Downregulation of microRNA-92b-3p suppresses proliferation, migration, and invasion of gastric cancer SGC-7901 cells by targeting Homeobox D10.

To investigate the effect and mechanism of microRNA-92b-3p (miR-92b-3p) targeting Homeobox D10 (HOXD10) on proliferation, migration, and invasion of gastric cancer, we detected the expression of miR-92b-3p and HOXD10 in SGC-7901 cells. The effects of miR-92b-3p or HOXD10 on proliferation, migration, invasion, and matrix metalloproteinase (MMP)-2/9 expression in SGC-7901 cells were measured by the Cell Counting Kit-8 assay, Transwell assay, and Western blot, respectively. The results showed that miR-92b-3p expression was increased, and HOXD10 expression was decreased in SGC-7901 cells, compared with human normal gastric epithelial cells GES-1. Functional experiments demonstrated that cell proliferation, migration, invasion, and expression of MMP-2/9 in SGC-7901 cells were significantly inhibited by miR-92b-3p silencing and HOXD10 overexpression. Moreover, HOXD10 was a potential target gene of miR-92b-3p as evidenced by the TargetScan software and double luciferase reporter assay. In the rescue experiment, knockdown of HOXD10, accompanied by higher expression of MMP-2/9, could significantly eliminate the inhibitory effects of miR-92b-3p silencing on cell proliferation, migration, and invasion. In conclusion, miR-92b-3p is highly expressed in gastric cancer SGC-7901 cells, and interfering with its expression might inhibit SGC-7901 cell proliferation, migration, and invasion via downregulating MMP-2/9 expression and targeting HOXD10.

Genomic Alterations Correlated to Trastuzumab Resistance and Clinical Outcomes in HER2+/HR- Breast Cancers of Patients Living in Northwestern China.

Anti-HER2 therapy has significantly improved the survival rates of patients with HER2+ breast cancer. However, a subset of these patients eventually experience treatment failure, and the underlying genetic mechanisms remain largely unexplored. This underscores the need to investigate the genomic heterogeneity of HER2+ breast cancer. In this study, we focus on HER2+/HR- breast cancer, as it differs from HER2+/HR+ breast cancer in terms of genetic and biological characteristics. We performed gene-targeted genome sequencing on 45 HER2+/HR- breast cancer samples and identified 650 mutations across 268 cancer-related genes. TP53 (71.1%) and PIK3CA (35.6%) were the most frequently mutated genes in our sample. Additionally, ERBB2 (77.8%), CDK12 (42.2%), and MYC (11.1%) exhibited a high frequency of copy number amplifications (CNAs). Comparative analysis with two other HER2+/HR- breast cancer cohorts revealed that our cohort had higher genetic variation rates in ARID1A, PKHD1, PTPN13, FANCA, SETD2, BRCA2, BLM, STAG2, FAT1, TOP2A, POLE, ATM, KMT2B, FGFR4, and EPAS1. Notably, in our cohort, NF1 and ATM mutations were more prevalent in trastuzumab-resistant patients (NF1, p=0.016; ATM, p=0.006) and were associated with primary trastuzumab resistance (NF1, p=0.042; ATM, p=0.021). Moreover, patients with NF1 mutations (p=0.009) and high histological grades (p=0.028) were more likely to experience early relapse. Ultimately, we identified a unique cancer-related gene mutation profile and a subset of genes associated with primary resistance to trastuzumab and RFS in patients with HER2+/HR- breast cancer in Northwest China. These findings could lay the groundwork for future studies aimed at elucidating the mechanisms of resistance to trastuzumab and improving HER2-targeted treatment strategies.

Heme Metabolism-Related Gene TENT5C is a Prognostic Marker and Investigating Its Immunological Role in Colon Cancer.

Background: There is a strong correlation between consuming high amounts of heme and an elevated risk of developing various types of cancer, including colorectal cancer. However, the role of heme metabolism-related genes (HRGs) in colorectal cancer remains unclear. Our study aimed to identify prognostic markers for colorectal cancer patients based on these genes. Methods: The heme metabolism score was assessed using gene set variation analysis (GSVA). Potential prognostic HRGs were identified from the TCGA-COAD dataset using LASSO and COX regression analyses. The expression level of TENT5C was validated in the GEO database and clinical samples. To explore the association between TENT5C expression and immune cell infiltrations, we performed ESTIMATE and single-sample gene set enrichment analysis (ssGSEA). Results: The low level of heme metabolism score was associated with a poor prognosis in colorectal cancer patients. TENT5C is a prognostic gene and an independent prognostic biomarker for overall survival. Its expression was confirmed in multiple datasets and clinical samples, showing a positive correlation with immune cells and immune score. GSEA results suggested TENT5C's significant role in regulating immune and inflammatory responses in colorectal cancer. Conclusion: TENT5C can be used as a biomarker in colorectal cancer. Additionally, TENT5C is associated with both prognosis and immune infiltration. These findings lay a strong groundwork for future research to delve into the specific role of TENT5C in the development and advancement of colorectal cancer.

Construction of a Prognostic Nomogram Model for Patients with Mucinous Breast Cancer.

Objective: The objective of the study is to develop a nomogram for estimating three- and five-year survival rates in mucinous breast cancer patients. Methods: Between 2010 and 2016, the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) were searched as a data source for patients associated with mucinous breast cancer (MBC). A total of 3964 patients were recruited after screening. The multivariate Cox model and the univariate Kaplan-Meier (KM) approach were employed to evaluate the independent prognostic markers, followed by developing a nomogram for estimating three- and five-year survival rates in MBC patients. Consequently, the consistency index (C-index) was employed to assess the predictive accuracy of the generated nomogram. Results: Age, race, T stage, M stage, surgery, and radiotherapy were all independent predictive biomarkers for the MBC patients (P < 0.05). The nomogram was finally developed based on the underlined factors. Furthermore, the C-index of 0.803 and reliable calibration curves were obtained in the nomogram's assessment. Conclusions: In patients with mucinous breast cancer, the proposed nomogram provides a viable tool for accurate prognostic prediction. In clinical practice, it could serve as a personalized diagnosis tool, estimate prognosis, and help in suggesting treatment plans for patients with MBC.

Mesenchymal Stem Cells (MSCs) in Targeted Drug Delivery: Literature Review and Exploratory Data on Migrating and Differentiation Capacities of Bone MSCs into Hepatic Progenitor Cells.

BACKGROUND AND OBJECTIVE: Mesenchymal stem cells (MSCs), particularly bone MSCs (BMSCs) offer great potentials for targeted therapeutic applications owing to their migratory and differentiation capacities. Significant advances have been achieved in the differentiation of hepatocyte or hepatocyte-like cells both in vitro and in vivo. However, there is limited knowledge on the differentiation of BMSCs into bipotential hepatic progenitor cells or cholangiocyte. This study reviews the potentials and advances in using MSCs as vehicles for targeted drug delivery and proposes a new method for the induction of differentiation in rat BMSCs into hepatic progenitor cells in vitro and assesses the differential and migratory capacities. METHODS: The BMSCs of Sprague Dawley (SD) rats were harvested from the femur and the tibiae of the rats. After isolation and culturing, BMSCs from Passage 1 were used for the study. The in vitro differentiation of the hepatic progenitor cells was performed using a 2-step induction approach after 5-day serum deprivation from the BMSCs and culturing in Dulbecco's modified eagle medium. Spontaneous in vitro differentiation of BMSCs was examined in the absence of growth factors for 15 days as control treatment. Hepatocytes differentiation was achieved by exposing the culture to collagen type I-coated plates. Cholangiocytes differentiation was achieved with replating the BMC-HepPCs on a layer of Matrigel. Immunofluorescence was conducted on twelve-well plates to determine cell differentiations. Real-Time Quantitative Reverse Transcription PCR (qRTPCR) was used to determine the total RNA extracted using the Trizol LS reagent. In the hepatocyte differentiation group, after periodic acid-schiff (PAS) staining for glycogen, inverted microscope was used to determine differentiations and undifferentiated BMC-HepPCs served as controls. The amount of low-density lipoprotein (LDL) uptake by the BMSCs-derived hepatocytes was assessed using fluorescence microscopy. The secretion of rat albumin was quantified using a quantitative ELISA kit. RESULTS: Differentiation induction is indicative of the sequential supplementation of sodium butyrate and cytokines, which are involved in the embryonic development of the mammalian liver. Hepatic progenitor cells, derived from bone marrow, can be differentiated bidirectionally in vitro into both hepatocyte and cholangiocyte cell-lines. The differentiated cells, including hepatic progenitor cells, hepatocytes, and bile duct-like cells, were identified and analyzed at mRNA and protein levels. CONCLUSION: Our findings show that BMSCs can be utilized as novel bipotential hepatic progenitor cells and thereby for hepatobiliary disease treatment or hepatobiliary tissue-engineering.

The influence of ADAR1's regulation on lymphocyte cell function during rejection.

The RNA editing adenosine deaminase gene (ADAR1) expression is wide-spread in lymphocytes. We explore the mechanism of ADAR1 regulation on the function of T primary lymphocytes when rejection occurs by knock-down the expression of ADAR1 in mouse T primary lymphocytes in mixed lymphocyte cultures. The changes of cell proliferation, the expression of ADAR1 and the cell cycle related genes cyclin D1 and A1, cell cycle and apoptosis analysis and mouse gene expression profiles was evaluated. We found that treatment with ADAR1-specific siRNA inhibited allogenic antigen stimulated T cell proliferation, arrested T cell cycle at G(0)/G(1) phases and promoted T cell apoptosis, which was associated with down-regulation of some related key genes transcription. These findings suggest that ADAR1 is essential for the maintenance of function of T lymphocytes during acute rejection. The mechanism underlying ADAR1's action might include editing of a currently unknown substrate and interacting with other proteins.

Control of allograft rejection in mice by applying a novel neuropeptide, cortistatin.

INTRODUCTION: The action of cortistatin (CST), a novel cyclic neuropeptide, as an anti-inflammatory factor has been studied, but few investigations have explored the immunomodulatory role of CST in transplantation. In the present study, we examined whether CST affects the alloimmune response in a mouse model of skin transplantation and the effects of CST on T lymphocytes. METHODS: BALB/c (H-2K(d)) recipient mice (n=70) were divided into seven groups (n=10 per group) and given an intraperitoneal injection of CST or a somatostatin analog, SMS 201-995 (octreotide), on the day of skin transplantation from C57BL/6 (B6) (H-2K(b)) donors. Injections were continued for 7 consecutive days. Groups 1-3 received CST at doses of 0.02, 0.2, or 2 mg/kg, respectively. Groups 4-6 received SMS 201-995 at the same doses. Group 7 was a control group and received injections of phosphate buffered saline. Survival of the allografts was recorded. A semiquantitative reverse transcriptase polymerase chain reaction study of Foxp3 expression and a flow cytometry study of CD4 and CD25 markers of T lymphocytes were conducted to determine whether CD4(+)CD25(+) Foxp3(high) regulatory T cells (T(reg)) were generated in vivo. RESULTS: BALB/c mice given CST (0.2 or 2 mg/kg) had prolonged graft survival (median survival time [MST], 13 and 14 days, respectively; P<0.05 compared with controls). SMS 201-995 at the same concentrations did not have a significant effect on allograft survival (MST, 8 days for both groups). We found more than a twofold increase of CD4(+)CD25(+) T(reg) cells in the CD4(+) T-cell population and the expression of Foxp3 was up-regulated in the CST treatment groups, compared with control and SMS 201-995 treatment groups. CONCLUSION: In our study, CST induced a significant prolongation in survival time of allogeneic skin grafts and increased the generation of CD4(+)CD25(+) Foxp 3(high) T(reg) cells. These results suggest that CST may become a new modality in controlling allograft rejection.

A systemic analysis of S-1 regimens for treatment of patients with colon cancer.

BACKGROUND: Fluorouracil-based regimens have been widely accepted and recommended in the guidelines for treating patients with early or advanced staged colon cancer, although results are controversial. Here we performed a systemic analysis to evaluate the impact of S-1 based regimens on response and survival of patients with colon cancer. METHODS: Clinical studies evaluating the impact of S-1 based regimens on response and survival of patients with colon cancer were identified using a predefined search strategy. Summary response rates (RRs) to treatment were calculated. RESULTS: Six clinical studies which including 227 patients with advanced colorectal cancer were considered eligible for inclusion. Two studies were conducted using combination of S-1 and Oxaliplatin, and four studies featured S-1 and irinotecan. Systemic analysis showed that, in all patients, pooled RRs was 43.17%. Major adverse effects were hematological toxicities, gastrointestinal disturbance, neurosensory toxicity. No treatment related death occurred. CONCLUSION: This systemic analysis suggests that S-1 based regimens, both with oxaliplatin or irinotean are associated with acceptable response and toxicity in patients with colon cancer.