Endometrial microbiota from endometrial cancer and paired pericancer tissues in postmenopausal women: differences and clinical relevance.

OBJECTIVE: The incidence of postmenopausal endometrial cancer (EC) is rising, and the uterine microbiota has recently been suggested to be an etiology of EC. However, the differences in microbiota profiles in paired EC and the adjacent non-EC endometrium, and the functional microbiota of clinical relevance remain largely unknown. Therefore, we examined the differences in microbiota profiles between EC and non-EC endometrium and investigated their clinical relevance to EC. METHODS: Twenty-eight EC-affected postmenopausal women undergoing hysterectomy were enrolled. Endometrial microbiome from paired EC and adjacent non-EC tissue samples were detected using 16S rRNA sequencing, and the data were analyzed using R language software. RESULTS: The α diversity and evenness of the endometrial bacterial community significantly increased in EC tissues than those in pericancer tissues ( P < 0.05 for all variables). Lactobacillus and Gardnerella were the main bacterial genera present in both EC and adjacent non-EC-invading endometrium, whereas Prevotella , Atopobium , Anaerococcus , Dialister , Porphyromonas , and Peptoniphilus were more commonly enriched in the EC endometrium (corrected P < 0.05 for all variables). Finally, the abundance of some observed endometrial bacteria was associated with clinical aspects, particularly the vaginal pH, vaginal Lactobacillus abundance, and EC clinical stage. CONCLUSIONS: Paired EC and adjacent non-EC endometrium harbor different endometrial microbiota, and the functional bacteria residing in the endometrium are clinically relevant but require further investigation.

Exosomal MiR-423-3p inhibits macrophage M2 polarization to suppress the malignant progression of cervical cancer.

BACKGROUND: Cervical cancer (CC) is the leading cause of death among women-related cancers. MicroRNAs (miRNAs) exerting important impacts in the development of CC is widely recognized. MiR-423-3p was found to be with low expression in the plasma exosomes of patients with CC. Exo-miRNAs have been documented to be potential modulators of cancer progression, and exosomes have been reported to be associated with macrophage polarization. AIM: We aim to verify the potential function exosomal miR-423-3p may exert in CC cells as well as its underlying mechanism. METHODS: A co-culture model of exosomes and CC cells was established and the function of exosomal miR-423-3p was verified through Transwell, colony formation and other assays. A co-culture model of exosomes and macrophages, together with mechanism experiments in vitro and in vivo was taken to verify the molecular mechanism of exosomal miR-423-3p in CC. RESULTS: Exosomal miR-423-3p inhibited macrophage M2 polarization so as to suppress CC cell progression as well as tumor growth. MiR-423-3p regulated macrophage M2 polarization by targeting cyclin-dependent kinase 4 (CDK4) mRNA, and it inhibited the phosphorylation of signal transducer and activator of transcription 3 (STAT3) via CDK4 to silence Interleukin 6 (IL-6) expression. CONCLUSION: Exosomal miR-423-3p inhibited macrophage M2 polarization to suppress the progression of CC cells.

Up-regulation of MTHFD2 is associated with clinicopathological characteristics and poor survival in ovarian cancer, possibly by regulating MOB1A signaling.

BACKGROUND: MTHFD2 is a folate-coupled metabolic enzyme, which has been proved to participant in the metabolic reprogramming and tumor cell-sustaining proliferative capacity. However, the function of MTHFD2 in the development of ovarian cancer and its potential molecular mechanisms is still unclear. MATERIALS AND METHODS: The expression, various mutations, prognosis, and related network signaling pathways of MTHFD2 were analyzed using bioinformatics-related websites, including Oncomine, GEPIA, UCSC, cBioPortal, KM Plotter, TISIDB and TIMER. The prognostic value of MTHFD2 expression was validated by our own ovarian cancer samples using RT-qPCR. The migration ad invasion of ovarian cancer cells were further analyzed by CCK-8 and transwell assay. The Western-blot assay was performed to explore the protein levels of MTHFD2 and MOB1A. RESULTS: We obtained the following important results. (1) MTHFD2 expression was markedly up-regulated in ovarian cancer than normal samples. (2) Among patients with ovarian cancer, those with higher MTHFD2 expression was associated with lower survival rate. (3) The major mutation type of MTHFD2 in ovarian cancer samples was missense mutation. (4) MTHFD2 knockdown inhibited proliferation, migration, invasion, as well as the expression of MOB1A in vitro. CONCLUSION: MTHFD2, as a NAD + -dependent enzyme, accelerated tumor progression by up-regulating MBO1A, suggesting that this protein may be an independent prognostic factor and a potential therapeutic target for future ovarian cancer treatments.

Fabrication of polymer-based self-assembly nanocarriers loaded with a crizotinib and gemcitabine: potential therapeutics for the treatment of endometrial cancer.

Combination therapy in cancer therapy has been widely used for its positive attributes, such as minimizing the undesirable side effects of chemotherapies and enhancing the therapeutic effects on different cancers. Compared with free drugs crizotinib (CRZ) and gemcitabine (GEM), CRZ@GEM-NPs could remarkably improve the cytotoxicity for endometrial cancer (EC) cells (Ishikawa cells and KLE cells) after treatment with MTT assay. In this study, CRZ and GEM were conjugated to tri-block copolymer poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCL-PEG-PCL, known as NPs). The fabricated nanoparticles were characterized by the high-resolution transmission electron microscopy (HR-TEM), and the particles size and zeta potential were investigated by the dynamic light scattering analysis. Further, the morphological features of the EC cell lines were examined by the biochemical staining assays. Morphological changes in endometrial cells morphology revealed by nuclear fragmentation and nuclear condensation (the hallmarks of apoptosis) were noted upon treatment with CRZ@GEM-NPs to the Ishikawa and KLE cancer cells. In addition, resulting in the highest ratio of apoptosis and mitochondrial membrane potential shows the cell death through the mitochondrial membrane potential. In vivo, systemic toxicity studies showed no histological changes and substantial blood biochemical with the near-normal appearance of the organs upon treatment with CRZ@GEM-NPs. Overall, the targeted combination suitable therapeutic framework may be a promising candidate for improved EC therapy.

Exploring the malnutrition status and impact of total parenteral nutrition on the outcome of patients with advanced stage ovarian cancer.

BACKGROUND: Ovarian cancer is a common cancer type in women and is often associated with onset of malnutrition. Total parenteral nutrition (TPN) is a nutritional intervention method that has been reported to have controversial effect on cancer patients. In the present retrospective study, we sought to explore the prevalence of malnutrition assessed by the Nutritional Risk Index (NRI) and its association with survival in advanced stage ovarian cancer patients. We also compared the post-operative outcome of the malnourished patients treated with either TPN or conservative management. RESULTS: A total of 415 patients with advanced stage ovarian cancer were separated into 4 nutrition groups based on the NRI scores. We found that a number of factors were significantly different among the 4 nutrition groups, including age, serum albumin level, BMI and NRI; among which serum albumin level and NRI were identified to be independent predictors of progression-free and overall survival. In the moderately and severely malnourished patients, those who were treated with TPN had significantly shorter hospitalization period, lower serum albumin level and lower BMI after surgery. In addition, serum albumin level, use of TPN and number of patients with complications were closely related to the hospital stay duration. CONCLUSION: Malnutrition status is closely associated with survival of advanced stage ovarian cancer patients. These patients may benefit from TPN treatment for reduced hospitalization, especially with the onset of hypoalbuminemia.

Total Parenteral Nutrition Treatment Improves the Nutrition Status of Gynecological Cancer Patients by Improving Serum Albumin Level.

BACKGROUND: Malnutrition is often observed in gynecological cancer patients, however its prevalence in these patients remains largely unexplored. Total parenteral nutrition (TPN) is a nutritional intervention method that has controversial treatment outcome on gynecological cancer patients. The present retrospective study is designed to evaluate the nutrition status and TPN treatment outcome on patients diagnosed with endometrial, cervical or ovarian malignant tumors. METHODS: Medical records of a total of 263 patients treated at the First Hospital of Shanxi Medical University, China were included. Nutrition status was assessed by patient-generated subjective global assessment (PG-SGA). Patients were grouped based on nutrition status, cancer type or treatment strategy for clinical characteristic comparison. Multivariable logistic regression analysis was used to identify predictors for malnutrition status and hospital stay duration. RESULTS: Presence of endometrial and cervical cancer, body weight before nutritional intervention and serum albumin level (P < 0.001 for all) were found to be significant predictors for malnutrition status in gynecological cancer patients. In the malnourished patients, those who were treated with TPN had significantly lower serum albumin levels before and after treatment (P < 0.001) and PG-SGA scores after treatment. Also, TPN treatment could significantly increase the serum albumin levels in these patients after 1 week. In addition, shorter hospitalization period was needed for TPN-treated endometrial (P = 0.019) and ovarian (P < 0.001) patients. Moreover, serum albumin levels (P < 0.001), use of TPN treatment (P = 0.025) and nutrition status (P = 0.010) were identified to be independent predictors for hospital stay duration. CONCLUSION: Our results suggest that malnutrition is a significant clinical manifestation in gynecological cancer patients who may benefit from TPN treatment for reduced hospitalization and improved serum albumin levels.