Hasil untuk "q-bio.OT"

Dr.K.Murali Kizhakkemadham

Chayanee Ot-sup

พรอพอลิสจากรังชันโรง Trigona laeviceps ที่เก็บจากร้อยเอ็ด ประเทศไทย ได้ถูกนำมาสกัดด้วยไดคลอโรมีเทน และทดสอบฤทธิ์การยับยั้งการเจริญเติบโตของเชื้อรา Ascosphaera apis ที่ก่อโรคชอล์กบรูด พบว่าที่ความเข้มข้น 190 ppm ของสารสกัดสามารถยับยั้งการาเจริญเติบโตของเชื้อราได้ 50 เปอร์เซ็นต์ และที่ความเข้มข้น 250 ppm ของสารสกัดสามารถยับยั้งการาเจริญเติบโตของเชื้อราได้ 100 เปอร์เซ็นต์ ได้แยกสิ่งสกัดไดคลอโรมีเทนด้วยคอลัมน์โครมาโทรกราฟีได้ 7 ส่วนย่อย สารสกัดที่แยกได้ในส่วนที่ 3 และ 4 สามารถยับยั้งการเจริญเติบโตของ Ascosphaera apis ได้โดยใช้วิธี TLC autographic เมื่อนำพรอพอลิสมาวิเคราะห์หาองค์ประกอบด้วย gas chromatography-mass spectrometer พบว่าสารที่น่าจะเป็นองค์ประกอบคือ 2-methylpropyl ester, camphor, 2, 4 - bis (dimethylbenzyl) - 6 - t- butylphenol, 1H- cycloprop[e]azulen-7-ol, 6-oxohuperzine A และ 2,6-diphenyl-1,7-dihydrodipyrrolo[2,3-b:3',2'-E]pyridime สารที่ออกมาที่ Rt 13.02 นาที เป็นองค์ประกอบหลักในพรอพอลิส แต่ไม่มีข้อมูลตรงกับฐานข้อมูลของ Wiley ถึงแม้ว่า camphor ซึ่งเป็นส่วนประกอบหลักของส่วนที่ 3 การทดสอบฤทธิ์ยับยั้งการเจริญเติบโตของเชื้อราแสดงให้เห็นว่า camphor ไม่สามารถยับยั้งการเจริญเติบโตของเชื้อรา Ascosphaera apis

Ot Van Daalen

Dan Palade, Charles Moller, Chen Li et al.

Erika Hamilton, Carlos Alemany, Nancy U Lin et al.

Abstract Background: Endocrine therapy has been the primary treatment modality for HR+, HER2- metastatic breast cancer (MBC). Endocrine agents are administered sequentially, either in combination with targeted therapy or as monotherapy. The majority of patients with HR+, HER2- MBC will develop endocrine resistant disease. More effective and less toxic therapies are needed for the treatment of endocrine resistant disease. OP-1250 is a small molecule Complete Estrogen Receptor ANtagonist (CERAN) that completely inactivates Estrogen Receptor (ER), blocks ER-driven transcriptional activity, inhibits ER-driven breast cancer cell growth, and induces degradation of ER. OP-1250 demonstrates anti-cancer activity in vitro and in vivo, including activity against metastases in the brain and in tumors with activating mutations in ESR1. OP-1250 is orally bioavailable with a favorable pharmacokinetic profile supportive of once-daily dosing. OP-1250 is hypothesized to completely antagonize ER resulting in superior efficacy compared to agents that only have partial antagonism of ER. Its favorable pharmacologic profile makes it an attractive agent for chronic use in patients with MBC. Trial design: This is a Phase I/II open-label, first-in-human study to determine the Dose Limiting Toxicity (DLT), Maximum Tolerated Dose (MTD) and/or Recommended Phase II Dose (RP2D), to characterize the safety and pharmacokinetic (PK) profile, and to determine the preliminary efficacy of OP-1250 in adult subjects with HR+, HER2- MBC. Treatment will consist of oral, once a day dosing and subject evaluation will be performed in 28-day cycles. This study comprises 2 parts. Part 1 (Dose Escalation) will evaluate the safety and pharmacology of a range of doses of OP-1250 administered orally to subjects and to determine the maximum tolerated dose (if any) and/or the RP2D. Cohorts of 3 to 6 subjects will be sequentially enrolled and monitored for DLTs during the first cycle of study treatment. Part 2 (Dose Expansion) will evaluate the preliminary activity of OP-1250. Patients with and without central nervous system (CNS) disease will be enrolled at the RP2D. This is designed using a Simon 2 Stage Design. Total accrual will be determined by the number of dose levels needed to identify the RP2D. Eligibility criteria:Males and females, age 18 or older, with ER+, HER2− advanced or MBCPrior treatment with endocrine therapyECOG performance status of 0 or 1For dose expansion the subject must have measurable disease according to Response Evaluation Criteria in Solid Tumors Criteria (RECIST) 1.1 ObjectivesPart 1 (Dose Escalation)To identify the DLT, MTD and/or RP2D of OP-1250To assess the safety and tolerability of OP-1250To assess the pharmacokinetics of OP-1250 Part 2 (Phase II: Monotherapy Expansion)Objective response rate (ORR) of OP-1250 in subjects with HR+, HER2- MBC who have progressed on endocrine therapy and have no evidence of central nervous system (CNS) metastases.To conduct a preliminary assessment of the antitumor activity (ORR) of OP-1250 in subjects with HR+, HER2- MBC who have progressed on endocrine therapy and have CNS disease. Assessment of response will be determined according to RECIST 1.1 and Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria Correlative ScienceTo determine biomarker expression, such as, ER, PR, Ki67 and others in the most recently obtained archival tumor tissue sampleTo evaluate whether ESR1 in circulating tumor DNA (ctDNA) can be correlated with response and/or activity of OP-1250To examine ctDNA pre- and post-therapy for mutESR1 and PIK3CA variants, and other relevant markers For more information, please contact clinical@olemapharma.com Citation Format: Erika Hamilton, Carlos Alemany, Nancy U Lin, Pamela M Klein, Trinh Le, Peter J Kushner, Cyrus Harmon, Jo Anne Zujewski, Manish Patel. A phase I/II open-label, first-in-human, multicenter, dose escalation and dose expansion study of OP-1250 monotherapy in adult subjects with advanced and/or metastatic hormone receptor (HR)-positive, HER2-negative breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr OT-09-10.

Thomas Lynch, Ann Partridge, Alastair Thompson et al.

Abstract Background: Approximately 50,000 women in the U.S. are diagnosed with ductal carcinoma in situ (DCIS) annually. Without treatment, it is estimated that 20-30% of DCIS will lead to invasive breast cancer. Currently, more than 97% of women undergo surgery, with many also undergoing radiation. An alternative to surgery for low-risk DCIS is active monitoring (AM), an approach in which regularly scheduled mammography and physical exams are used to monitor breast changes and determine if, or when, surgery is needed. Trial design: COMET, a multicenter phase III prospective randomized trial, opened in the U.S. in June 2017 (clinicaltrials.gov reference: NCT02926911). The hypothesis is that management of low-risk DCIS using an AM approach does not yield inferior invasive breast cancer and/or quality of life outcomes compared to surgery. Eligibility criteria: Patients with a new diagnosis of unilateral, bilateral, unifocal, multifocal, or multicentric DCIS, or atypia verging on DCIS are eligible. Patients must be ≥40 years of age, have no contraindication for surgery, and pathologic confirmation of grade I/II DCIS. DCIS must be ER and/or PR≥ 10% and HER2-negative without invasion, diagnosed within 120 days of registration. Breast tissue, blood and imaging are collected at trial entry and if invasive cancer subsequently occurs, and are stored in central repositories. Specific aims: The primary aim is to assess whether the 2-yr ipsilateral invasive breast cancer rate for AM is non-inferior to surgery. Secondary aims include comparison of 2-, 5-, and 10-yr mastectomy rate, contralateral invasive breast cancer rate, overall survival and invasive breast cancer-specific survival, as well as 5- and 10-yr ipsilateral invasive breast cancer rate between groups. Patient reported outcomes (PRO) using validated tools are critical secondary endpoints, and will enable comparison of health-related quality of life and psychosocial outcomes between surgery and AM groups at prespecified time points over a period of 5 years. Statistical methods: An accrual goal of 1200 was estimated using a 2-group test of noninferiority of proportions, with the 2-yr invasive breast cancer rate in the surgery group assumed to be 0.10, including accounting for upstaging. The projected drop-out rate is 25%, for a total of 900 patients treated per allocation arm. The non-inferiority boundary was set at 0.05. Based on a 1-sided un-pooled z-test, with alpha=0.05, a sample size of n=446 per group will have 80% power to detect the specified noninferiority margin. Intention-to-treat analysis of the 2-yr invasive breast cancer rate will be conducted using all patients as randomized, and will be completed using Kaplan-Meier estimates, stratified by group, combined with Greenwood’s confidence interval. Several sensitivity analyses (per protocol, as-treated, and instrumental variable) are also planned to account for loss of follow-up, rejection of randomization allocation and withdrawals. Present and target accrual: Trial accrual as of 7/1/20 is 540 randomized patients from 84 activated Alliance for Clinical Trials in Oncology sites. Despite logistical challenges posed by the COVID-19 crisis, patients continue to be recruited to the COMET trial. Over 80% of patients have sample sets/images stored in the tissue and image repositories. This trial will provide definitive clinical, quality of life and biomarker evidence regarding the trade-offs of surgery vs AM in patients with low-risk DCIS. Support: CER-1503-29572; https://acknowledgments.alliancefound.org Contact: Thomas Lynch (Project Manager) - thomas.lynch2@duke.edu Citation Format: Thomas Lynch, Ann Partridge, Alastair Thompson, Elizabeth Frank, Donna Pinto, Deborah Collyar, Desiree Basila, Louise Davies, Jenny Donovan, Terry Hyslop, Linda McCall, Marc Ryser, Taylor O' Donnell, Anna Weiss, Shelley Hwang. Comparing an operation to monitoring, with or without endocrine therapy (COMET): A prospective randomized trial for low-risk DCIS (AFT-25) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr OT-08-02.

Hernández Rupérez MB

Chrissy Vogeley

Tony Gentry

L. M. Johnson

Garland A. Ludy

Chaim D. URBACH

Anita Longley

Ot. Vlaïcou