The shifting landscape of genetic alterations separating endometriosis and ovarian endometrioid carcinoma

xlomafota13 shared this article with you from Inoreader The shifting landscape of genetic alterations separating endometriosis and ovarian endometrioid carcinoma Via American Journal of Cancer Research Am J Cancer Res. 2021 Apr 15;11(4):1754-1769. eCollection 2021. ABSTRACT Ovarian cancer is one of the most common cancers worldwide, and is associated with a prior diagnosis of endometriosis in several cases. Our aim was to correlate genetic and methylation profile of ovarian endometrioid ovarian cancer and endometriosis patients. We evaluated the genetic profile of 50 ovarian endometriosis and 20 ovarian endometrioid carcinoma samples using next generation sequencing technology. In addition, the DNA methylation profile was evaluated for both cohorts of patients. We observed several mutated genes that were common for both types of patients, but we also identified mutated genes that were characteristic for each group: JAK3, KRAS and RB1 for endometriosis; and ATM, BRAF, CDH1, EGFR, NRAS, RET and SMO for ovarian endometrioid cancer. Also we idenfied genes that are highly methylated only in endometriosis sample s (PYCARD, RARB, RB1, IL2, CFTR, CD44 and CDH13) and MLH3 gene was methylated only in endometrioid ovarian carcinoma samples. Also, BRCA1, CADM1, PAX6 and PAH genes are mainly methylated in endometrioid ovarian carcinoma patients. We identified a correlation for the cancer group between tumor stage, copy number aberrations and the presence of metastases; more specifically, the presence of BRCA1 pathogenic variants was correlated with tumor differentiation degree, TP53 variants and copy number aberrations. This study was able to demonstrate the presence of similar pathways being altered in both endometriosis and ovarian endometrioid carcinoma, which could mean that a diagnosis of endometriosis could be an early marker for cancer diagnosis. In addition, we showed that GATA2 hypomethylation, ATM hypermethylation, CREM hypomethylation, higher tumor differentiation degree or higher tumor stage is associated with a poor prognosis in patients with ovarian endometrioid carcinoma. PMID:33948387 | PMC:PMC8085850 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

An immune-related signature that to improve prognosis prediction of breast cancer

xlomafota13 shared this article with you from Inoreader An immune-related signature that to improve prognosis prediction of breast cancer Via American Journal of Cancer Research Am J Cancer Res. 2021 Apr 15;11(4):1267-1285. eCollection 2021. ABSTRACT Although the classic molecular subtype of breast cancer (BRCA) has been widely used in clinical diagnosis, as a highly heterogeneous malignant tumor, the classic scheme is not enough to accurately predict the prognosis of breast cancer patients. Immune cells in the tumor microenvironment (TME) are thought to play a paramount role in tumor development and driving poor prognosis. In this study, we aimed to develop a TME-associated, immune-related signature to improve prognosis prediction of BRCA. BRCA_OURS enriched transcriptomic RNA sequencing (RNA-seq) of tumor tissue was acquired from 43 breast cancer patients before any treatment. On the immune gene profiles of 43 patients from BRCA_OURS and 932 BRCA patients from The Cancer Genome Atlas (TCGA), we identified a robust immune-related signature including one positive coefficients gene (IL-10) and other 9 genes (C1 4orf79, C1orf168, C1orf226, CELSR2, FABP7, FGFBP1, KLRB1, PLEKHO1, and RAC2), of which the negative coefficients suggesting higher expression were correlated with better prognosis. Based on the expression of these genes, patients were grouped into the high- and low-risk group with significant overall survival (OS) (P<0.0001). The high-risk group was likely to have inferior outcomes related to several important cancer-associated pathways, including mobilizing more Golgi vesicle-mediated transport and intensive DNA double-strand breaking, which are closely related to the infiltration of immune cells and holds the key for further growing and metastasizing. Collectively, our results highlight that the immunological value within BRCA is an essential determinant of prognostic factor. Our signature may provide an effective risk stratification tool for clinical prognosis assessment of patients with BRCA. PMID:33948357 | PMC:PMC8085862 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Natural killer cells: of-the-shelf cytotherapy for cancer immunosurveillance

xlomafota13 shared this article with you from Inoreader Natural killer cells: of-the-shelf cytotherapy for cancer immunosurveillance Via American Journal of Cancer Research Am J Cancer Res. 2021 Apr 15;11(4):1770-1791. eCollection 2021. ABSTRACT Natural killer (NK) cells are advantaged innate cytotoxic lymphocytes with characteristics of tumor immunosurveillance and microorganism elimination. Distinguish from the adaptive T and B lymphocytes, the autologous or allogeneic NK cells efficaciously fulfil the function of combating transformed hematological malignancies and metastatic solid tumors via the proverbial mechanisms including direct cytolytic effect and antibody-dependent cell-mediated cytotoxicity (ADCC) as well as paracrine effects dispense with antigen presentation. Herein, we review the candidate sources (e.g., peripheral blood, umbilical cord blood, placental blood, cell lines and stem cells) for large-scale and clinical-grade NK cell manufacturing, ex vivo cultivation (feeder-, cytokine cocktail- or physicochemical irritation-dependent strategies) for NK cell persistence and activation. Further more, we also figure out the promising prospects as well as the accompanied challenges of NK cell- or chimeric antigen receptor-transduced NK (CAR-NK) cell-based adoptive immunotherapy in standardizations for industrialized preparation and clinical practices. PMID:33948388 | PMC:PMC8085843 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Costunolide suppresses melanoma growth via the AKT/mTOR pathway in vitro and in vivo

xlomafota13 shared this article with you from Inoreader Costunolide suppresses melanoma growth via the AKT/mTOR pathway <em>in vitro</em> and <em>in vivo</em> Via American Journal of Cancer Research Am J Cancer Res. 2021 Apr 15;11(4):1410-1427. eCollection 2021. ABSTRACT Melanoma is the most common type of skin cancer and its incidence is rapidly increasing. AKT, and its related signaling pathways, are highly activated in many cancers including lung, colon, and esophageal cancers. Costunolide (CTD) is a sesquiterpene lactone that has been reported to possess neuroprotective, anti-inflammatory, and anti-cancer properties. However, the target and mechanism underlying its efficacy in melanoma have not been identified. In this study, we elucidated the mechanism behind the anti-cancer effect of CTD in melanoma in vitro and in vivo by identifying CTD as an AKT inhibitor. We first verified that p-AKT and AKT are highly expressed in melanoma patient tissues and cell lines. CTD significantly inhibited the proliferation, migration, and invasion of melanoma cells including SK-MEL-5, SK-MEL-28, and A375 that are overexpressed p- AKT and AKT proteins. We investigated the mechanism of CTD using a computational docking modeling, pull-down, and site directed mutagenesis assay. CTD directly bound to AKT thereby arresting cell cycle at the G1 phase, and inducing the apoptosis of melanoma cells. In addition, CTD regulated the G1 phase and apoptosis biomarkers, and inhibited the expression of AKT/mTOR/GSK3b/p70S6K/4EBP cascade proteins. After reducing AKT expression in melanoma cells, cell growth was significantly decreased and CTD did not showed further inhibitory effects. Furthermore, CTD administration suppressed tumor growth and weight in cell-derived xenograft mice models in vivo without body weight loss and inhibited the expression of Ki-67, p-AKT, and p70S6K in tumor tissues. In summary, our study implied that CTD inhibited melanoma progression in vitro and in vivo. In this study, we reported that CTD could affect melanoma growth by targeting AKT. Therefore, CTD has considerable potentia l as a drug for melanoma therapy. PMID:33948365 | PMC:PMC8085867 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

AKIP1 promotes glioblastoma viability, mobility and chemoradiation resistance via regulating CXCL1 and CXCL8 mediated NF-κB and AKT pathways

xlomafota13 shared this article with you from Inoreader AKIP1 promotes glioblastoma viability, mobility and chemoradiation resistance via regulating CXCL1 and CXCL8 mediated NF-κB and AKT pathways Via American Journal of Cancer Research Am J Cancer Res. 2021 Apr 15;11(4):1185-1205. eCollection 2021. ABSTRACT This study aimed to investigate the interaction of A-kinase-interacting protein 1 (AKIP1) with C-X-C motif chemokine ligand (CXCL)1, CXCL2, CXCL8, and their effects on regulating glioblastoma multiforme (GBM) malignant behaviors. AKIP1 expression was modified by pcDNA and pGPH1 vectors in U-87 MG and U-251 MG cells. Subsequently, multiple compensative experiments were conducted via adding CXCL1, CXCL2 and CXCL8 in the pGPH1-AKIP1 (AKIP1 knockdown) transfected U-87 MG and U-251 MG cells, respectively. Furthermore, AKIP1, CXCL1/2/8 expressions in 10 GBM and 10 low-grade glioma (LGG) tumor samples were detected. AKIP1 was elevated in various GBM cell lines compared to normal human astrocytes. AKIP1 overexpression promoted U-87 MG and U-251 MG cell proliferation and invasion while inhibited apoptosis; and it enhanced chemoresistance to temozolomide (but not cisplatin) and radiation resistance; then AKIP1 knockdown showed the opposite effects. Meanwhile, AKIP1 positively regulated CXCL1/2/8, NF-κB pathway, AKT pathway and PD-L1 expression. Further multiple compensative experiments uncovered that CXCL1 and CXCL8 promoted proliferation, invasion, chemoradiation resistance, NF-κB pathway, AKT pathway and PD-L1 expression in U-87 MG and U-251 MG cells, also in pGPH1-AKIP1 (AKIP1 knockdown) transfected U-87 MG and U-251 MG cells; although CXCL2 exhibited similar treads, but its effect was much weaker. Besides, NF-κB pathway inhibitor and AKT pathway inhibitor attenuated the effect of CXCL1&CXCL8 on promoting GBM cell malignant behaviors. Clinically AKIP1 and CXCL1/8 were elevated in GBM compared to LGG tumor samples, and they were inter-correlated. AKIP1 promotes GBM viability, mobility and chemoradiation resistance via regulating CXCL1 and CXCL8 mediated NF-κB and AKT pathways. PMID:33948353 | PMC:PMC8085855 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

LncRNAs link cancer stemness to therapy resistance

xlomafota13 shared this article with you from Inoreader LncRNAs link cancer stemness to therapy resistance Via American Journal of Cancer Research Am J Cancer Res. 2021 Apr 15;11(4):1051-1068. eCollection 2021. ABSTRACT Cancer stem cells (CSCs) are a cellular subpopulation accelerating cancer cell growth, invasion and metastasis and survival. After chemoradiotherapy, CSCs are enriched because of their survival advantages and lead to tumor relapse and metastasis. Elimination of CSCs is critically important for the radical treatment of human cancers. Long non-coding RNAs (lncRNAs) are a group of RNAs longer than 200 nucleotides and have no protein-coding potential. Aberrant expressions of lncRNAs are associated with human diseases including cancer. LncRNAs function as cancer biomarkers, prognostic factors and therapeutic targets. They induce cancer stemness by chromatin modification, transcriptional regulation or post-transcriptional regulation of target genes as a sponge or through assembling a scaffold complex. Several factors caused aberrant expressions of lncRNAs in CSCs such a s genes mutations, epigenetic alteration and environmental stimuli. Targeting of lncRNAs has been demonstrated to significantly reverse the chemoradioresistance of CSCs. In this review, we have summarized the progress of studies regarding lncRNAs-mediated therapy resistance of CSCs and clarified the molecular mechanisms. Furthermore, we have for the first time analyzed the influences of lncRNAs on cell metabolism and emphasized the effect of tumor microenvironment on lncRNAs functions in CSCs. Overall, the thorough understanding of the association of lncRNAs and CSCs would contribute to the reversal of therapy resistance. PMID:33948345 | PMC:PMC8085841 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Establishment and verification of prognostic model for gastric cancer based on autophagy-related genes

xlomafota13 shared this article with you from Inoreader Establishment and verification of prognostic model for gastric cancer based on autophagy-related genes Via American Journal of Cancer Research Am J Cancer Res. 2021 Apr 15;11(4):1335-1346. eCollection 2021. ABSTRACT Autophagy played a significant role in the development of cancer. In this study, we explored the value of autophagy-associated genes in gastric cancer. RNA sequencing and clinical information containing 375 gastric cancer and 32 normal tissues were gathered from the TCGA portal. Then we stochastically allocated the autophagy-associated genes (AAGs) to training and testing groups. Next, we screened the discrepantly expressed AAGs and the prognostic AAGs by Cox regression analysis and Lasso regression analysis. Afterwards, we structured the model by using the prognostic AAGs and plotted Kaplan-Meier (KM) and receiver operating characteristic (ROC) curves to verify the performance of models in both groups. Besides, we utilized Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses to explore the molecul ar mechanisms of AAGs in gastric cancer. Finally, we demonstrated discrepant expression of AAGs within gastric cancer and non-tumor tissues at protein level with immunohistochemistry. 28 discrepantly expressed AAGs were screened from the TCGA database which contained 375 gastric cancer and 32 non-tumor samples. Cox and Lasso regression analyses were performed in training group and then we got 5 prognostic AAGs to establish the prognostic model. The patients who had high risk possessed worse overall survival (OS) both in training group (5-year OS, 47.6% vs 23.1%; P < 0.0001) and test group (5-year OS, 49.2% vs 0%, P=0.019). The proportion under ROC curves (AUC) were significant both in training group and test group (5-year AUC, 0.736 vs 0.809). Through this study, we constructed a model for gastric cancer patients which may provide individual treatment and superior prognosis. PMID:33948361 | PMC:PMC8085875 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

The clinical significance of fHIT in migraine patient without vertigo symptom

xlomafota13 shared this article with you from Inoreader Correction to: The clinical significance of fHIT in migraine patient without vertigo symptom Via http://link.springer.com/journal/405,European archives of oto-rhino-laryngology,The European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino Eur Arch Otorhinolaryngol. 2021 May 5. doi: 10.1007/s00405-021-06852-z. Online ahead of print. NO ABSTRACT PMID:33950357 | DOI:10.1007/s00405-021-06852-z View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Soluble P-selectin levels in patients with obstructive sleep apnea: a systematic review and meta-analysis

xlomafota13 shared this article with you from Inoreader Soluble P-selectin levels in patients with obstructive sleep apnea: a systematic review and meta-analysis Via http://link.springer.com/journal/405,European archives of oto-rhino-laryngology,The European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino Eur Arch Otorhinolaryngol. 2021 May 5. doi: 10.1007/s00405-021-06831-4. Online ahead of print. ABSTRACT PURPOSE: Obstructive sleep apnea (OSA) patients are at increased risk for cardiovascular disease, stroke, atherosclerosis, hypertension, and venous thromboembolism. Elevated soluble P-selectin (sP-selectin) levels are also associated with increased risk of above diseases. But whether sP-selectin levels in OSA patients are higher than their counterparts remain unclear, since previous studies yielded inconsistent results. Therefore, a meta-analysis is warranted. METHODS: PubMed, Embase, Cochrane Library, and Web of Science databases were searched for eligible studies. Studies were included if they reported sP-selectin levels of both OSA patients and non-OSA controls. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated to determine the effect sizes. RESULTS: Nine eligible studies were fin ally evaluated. When all the studies were pooled, sP-selectin levels in OSA patients were significantly higher than that in controls (SMD = 0.54, 95% CI 0.29-0.78, I2 = 66%, p < 0.0001). In the subgroup analysis based on BMI matched groups, sP-selectin levels were significantly higher in OSA patients than that in controls (SMD = 0.52, 95% CI 0.27-0.76, I2 = 23%, p < 0.0001). In the subgroup analysis stratified by blood source, either serum sP-selectin levels or plasma sP-selectin levels in OSA patients were higher than that in controls. Moderate-to-severe OSA patients had significant higher sP-selectin levels (SMD = 0.80, 95% CI 0.45-1.15, I2 = 67%, p < 0.00001), while mild OSA patients showed no significant difference with controls. CONCLUSION: The pooled results reveal that OSA patients have higher sP-selectin levels than non-OSA controls. This conclusion remains unaltered in all subgroups other than the subgroup of mild OSA patients . Additional studies are warranted to better identify the role of sP-selectin as a potential biomarker in OSA patients. PMID:33950356 | DOI:10.1007/s00405-021-06831-4 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Expression of HLA class I and class II genes in patients with multiple skin warts

xlomafota13 shared this article with you from Inoreader Expression of HLA class I and class II genes in patients with multiple skin warts Via Experimental Dermatology Abstract Background Human leukocyte antigens (HLAs), which are genetic markers that have critical roles in the immune response against pathogens, vary greatly among individuals. Objectives To investigate the frequency of HLA class I (HLA‐A, HLA‐B, and HLAC) and class II (HLA‐DRB1, HLA‐DQB1, and HLA‐DQA1) genes in patients with multiple skin warts and to elucidate the role of these genes in the genetic susceptibility to skin warts. Methods Peripheral venous blood samples were collected from 100 patients with multiple skin warts and 300 healthy individuals (controls). HLA typing was performed after DNA isolation from the blood samples. Results The HLA‐A*02 (odds ratio (OR): 0.12; p = 0.002), HLA‐DQA1*03:01 (OR: 0.45; p = 0.002), and DQA1*05:01 (OR: 0.17; p < 0.001) genes were significantly more prevalent in the patients than in the healthy individuals and were thus identified as risk genes. The DQA1*01:01 (OR: 0.17; p < 0.001), DQA1*01:02 (OR: 0.17; p < 0.001), and DQA1*01:03 (OR: 0.11; p < 0.001) genes were classified as protective genes because of their low frequencies in the patients. Study limitation Human papillomavirus typing could not be performed while investigating the relationship between skin warts and HLA class I and class II genes. Conclusion Our data suggest the role of HLA genes in the development of skin warts. However, other components of the major histocompatibility complex system and acquired factors of the immune system could also be involved and should be further investigated. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

A high‐throughput screening platform for pigment regulating agents using pluripotent stem cell‐derived melanocytes

xlomafota13 shared this article with you from Inoreader A high‐throughput screening platform for pigment regulating agents using pluripotent stem cell‐derived melanocytes Via Experimental Dermatology Abstract In this study, we describe a simple and straightforward assay using induced pluripotent stem cell‐derived melanocytes and high‐throughput flow cytometry, to identify the effect induced by pigment regulating agents on melanin content. The assay is based on the correlation between forward light‐scatter characteristics and melanin content, with pigmented cells displaying high light absorption/low forward light scatter, while the opposite is true for lowly pigmented melanocytes, as a result of genetic background or chemical treatments. Orthogonal validation is then performed by regular melanin quantification. Such approach was validated using a set of 80 small molecules and yielded a confirmed hit. The assay described in this study may prove a useful tool to identify modulators of melanogenesis in human melanocytes. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.