BACKGROUND: Bone mineral density (BMD) is a measure of skeletal health that may foretell disorders like osteoporosis.METHODS: To reduce bone losses on Earth, treatments include exercise, diet, and drugs. Each impact osteoblast and osteoclast activity dictates skeletal remodeling and subsequent BMD changes. BMD loss is a concern during spaceflight. For astronauts, low BMD undermines in-flight tasks and compromises their postflight health.RESULTS: While bisphosphonates exhibited promise as an in-flight bone loss treatment, study results are mixed, and this class of drugs has numerous side-effects. While the role antiresorptive agents play in reducing BMD loss is discussed, this review focuses on exercise-induced strains and nutrition, two in-flight treatments without bisphosphonates’ side-effects.DISCUSSION: Evidence supports in-flight exercise and a healthy diet with vitamin D and Ca+2 supplementation to limit BMD loss. This review suggests how exercise and nutrition may limit BMD loss during spaceflight. Also discussed is an in-flight version of the inertial exercise trainer (IET; Impulse Technologies, Knoxville TN). By imparting high bone-strain magnitudes, rates, and frequencies with less mass, footprint, and power needs than other forms of in-flight resistance exercise hardware, the IET warrants inquiry for use aboard future long-term spaceflights.Caruso J, Patel N, Wellwood J, Bollinger L. Impact of exercise-induced strains and nutrition on bone mineral density in spaceflight and on the ground. Aerosp Med Hum Perform. 2023; 94(12):923–933.

2022-01-01·Clinical Cancer Research

Phase I/IIa Trial of BMS-986148, an Anti-mesothelin Antibody–drug Conjugate, Alone or in Combination with Nivolumab in Patients with Advanced Solid Tumors

Article

作者: Rottey, Sylvie ; Vezina, Heather ; Duca, Matteo ; Clarke, Jeffrey ; Santoro, Armando ; Koyama, Takafumi ; Lolkema, Martijn ; de Souza, Paul ; Aung, Kyaw ; Curigliano, Giuseppe ; Heinhuis, Kimberley M. ; Machiels, Jean-Pascal ; Brown, Michelle ; Markman, Ben ; Millward, Michael ; Chu, Quincy Siu-Chung ; Patel, Sandip Pravin ; He, Chunsheng

AbstractPurpose:To assess the safety and tolerability of BMS-986148, a mesothelin-directed antibody–drug conjugate (ADC) ± nivolumab, in patients with selected tumors.Patients and Methods:In an international phase I/IIa study [NCT02341625 (CA008-002)], patients received BMS-986148 monotherapy (0.1–1.6 mg/kg intravenously (i.v.) every 3 weeks or 0.4 or 0.6 mg/kg i.v. once weekly; n = 96) or BMS-986148 0.8 mg/kg + nivolumab 360 mg i.v. every 3 weeks (n = 30). The primary endpoint was safety and tolerability.Results:In CA008-002, the most common (≥ 10%) treatment-related adverse events (TRAEs) included increased aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase. Grade 3/4 TRAEs occurred in 42 patients (49%) receiving BMS-986148 every 3 weeks monotherapy, three (25%) receiving BMS-986148 once-weekly monotherapy, and 10 (33%) receiving BMS-986148 + nivolumab every 3 weeks. Overall, 17 of 126 patients (13%) discontinued because of a TRAE. The MTD of BMS-986148 was 1.2 mg/kg i.v. every 3 weeks. The safety profile of BMS-986148 + nivolumab was similar to that of BMS-986148 monotherapy (0.8 mg/kg). Active ADC exposures increased in a dose-proportional manner with both dosing regimens (every 3 weeks and once weekly). Preliminary clinical activity was observed with BMS-986148 ± nivolumab. No association between mesothelin expression and response was detected.Conclusions:BMS-986148 ± nivolumab demonstrated a clinically manageable safety profile and preliminary evidence of clinical activity, supporting additional studies combining directed cytotoxic therapies with checkpoint inhibitors as potential multimodal therapeutic strategies in patients with advanced solid tumors.

1985-11-01·Research communications in chemical pathology and pharmacology

Effects of certain CNS depressants and verapamil on cGMP in the cerebellum of rats.

Article

作者: Dodson, R A ; Johnson, W E ; Szot, P

The influence, individually and in combination, of certain general CNS depressants, Ca+2, A23187, and verapamil on rat cerebellar cGMP was studied. When Ca+2 was given to rats treated with ethanol, ether, or pentobarbital a minor increase in cGMP resulted. However, A23187 alone, or with Ca+2 did not produce a rise in cGMP levels in the presence of those drugs. A similar effect was seen with verapamil. Increasing doses of pentobarbital with verapamil enhanced the inhibition of cGMP.

项与 CA-002 相关的新闻（医药）

2021-03-09

·BioSpace

Camallergy Awarded £1.1 M Funding Under Innovate UK Biomedical Catalyst Award for Novel Peanut Allergy Treatment

March 9, 2021 06:18 UTC CAMBRIDGE, United Kingdom--(BUSINESS WIRE)-- Cambridge Allergy Ltd (“Camallergy” or “the Company”), a biopharmaceutical company dedicated to providing innovative, patient-centric treatments for life-threatening food allergies, today announced it has been awarded £1.1M funding under the Innovate UK Biomedical Catalyst Award program administered by Innovate UK, the United Kingdom’s research and innovation agency. The £1.1M in non-dilutive funding will be used to accelerate the Company’s peanut allergy immunotherapy, CA002, for planned Phase 3 clinical trials. The project commences in the first quarter of 2021, and as part of the project’s success, the Company intends to file its investigation new drug application with the FDA and submit a clinical trials application to the MHRA and EMA. “This innovation award is further testament to Camallergy’s leadership and capabilities in the field of peanut allergy immunotherapy,” said Dr Sarah Oakley-Mudge, Director of Clinical Development. “With the only cGMP-certified manufacturing facility in Europe dedicated to producing peanut allergy immunotherapy for human use we believe we are well positioned to utilize this award to accelerate the development of CA002 into Phase 3 trials and towards commercialization”. H.C. Wainwright Global Life Sciences Conference, March 9-10, 2021 Baxter Phillips III, Chief Executive Officer of Camallergy, will present at the virtual H.C. Wainwright Global Life Sciences Conference taking place March 9-10, 2021. The video webcast presentation will be available for viewing on demand beginning Tuesday, March 9, 2021, at 7:00 AM ET for those registered for the conference. In addition to the presentation, management will be available to participate in virtual one-on-one meetings with qualified members of the investor community who are registered to attend the conference. For more information about the event, please visit the conference website: . About Camallergy Camallergy (Cambridge Allergy Ltd) is a biopharmaceutical company dedicated to providing innovative, patient-centric treatments to address the millions of patients suffering worldwide from food allergies. Camallergy’s lead product, CA002, is a second-generation novel oral immunotherapy for the treatment of peanut allergy designed to offer “bite-proof” protection to patients within 14 weeks of therapy. The Company’s unique intellectual property and treatment regimen are based on the clinical work initiated at Cambridge University Hospitals NHS Foundation Trust in Cambridge, UK. For more information, visit . View source version on businesswire.com:

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2021-01-08

·BioSpace

Camallergy's UK Based Manufacturing Facility Receives cGMP Licences for Peanut Allergy Treatment

Jan. 8, 2021 07:00 UTC CAMBRIDGE, England--(BUSINESS WIRE)-- Cambridge Allergy Ltd (“Camallergy” or “the Company”), a biopharmaceutical company dedicated to providing innovative, patient-centric treatments for life-threatening food allergies, today announced that its manufacturing facility outside of Portsmouth, United Kingdom was approved by the MHRA, the Medicines and Healthcare products Regulatory Agency, to manufacture its proprietary peanut allergy treatment under current Good Manufacturing Practices (cGMP) standards. “This clearance is a pivotal regulatory milestone that further supports Camallergy’s leadership and capabilities in the field of peanut allergy immunotherapy with the only cGMP-certified manufacturing facility in Europe producing peanut oral immunotherapy,” said Sherden Timmins, Chief Technology Officer. The new manufacturing facility will handle cGMP production of CA002, the Company’s proprietary peanut allergy treatment, for planned pivotal clinical trials. Additionally, the facility will supply an ongoing early access programme. Camallergy’s manufacturing facility is the only European GMP production facility for peanut oral immunotherapy and is scalable for commercial production. It also complies with US and EU pharmaceutical regulations. “The completion of this state-of-the-art-facility manufacturing facility is a significant achievement for Camallergy and a testament to our team’s dedication and expertise. With this significant milestone achieved, we are in position to pursue our IND (Investigational New Drug) and IMPD (Investigational Medicinal Product Dossier) applications in the US, UK, and EU to initiate our pivotal Phase 3 studies planned to commence this year upon the closing of our Series B round,” commented Baxter Phillips, CEO of Camallergy. “Our recent US market research conducted with prominent key opinion leaders throughout the US shows a strong preference for CA002’s safety and tolerability profile compared to other peanut immunotherapy treatments. We are excited to progress this treatment to market so that the millions of children suffering with peanut allergy will have the choice of a safe and tolerable immunotherapy.” About Camallergy Camallergy (Cambridge Allergy Ltd) is a biopharmaceutical company dedicated to providing innovative, patient centric treatments to address the millions of patients suffering worldwide from food allergies. Camallergy’s lead product, CA002, is a novel oral immunotherapy for the treatment of peanut allergy designed to offer “bite-proof” protection to patients within 14 weeks of therapy. The Company’s unique intellectual property and treatment regimen are based on the clinical work initiated at Cambridge University Hospitals NHS Foundation Trust in Cambridge, UK. For more information, visit . View source version on businesswire.com:

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100 项与 CA-002 相关的药物交易

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