Targeted Therapies and Predictive Markers in Epithelial Malignancies of the Gastrointestinal Tract

McIntire, Maria; Redston, Mark

doi:10.5858/arpa.2011-0167-ra

Cited by 7 publications

(5 citation statements)

References 77 publications

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“…While c-kit expression in gastric carcinoma is very limited, Her2-neu expressed in less than 20% of them [34,35], and efforts for finding other molecular biomarker are currently in development.…”

Section: Discussionmentioning

confidence: 99%

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The clinicopathologic association of c-MET overexpression in Iranian gastric carcinomas; an immunohistochemical study of tissue microarrays

et al. 2012

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Backgroundc-MET is an oncogene protein that plays important role in gastric carcinogenesis and has been introduced as a prognostic marker and potential therapeutic target. The aim of this study was to evaluate the frequency of c-MET overexpression and its relationship with clinicopathological variables in gastric cancer of Iranian population using tissue microarray.MethodsIn a cross sectional study, representative paraffin blocks of 130 patients with gastric carcinoma treated by curative gastrectomy during a 2 years period of 2008–2009 in two university hospitals in Tehran-Iran were collected in tissue microarray and c-MET expression was studied by immunohistochemical staining.ResultsFinally 124 cases were evaluated, constituted of 99 male and 25 female with the average age of 61.5 years. In 71% (88/124) of tumors, c-MET high expression was found. c-MET high expression was more associated with intestinal than diffuse tumor type (P = 0.04), deeper tumor invasion, pT3 and pT4 versus pT1 and pT2 (P = 0.014), neural invasion (P = 0.002) and advanced TNM staging, stage 3 and 4 versus stage 1 and2 (P = 0.044). The c-MET high expression was not associated with age, sex, tumor location, differentiation grade and distant metastasis, but relative associations with lymph node metastasis (P = 0.065) and vascular invasion (P = 0.078) were observed.Conclusionsc-MET oncogene protein was frequently overexpressed in Iranian gastric carcinomas and it was related to clinicopathological characteristics such as tumor type, depth of invasion, neural invasion and TNM staging. It can also support the idea that c-MET is a potential marker for target therapy in Iranian gastric cancer.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9744598757151429

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Section: Discussionmentioning

confidence: 99%

“…Until now many new anti-c-MET drugs have been invented and most are in preclinical and clinical testing [34,36]. …”

Section: Discussionmentioning

confidence: 99%

The clinicopathologic association of c-MET overexpression in Iranian gastric carcinomas; an immunohistochemical study of tissue microarrays

et al. 2012

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“…In the era of personalised medicine with targeted therapy, monoclonal antibodies have become key molecules in the treatment of metastatic CRC (mCRC). Since 2004, the US Food and Drug Administration (FDA) has approved cetuximab, panitumumab and bevacizumab for the treatment of mCRC, which are humanised monoclonal antibodies directed against the epidermal growth factor receptor (EGFR; cetuximab and panitumumab) or the vascular endothelial growth factor (bevacizumab) (McIntire and Redston, 2012). With regard to cetuximab and panitumumab, treatment response largely depends on the absence of oncogenic mutations in key signalling molecules, for example, KRAS , NRAS and BRAF (Custodio and Feliu, 2013), and the drug can only be administered after molecular tests exclude the presence of somatic RAS -mutations in mCRC (companion diagnostics).…”

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confidence: 99%

HER2/neu testing in primary colorectal carcinoma

et al. 2014

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Background:Anti-HER2/neu therapy is well-established in breast and gastric carcinoma. The increased understanding of this pathway led to the identification of new promising drugs in addition to trastuzumab, offering further perspectives. The role of HER2/neu in colorectal carcinoma is controversially discussed, as discrepant data has been reported.Methods:Here, we retrospectively assessed the prevalence of HER2/neu positivity in a large series of colorectal carcinoma, testing HER2/neu status according to current recommendations. We correlated the results to clinico-pathological data and patient survival.Results:Overall, in 1645 primary colorectal carcinoma cases, 1.6% of the cases were HER2/neu positive. HER2/neu positivity significantly correlated with higher UICC stages (P=0.017) and lymph node metastases (P=0.029). In the subgroup of sigmoideal and rectal carcinomas, positive HER2/neu status was associated with T-category (P=0.041) and higher UICC stages (P=0.022). Although statistically not significant, HER2/neu-positive colorectal carcinomas displayed a tendency to poorer overall survival.Conclusions:These results illustrate the importance of testing HER2/neu by approved diagnostic techniques and scoring systems. We assume that although the prevalence of HER2/neu positivity in colorectal carcinoma is low, HER2/neu testing in advanced, nodal-positive colorectal carcinoma is reasonable, offering a potential target in high risk colorectal carcinoma.

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“…This critically affects influencing the quality of life of patients (4)(5)(6). With the broad development of tumor marker and molecular targeted therapy (7), a more detailed understanding of the mechanisms contributing to the carcinogenesis of TSCC would be of value to improve the therapeutic effect of TSCC at the molecular level.…”

Section: Introductionmentioning

confidence: 99%

miR‑409‑3p suppresses the proliferation, invasion and migration of tongue squamous cell carcinoma via targeting RDX

Chen

Dai

2018

Oncol Lett

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The aim of the present study is to investigate the role of microRNA (miRNA/miR)-409-3p in the proliferation, invasion and migration of tongue squamous cell carcinoma (TSCC) cells via targeting radixin () gene. The expression of miR-409-3p was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in TSCC tissue and cell lines. The binding of miR-409-3p to was investigated by performing a dual-luciferase reporter gene assay. Tca8113 cells were selected to transfect with miR-409-3p mimic/inhibitor, small interfering (si)-RDX, and miR-409-3p inhibitor + si-RDX, as well as negative control (NC) respectively. The proliferative, migratory and invasive abilities of transfected Tca8113 cells were investigated by cell-counting-kit-8, wound-healing and Transwell assays, respectively. Additionally, a tumor xenograft model was constructed to examine the effects of miR-409-3p on the tumor growth and lymphatic metastasis in nude mice. A significant downregulation was detected in miR-409-3p expression in TSCC tissues and cells (all P<0.05) compared with normal tongue mucosa tissues and cell line, which was associated with lymph node metastasis and tumor-node metastasis staging (both P<0.05). The results from the dual-luciferase reporter gene assay indicated that is a potential target gene of miR-409-3p. Compared with the blank group, a marked reduction in RDX expression, cell proliferation, migration and invasion was detected in the miR-409-3p mimic group and si-RDX group (all P<0.05). Conversely, the reverse was observed in cells that were transfected with the miR-409-3p inhibitor. Furthermore, si-RDX is able to reverse the effect of miR-409-3p inhibitor on cell proliferation, invasion and migration (all P<0.05). The results form the tumor xenograft model of nude mice verified that miR-409-3p mimic is able to inhibit the growth of Tca8113 tumor cells and lymph node metastasis in nude mice. miR-409-3p may delay the proliferation of TSCC cells by inhibiting of so as to decrease its migratory and invasive abilities. Therefore, miR-409-3p may be a potential target for the clinical treatment of TSCC.

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Targeted Therapies and Predictive Markers in Epithelial Malignancies of the Gastrointestinal Tract

Cited by 7 publications

References 77 publications

The clinicopathologic association of c-MET overexpression in Iranian gastric carcinomas; an immunohistochemical study of tissue microarrays

The clinicopathologic association of c-MET overexpression in Iranian gastric carcinomas; an immunohistochemical study of tissue microarrays

HER2/neu testing in primary colorectal carcinoma

miR‑409‑3p suppresses the proliferation, invasion and migration of tongue squamous cell carcinoma via targeting RDX

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