Comprehension of rectosigmoid junction cancer molecular features by comparison to the rectum or sigmoid colon cancer.

Background: Colorectal cancer (CRC) is a heterogeneous cancer. Its treatment depends on its anatomical site and molecular features. Carcinomas of the rectosigmoid junction are frequent; however, specific data on these tumors are sparse, as they are frequently assigned to either the colon or rectum. This study sought to identify the molecular features of rectosigmoid junction cancer to determine whether there should be any difference between the therapeutic management of rectosigmoid junction cancer and that of sigmoid colon or rectum cancer. Methods: The data of 96 CRC patients with carcinomas in the sigmoid colon, rectosigmoid junction, and rectum were retrospectively summarized. The next-generation sequencing (NGS) data of the patients were analyzed to study the molecular characteristics of the carcinomas in different locations of the bowel. Results: In total, there was no difference in the clinicopathologic characteristics of the three groups. TP53, APC, and KRAS genes were the top 3 alteration genes in sigmoid colon, rectosigmoid junction, and rectum cancer. The rates of the KRAS, NRAS, and PIK3CA increased as the location moved distally, while the rates of APC and BRAF decreased. Almost no significant molecular differences were found among the three groups. The prevalence of the FLT3, fms-related tyrosine kinase 1 (FLT1), and phosphoenolpyruvate carboxykinase 1 (PCK1) mutation was lower in the rectosigmoid junction group than the sigmoid colon and rectum groups (P>0.05). The proportion of the transforming growth factor beta pathway was higher in the rectosigmoid junction and rectum groups than the sigmoid colon group (39.3% vs. 34.3% vs. 18.2%, respectively, P=0.121, P=0.067, P=0.682); a higher proportion of MYC pathway was also observed in the rectosigmoid junction than that in rectum and sigmoid colon (28.6% vs. 15.2% vs. 17.1%, P=0.278, P=0.202, P=0.171). Regardless of the clustering method employed, the patients were divided into two clusters, and the composition of clusters revealed no significant differences in terms of the different locations. Conclusions: Rectosigmoid junction cancer has a distinctive molecular profile compared to the molecular profiles of the adjacent bowel segment cancers.

Association of the CD4+/CD8+ ratio with response to PD-1 inhibitor-based combination therapy and dermatological toxicities in patients with advanced gastric and esophageal cancer.

The host immune system affects the treatment response to immune checkpoint inhibitors and can be reflected by circulating immune cells. This study aimed to evaluate whether circulating T cell subtypes are correlated with clinical response and dermatological toxicities in patients with advanced gastric and esophageal cancer receiving PD-1 inhibitor-based combination therapy (n = 203). In the training cohort, Eastern Cooperative Oncology Group performance status (ECOG PS), PD-L1 expression, antibiotic use, and CD4+/CD8+ ratio were identified as independent prognostic factors in these patients, using a Cox regression model. A nomogram to predict the overall survival (OS) and survival probabilities was constructed using these factors. The nomogram showed good discrimination ability (C-index, 0.767) and was externally confirmed in the validation and test cohorts. Kaplan-Meier analysis showed that median OS in patients with a CD4+/CD8+ ratio ≥1.10 was 6.2 months, which was significantly shorter than that in patients with a CD4+/CD8+ ratio <1.10 (P < 0.001). Patients with a CD4+/CD8+ ratio <1.10 had a superior objective response (43.8% vs. 23.1%) and disease control (72.9% vs. 59.0%) rate, relative to those with ratio ≥ 1.10. In addition, PD-L1 expression, corticosteroid use, and CD4+/CD8+ ratio can independently predict dermatological toxicities. In conclusion, baseline CD4+/CD8+ ratio is a potential prognostic factor for patients with advanced gastric and esophageal cancer treated with PD-1 inhibitor-based combination therapy, and can independently predict dermatological toxicities. In addition, a nomogram incorporating CD4+/CD8+ ratio, ECOG PS, PD-L1 expression, and antibiotic use can predict OS with considerable accuracy.

Is It a "Colon Perforation"? A Case Report and Review of the Literature.

Background: Intrauterine devices (IUDs) are commonly used as a contraceptive method. IUD migration and colon perforation are rare but serious complications occurring sometimes years after insertion. Case: A 42-year-old woman with complaints of slight abdominal pain underwent a colonoscopy. Colonoscopy showed that a "nail" had penetrated the ascending colon wall and that an arm of the "nail" was embedded in the colon wall. We did not remove the "nail" rashly under colonoscopy. Considering the safety and effectiveness of the patient's operation, we were able to remove the "nail" easily by performing laparoscopic-endoscopic cooperative surgery (LECS) combined with hysteroscopy at the same time. Conclusion: We report a case of successful removal of a colonic perforation device by colonoscopy, laparoscopy, and hysteroscopy, which is the first method used.

Two Cu(II) and Co(II) Coordination Polymers: Important Values on Colon Cancer Patients by Reducing Insulin Resistance.

In the current study, via utilizing H5L (H5L = 2,4-di(3',5'-dicarboxylphenyl)benzoic acid), the symmetrical rigid polycarboxylic acid ligand with V-shape geometry, two new coordination polymers containing Cu(II) and Co(II) have been produced, and their chemical formulae respectively are {[Co5(L)2(H2O)12]·6H2O} n (1) and {[H2N(Me)2][Cu2(L)(H2O)]·DMF·H2O} n (2), leading to a variety kinds of coordination patterns of H5L and multifunctional skeletons. Their inhibitory activity on the insulin resistance of colon cancer patients was assessed. In addition, the detailed mechanism of the compound was also investigated. Firstly, the detection of enzyme-linked immunosorbent assay was carried out and the Tumor Necrosis Factor-α (TNF-α) level and the Interleukin-1ß (IL-1ß) level was detected. Then, the glucose concentration was determined with blood glucose meter. Next, the insulin receptor expression levels of ß cells were determined with the real time reverse transcription-polymerase chain reaction assay. Ultimately, the cytotoxicity of compounds 1 and 2 was determined with Cell Counting Kit-8 assay.

FAM46C suppresses gastric cancer by inhibition of Wnt/beta-catenin.

Gastric cancer (GC) is the most common cancer with a poor prognosis and the third leading cause of cancer death in the world, for which no effective therapeutic target exists. We tested the hypothesis that FAM46C might be involved in regulation of proliferation and apoptosis in GC. FAM46C was down-regulated and its expression negatively correlated with the expression of b-catenin that drives proliferation and apoptosis. Overexpression of FAM46C inhibited cell proliferation, induced G1 phase arrest and promoted apoptosis.  Activation of Wnt/b-catenin signaling pathway in GC cell lines quenched the effect of FAM46C overexpression. On the other hand, FAM46C silencing attenuated DKK1-mediated inhibition of G1 phase, cessation of proliferation and induction apoptosis. Together, these data show that FAM46C shows tumor suppressor properties and such effects are mediated, at least in part, by Wnt/b-catenin in GC.

MicroRNA-222 promotes drug resistance to doxorubicin in breast cancer via regulation of miR-222/bim pathway.

Resistance to doxorubicin (DOX) is the most common clinical problem in breast cancer therapy, and the underlying molecular mechanism remains to be investigated. MicroRNAs (miRNAs) exhibit important regulatory functions in various malignant tumors including breast cancer. The aim of the present study was to find the relationship between miR-222 and DOX resistance. We found that miR-222 was highly expressed in patients' serum and DOX-resistant cell line MCF-7-R and that miR-222 could promote proliferation and migration of breast cancer cells. Our results also showed that inhibition of miR-222 in MCF-7-R significantly increased Bcl-2 interacting mediator (Bim) expression both in mRNA and protein levels by using quantitative real-time PCR (qRT-PCR) and Western blot. MTT and flow cytometry suggested that lower expressed miR-222 enhanced apoptosis and decreased IC50 of MCF-7-R cells. Conversely, in MCF-7 cells transfected with miR-222 mimics, up-regulation of miR-222 was associated with decreased Bim level accompanied by less apoptosis and higher IC50 Moreover, miR-222 inhibitors reversed DOX resistance via miR-222-Bim-caspase pathway. Collectively, these data first elucidated that miR-222 could function as an oncogene and was able to reduce the sensitivity of breast cancer cells to DOX through miR-222-Bim-caspase pathway, which provided a potential target to increase DOX sensitivity in clinical breast cancer treatment.

MiR-429 Induces Gastric Carcinoma Cell Apoptosis Through Bcl-2.

BACKGROUND/AIMS: MicroRNAs (miRNAs) play an essential role in the tumorigenesis of gastric carcinoma (GC). MiR-429 has been recently reported to inhibit GC growth, but the underlying mechanisms are not clear. METHODS: Here, we studied the levels of miR-429 and anti-apoptotic protein Bcl-2 in GC specimens. We performed bioinformatics analyses and used luciferase-reporter assay to analyze the relationship between miR-429 and Bcl-2 in GC cells. Cell survival upon Fluorouracil treatment was analyzed in a CCK assay. Cell apoptosis was measured by flow cytometry based FITC Annexin V apoptosis detection assay. RESULTS: MiR-429 levels were significantly decreased and Bcl-2 levels were significantly increased in GC specimens, compared to the paired adjacent non-tumor gastric tissue. Moreover, the levels of miR-429 and Bcl-2 inversely correlated in GC specimens. MiR-429-low subjects had an overall inferior survival, compared to miR-429-high subjects. Bioinformatics analyses showed that miR-429 targeted the 3'-UTR of Bcl-2 mRNA to inhibit its translation, which was confirmed by luciferase-reporter assay. Overexpression of miR-429 inhibited Bcl-2-mediated cell survival against apoptosis induced by Fluorouracil, while depletion of miR-429 augmented it. CONCLUSION: Our data suggest that miR-429 suppression in GC promotes Bcl-2-mediated cancer cell survival against chemotherapy-induced cell death. Re-expression of miR-429 levels in GC cells may enhance cancer apoptosis during chemotherapy.