antiapoptotic function of HSP110 in a dominant-negative manner. HSP110ΔE9 overexpression caused the sensitization of cells to anticancer agents such as oxaliplatin and 5-fluorou…
Survivin is regulated by interleukin-4 in colon cancer stem cells
2010
Colorectal cancer has provided an important model to test the stem cell hypothesis of cancer origin, which implies that cancer arises as a result of genetic aberrations in stem cells leading to deregulation of the proliferation/differentiation balance. We and others have demonstrated that, similarly to other solid tumors, colon carcinogenesis and progression are dictated by highly apoptosis-resistant stem-like cells. Our data have suggested that protection from apoptosis is achieved by autocrine production of interleukin-4 (IL-4) through up-regulation of anti-apoptotic mediators. In this study, we extend our analysis to another apoptosis inhibitor widely expressed in tumors, namely survivin…
Imaging standardisation in metastatic colorectal cancer: a joint EORTC-ESOI-ESGAR expert consensus recommendation
2022
Background: Treatment monitoring in metastatic colorectal cancer (mCRC) relies on imaging to evaluate the tumor burden. Response Evaluation Criteria in Solid Tumors (RECIST) provide a framework on reporting and interpretation of imaging findings yet offer no guidance on a standardized imaging protocol tailored to mCRC patients. Imaging protocol heterogeneity remains a challenge for the reproducibility of conventional imaging endpoints and is an obstacle for research on novel imaging endpoints. Patients and methods: Acknowledging the recently highlighted potential of radiomics and artificial intelligence (AI) tools as decision support for patient care in mCRC, a multidisciplinary, internatio…