Exosomal transfer of miR-429 confers chemoresistance in epithelial ovarian cancer

xlomafota13 shared this article with you from Inoreader Exosomal transfer of miR-429 confers chemoresistance in epithelial ovarian cancer Via American Journal of Cancer Research Am J Cancer Res. 2021 May 15;11(5):2124-2141. eCollection 2021. ABSTRACT The development of multidrug resistance during chemotherapy is the main obstacle for epithelial ovarian cancer (EOC) treatment. Exosomal transfer of carcinogenic microRNAs (miRNAs) might strengthen chemoresistance in recipient cells. Here, we identified through microarray analysis higher miR-429 expression in multidrug-resistant SKOV3 cells and their secreted exosomes (SKOV3-EXO) than in sensitive A2780 cells and their secreted exosomes. SKOV3-derived exosomes were internalized by A2780 cells, which permitted the transfer of miR-429. Exosomal miR-429 enhanced the proliferation and drug resistance of A2780 cells by targeting calcium-sensing receptor (CASR)/STAT3 pathway in vitro and in vivo. In addition, NF-κB-p65 was predicted to bind to the miR-429 promoter region, and the inhibition of NF-κB reduced the expression of miR-429 and led to the sensitivity of EOC c ells. Consistently, A2780 cells co-incubated with SKOV3 pretreated with an NF-κB inhibitor or miR-429 antagomir showed sensitivity to cisplatin and exhibited attenuated cell proliferation. Based on our data, exosomal miR-429 functions as a primary regulator of the chemoresistance and malignant phenotypes of EOC by targeting CASR through a mechanism promoted by NF-κB and might be a therapeutic target for EOC. PMID:34094673 | PMC:PMC8167704 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Association of pretreatment body mass index with risk of head and neck cancer: a large single-center study

xlomafota13 shared this article with you from Inoreader Association of pretreatment body mass index with risk of head and neck cancer: a large single-center study Via American Journal of Cancer Research Am J Cancer Res. 2021 May 15;11(5):2343-2350. eCollection 2021. ABSTRACT Smoking and alcohol exposure continue to be the dominant risk factors for the development of head and neck squamous cell carcinoma (SCCHN) worldwide. Moreover, human papillomavirus (HPV) is associated with SCCHN, particularly SCC of the oropharynx (SCCOP). Body mass index (BMI) has been reported as a possible risk factor for SCCHN, yet the data available so far about the relationship between BMI and SCCHN risk have been mixed. We sought to clarify this relationship. BMI and demographic, clinical, and epidemiological information at diagnosis were collected from 2310 SCCHN cases and 1915 controls (who were cancer-free) from October 2001 through May 2013. The odds ratios (ORs) and 95 percent confidence intervals (95% CI) were determined using the logistic regression process. Multivariable models were used to evaluate the strength of the relation between BMI and SCCHN risk. At diagnosis, 64 (2.8%) of the cases were underweight (BMI <18.5 kg/m2), 661 (28.6%) were normal weight (BMI 18.5<25 kg/m2), 833 (36.1%) were overweight (BMI 25<30 kg/m2), and 752 (32.6%) were obese (BMI ≥30 kg/m2). Comparatively, the ORs (95% CIs) for SCCHN associated with being underweight, overweight, and obese were 2.6 (1.54.7), 0.7 (0.6-0.8), and 0.8 (0.7-0.9), respectively, after adjusting for age, gender, race/ethnicity, smoking, and alcohol consumption. On analysis stratified by tumor sites, the risk of SCCOP among patients seropositive for HPVE6 and/or HPVE7 was higher among the overweight (OR, 5.4, 95% CI, 1.3-23.1) and obese patients (OR, 2.4, 95% CI, 1.1-7.6) compared to the normal weight patients. These findings suggest that pretreatment BMI could be a major risk factor for SCCHN, and the association between BMI and HPV may increase the risk of SCCOP. PMID:34094690 | PMC:PMC8167690 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Necroptosis pathway blockage attenuates PFKFB3 inhibitor-induced cell viability loss and genome instability in colorectal cancer cells

xlomafota13 shared this article with you from Inoreader Necroptosis pathway blockage attenuates PFKFB3 inhibitor-induced cell viability loss and genome instability in colorectal cancer cells Via American Journal of Cancer Research Am J Cancer Res. 2021 May 15;11(5):2062-2080. eCollection 2021. ABSTRACT Cancer cells prone to utilize aerobic glycolysis other than oxidative phosphorylation to sustain its continuous cell activity in the stress microenvironment. Meanwhile, cancer cells generally suffer from genome instability, and both radiotherapy and chemotherapy may arouse DNA strand break, a common phenotype of genome instability. Glycolytic enzyme PFKFB3 (6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase isoform 3), plays essential roles in variety physiology and pathology processes, and generally maintain high level in cancer cells. Although this protein has been reported to involve in genome instability, its role remains unclear and controversial. Here, we showed that PFK-15, a PFKFB3 inhibitor, obviously induced apoptosis, cell viability loss, and inhibited cell proliferation/migration. Besides, PFK-15 was also found to induce necroptosis, as it not only u p-regulated the phosphorylated RIP1, RIP3 and MLKL, but also enhanced the interaction between RIP3 and RIP1/MLKL, all of which are characterization of necroptosis induction. Both genetically and pharmacologically deprivation of necroptosis attenuated the cytotoxic effect of PFK-15. Besides, PFK-15 increased the γ-H2AX level and micronuclei formation, markers for genome instability, and inhibition of necroptosis attenuated these phenotypes. Collectively, the presented data demonstrated that PFK-15 induced genome instability and necroptosis, and deprivation of necroptosis attenuated cytotoxicity and genotoxicity of PFK-15 in colorectal cancer cells, thereby revealing a more intimate relationship among PFKFB3, necroptosis and genome instability. PMID:34094669 | PMC:PMC8167677 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

CDK inhibitors in cancer therapy, an overview of recent development

xlomafota13 shared this article with you from Inoreader CDK inhibitors in cancer therapy, an overview of recent development Via American Journal of Cancer Research Am J Cancer Res. 2021 May 15;11(5):1913-1935. eCollection 2021. ABSTRACT Dysregulated cell division, which leads to aberrant cell proliferation, is one of the key hallmarks of cancer. Therefore, therapeutic targets that block cell division would be effective for cancer treatment. Cell division is mainly controlled by a complex composed of cyclin and cyclin dependent kinases (CDKs). To date, the CDK inhibitors (CDKIs), specifically the ones that block the enzyme activity of CDK4 and CDK6 (CDK4/6), have been approved by FDA for the treatment of metastatic hormone receptor positive breast cancer. However, due to the non-selectivity and significant toxicity, most of the first generation CDK inhibitors (so called pan-CDK inhibitors that target several CDKs), have not been approved for clinical application. Despite this, great efforts and progress have been made to enable pan-CDK inhibitors application in the clinical setting. Notably, the d evelopment of combination therapy strategies in recent years has made it possible to reduce the toxicity and side effects of pan-CDK inhibitors. Thus, as a combination therapy approach, pan-CDK inhibitors regain great potential in clinical application. In this review, we introduced the CDK family members and discussed their major functions in cell cycle controlling. Then, we summarized the research progress regarding CDK inhibitors, especially those other than CDK4/6 inhibitors. We reviewed first-generation pan-CDKIs Flavopiridol and Roscovitine, and second-generation CDKIs Dinaciclib, P276-00, AT7519, TG02, Roniciclib, RGB-286638 by focusing on their developing stages, clinical trials and targeting cancers. The specific CDKIs, which targets to increase specificity and decrease the side effects, were also discussed. These CDKIs include CDK4/6, CDK7, CDK9, and CDK12/13 inhibitors. Finally, the efficacy and discrepancy of combination therapy with CDK inhibitors and PD1/PDL1 antibodies were analyzed, which might give insights into the development of promising strategy for cancer treatment. PMID:34094661 | PMC:PMC8167670 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Anomalous hyperplastic anterior choroidal artery and its mimicker: a case series

xlomafota13 shared this article with you from Inoreader Anomalous hyperplastic anterior choroidal artery and its mimicker: a case series Via radiol anat Surg Radiol Anat. 2021 Jun 5. doi: 10.1007/s00276-021-02777-8. Online ahead of print. ABSTRACT The anomalous hyperplastic anterior choroidal artery (AchoA) is a rare anomaly due to incomplete distal annexation between the primitive AchoA and posterior cerebral artery (PCA). It is often misdiagnosed or misunderstood as a duplicated or fetal type PCA because of its supply distribution. In addition, its aneurysm incidence is much higher than the overall aneurysm incidence of Ac hoA. Thus, endovascular procedures or surgery without comprehensive understanding of this anomaly can cause critical complications. Herein, we present a case series of anomalous hyperplastic AchoA and its mimicker, along with schematic images for comprehensive understanding. PMID:34089349 | DOI:10.1007/s00276-021-02777-8 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Vocal Fold Cyst Formation after Photoangiolytic KTP Laser Treatment of Early Glottic Cancer

xlomafota13 shared this article with you from Inoreader Vocal Fold Cyst Formation after Photoangiolytic KTP Laser Treatment of Early Glottic Cancer Via otol rhinol Ann Otol Rhinol Laryngol. 2021 Jun 4:34894211022233. doi: 10.1177/00034894211022233. Online ahead of print. ABSTRACT OBJECTIVE: The incidence of post-operative glottic cyst (POGC) formation in patients treated with transoral laser microsurgery with potassium-titanyl-phosphate laser (TLM-KTP) photoablation of early glottic carcinoma (EGC) has not previously been described. METHODS: A retrospective chart review was performed to identify all patients with early glottic can cer who underwent with single-modality TLM-KTP at our institution. Each patient received regular follow up with videostroboscopy for tumor surveillance. New glottic cysts seen on surveillance examinations were noted and their management was documented. RESULTS: A total of 33 patients met inclusion criteria. Eight patients (24%) developed POGC's within the original geographic perimeter of the cancerous vocal fold(s): 6 in the infraglottic region and 2 near the vocal process, at an average of 8 months after their initial cancer surgery. Of these 8 POGC's, 7 were at the periphery of the original tumor distribution and 1 was in the center of it. No POGC's were associated with any change in voice. Four of the 8 POGC's were phonosurgically excised, all without evidence of malignancy on pathology. The remaining 4 were monitored: 2 were stable for an average of 49 months of follow up; the remaining 2 resolved spontaneously by 7 and 31 months after first identification. CONCLUSIO NS: POGC's are a frequent sequela of TLM-KTP for EGC. While these results suggest that they are unlikely to represent submucosal recurrences, surgeons should have a low threshold to biopsy if there is clinical concern for such and should counsel patients pre-operatively about the potential for their formation. PMID:34088223 | DOI:10.1177/00034894211022233 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Frugal 3D scanning using smartphones provides an accessible framework for capturing the external ear

xlomafota13 shared this article with you from Inoreader Frugal 3D scanning using smartphones provides an accessible framework for capturing the external ear Via Journal of plastic, reconstructive & aesthetic surgery : JPRAS J Plast Reconstr Aesthet Surg. 2021 May 3:S1748-6815(21)00238-2. doi: 10.1016/j.bjps.2021.03.131. Online ahead of print. ABSTRACT Three-dimensional (3D) scanning technologies, such as medical imaging and surface scanning, have important applications for capturing patient anatomy to create personalised prosthetics. Digital approaches for capturing anatomical detail as opposed to traditional, invasive impression techniques significantly reduces turnaround times and lower production costs while still maintaining the high aesthetic quality of the end product. While previous case studies utilise expensive 3D scanning and modelling frameworks, their clinical translation is limited due to high equipment costs. In this study, we develop and validate a low-cost framework for clinical 3D scanning of the external ear using photogrammetry and a smartphone camera. We recruited five novice operators who watched an instructional video before scanning 20 healthy adult participant ears who did not have microtia. Our results show that the smartphone-based photogrammetry methodology produces 3D scans of the external ear that were accurate to (1.5 ± 0.4) mm and were (71 ± 14) % complete compared with those from a gold standard reference scanner, with no significant difference observed between operators. A moderate to strong interrater reliability was determined for all novice operators, suggesting that all novice operators were able to capture repeatable scans. The development of this smartphone photogrammetry approach has the potential to provide a non-invasive, inexpensive and accessible means to capture patient morphology for use in clinical assessment and personalised device manufacture, specifically for ear prostheses. We also demonstrate that inexperienced operators can rapidly learn and apply smartphone photogrammetry for accurate and reliable scans of the external ear with important applications for future clinical transla tion. PMID:34088646 | DOI:10.1016/j.bjps.2021.03.131 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.