Diabetes mellitus and the incidence of colorectal cancer: an updated systematic review and meta-analysis.

AIM: The purpose of this study was to determine whether diabetes mellitus is associated with an increased risk of colorectal cancer. METHODS: Relevant studies were identified in MEDLINE and EMBASE (up until November 1st, 2011). Inclusion criteria were original, peer-reviewed publications, with case-control and cohort studies (for studies on diabetes mellitus and colorectal cancer). Summary relative risks with 95% confidence intervals were calculated with a random-effects model. RESULTS: Twenty-four studies including eight case-control and 16 cohort studies, with a total of 3,659,341 participants, were included in this updated systematic review and meta-analysis, and all involved diabetes mellitus and colorectal cancer risk. Meta-analysis of the 24 included studies indicated that diabetes was associated with an increased risk of colorectal cancer, compared with no diabetes (summary RR of colorectal cancer incidence = 1.26, 95% CI = 1.20-1.31), without heterogeneity between studies (P(heterogeneity) = 0.296). Sub-group analyses found that these results were consistent between case-control and cohort studies and among studies conducted in different areas. The association between diabetes and colorectal cancer incidence did not differ significantly by sex and sub-sites. Insulin therapy was also positively associated with risk of colorectal cancer (summary RR = 1.61, 95% CI 1.18-1.35), with evidence of heterogeneity between studies (P(heterogeneity) = 0.014). CONCLUSIONS: Our findings further support a relationship between diabetes and increased risk of colon and rectal cancer in both women and men, and insulin therapy for diabetes may increase this risk.

Primary colon natural killer (NK)/T-cell lymphoma, nasal type, with perforations: a case report and literature review.

Extranodal natural killer (NK)/T-cell lymphoma-nasal type (ENKTL-NT) is a rare, aggressive subtype of non-Hodgkin's lymphoma associated with Epstein-Barr virus (EBV) infection and has a poor prognosis. ENKTL-NT primarily involves the nasal cavity, and the colon as the primary site has rarely been reported. Its lack of a characteristic clinical presentation makes early diagnosis difficult to diagnose early, and misdiagnosis is common without the use of immunohistochemistry of specimens. To further understand this rare solid tumor, we report a case in a 51-year-old male patient admitted to hospital with abdominal pain as the primary symptom. A provisional diagnosis of gastrointestinal perforation was made on the basis of enhanced computed tomography of the abdomen, and emergency surgery was performed. However, 58 days after discharge, he suffered a second colonic perforation, underwent emergency surgery and was diagnosed with primary colonic ENKTL-NT based on the immunohistochemical results of the surgical specimen. He was transferred to the oncology department for chemotherapy after recovery from surgery, with gemcitabine, oxaliplatin, and pegaspargase as the chemotherapy regimen. To date, he has completed 11 courses of chemotherapy, and is now in a significantly improved general condition with no signs of tumor recurrence. We also reviewed and compared the literature related to primary colonic ENKTL-NT.

Ferroptosis-Associated Classifier and Indicator for Prognostic Prediction in Cutaneous Melanoma.

Ferroptosis plays a critical role in different types of cancers, but the prognostic impact of ferroptosis in cutaneous melanoma remains lacking. Therefore, ferroptosis-related genes (FRGs) were firstly obtained from the FerrDb database and the differentially expressed FRGs were identified by the "limma" algorithm. Next, the prognostic differentially expressed FRGs were screened out by univariate Cox regression, which were subsequently used to cluster melanomas into two subtypes (clusters A and B). Besides, the Boruta algorithm and principal component analysis (PCA) were performed to build a 15-FRGs indicator, which can robustly predict patients' overall survival (OS) and be considered as an independent prognostic factor in melanoma. The melanoma patients were further divided into high- and low-FRGs score groups. The high score group have a good prognosis, with higher T cell immune infiltrating and lower mutation frequencies in NRAS, KRAS, and NF1. Finally, we discovered that many immune processes and several chemotherapy drugs were closely associated with FRGs score. Thus, our study provides a novel ferroptosis-associated classifier and indicator to predict the prognosis of melanoma. Besides, we identified several potential chemotherapy drugs to induce ferroptosis and could supply additional effective treatments.

Expression and prognostic significance of thrombospondin gene family in gastric cancer.

BACKGROUND: Thrombospondins (THBSs) are glycoproteins expressed in the extracellular matrix (ECM) and have critical roles in tumor development and metastasis. However, the diverse expression patterns and prognostic roles of distinct THBS genes in gastric cancer have not been fully elucidated. In the current study, we aimed to investigate the expression patterns of THBSs in gastric cancer (GC) and determine whether they are prognostic markers for this malignancy. METHODS: mRNA expression status and genetic mutations of THBS family members were performed by using ONCOMINE, UCSC Xena browser, GEPIA, and cBioPortal databases. Prognostic values and function enrichment analysis of the members were assessed via Kaplan-Meier plotter and Metascape. RESULTS: we found that the mRNA expression of THBS1, THBS2, THBS4, and COMP were higher in patients with GC tissues than those in normal gastric mucosa and there was no difference in the mRNA expression of THBS3 between GC and normal tissue. Survival analysis revealed that mRNA levels of THBSs were strongly related to worse OS in GC patients (P<0.05). Overexpression of THBSs indicated poor OS in stage III/IV GC and high expression of THBS1, THBS3, THBS4, and COMP were related to worse OS in stage II GC. CONCLUSIONS: Bioinformatics analysis revealed a better understanding the value of THBS family members in GC and suggest that THBSs might serve as potential prognostic biomarkers for GC.

c-Met upregulates aquaporin 3 expression in human gastric carcinoma cells via the ERK signalling pathway.

Aquaporin 3 (AQP3) and c-Met are both overexpressed in human gastric carcinoma and highly associated with its metastasis and invasion. However, it still remains unknown whether c-Met and AQP3 correlate with each other. Herein, we demonstrated that c-Met expression in gastric cancer tissues significantly correlated with differentiation, lymph node metastasis and lymphovascular invasion, and c-Met exhibited marked association with AQP3 expression. Immunoblotting assays showed that hHGF phosphorylated c-Met in SGC7901 and AGS cells and upregulated AQP3 expression in a dose- or time-dependent way. RNAi against c-Met reduced total c-Met levels by about two thirds in both AGS and SGC7901 cells and attenuated hHGF-induced AQP3 expression significantly. In vitro migration and proliferation assays showed that siRNA against AQP3 noticeably restrained HGF-promoted migration and proliferation of these cells. Furthermore, Immunoblotting studies revealed that HGF induced phosphorylation of ERK, and pre-treatment with U0126, a MAPK/ERK inhibitor, partially inhibited hHGF-induced increase in AQP3 expression. Together, these data provide initial evidence that c-Met regulates the expression of AQP3 via the ERK signalling pathway in gastric carcinoma. These findings assist in understanding the mechanism of growth and invasion of gastric carcinoma, and provide a possible strategy for the inhibition of gastric tumor metastasis.

Antitumor activity of mutant bacterial cytosine deaminase gene for colon cancer.

AIM: To evaluate bacterial cytosine deaminase (bCD) mutant D314A and 5-fluorocytosine (5-FC) for treatment of colon cancer in a mouse model. METHODS: Recombinant lentivirus vectors that contained wild-type bCD gene (bCDwt), and bCD mutant D314A gene (bCD-D314A) with green fluorescence protein gene were constructed and used to infect human colon carcinoma LoVo cells, to generate stable transfected cells, LoVo/null, LoVo/bCDwt or LoVo/bCD-D314A. These were injected subcutaneously into Balb/c nude mice to establish xenograft models. Two weeks post-LoVo cell inoculation, PBS or 5-FC (500 mg/kg) was administered by intraperitoneal (i.p.) injection once daily for 14 d. On the day after LoVo cell injection, mice were monitored daily for tumor volume and survival. RESULTS: Sequence analyses confirmed the construction of recombinant lentiviral plasmids that contained bCDwt or bCD-D314A. The lentiviral vector had high efficacy for gene delivery, and RT-PCR showed that bCDwt or bCD-D314A gene was transferred to LoVo cells. Among these treatment groups, gene delivery or 5-FC administration alone had no effect on tumor growth. However, bCDwt/5-FC or bCD-D314A/5-FC treatment inhibited tumor growth and prolonged survival of mice significantly (P < 0.05). Importantly, the tumor volume in the bCD-D314A/5-FC-treated group was lower than that in the bCDwt/5-FC group (P < 0.05), and bCD-D314A plus 5-FC significantly prolonged survival of mice in comparison with bCDwt plus 5-FC (P < 0.05). CONCLUSION: The bCD mutant D314A enhanced significantly antitumor activity in human colon cancer xenograft models, which provides a promising approach for human colon carcinoma therapy.