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.

USP47 stabilizes BACH1 to promote the Warburg effect and non-small cell lung cancer development via stimulating Hk2 and Gapdh transcription

xlomafota13 shared this article with you from Inoreader USP47 stabilizes BACH1 to promote the Warburg effect and non-small cell lung cancer development via stimulating Hk2 and Gapdh transcription Via American Journal of Cancer Research Am J Cancer Res. 2022 Jan 15;12(1):91-107. eCollection 2022. ABSTRACT Increasing studies demonstrated that ubiquitination plays a crucial part in the pathogenesis of non-small cell lung cancer (NSCLC), and targeted adjustment of the deubiquitination enzymes is a potential means for cancer treatment. However, the role of ubiquitin carboxyl-terminal hydrolase 47 (USP47) in NSCLC is still unclear. Here, we show that USP47 was upregulated in NSCLC clinical tissues and greatly related to advanced tumor stages and survival rate. Functional experimental results showed that USP47 promoted the cell proliferation in vitro and tumor growth in vivo. And the overexpression of USP47 promoted the glycolysis capacity of lung cancer cells. Mechanistic investigations showed that USP47 promoted NSCLC development, which depends a lot on directly binding to and deubiquitination of the basic leucine zipper transcription factor 1 (BACH1, BTB an d CNC homology 1). BACH1 was also significantly overexpressed in primary NSCLC tissues and positively correlated with the expression of USP47. The promotion of USP47 on the Warburg effect and NSCLC progression was mediated by the deubiquitination of BACH1 and the downstream transcriptional regulation of hexokinase 2 (Hk2) and glyceraldehyde-phosphate dehydrogenase (Gapdh). Therefore, targeting USP47/BACH1 axis might offer a new way to inhibit the progression of NSCLC. PMID:35141006 | PMC:PMC8822287 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.

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.