Mifepristone Versus Misoprostol for Cervical Preparation Prior to Procedural Abortion at 12 to 16 Weeks' Gestation in an Academic Medical Center: a Randomized Controlled Pilot Trial

The Investigator team hypothesizes that in a randomized trial comparing mifepristone-alone or misoprostol-alone for cervical preparation for procedural abortions at 12 to 16 weeks in hospital-based care, the proportion of patients who achieve successful cervical dilation will be different between the study groups.

Start Date01 Oct 2024

Sponsor / Collaborator

Montefiore Medical Center

NCT06394999 / Not yet recruitingPhase 3IIT

Prospective Phase III Multi-center Open-label Study of the Efficacy, Safety, and Acceptability of Mifepristone 50 mg Once-weekly as a Contraceptive

Participants in the study will use mifepristone 50 mg once-a-week for one year as a contraceptive. With this, we want to confirm that the chances of getting pregnant while using this contraceptive are very small. We also want to demonstrate that the use of mifepristone is safe, and it does not lead to any severe health problems. We expect fewer side effects compared to other frequently used contraceptives with hormones. Mifepristone does not contain these hormones. It is important to know how people experience that use of one tablet a week.

Start Date01 Sep 2024

Sponsor / Collaborator

Academisch Ziekenhuis Leiden

[+2]

100 Clinical Results associated with PR x GR

100 Translational Medicine associated with PR x GR

0 Patents (Medical) associated with PR x GR

672

Literatures (Medical) associated with PR x GR

18 Oct 2024·Acta ophthalmologica

Responsiveness of anti-VEGF treatment for polypoidal choroidal vasculopathy based on aqueous humour proteomics: A preliminary study.

Article

Author: Meng, Lihui ; Duan, Jialiang ; Chen, Huan ; Zhou, Huiying ; Li, Zhiqing ; Xing, Dongjun ; Wang, Yuelin ; Geng, Shuang ; Ma, Jingxue ; Han, Ruoan ; Chen, Youxin

OBJECTIVESPatients with polypoidal choroidal vasculopathy (PCV) exhibit variability in response to anti-VEGF therapy. This study aimed to analyse the aqueous humour proteomic profiles of PCV patients and provide preliminary insights for the identification of biomarkers associated with anti-VEGF drug responsiveness.METHODSPCV patients who were treatment-naïve or untreated for more than 3 months were prospectively recruited from two hospitals in Beijing and Tianjin. Based on the relative changes in central macular thickness (ΔCMT/baseline-CMT) before and after anti-VEGF treatment, the PCV patients were divided into a good response (GR) group (≤-25%) and a poor response (PR) group (>-25%). Aqueous humour proteomics was performed by the Data-independent Acquisition-Mass Spectrometry (DIA-MS) method, and differentially expressed proteins (DEPs) analysis between the different PCV groups and the control group was conducted. Key DEPs were selected for preliminary validation in the aqueous humour using the Luminex method retrospectively.RESULTSA total of 31 PCV patients (31 eyes) were included, 13 in the GR group and 18 in the PR group. A total of 414 DEPs were identified, including 36 significantly upregulated proteins, such as G protein regulatory factor 10 (RGS10), podocin (PODN) and epidermal growth factor (EGF), and 32 downregulated proteins, including RAB11FIP4 (Rab11 family-interacting protein 4), α-synuclein (SNCA), haemoglobin subunit δ (HBD) and interleukin 6 (IL6). Compared to the cataract control group (10 eyes), 134 proteins were significantly upregulated, and 72 were downregulated. KEGG pathway enrichment analysis revealed that the GR and PR groups differ in terms of cell communication, and cell signal transduction. Protein-protein interaction analysis revealed interactions between EGF and various DEPs. Validation of aqueous humour proteins using the Luminex method revealed that changes in the levels of EGF were associated with the anti-VEGF treatment response in PCV patients.CONCLUSIONSPCV patients with good or poor anti-VEGF responses exhibit distinct aqueous humour proteomic profiles. Aqueous EGF may serve as a biomarker for the 'precise treatment' of PCV.

01 Oct 2024·The Journal of Steroid Biochemistry and Molecular Biology

Glucocorticoid receptor-mediated oncogenic activity is dependent on breast cancer subtype

Article

Author: Clark, Abigail B ; Conzen, Suzanne D

Breast cancer incidence has been steadily rising and is the leading cause of cancer death in women due to its high metastatic potential. Individual breast cancer subtypes are classified by both cell type of origin and receptor expression, namely estrogen, progesterone and human epidermal growth factor receptors (ER, PR and HER2). Recently, the importance and context-dependent role of glucocorticoid receptor (GR) expression in the natural history and prognosis of breast cancer subtypes have been uncovered. In ER-positive breast cancer, GR expression is associated with a better prognosis as a result of ER-GR crosstalk. GR appears to modulate ER-mediated gene expression resulting in decreased tumor cell proliferation and a more indolent cancer phenotype. In ER-negative breast cancer, including GR-positive triple-negative breast cancer (TNBC), GR expression enhances migration, chemotherapy resistance and cell survival. In invasive lobular carcinoma, GR function is relatively understudied, and more work is required to determine whether lobular subtypes behave similarly to their invasive ductal carcinoma counterparts. Importantly, understanding GR signaling in individual breast cancer subtypes has potential clinical implications because of the recent development of highly selective GR non-steroidal ligands, which represent a therapeutic approach for modulating GR activity systemically.

01 Oct 2024·The Journal of Steroid Biochemistry and Molecular Biology

Glucocorticoid receptors orchestrate a convergence of host and cellular stress signals in triple negative breast cancer

Review

Author: Lange, Carol A ; Posani, Sai Harshita ; Gillis, Noelle E

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that lacks expression of the nuclear steroid receptors that bind estrogens (ER) and progestogens (PRs) and does not exhibit HER2 (Human epidermal growth factor 2) receptor overexpression. Even in the face of initially effective chemotherapies, TNBC patients often relapse. One primary cause for therapy-resistant tumor progression is the activation of cellular stress signaling pathways. The glucocorticoid receptor (GR), a corticosteroid-activated transcription factor most closely related to PR, is a mediator of both endocrine/host stress and local tumor microenvironment (TME)-derived and cellular stress responses. Interestingly, GR expression is associated with a good prognosis in ER+ breast cancer but predicts poor prognosis in TNBC. Classically, GR's transcriptional activity is regulated by circulating glucocorticoids. Additionally, GR is regulated by ligand-independent signaling events. Notably, the stress-activated protein kinase, p38 MAP kinase, phosphorylates GR at serine 134 (Ser134) in response to TME-derived growth factors and cytokines, including HGF and TGFβ1. Phospho-Ser134-GR (p-Ser134-GR) associates with cytoplasmic and nuclear signaling molecules, including 14-3-3ζ, aryl hydrocarbon receptors (AhR), and hypoxia-inducible factors (HIFs). Phospho-GR/HIF-containing transcriptional complexes upregulate gene sets whose protein products include the components of inducible oncogenic signaling pathways (PTK6) that further promote cancer cell survival, chemoresistance, altered metabolism, and migratory/invasive behavior in TNBC. Recent studies have implicated liganded p-Ser134-GR (p-GR) in dexamethasone-mediated upregulation of genes related to TNBC cell motility and dysregulated metabolism. Herein, we review the tumor-promoting roles of GR and discuss how both ligand-dependent and ligand-independent/stress signaling-driven inputs to p-GR converge to orchestrate metastatic TNBC progression.

News (Medical) associated with PR x GR

20 Oct 2023

·www.biospace.com

Res Nova Biologics Announces First Cancer Patient Treated with FloraStilbene™

Therapeutic Solutions International Immuno-Oncology Subsidiary Makes Abortion Pill-Based Drug Available by Prescription through Cure Stat Rx Compounding Pharmacy ELK CITY, Idaho--(BUSINESS WIRE)-- Therapeutic Solutions International, Inc. (TSOI), announced today the successful first treatment of a patient with FloraStilbene™, a patent pending formulation of the abortion pill’s active ingredient, RU486, and pterostilbene. The Company has been utilizing pterostilbene, a naturally occurring analog of resveratrol, found in blueberries, for the treatment of cancer and immune modulation for several years, including being granted a patent on synergies with conventional immunotherapies1. In May of this year, Res Nova signed a collaborative agreement with compounding pharmacy Cure Stat Rx for developing a compounded formulation of FloraStilbene™2. “I have worked with Dr. Ramesh Chigurupati, President, and CEO of Cure Stat Rx for many years and have always been impressed by the efficiency and excellence in ability to provide compounded drugs and formulations,” said Dr. James Veltmeyer, Chief Medical Officer of Res Nova Bio. “We look forward to offering FloraStilbene™ to all patients taking immunotherapy, chemotherapy, or radiation therapy that can benefit from immune stimulation of NK cells, T cells, and dendritic cells.” FloraStilbene™ has previously been shown to enhance immunotherapy of various tumors3, as well as chemotherapy efficacy4. “The strategic objective of Therapeutic Solutions International is to develop intellectual property, use it to seed a subsidiary company, and let the subsidiaries grow and flourish,” stated Timothy Dixon, President, and CEO of Therapeutic Solutions International. “I am extremely proud of the leadership role of Ms. Ramos who in the period of less than a year was able to take FloraStilbene™ from concept to patient. This is literally unheard of in traditional biotechnology development models.” In addition to Res Nova, Therapeutic Solutions International has multiple subsidiaries including a) Campbell Neurosciences, focused on the identification of suicidal propensities using a proprietary test and various interventions5; b) Breath Biologics, which is in discussions with the FDA for its filed Phase I/II trial in COPD6; c) CTE Biologics, which is advancing its clinical stage technology for treating Chronic Traumatic Encephalopathy7; and d) VasoSome Vascular, which is in preclinical development of mesenchymal stem cell derived exosomes for treatment of aortic aneurysms8. “I am thankful for our translational medicine team that has worked closely with Drs Veltmeyer and Chigurupati for making this first patient treatment a reality,” said Famela Ramos, President, and CEO of Res Nova Bio. “Although we plan on performing clinical trials to formally establish a level of efficacy, we believe it is imperative to get this drug into the hands of physicians as soon as possible, and we are thankful for having the opportunity to do this today.” About Therapeutic Solutions International, Inc. Therapeutic Solutions International is focused on immune modulation for the treatment of several specific diseases. The Company's corporate website is . 1 US9682047B2 - Augmentation of oncology immunotherapies by pterostilbene containing compositions - Google Patents 2 Therapeutic Solutions International Spin-Off Res Nova Bio Partners with Cure Stat Rx to Manufacture First in Class Breast Cancer Immunotherapy Product FloraStilbene™ | Business Wire 3 Novel Mechanism of Action of FloraStilbene Suggests Potential for Enhancing Efficacy of Checkpoint Inhibitor, CAR-T Therapies (pharmacytimes.com) 4 FloraStilbene™ Demonstrates Synergy with Conventional Chemotherapy and Immunotherapy in Reducing Triple Negative Breast Cancer | BioSpace 5 Therapeutic Solutions International Spin-Off Campbell Neurosciences Provides Progress Update in Quest for Addressing Suicide as a Medical Condition | Business Wire 6 Spinoff Breathe Biologics to Lead TSOI's Stem Cell Therapy Research | COPD News Today 7 Therapeutic Solutions International Launches Subsidiary Company to Commercialize Clinical Data and IND for Treatment of Chronic Traumatic Encephalopathy (CTE) with JadiCell Universal Adult Stem Cells | Business Wire 8 Therapeutic Solutions Launches VasoSome Vascular Inc. to Commercialize Aortic Aneurysm Treatment - Endovascular Today (evtoday.com)

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