βKlotho, a direct target of miR-206, contributes to the growth of hepatoblastoma through augmenting PI3K/Akt/mTOR signaling

xlomafota13 shared this article with you from Inoreader βKlotho, a direct target of miR-206, contributes to the growth of hepatoblastoma through augmenting PI3K/Akt/mTOR signaling Via American Journal of Cancer Research Am J Cancer Res. 2021 May 15;11(5):1982-2004. eCollection 2021. ABSTRACT Hepatoblastoma (HB) is the most frequent pediatric liver malignancy. However, the treatment outcome for patients with advanced-stage HB remains unsatisfactory. Accumulating evidence indicates that βKlotho (KLB) acts as an oncogene or a tumor-suppressor gene in a context-dependent manner. Despite this, the expression profile and effects of KLB on the growth of HB are still elusive. This study aimed to explore the effect of miR-206/KLB axis on HB growth. The expression of KLB was explored in HB cells (HepG2 and HuH6) and tissues using quantitative polymerase chain reaction (qPCR), Western blot analysis, and immunohistochemistry. Besides, miR-206 expression was determined in HB cells and tissues using qPCR and fluorescence in situ hybridization. The prognostic value of KLB or miR-206 in our patients with HB was investigated using the Kaplan-Meier method. The biologi cal effects of KLB or miR-206 on HB cells were identified in vitro. The proliferative effects of KLB on HuH6 cells were also investigated in vivo. Moreover, the mechanical signaling of KLB in HB was determined through bioinformatics analysis followed by experimental validation. The results showed a significant upregulation of KLB in HB tissues and cells. Elevated level of KLB was found to be significantly correlated with the aggressive phenotype and poor overall survival for children with HB. The in vitro function assay demonstrated that KLB knockdown promoted apoptosis and suppressed the proliferation, migration, and invasion of HB cells. Besides, KLB knockdown inhibited the proliferation of HuH6 cells in vivo, while KLB overexpression had the opposite effect. Furthermore, KLB was proved to be the direct target of miR-206. Low level of miR-206 served as an independent risk factor for poor prognosis in children with HB. The overexpression of miR-206 negat ively regulated the aggressive biological behaviors of HB cells, which was partially rescued by KLB overexpression. Mechanically, the miR-206/KLB axis played a vital role in HB growth through augmenting the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling. In conclusion, the data demonstrated that the miR-206/KLB axis might serve as an important biomarker/therapeutic target for HB. PMID:34094665 | PMC:PMC81676 75 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Association between the polygenic liabilities for prostate cancer and breast cancer with biochemical recurrence after radical prostatectomy for localized prostate cancer

xlomafota13 shared this article with you from Inoreader Association between the polygenic liabilities for prostate cancer and breast cancer with biochemical recurrence after radical prostatectomy for localized prostate cancer Via American Journal of Cancer Research Am J Cancer Res. 2021 May 15;11(5):2331-2342. eCollection 2021. ABSTRACT Prostate and breast cancers are hormone-related malignancies and are characterized by a complex interplay of hundreds of susceptibility loci throughout the genome. Prostate cancer could be inhibited by eliminating androgens through castration or estrogen administration, thus facilitating long-term treatment of prostate cancer; however, the role of estrogen in prostate cancer remains unclear. This study aimed to determine whether polygenic risk scores (PRSs) comprising combinations of genome-wide susceptibility variants influence the clinical outcomes of prostate cancer patients. The study subjects were recruited from four medical centers in Taiwan, and genome-wide genotyping data were obtained from 643 prostate cancer patients. We derived the PRS for prostate cancer (PRS-PC) and for breast cancer (PRS-BC) for each patient. The association between the PRS-PC/PRS-BC at the age of prostate cancer onset and recurrence within seven years was evaluated using a regression model adjusted for population stratification components. A higher PRS-PC was associated with an earlier onset age for prostate cancer (beta in per SD increase in PRS = -0.89, P = 0.0008). In contrast, a higher PRS-BC was associated with an older onset age for prostate cancer (beta = 0.59, P = 0.02). PRS-PC was not associated with the risk of recurrence (hazard ratio = 1.03, P = 0.67), whereas a higher PRS-BC was associated with a low recurrence risk (hazard ratio = 0.86, P = 0.03). These results indicate that the genetic predisposition to breast cancer is associated with a low risk of prostate cancer recurrence. Further studies are warranted to explore the role of breast cancer susceptibility variants and estrogen signaling in prostate cancer progression. PMID:34094689 | PMC:PMC8167673 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

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.

Subglottic Mass as Isolated Manifestation of Relapsing Polychondritis at Presentation

xlomafota13 shared this article with you from Inoreader Subglottic Mass as Isolated Manifestation of Relapsing Polychondritis at Presentation Via ear nose throat Ear Nose Throat J. 2021 Jun 3:1455613211016718. doi: 10.1177/01455613211016718. Online ahead of print. ABSTRACT Relapsing polychondritis (RP) is a rare systemic disease that is characterized by recurrent episodic inflammation of the cartilaginous structures of the body, resulting in their progressive destruction and subsequent replacement with fibrotic scar. We present a case of RP that initially manifested with subglottic involvement and we propose an innovative strategy fo r the treatment for laryngeal RP in phase of active inflammation. A multidisciplinary approach (rheumatologist, otolaryngologist, immunologist, internist, cardiologist, etc) and adequate follow-up are essential. The timeliness of the diagnosis is fundamental to contain the destructive effects on the cartilages involved. PMID:34082611 | DOI:10.1177/01455613211016718 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Tympanic membrane regeneration using platelet-rich fibrin: a systematic review and meta-analysis

xlomafota13 shared this article with you from Inoreader Tympanic membrane regeneration using platelet-rich fibrin: 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 Jun 4. doi: 10.1007/s00405-021-06915-1. Online ahead of print. ABSTRACT PURPOSE: Platelet-rich fibrin (PRF) results in satisfactory wound healing. This analysis focuses on assessing the effectiveness of PRF in the treatment of tympanic membrane (TM) perforations. MATERIALS AND METHODS: The literature was searched using PubMed, Embase, Cochrane Library and Web of Science databases from inception to February 28th, 2021. The following healing and hearing outcomes were measured: closure rate, pre-and postoperative auditory results, and incidence of postoperative infections. Data were pooled and expressed as the odds ratio (OR). RESULTS: Ten studies were eligible for qualitative review, and seven of them were included for the final quantitative comparison. The OR for the closure rate of acute perforations was 4.30 (95% CI 1.35-13.70, I2 = 0%), and the OR in the chronic subgroup was 5.42 (95% CI 2.57-11.43, I2 = 0%). The total OR value for the completed closure rate was 5.10 (95% CI 2.72-9.54, I2 = 0%), indicating that the utilization of PRF can enhance the closure of both acute and chronic perforations. The qualitative review did not find improved hearing results with the use of PRF. In addition to promoting closure, PRF can reduce the incidence of infections (OR = 0.14). The sensitivity analysis did not change the final results, and there was no publication bias in this analysis. CONCLUSION: PRF can increase the closure rate of acute perforations, enhance the survival rate of autografts in TM surgeries and reduce the incidence of infections. However, the literature indicates that PRF does not influence the hearing outcomes. This study shows that PRF is an effective agent for TM regeneration. PMID:34086080 | DOI:10.1007/s00405-021-06915-1 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Understanding Dizzy Patients a Cross-Sectional Analysis of Attitudes toward Diagnosis, Providers, and Treatment

xlomafota13 shared this article with you from Inoreader Understanding Dizzy Patients a Cross-Sectional Analysis of Attitudes toward Diagnosis, Providers, and Treatment Via otol rhinol Ann Otol Rhinol Laryngol. 2021 Jun 4:34894211022095. doi: 10.1177/00034894211022095. Online ahead of print. ABSTRACT OBJECTIVE: To evaluate patients' attitudes regarding their dizziness, provider capabilities, and receptiveness toward treatment. STUDY DESIGN: Cross-sectional study. SETTING: Tertiary care vestibular clinic. PATIENTS: Ages 18 years or older, fluent in English, and who presented with a chief complaint of dizziness or vertigo. INTERVENTION (S): N/A. MAIN OUTCOMES MEASURE(S): Non-validated questionnaire surveying patients' beliefs regarding the cause of their dizziness, likelihood of successful treatment, and openness to various treatment modalities. RESULTS: Patients were asked to complete an online non-validated survey regarding their dizziness prior to being evaluated in neurotology clinic. About 67 surveys were completed between January 2017 and September 2018. A majority of patients attributed their dizziness to their ears (n = 47, 70%), followed by the brain (n = 29, 43%). Most subjects chose "neither agree nor disagree" about whether their provider could identify the cause of their dizziness (27%). Most subjects also chose "neither agree nor disagree" that their dizziness would resolve with treatment (31%). These attitudes were not influenced by demographics, dizziness severity, anxiety, depression, or quality of life on multivariate ordinal regression modeling. CONCLUSIONS: Patients who experi ence dizziness have neutral attitudes with regards to believing that their provider will be able to identify the cause of their dizziness and whether their dizziness will resolve with treatment. These neutral attitudes are experienced by a plurality of patients and do not differ by demographic information, dizziness handicap, quality of life, depression, or anxiety. PMID:34085539 | DOI:10.1177/00034894211022095 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Efficacy and safety of polyethylene glycol dural sealant system in cranial and spinal neurosurgical procedures: Meta-analysis

xlomafota13 shared this article with you from Inoreader Efficacy and safety of polyethylene glycol dural sealant system in cranial and spinal neurosurgical procedures: Meta-analysis Via leak of cerebrospinal fluid Surg Neurol Int. 2021 Apr 26;12:182. doi: 10.25259/SNI_132_2021. eCollection 2021. ABSTRACT BACKGROUND: We aimed to assess the efficacy of polyethylene glycol (PEG) dura sealant to achieve watertight closure, prevention of cerebrospinal fluid (CSF) leak and to investigate its possible side effects. METHODS: We searched Medline (through PubMed), Scopus, and the Cochrane Library through December 2019. We included articles demonstrating cranial or spinal procedures with the use of PEG material as a dural sealant. Data on intraoperative watertight closure, CSF leak, and surgical complications were extracted and pooled in a meta-analysis model using RevMan version 5.3 and OpenMeta (Analyst). RESULTS: Pooling the controlled trials showed that PEG resulted in significantly more intraoperative watertight closures than standard care (risk ratio [RR] = 1.44, 95% confidence interval [CI] [1.24, 1.66]). However, the combined effect estimate d id not reveal any significant difference between both groups in terms of CSF leaks, the incidence of surgical site infections, and neurological deficits (P = 0.7, 0.45, and 0.92, respectively). On the other hand, pooling both controlled and noncontrolled trials showed significance in terms of leak and neurological complications (RR = 0.0238, 95% CI [0.0102, 0.0373] and RR = 0.035, 95% CI [0.018, 0.052]). Regarding intraoperative watertight closure, the overall effect estimate showed no significant results (RR=0.994, 95% CI [0.986, 1.002]). CONCLUSION: Dura seal material is an acceptable adjuvant for dural closure when the integrity of the dura is questionable. However, marketing it as a factor for the prevention of surgical site infection is not scientifically proved. We suggest that, for neurosurgeons, using the dural sealants are highly recommended for duraplasty, skull base approaches, and in keyhole approaches. PMID:34084610 | PMC:PMC8168650 | DOI:10.25259/SNI_132_2021 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.