Phase 1 dose-escalation study of a novel oral PI3K/mTOR dual inhibitor, LY3023414, in patients with cancer
We report results of a 3 + 3 dose-escalation Phase 1 study for twice-daily (BID) dosing of LY3023414 monotherapy in Japanese patients with advanced malignancies. The primary objective was to evaluate tolerability and safety of LY3023414. Secondary objectives were to evaluate pharmacokinetics and to explore antitumor ac tivity. A total of 12 patients were enrolled and received 150 mg (n = 3) or 200 mg (n = 9) LY3023414 BID. Dose-limiting toxicities were only reported at 200 mg LY3023414 for 2 patients with Grade 3 stomatitis. Common treatment-related adverse events (AEs) across both the dose levels included stomatitis (75.0%), nausea (66.7%), decreased appetite (58.3%), diarrhea, and decreased platelet count (41.7%), and they were mostly mild or moderate in severity. Related AEs Grade ≥ 3 reported for ≥1 patient included anemia, stomatitis, hypophosphatemia, and hyperglycemia (n = 2, 16.7%). Two patients discontinued due to AEs (interstitial lung disease and stomatitis). No fatal events were reported. The pharmacokinetic profile of LY3023414 was characterized by rapid absorption and elimination. Five patients had a best overall response of stable disease (150 mg,n = 3; 200 mg,n = 2) for a 55.6% disease control rate. LY3023414 up to 200 mg BID is tolerable and safe in Japanese patients with advanced malignancies.
In conclusion, our study demonstrates that SHMT2 contributes to tumorigenesis in FP RMS and that SHMT2 amplification predicts differential response to drugs targeting this metabolic pathway.
Analyst, 2021, Accepted Manuscript DOI: 10.1039/D1AN01071A, PaperHuiying Xu, Lu Zheng, Yu Zhou, Bang-Ce Ye Tumor-related exosomes, which are heterogeneous membrane-enclosed nanovesicles shed from cancer cells, have been widely recognized as potential noninvasive biomarkers for early cancer diagnosis. Herein, an artificial enzyme cascade amplification strategy... The content of this RSS Feed (c) The Royal Society of Chemistry
In NIEHS-sponsored talk, Yu-Ying He, Ph.D., suggested RNA modifications are crucial players in regulating gene-environment interactions. (read more)
Background: In a previous exploratory study, we reported lower concentrations of the ovarian reserve biomarker anti-Müllerian hormone (AMH) in adulthood with prenatal farm exposure. We now examine this association as well as childhood farm exposure using enrollment data from the Sister Study, a large US cohort of women. Methods: We collected prenatal and childhood farm exposure data by questionnaire and telephone interview. However, serum AMH data were available only for a nested subset: premenopausal women ages 35–54 subsequently diagnosed with breast cancer (n = 418 cases) and their matched controls...
Conclusion: The incidence of penile and anal high-grade intraepithelial neoplasia and SCC in men with diabetes was increased compared with men without diabetes. For penile and anal SCCs, this was primarily due to an increased risk in men with T2D.
New UCLA-led research indicates that simple text messages emphasizing the easy availability of COVID-19 vaccines successfully boosted the number of people who got the shot.The researchers, from theDavid Geffen School of Medicine at UCLA, theUCLA Anderson School of Management and Carnegie Mellon University, say their findings held true across all demographics, including groups that have been hesitant to receive the vaccine.“We found that text messages that stressed the accessibility of the vaccine and that included ‘ownership’ language — such as ‘The vaccine has just been made available for you...
June 1, 2021 (RARITAN, N.J.) – The Janssen Pharmaceutical Companies of Johnson &Johnson announced today that more than 30 company-sponsored studies, including six oral presentations, will be featured during the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, June 4-8. Janssen presentations will include new data and updates for both approved and investigational therapeutics that are being studied for the treatment of various solid tumors and blood cancers. Immediately following ASCO, additional data will be featured during the European Hematology Association (EHA) Virtual Congress, June 9-17. A c...
Conclusion.This S‐1 and PTX cotherapy dose and schedule showed satisfactory efficacy, with mild toxicities, in patients with previously treated advanced NSCLC.
CONCLUSION: This S-1 and PTX cotherapy dose and schedule showed satisfactory efficacy, with mild toxicities, in patients with previously treated advanced NSCLC. PMID: 31040252 [PubMed - as supplied by publisher]
Conclusion.This S‐1 and PTX cotherapy dose and schedule showed satisfactory efficacy with mild toxicities in elderly patients with advanced NSCLC.