The use of hormone replacement therapy (HRT) for menopausal women has been the subject of much controversy in recent years, particularly concerning the carcinologic risks. The purpose of this review is to evaluate the impact of the use of HRT on the risk of gynecological but also extra-gynecological cancers. The effect of the type and the duration of use of HRT in menopausal women will also be discussed. The beneficial impact of HRT on overall mortality is also an element that will be discussed and must be taken into account when evaluating the benefit-risk balance of HRT for menopausal women.

OBJECTIVE: To investigate clinical outcome and predicting factors of local failures in patients with colorectal cancer treated for unresectable liver metastases with stereotactic body radiation therapy (SBRT).
METHODS: We restrospectively reviewed the medical records of 67 patients treated with the Cyberknife SBRT system for 99 hepatic metastases between January 2007 and December 2015 in our center. In total, 37.5 to 54.0Gy in 3 to 5 fractions were prescribed to the 80% isodose line. Local control (LC), intrahepatic progression incidence, Progression-Free Survival (PFS), Overall Survival (OS) and toxicity were evaluated.
RESULTS: The median follow-up was 47 months (IQR, 28-59 months). The median OS was 53 months, the 2-year OS and PFS rates were 81.4% and 54.0%. The 1- and 2-year LC rates were 86.6% and 72.4%. In the multivariate analysis, the degree of differentiation was the only prognostic factor for LC (HR 0.31, 95% CI, 0.10-0.98, P=0.046). Margin expansion>5mm was not associated with a better LC (HR 0.72, 95% CI, 0.38-1.37, P=0.317). Performans Status≥2 (HR 3.27, 95% CI, 1.07-9.98, P=0.038), chemotherapy for metastases before SBRT (HR 0.36, 95% CI, 0.18-0.75, P=0.006) and regional lymph node at diagnosis (HR 2.19, 95% CI, 1.09-4.43, P=0.029) were independent prognostic factors for OS. We report 2 cases of grade≥3 toxicity (3.0%) - one grade 3 acute nausea and one grade 3 late gastric ulcer.
CONCLUSIONS: Stereotactic body radiation therapy is an effective and well-tolerated treatment that allow high LC for liver metastases from colorectal cancer during the first two years. A prescription dose of 45Gy in 3 fractions to the 80% isodose line with a risk adapted schedule to respect Organ At Risk constraints allows a low rate of toxicity.

OBJECTIVE: Diabetes mellitus (DM) is associated with an elevated risk of various cancers, including colorectal cancer (CRC). Similarly, pre-existing DM may also influence prognosis among patients with CRC. We performed a systematic review and meta-analysis to assess the association between DM and risk of death and relapse after a diagnosis of CRC.
METHODS: PubMed, Scopus, Web of Science, The Cochrane Library and Embase were searched from inception until July 2019 for studies reporting prognosis of patients with DM and CRC. The primary outcome of the study refers to overall mortality in patients with vs without diabetes. Secondary endpoints were cancer-specific mortality and progression or relapse-free survival. The risk of death and relapse are reported as hazard ratio (HR) with 95% confidence interval (CI), and an HR >1 was associated with worst outcome in patients with diabetes compared to those without diabetes.
RESULTS: Mortality and relapse associated with DM in patients with CRC were evaluated among 5,267,980 participants (total of 82 studies). Overall, concomitant diagnosis of CRC and DM were associated with an independent increased risk of overall mortality (HR, 1.21; 95% CI, 1.17 to 1.25; p<0.01) and CSM (HR, 1.11; 95% CI, 1.05 to 1.17; p<0.01). Patients were also at increased risk of relapse (HR, 1.09; 95% CI, 1.02 to 1.16; p<0.01).
CONCLUSIONS: In CRC patients with DM, diabetes decreased survival and increased the risk of relapse. Adequate control of lifestyle choices, more intensive follow ups, use of some oral antidiabetics, dietary restrictions, physical activity and monitoring of diabetes-associated complications are measures for reducing mortality in this setting.

Colorectal cancer (CRC) is the third-most prevalent malignant tumor. Taurine upregulated gene 1 (TUG1), a long non-coding RNA (lncRNA), is reportedly involved in the physiological and pathological processes of CRC. However, the role of TUG1 in the progression of CRC and its underlying mechanisms are largely unknown. Here, we measured the expression of TUG1 in clinical samples from CRC patients and found that the expression level of TUG1 was higher in CRC tissues compared with the normal adjacent tissues. We then performed knockdown of TUG1 with siRNAs in two CRC cell lines and found that TUG1 knockdown inhibited the viability, proliferation, and migration of CRC cells, and reduced the ability of CRC cells to form subcutaneous tumors. Furthermore, we discovered that TUG1 affects the cellular processes in CRC cells by sponging miR-145-5p. We further found that miR-145-5p inhibits the expression of the protein-encoding gene Transient Receptor Potential Cation Channel Subfamily C Member 6 (TRPC6), and that overexpression of TRPC6 restored the inhibitory role of miR-145-5p in CRC cells. In conclusion, we have demonstrated that TUG1 exerts its role by modulating the TUG1-miR-145-5p-TRPC6 regulatory axis, thus revealing a novel molecular mechanism for the effects of TUG1 in the progression of CRC. Our data indicate that the TUG1-miR-145-5p-TRPC6 signaling pathway could serve as a target for the diagnosis and treatment of CRC.

There is an increasing incidence of hepatotoxicity induced by oxaliplatin (OXA); therefore, researchers\' attention has been drawn to therapeutic alternatives that may decrease OXA-induced hepatotoxicity. Studies indicate that oxidative stress plays a major role in OXA-induced liver injury. As several pharmacological effects of 7-chloro-4-(phenylselanyl) quinole (4-PSQ) involve its antioxidant action, the hypothesis that this organoselenium compound could be promising for the treatment or prevention of hepatotoxicity induced by treatment with OXA was investigated. To test this hypothesis, male Swiss mice received OXA (10 mg·kg-1) on days 0 and 2, followed by oral administration of 4-PSQ (1 mg·kg-1) on days 2 to 14. 4-PSQ reduced the plasma aspartate, and alanine aminotransferase activity increased by exposure to OXA. The histopathological examination of the liver showed that 4-PSQ markedly improved OXA-induced hepatic injury. In addition, treatment with 4-PSQ reduced the oxidation of lipids and proteins (thiobarbituric acid reactive species levels and protein carbonyl content) and attenuated the increase of hepatic catalase and glutathione peroxidase activity caused by OXA. The inhibition of hepatic δ-aminolevulinic dehydratase activity induced by OXA was reverted by 4-PSQ. In conclusion, results indicate that 4-PSQ may be a good therapeutic strategy for attenuating OXA-induced liver damage.

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To determine associations between physical activity (PA), sedentary behavior (SB), and oxidative stress in colorectal cancer patients, ColoCare Study participants in Germany wore an accelerometer 6 and/or 12 months after surgery. Spearman partial correlations were used to assess associations between PA and urinary concentrations of oxidized guanine, a validated marker of oxidative stress. There were no significant associations between PA or SB and oxidized guanine in n = 76 measurements (ng/mg creatinine; r = 0.03, p = 0.76 for PA, r = -0.05, p = 0.69 for SB). Novelty Objectively measured PA was not associated with a marker of oxidative stress in colorectal cancer patients.

Schistosomiasis infection is endemic in many parts of Tanzania. The morbidity due to Schistosomiasis and its association with cancer remains to be of great concern and poses greater challenge that needs to be assessed. Cancer is an increasing public health problem in most sub-Saharan African countries, and yet, cancer control programs and the provision of early detection and treatment services are limited despite this increasing burden. This article aims to discuss case series of patients diagnosed with urinary bladder, prostate and colorectal cancer together with Schistosoma infection. We further highlight the opportunities for combating new Schistosomiasis infection, a potential to reduce its oncological complications particularly in low-resource setting.

Colorectal cancer is a common malignancy. NTS receptor 3 (NTSR3) is known to play an important role in several cancers. This study examined the effects of NTSR3 on cell growth and metastasis in colorectal cancer. Western blot analysis, real-time PCR, immunofluorescence staining, MTT, cell cycle assay, cell apoptosis assay, Hoechst staining, caspase-3 and caspase-9 activity assays, cell adhesion assay, wound healing assay, and a Transwell assay were used in this study. We found that NTSR3 was expressed at relatively high levels in the colorectal cancer cell lines SW620 and SW480. NTSR3 knockdown suppressed cell growth and promoted cell apoptosis. Meanwhile, the protein expression levels of cyclinD1, cyclinE1, CDK4, and p-RB were reduced, and the levels of p-P27, P15, P21, cleaved caspase-3, and cleaved caspase-9 protein were increased. Cell invasiveness and cell migration were reduced with knockdown of NTSR3. In addition, our rescue experiments demonstrated that overexpression of the siRNA-resistant alleles of NTSR3 abrogated the NTSR3-siRNA-mediated effects on cell function. Further, down-regulation of NTSR3 inactivated the PI3K-AKT and MAPK signaling pathways. Collectively, these data demonstrate that knockdown of NTSR3 inhibits cell growth and metastasis, as well as the PI3K-AKT and MAPK signaling pathways in colorectal cancer. Thus, our results indicate that NTSR3 is a potential therapeutic target for treating colorectal cancer.

The purpose of this study was to characterize the expression of procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2), a membrane-bound homodimeric enzyme that specifically hydroxylates lysine in the telopeptide of procollagens, and assess the clinical significance of PLOD2 in colorectal cancer (CRC). Our results show that PLOD2 is highly expressed in CRC tumor tissues and cell lines, both at the mRNA and protein levels. Next, we found that PLOD2 was positively correlated with tumor grade (P = 0.001), T stage (P = 0.001), N stage (P < 0.001), and an advanced TNM stage (P < 0.001). Knockdown of PLOD2 attenuated CRC cell proliferation, migration, and invasiveness, in vitro. Our analysis of the mechanism behind the effects of PLOD2 suggests that PLOD2 affected glycolysis by regulating the expression of hexokinase 2 (HK2). HK2 reverses the inhibitory effects of PLOD2 knockdown in CRC. Furthermore, the data suggest that PLOD2 regulates the expression of HK2 via the STAT3 signaling pathway. Survival analysis revealed that high expression levels of PLOD2 (HR = 3.800, P < 0.001) and HK2 expression (HR = 10.222, P < 0.001) correlated with the overall survival rate. After analyzing their expression and correlation, PLOD2 positively correlated with HK2 (r = 0.590, P < 0.001). Our findings have revealed that PLOD2 is a novel regulatory factor in glucose metabolism, exerted via controlling HK2 expression in CRC cells, suggesting PLOD2 as a promising therapeutic target for CRC treatment.