Downregulation of NEAT1 sensitizes gemcitabine-resistant pancreatic cancer cells to gemcitabine through modulation of the miR-506-3p/ZEB2/EMT axis

xlomafota13 shared this article with you from Inoreader Downregulation of NEAT1 sensitizes gemcitabine-resistant pancreatic cancer cells to gemcitabine through modulation of the miR-506-3p/ZEB2/EMT axis Via American Journal of Cancer Research Am J Cancer Res. 2021 Aug 15;11(8):3841-3856. eCollection 2021. ABSTRACT Chemoresistance is a major cause of treatment failure in pancreatic cancer (PC). It has been demonstrated that epithelial-to-mesenchymal transition (EMT) is closely related to drug resistance in PC; however, the underlying mechanisms are not yet fully understood. Recently found evidence has suggested that nuclear-enriched abundant transcript 1 (NEAT1) is involved in the development of chemoresistance. However, the role and mechanism of NEAT1 in PC gemcitabine resistance remain unknown. In the present study, we first established two independent gemcitabine-resistant (GR) PC cell lines, PANC-1/GR and SW1990/GR. We found that GR cells displayed markedly enhanced migration and invasion abilities, decreased expression of E-cadherin, and upregulation of N-cadherin, Vimentin, Snail, ZEB1, and ZEB2. Our findings suggested that downregulation of NEAT1 enhanced the sensitiv ity of GR cells to gemcitabine by reversing the EMT process. Mechanistically, NEAT1 mediates ZEB2 mRNA expression through sponging miR-506-3p. Downregulation of NEAT1 can reverse the EMT process of GR PC cells by reducing the expression of ZEB2, thus enhancing the sensitivity of GR PC cells to gemcitabine. These findings were further confirmed in a nude mouse xenograft model. Taken together, downregulation of NEAT1 sensitized the GR PC cells to gemcitabine through modulation of the miR-506-3p/ZEB2/EMT axis. These results provide the novel evidence for understanding the function and molecular mechanism of NEAT1, and a new direction for improving the chemotherapeutic effects in PC. PMID:34522453 | PMC:PMC8414385 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Diagnosis of 'cribriform' prostatic adenocarcinoma: an interobserver reproducibility study among urologic pathologists with recommendations

xlomafota13 shared this article with you from Inoreader Diagnosis of "cribriform" prostatic adenocarcinoma: an interobserver reproducibility study among urologic pathologists with recommendations Via American Journal of Cancer Research Am J Cancer Res. 2021 Aug 15;11(8):3990-4001. eCollection 2021. ABSTRACT Accurate diagnosis of cribriform Gleason pattern 4 (CrP4) prostate adenocarcinoma (PCa) is important due to its independent association with adverse clinical outcomes and as a growing body of evidence suggests that it impacts clinical decision making in PCa management. To identify reproducible features for diagnosis of CrP4, we assessed interobserver agreement among 27 experienced urologic pathologists of 60 digital images from 44 radical prostatectomies (RP) that represented a broad spectrum of potential CrP4. The following morphologic features were correlated with the consensus diagnosis (defined as 75% agreement) for each image: partial vs. transluminal glandular bridging, intraglandular stroma, <12 vs. ≥12 lumina, well vs. poorly formed lumina, mucin (mucinous fibroplasia, extravasation, or extracellular pool), size (compared to benign glands and number o f lumina), number of attachments with gland border by tumor cells forming a "glomeruloid-like" pattern, a clear luminal space along the periphery of gland occupying <50% of glandular circumference, central nerve, dense (cell mass occupying >50% of luminal space) vs. loose, and regular vs. irregular contour. Interobserver reproducibility for the overall diagnostic agreement was fair (k=0.40). Large CrP4 had better agreement (k=0.49) compared to small CrP4 (k=0.40). Transluminal bridging, dense cellular proliferation, a clear luminal space along the periphery of gland occupying <50% of gland circumference, lack of intraglandular mucin, and lack of contact between the majority of intraglandular cells with stroma were significantly associated with consensus for CrP4. In contrast, partial bridging, majority of intraglandular cells in contact with stroma, mucinous fibroplasia, only one attachment to the gland border by tumor cells forming a "glomeruloid-like" pattern, and a clear luminal space along the periphery of gland accounting for >50% of the glandular circumference were associated with consensus against CrP4. In summary, we identified reproducible morphological features for and against CrP4 diagnosis, which could be used to refine and standardize the diagnostic criteria for CrP4. PMID:34522463 | PMC:PMC8414383 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

New insights of structural activity relationship of curcumin and correlating their efficacy in anticancer studies with some other similar molecules

xlomafota13 shared this article with you from Inoreader New insights of structural activity relationship of curcumin and correlating their efficacy in anticancer studies with some other similar molecules Via American Journal of Cancer Research Am J Cancer Res. 2021 Aug 15;11(8):3755-3765. eCollection 2021. ABSTRACT Recently, Cancer is the widespread category of different diseases in human beings, and its progress is linked with a number of factors such as estrogen level, diet, hereditary etc. Curcumin is a naturally occurring compound which appears to be significant clinical for applications in vitro as well as in vivo studies. Many of the research groups have been paying attention towards natural products for the development of anticancer drugs. Curcumin, Rosmarinic acid and Chalcone are the naturally occurring compounds, which are chemopreventive and chemotherapeutic. In present review the anticancer activity of curcumin and similar analogues in vitro has been discussed on the basis of inhibitory concentration (IC50). Also this data is compared with the inhibitory concentration of chalcone, its derivatives and rosmarinic acid. PMID:34522447 | PMC:PMC8414381 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

bFGF-mediated phosphorylation of δ-catenin increases its protein stability and the ability to induce the nuclear redistribution of β-catenin

xlomafota13 shared this article with you from Inoreader bFGF-mediated phosphorylation of δ-catenin increases its protein stability and the ability to induce the nuclear redistribution of β-catenin Via American Journal of Cancer Research Am J Cancer Res. 2021 Aug 15;11(8):3877-3892. eCollection 2021. ABSTRACT Recently, we have shown that δ-catenin strengthened the epidermal growth factor receptor (EGFR)/Erk1/2 signaling pathway through the association between EGFR and δ-catenin. Now, we further analyzed the correlation between basic fibroblast growth factor (bFGF)/fibroblast growth factor receptor 1 (FGFR1) and δ-catenin in prostate cancer and investigated the molecular mechanism underlying the role of bFGF/FGFR1 modulation in CWR22Rv-1 (Rv-1) cells. Here, we demonstrated that bFGF phosphorylated the tyrosine residues of δ-catenin in Rv-1 cells and further proved that the bFGF mediated FGFR1/δ-catenin tyrosine phosphorylation was time dependent. Furthermore, we demonstrated that bFGF stabilized the expression of δ-catenin through weakening its association with GSK3β and enhancing its stability to induce β-catenin into the nuclear by strengthening the processing of E-cadherin. In a word, these results indicated that bFGF/FGFR1 signaling pathway could enhance the tumor progression of prostate cancer via δ-catenin. PMID:34522455 | PMC:PMC8414378 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

A review of the endocrine resistance in hormone-positive breast cancer

xlomafota13 shared this article with you from Inoreader A review of the endocrine resistance in hormone-positive breast cancer Via American Journal of Cancer Research Am J Cancer Res. 2021 Aug 15;11(8):3813-3831. eCollection 2021. ABSTRACT Hormone-positive breast cancer (BC) is a unique heterogeneous disease with a favorable prognosis compared to other types of breast cancer. As tumor biology influences the prognosis and clinical treatment, a deep understanding of how the molecular mechanisms regulate hormone sensitivity or resistance is critical in improving the efficacy and overcoming the endocrine resistance. This article comprehensively reviews the endocrine resistance in hormone-positive BC from a molecular and genetic perspective, encompassing the updated treatment and developing direction. This review includes the mechanisms of hormone resistance, which vary from epigenetic changes, crosstalk between signaling networks, cell cycle aberrance, and even change in the tumor microenvironment (TME) or stem cell. These mechanisms may contribute to treatment resistance. Current targeted therapy for h ormone-resistant tumors includes PI3K/AKT/mTOR and cdk4/6 inhibitors. Several relevant pathways, biomarkers, and predictor genes have also been identified. Immunotherapy so far has a relatively less crucial role in hormone-positive than in triple-negative BC. Furthermore, the methodology to identify the PDL1 is not standardized. In a molecule and gene study, next-generation sequencing with circulating tumor DNA (ctDNA) has recently appeared as a sensitive and minimally invasive tool worth investigating. PMID:34522451 | PMC:PMC8414389 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Phonosurgery Training in Human Larynx Preserved with Thiel’s Embalming Method

xlomafota13 shared this article with you from Inoreader Phonosurgery Training in Human Larynx Preserved with Thiel's Embalming Method Via O.R.L. Journal for oto-rhino-laryngology and its borderlands Background: To describe the suitability of larynges preserved with Thiel's embalming method for phonosurgery training. Methods: A training model for phonosurgery techniques simulating vocal pathology and glottal insufficiency is developed to compare and evaluate the perception of embalmed vocal cords through a voluntary and anonymous survey rated on a scale of 1–5. A total of 10 residents and young otolaryngologists participated in the surgical training in phon osurgery. Results: Ten larynges preserved in formalin and 10 Thiel's embalmed larynges were used for the investigation. Phonosurgery procedures were performed following microflap and injection laryngoplasty techniques. The larynges preserved with Thiel's method demonstrated vocal cords that maintain their pliability and good tissue quality allowing a sensation of realism compared to the living body and providing suitable conditions for realistic laryngeal training. Participants held a positive experience, believed them to be useful and that these models of embalmed larynges were similar to the clinical setting and improved skills and confidence in performing phonosurgery. Conclusions: The human larynges embalmed with Thiel's method maintain the pliability of the vocal cords, thus representing a unique model to practice and reproduce training for endolaryngeal procedures without the risks of contamination, anatomical variation, or rigidity of other m odels. ORL View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Protective action of ultrasound-guided intraparenchymal transplantation of BMSCs in adriamycin nephropathy rats through the RIPK3/MLKL and NLRP3 pathways

xlomafota13 shared this article with you from Inoreader Protective action of ultrasound-guided intraparenchymal transplantation of BMSCs in adriamycin nephropathy rats through the RIPK3/MLKL and NLRP3 pathways Via histochem Acta Histochem. 2021 Sep 10;123(7):151773. doi: 10.1016/j.acthis.2021.151773. Online ahead of print. ABSTRACT BACKGROUND: Bone marrow stromal cells (BMSCs) are an effective new strategy for the treatment of kidney diseases. At present, noninvasive and efficient transplantation approaches to homing BMSCs to the renal parenchyma is still a serious challenge. The aim of this study was to investigate the feasibility and potential mechanism of ultrasound-guided intraparenchymal t ransplantation of BMSCs for the treatment of adriamycin nephropathy (AN) in rats. MATERIALS AND METHODS: A rat AN model was induced by 2 injections of doxorubicin. The rats were randomly divided into 4 groups (n = 10 animals in each group) : normal group (N group, no treatment), control medium group (CM group, transplant medium 1.0 mL), adriamycin nephropathy group (ADR group, phosphate buffered saline 1.0 mL), or BMSCs group (BMSCs fluid 1.0 mL). Intraparenchymal injection was completed under ultrasound guidance. After 4 weeks of treatment, blood samples were collected for serum biochemical measurements and ELISAs. The kidneys were removed for histopathological examination, electron microscopy, terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL), and western blot analysis. RESULTS: No deaths occurred in any group after BMSCs transplantation through the renal parenchyma under ultrasound guidance. Compared with the N and CM groups, in the ADR group, bloo d serum creatinine (SCr), blood urea nitrogen (BUN) and urine albumin (ALb) were higher, glomerular and tubular dilatation was observed, the number of apoptotic cells was higher, and the protein levels of receptor-interacting protein kinase 3 (RIPK3)/mixed lineage kinase domain-like protein (MLKL) and nucleotide leukin-rich polypeptide 3 (NLRP3), key components of pathways in rat kidney, were significantly higher. Compared with those in the ADR group, the levels of SCr, BUN, ALb and serum proinflammatory cytokines in the BMSCs group were lower, the pathological structure of the kidney was improved, the number of apoptotic cells was lower, and the levels of RIPK3/MLKL and NLRP3 were significantly lower. CONCLUSION: Ultrasound-guided intraparenchymal transplantation of BMSCs regulated the RIPK3/MLKL and NLRP3 pathways in a minimally invasive and safe manner, thereby inhibiting renal necrosis and inflammation and playing a protective role in rat AN. PMID:34517258 | DOI:10.1016/j.acthis.2021.151773 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.