A negative feedback loop between KLF9 and the EMT program dictates metastasis of hepatocellular carcinoma.

Metastasis is the primary cause of death of hepatocellular carcinoma (HCC), while the mechanism underlying this severe disease remains largely unclear. The Kruppel-like factor (KLF) family is one of the largest transcription factor families that control multiple physiologic and pathologic processes by governing the cellular transcriptome. To identify metastatic regulators of HCC, we conducted gene expression profiling on the MHCC97 cell series, a set of subclones of the original MHCC97 that was established by in vivo metastasis selection therefore harbouring differential metastatic capacities. We found that the expression of KLF9, a member of the KLF family, was dramatically repressed in the metastatic progeny clone of the MHCC97 cells. Functional studies revealed overexpression of KLF9 suppressed HCC migration in vitro and metastasis in vivo, while knockdown of KLF9 was sufficient to promote cell migration and metastasis accordingly. Mechanistically, we found the expression of KLF9 can reverse the pro-metastatic epithelial-mesenchymal transition (EMT) program via direct binding to the promoter regions of essential mesenchymal genes, thus repressing their expression. Interestingly, we further revealed that KLF9 was, in turn, directly suppressed by a mesenchymal transcription factor Slug, suggesting an intriguing negative feedback loop between KLF9 and the EMT program. Using clinical samples, we found that KLF9 was not only downregulated in HCC tissue compared to its normal counterparts but also further reduced in the HCC samples of whom had developed metastatic lesions. Together, we established a critical transcription factor that represses HCC metastasis, which is clinically and mechanically significant in HCC therapies.

Association of KMT2C/D loss-of-function variants with response to immune checkpoint blockades in colorectal cancer.

Immune checkpoint inhibitors (ICIs) have become important treatment strategies, yet responses vary among patients and predictive biomarkers are urgently needed. Mutations in KMT2C and KMT2D lead to increased levels of genomic instability. Therefore, we aimed to examine whether KMT2C/D mutations might be a predictor of immunotherapeutic efficacy. Here, we investigated the associations of KMT2C/D loss-of-function (LOF) variants with tumor mutation burden (TMB), MSI-H, PD-L1 expression, the levels of tumor-infiltrating leukocytes (TILs), and clinical response to ICIs. It was found that KMT2C/D LOF variants were associated with higher TMB. Compared with the non-LOF group, the proportion of patients with MSI-H tumors was larger in the LOF group. PD-L1 expression was higher in the LOF group only for colorectal cancer in both the Chinese and The Cancer Genome Atlas cohorts. Importantly, KMT2C/D LOF variants were associated with decreased regulatory T cells and increased levels of CD8+ T cells, activated NK cells, M1 macrophages, and M2 macrophages in colorectal cancer. However, there was no significant association between KMT2C/D LOF and TILs levels in other cancer types. Consistently, the results showed that KMT2C/D LOF variants were associated with prolonged overall survival only in colorectal cancer (p = 0.0485). We also presented that patients with KMT2C/D LOF mutations exhibited a better clinical response to anti-PD-1 therapy in a Chinese colorectal cancer cohort (p = 0.002). Taken together, these results suggested that KMT2C/D LOF variants could be a useful predictor for ICIs efficacy in colorectal cancer. In addition, the predictive value of KMT2C/D LOF variants was consistent with their association with TILs levels.

Functionalization of curcumin nanomedicines: a recent promising adaptation to maximize pharmacokinetic profile, specific cell internalization and anticancer efficacy against breast cancer.

Owing to its diverse heterogeneity, aggressive nature, enormous metastatic potential, and high remission rate, the breast cancer (BC) is among the most prevalent types of cancer associated with high mortality. Curcumin (Cur) is a potent phytoconstituent that has gained remarkable recognition due to exceptional biomedical viability against a wide range of ailments including the BC. Despite exhibiting a strong anticancer potential, the clinical translation of Cur is restricted due to intrinsic physicochemical properties such as low aqueous solubility, chemical instability, low bioavailability, and short plasma half-life. To overcome these shortcomings, nanotechnology-aided developments have been extensively deployed. The implication of nanotechnology has pointedly improved the physicochemical properties, pharmacokinetic profile, cell internalization, and anticancer efficacy of Cur; however, majority of Cur-nanomedicines are still facing grandeur challenges. The advent of various functionalization strategies such as PEGylation, surface decoration with different moieties, stimuli-responsiveness (i.e., pH, light, temperature, heat, etc.), tethering of specific targeting ligand(s) based on the biochemical targets (e.g., folic acid receptors, transferrin receptors, CD44, etc.), and multifunctionalization (multiple functionalities) has revolutionized the fate of Cur-nanomedicines. This study ponders the biomedical significance of various Cur-nanomedicines and adaptable functionalizations for amplifying the physicochemical properties, cytotoxicity via induction of apoptosis, cell internalization, bioavailability, passive and active targeting to the tumor microenvironment (TME), and anticancer efficacy of the Cur while reversing the multidrug resistance (MDR) and reoccurrence in BC. Nevertheless, the therapeutic outcomes of Cur-nanomedicines against the BC have been remarkably improved after adaptation of various functionalizations; however, this evolving strategy still demands extensive research for scalable clinical translation.

Identification of RET fusions in a Chinese multicancer retrospective analysis by next-generation sequencing.

Fusion of RET with different partner genes has been detected in papillary thyroid, lung, colorectal, pancreatic, and breast cancer. Approval of selpercatinib for treatment of lung and thyroid cancer with RET gene mutations or fusions calls for studies to explore RET fusion partners and their eligibility for RET-based targeted therapy. In this study, RET fusion patterns in a large group of Chinese cancer patients covering several cancer types were identified using next-generation sequencing. A total of 44 fusion patterns were identified in the study cohort with KIF5B, CCDC6, and ERC1 being the most common RET fusion partners. Notably, 17 novel fusions were first reported in this study. Prevalence of functional RET fusions was 1.05% in lung cancer, 6.03% in thyroid cancer, 0.39% in colorectal cancer, and less than 0.1% in gastric cancer and hepatocellular carcinoma. Analysis showed a preference for fusion partners in different tumor types, with KIF5B being the common type in lung cancer, CCDC6 in thyroid cancer, and NCOA4 in colorectal cancer. Co-occurrence of EGFR mutations and RET fusions with rare partner genes (rather than KIF5B) in lung cancer patients was correlated with epidermal growth factor receptor-tyrosine kinase inhibitor resistance and could predict response to targeted therapies. Findings from this study provide a guide to clinicians in determining tumors with specific fusion patterns as candidates for RET targeted therapies.

Betulin ameliorates 7,12-dimethylbenz(a)anthracene-induced rat mammary cancer by modulating MAPK and AhR/Nrf-2 signaling pathway.

The aim of the present study is to explore the preventive efficacy of betulin (BE) in 7,12-dimethylbenz(a)anthracene (DMBA)-administered mammary cancer by modulating Ahr/Nrf2 signaling in experimental models. The mammary cancer was stimulated by the addition of DMBA (25 mg/kg/b.Wt) mixed in 1 ml of vehicle solution (sunflower oil and saline 1:1) through subcutaneous injection. The DMBA-exposed mammary tumor models showed low bodyweight, elevated quantities of lipid peroxidation molecules (TBARS and LOOH), and low enzymatic (GPx, SOD, and CAT), and nonenzymatic (GSH, vitamin C, and vitamin E) antioxidant activities in plasma and mammary tissues. Moreover, histopathological studies confirmed that invasive ductal carcinoma was observed in DMBA-induced mammary tissue of the experimental model. Dietary oral supplementation of BE prevents the loss of bodyweight, overproduces lipid peroxidation, and restores the antioxidant activities in DMBA-exposed experimental animals. The nuclear factor erythroid 2-related factor 2 (Nrf2) is a crucial antioxidant protein that involves preventing numerous cancers. Therefore, Nrf2-associated signaling concern is a significant target for preventing mammary cancer. This study observed an increased expression of MAPKs, Keap1, ARNT, AhR, and CYP1A1, whereas decreased expression of HO-1 and Nrf2 in DMBA-induced cancer-bearing experimental animals. The oral supplementation of BE effectively modulates the expression of MAPKs, AhR/Nrf2-associated protein expressions in DMBA-exposed experimental animals. This current study concluded that BE is a strong antioxidant, which triggers the MAPKs-mediated oxidative stress and inhibits proliferative markers by restoring the activity of Nrf2 signaling.

Development and validation of a nomogram for predicting suicide risk and prognostic factors in bladder cancer patients following diagnosis: A population-based retrospective study.

This study sought to identify independent risk factors associated with suicide following a diagnosis of bladder cancer and to develop a predictive model with the potential to contribute to suicide rate reduction. Harnessing data from the Surveillance, Epidemiology, and End Results (SEER) database, we identified bladder cancer patients diagnosed between 2004 and 2015, randomly assigning them to training and validation cohorts. The Cox proportional hazard model was employed to identify relevant predictors, leading to the construction of prediction nomogram models. Validation of prognostic nomograms involved assessing the consistency index (C-index), receiver operating characteristic (ROC) curve, and calibration curve. A total of 109,961 eligible bladder cancer patients were enrolled, randomly divided into training and validation sets. Multivariate Cox regression analysis revealed that sex, marital status, tumor local status (T Stage), and lymph node metastatic conditions (N Stage) were independent predictors for suicide in bladder cancer patients. Evaluation of the nomogram's accuracy through the C-index and ROC curve demonstrated acceptable performance in both training and validation sets. Moreover, the calibration plot indicated moderate accuracy of the nomogram in both datasets. Overall, this study successfully identified risk factors for suicide among bladder cancer patients and developed a nomogram, offering individualized diagnosis, intervention, and risk assessment to mitigate the risk of suicide in this patient population.

Enhanced biomass production and harvesting efficiency of Chlamydomonas reinhardtii under high-ammonium conditions by powdered oyster shell.

Chlamydomonas reinhardtii prefers ammonium (NH4+) as a nitrogen source, but its late-stage growth under high-NH4+ concentrations (0.5 âˆ¼ 1 g/L) is retarded due to medium acidification. In this study, oyster shell powders were shown to increase the tolerance of C. reinhardtii to NH4+ supplementation at 0.7 g/L in TAP medium in 1-L bubble-column bioreactors, resulting in a 22.9 % increase in biomass production, 62.1 % rise in unsaturated fatty acid accumulation, and 19.2 % improvement in harvesting efficiency. Powdered oyster shell mitigated medium acidification (pH 7.2-7.8) and provided dissolved inorganic carbon up to 8.02 × 103 µmol/L, facilitating a 76.3 % NH4+ consumption, release of up to 189 mg/L of Ca2+, a 42.1 % reduction in ζ-potential and 27.7 % increase in flocculation activity of microalgae cells. This study highlights a promising approach to utilize powdered oyster shell as a liming agent, supplement carbon source, and bio-flocculant for enhancing biomass production and microalgae harvesting in NH4+-rich environments.

Identification of PFKFB3 as a key factor in the development of colorectal cancer and immunotherapy resistance.

Resistance to immunotherapy poses a significant challenge in the treatment of colorectal cancer (CRC), and the underlying mechanisms are not fully understood. Recent studies have implicated PFKFB3, a crucial glycolytic enzyme, in shaping the tumor microenvironment in CRC. Our study aimed to systematically study the role of PFKFB3 in CRC. Bioinformatic analysis revealed that PFKFB3 expression is notably elevated in CRC tissues compared to normal counterparts. In vivo experiments confirmed that suppressing PFKFB3 reduces the tumorigenesis of CRC. We identified multiple cancer-associated pathways positively correlated with high expression of PFKFB3, such as epithelial-mesenchymal transition (EMT), hypoxia, KRAS signaling, angiogenesis, PI3K/AKT/mTOR, Hedgehog, and Notch pathways. Additionally, PFKFB3 exhibited significant correlations with various immune-related pathways, including complement, IL-2/STAT5, IL-6/JAK/STAT3, IFN-α/IFN-γ, TGF-ß, and TNF-α/NF-κB, as well as several immunosuppressive cell markers found in regulatory T cells (CCR8, TGFB1, STAT5B, FOXP3), M2 macrophages (CD163, VSIG4, MS4A4A), T cell exhaustion markers (CTLA-4, PDCD1, LAG3), and PD-L1. Intriguingly, increased PFKFB3 expression was observed in PD-L1 blockade-resistant patients and was associated with shorter overall survival. In a nutshell, PFKFB3 plays an important role in CRC tumorigenesis and resistance to immunotherapy. Targeting PFKFB3 inhibits tumor formation and enhances the efficacy of immunotherapy. Our findings underscore the functions of PFKFB3 in CRC, shedding light on both cancer-related and immunosuppressive pathways.

Medicarpin suppresses lung cancer cell growth in vitro and in vivo by inducing cell apoptosis.

Lung cancer (LC) is the leading cause of cancer deaths worldwide. Surgery, chemoradiotherapy, targeted therapy, and immunotherapy are considered dominant treatment strategies for LC in the clinic. However, drug resistance and meta-stasis are two major challenges in cancer therapies. Medicarpin (MED) is an isoflavone compound isolated from alfalfa, which is usually used in traditional medicine. This study was de sig ned to evaluate the anti-LC effect and reveal the underlying mechanisms of MED in vivo and in vitro. We found that MED could significantly inhibit proliferation, induce apoptosis, and cell cycle arrest of A549 and H157 cell lines. Basically, MED induced cell apoptosis of LC cells by upregu lating the expression of pro-apoptotic proteins BAX and Bak1, leading to the cleavage of caspase-3 (Casp3). Moreover, MED inhibited the proliferation of LC cells via downregulating the expression of proliferative protein Bid. Overall, MED inhibited LC cell growth in vitro and in vivo via suppressing cell proliferation and inducing cell apoptosis, suggesting the therapeutic potential of MED in treating LC.

The Biological Characteristics of Eutopic and Ectopic Endometrial Progenitor Cells in Endometriosis.

AIM: The aim of this study was to identify the biological characteristics and potential roles of endometrial progenitor cells in the pathogenesis of endometriosis. BACKGROUND: It is generally believed that progenitor cells in human endometrium are responsible for rapid endometrial regeneration. However, the biological characteristics and potential roles of the paired eutopic and ectopic endometrial progenitor cells in endometriosis remain unclear. OBJECTIVE: This study intends to isolate the epithelial progenitor (EP) cells and endometrial mesenchymal stem cells (eMSCs) from the eutopic and ectopic endometria from endometriosis patients, further to reveal their features and functions respectively. METHODS: The distributions of EP cells and eMSCs and the expression of steroid hormone receptors in the endometrium and endometriotic tissues were assessed by immunohistochemistry. EP cells and eMSCs were sorted from paired eutopic and ectopic endometria with epithelial cell adhesion molecule (EpCAM) magnetic beads. The clonogenicity, cell viability after being treated with estradiol and progesterone, and cell markers expression were evaluated with colony forming on Matrigel, CCK-8 and immunofluorescence staining, respectively. The differentially expressed genes (DEGs) were further identified with RNA sequencing. RESULTS: SSEA-1- and PDGFRß-positive cells were distributed in the epithelial and stromal layers. The ERß staining was much more intense in endometriotic tissues, but PR expression was almost absent. The ectopic EP cells exhibit strong clonogenicity and ERß expression but weak PR expression, leading to progesterone resistance. There are 12604 and 13242 DEGs revealed by RNA sequencing between eutopic and ectopic EP cells or eMSCs. GO and KEGG analyses revealed that the functions and pathways of DEGs enriched in cellular energy metabolism and regulation of the immune response, respectively. Additionally, ERß targets were mainly enriched in ectopic EP cells. CONCLUSION: Both EP cells and eMSCs may engage in ectopic lesion formation in endometriosis by modifying the metabolic mode and immune tolerance. These data not only help to understand the molecular mechanism of endometriosis but also could potentially contribute to the discovery of therapeutic targets for endometriosis.

Medicarpin induces G1 arrest and mitochondria-mediated intrinsic apoptotic pathway in bladder cancer cells.

Bladder cancer (BC) is the tenth most commonly diagnosed cancer. High recurrence, chemoresistance, and low response rate hinder the effective treatment of BC. Hence, a novel therapeutic strategy in the clinical management of BC is urgently needed. Medicarpin (MED), an isoflavone from Dalbergia odorifera, can promote bone mass gain and kill tumor cells, but its anti-BC effect remains obscure. This study reve aled that MED effectively inhibited the proliferation and arrested the cell cycle at the G1 phase of BC cell lines T24 and EJ-1 in vitro. In addition, MED could significantly suppress the tumor growth of BC cells in vivo. Mechanically, MED induced cell apoptosis by upregulating pro-apoptotic proteins BAK1, Bcl2-L-11, and caspase-3. Our data suggest that MED suppresses BC cell growth in vitro and in vivo via regulating mitochondria-mediated intrinsic apoptotic pathways, which can serve as a promising candidate for BC therapy.

Glabridin inhibits urothelial bladder carcinoma cell growth in vitro and in vivo by inducing cell apoptosis and cell cycle arrest.

Glabridin (GLA) has a variety of biological activities and therapeutic effects in cancers. Whereas the effect of GLA on urothelial bladder carcinoma (UBC) cells and its underlying mechanisms remain unknown. The study revealed the effect of GLA on UBC and the potential mechanism of inducing cell apoptosis in vivo and in vitro. After treated with different concentrations of GLA, the cell activity decreased in a time- and dose-dependent manner. The IC50 values of BIU-87 and EJ cells at 48 h were 6.02 µg/ml (18.6 µm) and 4.36 µg/ml (13.4 µm), respectively. Additionally, GLA-induced apoptosis and cycle arrest of BIU-87 and EJ cells in G2 phase. Furthermore, wound healing experiments showed that GLA significantly reduced the migration activities of BIU-87 and EJ cells. Mechanically, GLA obviously increased the expression of BIM, BAK1, and CYCS in both mRNA and protein levels, which led to the activation of the endogenous apoptotic pathway. Finally, GLA remarkably inhibited the growth of UBC tumors in vivo. In summary, GLA inhibited UBC cells growth in vitro and in vivo by inducing cell apoptosis and cell cycle arrest, highlighting that GLA could be utilized as a component to design a novel anti-UBC drug.

Recent Development and Future Prospects of Molecular Targeted Therapy in Prostate Cancer.

Prostate cancer (PC) is a rapidly increasing ailment worldwide. The previous decade has observed a rapid advancement in PC therapies that was evident from the number of FDA approvals during this phase. Androgen deprivation therapies (ADT) have traditionally remained a mainstay for the management of PCs, but the past decade has experienced the emergence of newer classes of drugs that can be used with or without the administration of ADT. FDA approved poly (ADP-ribose) polymerase inhibitors (PARPi) such as olaparib and rucaparib after successful clinical trials against gene-mutated metastatic castration-resistant prostate cancer. Furthermore, drugs like apalutamide, darolutamide and enzalutamide with androgen-targeted mechanism of action have manifested superior results in non-metastatic castration-resistant prostate cancer (nmCRPC), metastatic castration- sensitive prostate cancer (mCSPC), and metastatic castration-resistant prostate cancer (m- CRPC) respectively with or without previously administered docetaxel. Relugolix, an oral gonadotropin- releasing hormone antagonist and a combination of abiraterone acetate plus prednisone were also approved by FDA after a successful trial in advanced PC and mCRPC respectively. This review aims to analyze the FDA-approved agents in PC during last decade and provide a summary of their clinical trials. It also presents an overview of the ongoing progress of prospective molecules still under trial.

Construction of a miRNA Signature Using Support Vector Machine to Identify Microsatellite Instability Status and Prognosis in Gastric Cancer.

Background: The specific role and prognostic value of DNA repair and replication-associated miRNAs in gastric cancer (GC) have not been clearly elucidated. Therefore, comprehensive analysis of miRNAs in GC is crucial for proposing therapeutic strategies and survival prediction. Methods: Firstly, clinical information and transcriptome data of TCGA-GC were downloaded from the database. In the entire cohort, we performed differential analysis in all miRNAs and support vector machine (SVM) was used to eliminate redundant miRNAs. Subsequently, we combined survival data and cox regression analysis to construct a miRNA signature in the training cohort. In addition, we used PCA, Kaplan-Meier, and ROC analysis to explore the prognosis value of risk score in the training and testing cohort. It is worth noting that multiple algorithms were used to evaluate difference of immune microenvironment (TME), microsatellite instability (MSI), tumor mutational burden (TMB), and immunotherapy in different risk groups. Finally, we investigated the potential mechanism about miRNA signature. Results: We constructed miRNA signature based on the following 4 miRNAs: hsa-miR-139-5p, hsa-miR-139-3p, hsa-miR-146b-5p, and hsa-miR-181a-3p. Univariate and multivariate Cox regression analyses suggested that risk score is a risk factor and an independent prognostic factor in GC patients. The AUC value of ROC analysis showed a robust prediction accuracy in each cohort. Moreover, significant differences in immune functions, immune cell content, immune checkpoint, MSI status, and TMB score were excavated in different groups distinguished by risk score. Finally, based on the above four miRNA target genes, we revealed that the signature was enriched in DNA repair and replication. Conclusion: We have developed a robust risk-formula based on 4 miRNAs that provides accurate risk stratification and prognostic prediction for GC patients. In addition, different risk subgroups may potentially guide the choice of targeted therapy.

Neuroprotective potential of fisetin in an experimental model of spinal cord injury: via modulation of NF-κB/IκBα pathway.

AIM: To evaluate neuroprotective efficacy of fisetin against the experimental model of spinal cord injury (SCI). MATERIALS AND METHODS: SCI was induced in male Sprague-Dawley rats by placing an aneurysm clip extradurally. Rats were treated either with vehicle or fisetin for 28 days after SCI. RESULTS: Treatment with fisetin significantly attenuated SCI-induced alternations in mechano-tactile and thermal allodynia, hyperalgesia and nerve conduction velocities. SCI-induced upregulated tumor necrosis factor-alpha, interleukins, inducible nitric oxide synthase, cyclooxygenase-II, Bcl-2-associated X protein and caspase-3 mRNA expressions in the spinal cord and these were markedly reduced by fisetin. Spinal nuclear factor kappa B and nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor-alpha protein levels were also significantly downregulated by fisetin. Hematoxylin and eosin staining of spinal cord suggested that fisetin significantly ameliorated histological aberrations such as neuronal degeneration, necrosis and inflammatory infiltration induced in it. CONCLUSION: Fisetin exerts neuroprotection via modulation of nuclear factor kappa B/nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor-alpha pathway by inhibiting release of inflammatory mediators (inducible nitric oxide synthase and cyclooxygenase-II), proinflammatory cytokines (tumor necrosis factor-alpha and interleukins), apoptotic mediators (Bcl-2-associated X protein and caspase-3).

Clinical values and potential pathways of miR-183-5p in gastric cancer: a study based on integrational bioinformatics analysis.

BACKGROUND: The clinicopathological value and exploration of the potential molecular mechanism of microRNA-183-5p (miR-183-5p) have been investigated in various cancers. This study further explored the transcriptome profile regulated by miR-183-5p. METHODS: Messenger RNA (mRNA) expression data, miRNA expression, and clinical information of stomach adenocarcinoma (STAD) were downloaded from The Cancer Genome Atlas (TCGA) database. Differentially expressed genes (DEGs) that related to mir-189-5p expression and cancer proliferation were acquired using bioinformatics analysis. The biological functions of these genes were analyzed in terms of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Hub genes relating to gastric cancer (GC) signal pathway were explored. The results were validated by further experiments. RESULTS: A total of 308 genes were found to be regulated by miR-183-5p, and they were related to cancer and GC patients' survival outcome. The biological function of these genes was found to act mainly on biological processes and the involved signal pathways included neuroactive ligand-receptor interaction, cell adhesion molecules, and axon guidance. In addition, miR-183-5p was also shown to regulate the mTOR, Wnt, MAPK, and PI3K-Akt signaling pathways through the genes WNT2B, NGFR, and NTRK2. CONCLUSIONS: The miRNA miR-183-5p participates in the tumorigenesis and development of GC via certain signaling pathways, in particular the nerve- and immunity-related genes.

Frontiers in Bladder Cancer Genomic Research.

Most of the etiology studies of bladder cancer focus on genetic changes, mainly including mutation and activation of oncogenes, mutation and inactivation of tumor suppressor genes, and rearrangement or heterozygous deletion of chromosomes. Moreover, bladder cancer is highly heterogeneous mainly due to abnormal changes in the genome and proteome of tumor cells. Surgery is the main treatment for bladder cancer, but because the recurrence rate is high after surgery and most of the muscle-invasive bladder cancer acquires distant metastasis. Therefore, there is a need to combine with chemotherapy to consolidate the treatment effect. However, there are differences in chemosensitivity among patients. In this article, we review the up-to-date genomic researches on bladder cancer occurrence, development, metastasis, and chemosensitivity in patients, in order to provide some theoretical support for the diagnosis and treatment strategy for bladder cancer.

Perfect pair, scopes unite - laparoscopic-assisted transumbilical gastroscopy for gallbladder-preserving polypectomy: A case report.

BACKGROUND: Gallbladder polyps are one indication for cholecystectomy, but this procedure carries some disadvantages, including the potential for severe injury and high risk of post-operative complications. Laparoscopy combined with endoscopic surgery is a minimally invasive treatment option. We herein report a young patient with a gallbladder polyp who was successfully discharged from the hospital after laparoscopic-assisted endoscopy. This procedure may offer an alternative in the management of such lesions. CASE SUMMARY: A 24-year-old female patient was hospitalized primarily for a gallbladder polyp. Due to the surgical risk associated with cholecystectomy and the low post-operative quality of life, the woman underwent laparoscopic-assisted transumbilical gastroscopy for gallbladder-preserving polypectomy under endotracheal intubation and general anaesthesia. The operation went smoothly. CONCLUSION: We conclude laparoscopic-assisted transumbilical gastroscopy for gallbladder-preserving polypectomy is a safe and effective technique for the treatment of gallbladder polyps.

miR-320/ELF3 axis inhibits the progression of breast cancer via the PI3K/AKT pathway.

There is increasing evidence demonstrating that disorders affecting microRNAs (miRs) influence tumorigenesis and progression, which results in a poor prognosis in patients with breast cancer (BC). In the present study, the precise molecular mechanism underlying the role of miR-320 in the progression of BC was investigated. Reverse transcription-quantitative PCR was conducted to determine mRNA expression, and western blot analysis was used to test protein levels. An MTT assay was conducted to detect cell viability and Transwell assays were used to analyze cell migration and invasion abilities. Furthermore, E74-like factor 3 (ELF3) protein density was tested via immunohistochemistry. Tumor volume was detected by xenograft tumor formation assay. The current results indicated that miR-320 expression was downregulated in BC tissues and cells, and was associated with a poor prognosis of patients with BC. Overexpression of miR-320 inhibited cell proliferation, migration and invasion via inhibition of the epithelial-mesenchymal transition and the PI3K/AKT signaling pathway in BC cells. Furthermore, it was revealed that the tumor size and weight were smaller in nude mice that had been transfected to overexpress miR-320. The luciferase reporter assay demonstrated the direct binding of miR-320 to the 3' untranslated region of ELF3 mRNA, which may further downregulate ELF3. Overall, the present results provided evidence that miR-320 may be a tumor suppressor in BC, and that the miR-320/ELF3 axis regulated tumor progression via the PI3K/AKT signaling pathway, which may represent a novel treatment strategy for BC.

MicroRNA-125b as a tumor suppressor by targeting MMP11 in breast cancer.

BACKGROUND: Breast cancer is a common type of tumor in women worldwide. MicroRNAs have been identified as regulators in many human cancers. The aim of this study was therefore to investigate the functional role of miR-125b in regulating breast cancer progression. METHODS: We used the StarBase database to investigate the expression of miRNA-125b in breast cancer and adjacent normal tissues. MMP11 3'-UTR construct and luciferase reporter assays was performed for target genes. Cell proliferation was evaluated by CCK-8 and colony formation assay. The migration and invasion were assessed by transwell assay. RESULTS: Luciferase reporter assays showed miRNA-125b directly targeted MMP11. miRNA-125b by transfection with its mimic in breast cancer cells significantly suppressed breast cancer cell proliferation and migration. Western blot revealed that overexpression of miRNA-125b substantially reduced MMP11 protein expression. We used the UALCAN database to investigate the expression of MMP11 in human breast cancer and adjacent normal tissues. In addition, we found that miRNA-125b spoiled MMP11 induced breast cancer cell proliferation and migration promotion effect. CONCLUSIONS: miRNA-125b mimic inhibited proliferation, migration, and invasion of breast cancer cells through targeting MMP11 protein.