STAMP2 suppresses autophagy in prostate cancer cells by modulating the integrated stress response pathway

xlomafota13 shared this article with you from Inoreader STAMP2 suppresses autophagy in prostate cancer cells by modulating the integrated stress response pathway Via American Journal of Cancer Research Am J Cancer Res. 2022 Jan 15;12(1):327-336. eCollection 2022. ABSTRACT Six Transmembrane Protein of Prostate 2 (STAMP2) is critical for prostate cancer (PCa) growth. We previously showed that STAMP2 regulates the expression of stress induced transcription factor ATF4, which is implicated in starvation-induced autophagy. We therefore investigated whether STAMP2 is involved in the regulation of autophagy in PCa cells. Here we show that STAMP2 suppresses autophagy in PCa cells through modulation of the integrated stress response axis. We also find that STAMP2 regulates mitochondrial respiration. These findings suggest that STAMP2 has significant metabolic effects through mitochondrial function and autophagy, both of which support PCa growth. PMID:35141021 | PMC:PMC8822275 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Concomitant use of oral anticoagulants in patients with advanced prostate cancer receiving apalutamide: A post-hoc analysis of TITAN and SPARTAN studies

xlomafota13 shared this article with you from Inoreader Concomitant use of oral anticoagulants in patients with advanced prostate cancer receiving apalutamide: A post-hoc analysis of TITAN and SPARTAN studies Via American Journal of Cancer Research Am J Cancer Res. 2022 Jan 15;12(1):445-450. eCollection 2022. ABSTRACT Apalutamide, an androgen receptor signaling inhibitor, in combination with androgen-deprivation therapy (ADT), is approved for treatment of patients with nonmetastatic castration-resistant prostate cancer and metastatic castration-sensitive prostate cancer, based on the data from the phase 3 SPARTAN and TITAN studies respectively. Apalutamide is an inducer of cytochrome P450 enzymes and P-glycoprotein, which are involved in the metabolism of oral anticoagulants (OACs) and may thus have potential drug-drug interactions when co-administered with OACs. Concomitant use of certain OACs such as apixaban, rivaroxaban, edoxaban, dabigatran, and warfarin was allowed in the SPARTAN and TITAN studies. A post-hoc analysis was conducted to evaluate the incidence of treatment-emergent thrombotic and embolic adverse events (AEs) in patients receiving concomitant OACs with apalutam ide + ADT or placebo + ADT in both the studies. Anticoagulants were identified by WHO Drug Anatomical Therapeutic Chemical level 4 classifications. Thrombotic and embolic AEs were coded using the Medical Dictionary for Regulatory Activities Version 22.1. Data were analyzed from patients receiving concurrent OACs among all treated patients in SPARTAN (apalutamide + ADT: 95/803 [11.8%]; placebo + ADT: 48/398 [12.1%]) and TITAN (apalutamide + ADT: 31/524 [5.9%]; placebo + ADT: 28/527 [5.3%]). No consequential differences were observed in the occurrence of thrombotic and embolic events between apalutamide + ADT and placebo + ADT groups receiving concomitant OACs in SPARTAN (11.6% vs 12.5%) or TITAN (19.4% vs 21.4%). Grade 3/4 thrombotic and embolic AEs observed in patients receiving concomitant OACs with apalutamide + ADT or placebo + ADT were 6 (6.3%) vs 5 (10.4%) in SPARTAN and 3 (9.7%) vs 1 (3.6%) in TITAN. This analysis suggests that when necessary, concomitant OACs can be used with apalutamide with appropriate monitoring. PMID:35141028 | PMC:PMC8822273 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

De-glycosylated membrane PD-L1 in tumor tissues as a biomarker for responsiveness to atezolizumab (Tecentriq) in advanced breast cancer patients

xlomafota13 shared this article with you from Inoreader De-glycosylated membrane PD-L1 in tumor tissues as a biomarker for responsiveness to atezolizumab (Tecentriq) in advanced breast cancer patients Via American Journal of Cancer Research Am J Cancer Res. 2022 Jan 15;12(1):123-137. eCollection 2022. ABSTRACT The atezolizumab (Tecentriq), a humanized antibody against human programmed death ligand 1 (PD-L1), combined with nab-paclitaxel was granted with accelerated approval to treat unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) due to the encouraging positive results of the phase 3 IMpassion130 trial using PD-L1 biomarker from immune cells to stratify patients. However, the post-market study IMpassion131 did not support the original observation, resulting in the voluntary withdrawal of atezolizumab from the indication in breast cancer by Genentech in 2021. Emerging evidence has revealed a high frequency of false negative result using the standard immunohistochemical (IHC) staining due to heavy glycosylation of PD-L1. The removal of glycosylation prevents from the false negative staining, enabling more accurate assessment of PD-L1 levels and improving prediction for response to immune checkpoint therapy. In the present study, the natural and de-glycosylated PD-L1 expression in tumor and immune cells from nine TNBC patients were analyzed by using clone 28-8 monoclonal antibody to correlate with treatment outcome. Our results demonstrate that: (1) Removal of the glycosylation indeed enhances the detection of PD-L1 by IHC staining, (2) The PD-L1 levels on tumor cell surface after removal of the glycosylation correlates well with clinical responses for atezolizumab treatment; (3) The criteria used in the IMpassion130 and IMpassion131 trials which scored the natural PD-L1 in the immune cells failed to correlate with the clinical response. Taken together, tumor cell surface staining of PD-L1 with de-glycosylation has a significant correlation with the clinical response for atezolizumab treatment, suggesting that treatment of atezolizumab may be worthy of further consideration with de-glycosylation procedure as a patient s tratification strategy. A larger cohort to validate this important issue is warranted to ensure right patient population who could benefit from the existing FDA-approved drugs. PMID:35141008 | PMC:PMC8822291 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Artificial intelligence for early diagnosis of lung cancer through incidental nodule detection in low- and middle-income countries-acceleration during the COVID-19 pandemic but here to stay

xlomafota13 shared this article with you from Inoreader Artificial intelligence for early diagnosis of lung cancer through incidental nodule detection in low- and middle-income countries-acceleration during the COVID-19 pandemic but here to stay Via American Journal of Cancer Research Am J Cancer Res. 2022 Jan 15;12(1):1-16. eCollection 2022. ABSTRACT Although the coronavirus disease of 2019 (COVID-19) pandemic had profound pernicious effects, it revealed deficiencies in health systems, particularly among low- and middle-income countries (LMICs). With increasing uncertainty in healthcare, existing unmet needs such as poor outcomes of lung cancer (LC) patients in LMICs, mainly due to late stages at diagnosis, have been challenging-necessitating a shift in focus for judicious health resource utilization. Leveraging artificial intelligence (AI) for screening large volumes of pulmonary images performed for noncancerous reasons, such as health checks, immigration, tuberculosis screening, or other lung conditions, including but not limited to COVID-19, can facilitate easy and early identification of incidental pulmonary nodules (IPNs), which otherwise could have been missed. AI can review every chest X-ray or computed tom ography scan through a trained pair of eyes, thus strengthening the infrastructure and enhancing capabilities of manpower for interpreting images in LMICs for streamlining accurate and early identification of IPNs. AI can be a catalyst for driving LC screening with enhanced efficiency, particularly in primary care settings, for timely referral and adequate management of coincidental IPN. AI can facilitate shift in the stage of LC diagnosis for improving survival, thus fostering optimal health-resource utilization and sustainable healthcare systems resilient to crisis. This article highlights the challenges for organized LC screening in LMICs and describes unique opportunities for leveraging AI. We present pilot initiatives from Asia, Latin America, and Russia illustrating AI-supported IPN identification from routine imaging to facilitate early diagnosis of LC at a potentially curable stage. PMID:35141002 | PMC:PMC8822269 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Association of machine learning ultrasound radiomics and disease outcome in triple negative breast cancer

xlomafota13 shared this article with you from Inoreader Association of machine learning ultrasound radiomics and disease outcome in triple negative breast cancer Via American Journal of Cancer Research Am J Cancer Res. 2022 Jan 15;12(1):152-164. eCollection 2022. ABSTRACT Triple negative breast cancer (TNBC) is a breast cancer subtype with unfavorable prognosis. We aimed to establish a machine learning-based ultrasound radiomics model to predict disease-free survival (DFS) in TNBC. Invasive TNBC>T1b between January 2009 and June 2018 with preoperative ultrasound were enrolled and assigned to training and independent test cohort. Radiomics and clinicopathological features related with DFS were selected by univariate and multivariate regression analysis. Training cohort of combined features was resampled with SMOTEENN to balance distribution and put into classifiers. Areas Under Curves (AUCs) of models were compared by DeLong's test. 562 women were included with 68 DFS events observed. Twenty prognostic radiomics features were extracted. Machine learning model by Naïve Bayes combining radiomics, clinicopathological features, and SM OTEENN had an AUC of 0.86 (95% CI 0.84-0.88), with sensitivity of 74.7% and specificity of 80.1% in training cohort. In independent test cohort, this three-combination model delivered an AUC of 0.90 (95% CI 0.83-0.95), higher than models based on radiomics (AUC=0.69, P=0.016) or radiomics + SMOTEENN (AUC=0.73, P=0.019). Integrating machine learning radiomics model based on ultrasound and clinicopathological features can predict DFS events for TNBC patients. PMID:35141010 | PMC:PMC8822271 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Radiofrequency Ablation for Papillary Microcarcinoma of the Thyroid

xlomafota13 shared this article with you from Inoreader Radiofrequency Ablation for Papillary Microcarcinoma of the Thyroid Via JAMA Otolaryngology–Head & Neck Surgery Online First This systematic review and meta-analysis evaluates the effectiveness and safety of radiofrequency ablation for low-risk papillary microcarcinoma of the thyroid. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Ultrasonography vs Computed Tomography for Papillary Thyroid Cancer Cervical Lymph Node Metastasis

xlomafota13 shared this article with you from Inoreader Ultrasonography vs Computed Tomography for Papillary Thyroid Cancer Cervical Lymph Node Metastasis Via JAMA Otolaryngology–Head & Neck Surgery Current Issue This systematic review and meta-analysis compares ultrasonography and computed tomography in the preoperative evaluation of papillary thyroid cancer for cervical lymph node metastasis. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Evaluation of Surgical Margin Status in Patients With Salivary Gland Cancer

xlomafota13 shared this article with you from Inoreader Evaluation of Surgical Margin Status in Patients With Salivary Gland Cancer Via JAMA Otolaryngology–Head & Neck Surgery Current Issue This cohort study evaluates the association of surgical margin status with use of postoperative radiotherapy and survival in patients with salivary gland cancer. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Trends in Diagnosis of NIFTP and Total Thyroidectomies for Papillary Thyroid Neoplasms

xlomafota13 shared this article with you from Inoreader Trends in Diagnosis of NIFTP and Total Thyroidectomies for Papillary Thyroid Neoplasms Via JAMA Otolaryngology–Head & Neck Surgery Current Issue This cohort study determines adoption rates of 2 recent strategies developed to limit overtreatment of low-risk thyroid cancers: a new classification, noninvasive follicular thyroid neoplasm with papillarylike nuclear features, and hemithyroidectomy for selected papillary thyroid carcinomas up to 4 cm in size. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Overcoming Vaccine Hesitancy Around Bell Palsy in Otolaryngology–Head and Neck Surgery—Reply

xlomafota13 shared this article with you from Inoreader Overcoming Vaccine Hesitancy Around Bell Palsy in Otolaryngology–Head and Neck Surgery—Reply Via JAMA Otolaryngology–Head & Neck Surgery Current Issue In Reply We thank the authors of the Letter to the Editor for stimulating further discussion. Tamaki et al explored the relationship between COVID-19 and the COVID-19 vaccine on Bell palsy (BP). Patients were counted as having Bell palsy if they received a diagnosis of International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) code G51.0. Granular patient-level data may be lacking in an analysis of this magnitude, and it was not possible to differentiate persistent or recurrent BP. Likewise, it is difficult to accurately quality check the accuracy of coding without the benefit of reviewing clinical data. We plan to expand on our work with further analysis. We agree that research using large databases may be at risk for misclassification. However, such databases can be an effective resource i n studying rare pathologies, especially in specific populations such as those who have had COVID-19 or received the COVID-19 vaccination. Our propensity score matched analysis suggests that rates of BP are higher in patients who are positive for COVID-19 and this incidence exceeds the reported incidence of BP with the COVID-19 vaccine. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

The clinicopathological and prognostic significances of LATS1 expression in breast cancer

xlomafota13 shared this article with you from Inoreader The clinicopathological and prognostic significances of LATS1 expression in breast cancer Via Cellular and Molecular Biology Histol Histopathol. 2022 Feb 10:18433. doi: 10.14670/HH-18-433. Online ahead of print. ABSTRACT AIM: Large tumor suppressor gene 1 (LATS1) belongs to the PKA/PKG/PKC serine/threonine kinase subfamily of the Hippo signaling pathway and inactivates nuclear co-activators YAP1 and WWTR1 by phosphorylation. This study aimed to discern the clinicopathological and prognostic significances of LATS1 expression in breast cancer. METHODS: We examined LATS1 expression in breast carcinogenesis and compared it with clinicopathological parameters and survival information of breast cancer patients using immunohistochemistry, western blotting, RT-PCR, and bioinformatics analysis. RESULTS: LATS1 expression was downregulated in breast cancer at both mRNA and protein levels (P<0.05). LATS1 mRNA expression was negatively correlated with young age, nodal metastasis status, TNM staging, ER and PR expression, TP53 mutation, aggressive subtypes (TNBC and HER2+ vs. luminal), and poor survival (P<0.05). Its protein expression was negatively linked to patient age, T stage, N stage, histological grade, PR status, and unfavorable prognosis (P<0.05). There was a positive correlationship between nuclar and cytoplasmic LATS1 expression in breast cancer (P<0.05). CONCLUSIONS: The downregulation of LATS1 expression plays a vital role in the carcinogenesis and progression of breast cancer. Thus, LATS1 loss was employed to indicate the aggressive behaviors and poor prognosis of breast cancer. PMID:35142365 | DOI:10.14670/HH-18-433 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Secondary Syphilis Presenting as Recurrent Oral Mucocutaneous Lesions

xlomafota13 shared this article with you from Inoreader Secondary Syphilis Presenting as Recurrent Oral Mucocutaneous Lesions Via ear nose throat Ear Nose Throat J. 2022 Feb 10:1455613221078179. doi: 10.1177/01455613221078179. Online ahead of print. NO ABSTRACT PMID:35142533 | DOI:10.1177/01455613221078179 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.