Mutations in TGFBR2, a component of the transforming growth factor (TGF)-β signaling pathway, occur in high-frequency microsatellite instability (MSI-H) colorectal cancer (CRC). In mouse models, Tgfbr2 inactivation in the intestinal epithelium accelerates the development of malignant intestinal tumors in combination with disruption of the Wnt-β-catenin pathway. However, no studies have further identified the genes influenced by TGFBR2 inactivation following disruption of the Wnt-β-catenin pathway. We previously described CDX2P-G19Cre;Apcflox/flox mice, which is stochastically null for Apc in the colon epithelium. In this study, we generated CDX2P-G19Cre;Apcflox/flox;Tgfbr2flox/flox mice, with simultaneous loss of Apc and Tgfbr2. These mice developed tumors, including adenocarcinoma in the proximal colon. We compared gene expression profiles between tumors of the two types of mice using microarray analysis. Our results showed that the expression of the murine homolog of GSDMC was significantly upregulated by 9.25-fold in tumors of CDX2P-G19Cre;Apcflox/flox;Tgfbr2flox/flox mice compared with those of CDX2P-G19Cre;Apcflox/flox mice. We then investigated the role of GSDMC in regulating CRC tumorigenesis. The silencing of GSDMC led to a significant reduction in the proliferation and tumorigenesis of CRC cell lines, whereas the overexpression of GSDMC enhanced cell proliferation. These results suggested that GSDMC functioned as an oncogene, promoting cell proliferation in colorectal carcinogenesis. In conclusion, combined inactivation of both Apc and Tgfbr2 in the colon epithelium of a CRC mouse model promoted development of adenocarcinoma in the proximal colon. Moreover, GSDMC was upregulated by TGFBR2 mutation in CRC and promoted tumor cell proliferation in CRC carcinogenesis, suggesting that GSDMC may be a promising therapeutic target.
Colon cancer (CC) is a leading cause of cancer mortality. Novel biomarkers are needed to identify CC patients at high risk of recurrence and those who may benefit from therapeutic intervention. The aim of this study is to investigate if miR-21 expression from RNA isolated from formalin-fixed paraffin-embedded (FFPE) tissue sections is associated with prognosis and therapeutic outcome for patients with CC. The expression of miR-21 was measured by quantitative reverse transcriptase-polymerase chain reaction in a Japanese cohort (stage I–IV, n = 156) and a German cohort (stage II, n = 145). High miR-21 expression in tumors was associated with poor survival in both the stage II/III Japanese (P = 0.0008) and stage II German (P = 0.047) cohorts. These associations were independent of other clinical covariates in multivariable models. Receipt of adjuvant chemotherapy was not beneficial in patients with high miR-21 in either cohort. In the Japanese cohort, high miR-21 expression was significantly associated with poor therapeutic outcome (P = 0.0001) and adjuvant therapy was associated with improved survival in patients with low miR-21 (P = 0.001). These results suggest that miR-21 is a promising biomarker to identify patients with poor prognosis and can be accurately measured in FFPE tissues. The expression of miR-21 may also identify patients who will benefit from adjuvant chemotherapy.
Sarpogrelate reduces the myocardial infarct size by inhibiting the serotonin release followed by enhancement of PKC-epsilon translocation and opening of the mitochondrial KATP channel in ischemic myocytes.
BackgroundRobotic surgery is a new technique with the benefits of a three-dimensional view, the ability to use multi-degree-of-freedom forceps, the elimination of physiological tremors, and a stable camera view. The aim of this study was to evaluate the feasibility and short-term outcomes of robotic surgery for colorectal cancer as initial cases, compared with conventional laparoscopic surgery.MethodsFrom July 2010 to June 2013, ten patients with left-sided colon and rectal cancer underwent robotic surgery, and 121 received conventional laparoscopic surgery. Both groups were balanced in terms of age, gender, American Society of Anesthesiologists (ASA) score, body mass index (BMI), operative history, TNM staging, and tumor location. Moreover, in order to improve objectivity and approximate a randomized controlled study, we used the propensity score matching method. The matching was successful because the ROC analysis showed a well-balanced curve (C = 0.535).ResultsFollowing propensity score matching, ten patients were included in the robotic surgery group and 20 patients were included in the conventional laparoscopic surgery group. There were no significant differences in the short-term clinicopathologic outcomes between the robotic surgery group and the conventional laparoscopic surgery group. However, the operative time was significantly longer in the robotic surgery group than in the conventional laparoscopic surgery group.ConclusionsThere were no significant differences between the robotic surgery group and the conventional laparoscopic surgery group with respect to short-term clinicopathologic outcomes, with the exception of the operative time. Our early experience indicates that robotic surgery is a promising tool, particularly in patients with rectal cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s12957-015-0517-6) contains supplementary material, which is available to authorized users.
Our results suggest a possible induction of HIF-1α expression by mutant PIK3CA. The expressions of HIF-1α and VEGF in liver metastases significantly correlated with those in the corresponding primary tumor. Overexpression of HIF-1α was an independent risk factor for recurrence after curative resection of CRLM, suggesting that HIF-1α represents an important candidate for the treatment of CRLM in a subset of patients with high HIF-1α expression.
Serum PCT is more reliable laboratory marker for the early diagnosis of SSI after elective colorectal cancer surgery, compared with conventional inflammatory indicators. PCT could serve as an additional diagnostic tool for the early identification of SSI to improve clinical decision making.
BackgroundSingle-port laparoscopic surgery is a new technique that leaves no visible scar. This new technique has generated strong interest among surgeons worldwide. However, single-port laparoscopic colon surgery has not yet been standardized. Our aim in this study was to evaluate the feasibility of single-port laparoscopic colectomy compared with conventional laparoscopic colectomy for colon cancer.MethodsWe conducted a case-matched, controlled study comparing single-port laparoscopic colectomy to conventional laparoscopic colectomy for right-sided colon cancer.ResultsA total of ten patients were included for the single-port laparoscopic colectomy (S-LAC) group and ten patients for the conventional laparoscopic colectomy (C-LAC) group. The length of the skin incision in the S-LAC group was significantly shorter than that of the C-LAC group.ConclusionOur early experiences indicated that S-LAC for right-sided colon cancer is a feasible and safe procedure and that S-LAC results in a better cosmetic outcome.
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