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CCNU-Dependent Potentiation of TRAIL/Apo2l-Induced Apoptosis in Human Glioma Cells Is P53-Independent but May Involve Enhanced Cytochrome C Release
Oncogene (2001) 20, 4128 ± 4137 ã 2001 Nature Publishing Group All rights reserved 0950 ± 9232/01 $15.00 www.nature.com/onc CCNU-dependent potentiation of TRAIL/Apo2L-induced apoptosis in human glioma cells is p53-independent but may involve enhanced cytochrome c release Till A RoÈ hn1, Bettina Wagenknecht1, Wilfried Roth1, Ulrike Naumann1, Erich Gulbins2, Peter H Krammer3, Henning Walczak4 and Michael Weller*,1 1Laboratory of Molecular Neuro-Oncology, Department of Neurology, University of TuÈbingen, Medical School, TuÈbingen, Germany; 2Institute of Physiology, University of TuÈbingen, Medical School, TuÈbingen, Germany; 3Department of Immunogenetics, German Cancer Research Center, Heidelberg, Germany; 4Department of Apoptosis Regulation, German Cancer Research Center, Heidelberg, Germany Death ligands such as CD95 ligand (CD95L) or tumor apy may be an eective therapeutic strategy for these necrosis factor-related apoptosis-inducing ligand/Apo2 lethal neoplasms. Oncogene (2001) 20, 4128 ± 4137. ligand (TRAIL/Apo2L) induce apoptosis in radio- chemotherapy-resistant human malignant glioma cell Keywords: brain; apoptosis; neuroimmunology; cyto- lines. The death-signaling TRAIL receptors 2 kines; immunotherapy (TRAIL-R2/death receptor (DR) 5) and TRAIL-R1/ DR4 were expressed more abundantly than the non- death-inducing (decoy) receptors TRAIL-R3/DcR1 and Introduction TRAIL-R4/DcR2 in 12 human glioma cell lines. Four of the 12 cell lines were TRAIL/Apo2L-sensitive in the Death receptor targeting is an attractive approach of absence of a protein synthesis inhibitor, cycloheximide experimental treatment for solid tumors that are (CHX). Three of the 12 cell lines were still TRAIL/ resistant to radiotherapy and chemotherapy, including Apo2L-resistant in the presence of CHX. -
(12) Patent Application Publication (10) Pub. No.: US 2006/0110428A1 De Juan Et Al
US 200601 10428A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2006/0110428A1 de Juan et al. (43) Pub. Date: May 25, 2006 (54) METHODS AND DEVICES FOR THE Publication Classification TREATMENT OF OCULAR CONDITIONS (51) Int. Cl. (76) Inventors: Eugene de Juan, LaCanada, CA (US); A6F 2/00 (2006.01) Signe E. Varner, Los Angeles, CA (52) U.S. Cl. .............................................................. 424/427 (US); Laurie R. Lawin, New Brighton, MN (US) (57) ABSTRACT Correspondence Address: Featured is a method for instilling one or more bioactive SCOTT PRIBNOW agents into ocular tissue within an eye of a patient for the Kagan Binder, PLLC treatment of an ocular condition, the method comprising Suite 200 concurrently using at least two of the following bioactive 221 Main Street North agent delivery methods (A)-(C): Stillwater, MN 55082 (US) (A) implanting a Sustained release delivery device com (21) Appl. No.: 11/175,850 prising one or more bioactive agents in a posterior region of the eye so that it delivers the one or more (22) Filed: Jul. 5, 2005 bioactive agents into the vitreous humor of the eye; (B) instilling (e.g., injecting or implanting) one or more Related U.S. Application Data bioactive agents Subretinally; and (60) Provisional application No. 60/585,236, filed on Jul. (C) instilling (e.g., injecting or delivering by ocular ion 2, 2004. Provisional application No. 60/669,701, filed tophoresis) one or more bioactive agents into the Vit on Apr. 8, 2005. reous humor of the eye. Patent Application Publication May 25, 2006 Sheet 1 of 22 US 2006/0110428A1 R 2 2 C.6 Fig. -
Revlimid U.S. Full Prescribing Information
HIGHLIGHTS OF PRESCRIBING INFORMATION • FL or MZL: 20 mg once daily orally on Days 1-21 of repeated 28-day cycles for up to These highlights do not include all the information needed to use REVLIMID® safely 12 cycles (2.4). and effectively. See full prescribing information for REVLIMID. • Renal impairment: Adjust starting dose based on the creatinine clearance value (2.6). • For concomitant therapy doses, see Full Prescribing Information (2.1, 2.4, 14.1, 14.4). REVLIMID (lenalidomide) capsules, for oral use Initial U.S. Approval: 2005 ------------------------- DOSAGE FORMS AND STRENGTHS ------------------------- Capsules: 2.5 mg, 5 mg, 10 mg, 15 mg, 20 mg, and 25 mg (3). WARNING: EMBRYO-FETAL TOXICITY, HEMATOLOGIC TOXICITY, -------------------------------- CONTRAINDICATIONS -------------------------------- and VENOUS and ARTERIAL THROMBOEMBOLISM • Pregnancy (Boxed Warning, 4.1, 5.1, 8.1). See full prescribing information for complete boxed warning. • Demonstrated severe hypersensitivity to lenalidomide (4.2, 5.9, 5.15). EMBRYO-FETAL TOXICITY --------------------------- WARNINGS AND PRECAUTIONS --------------------------- • Lenalidomide, a thalidomide analogue, caused limb abnormalities in a developmental monkey study similar to birth defects caused by thalidomide • Increased Mortality: serious and fatal cardiac adverse reactions occurred in patients in humans. If lenalidomide is used during pregnancy, it may cause birth with CLL treated with REVLIMID (lenalidomide) (5.5). defects or embryo-fetal death. • Second Primary Malignancies (SPM): Higher incidences of SPM were observed in • Pregnancy must be excluded before start of treatment. Prevent pregnancy controlled trials of patients with MM receiving REVLIMID (5.6). during treatment by the use of two reliable methods of contraception (5.1). • Increased Mortality: Observed in patients with MM when pembrolizumab was added REVLIMID is available only through a restricted distribution program, called the to dexamethasone and a thalidomide analogue (5.7). -
ACNU-Based Chemotherapy for Recurrent Glioma in the Temozolomide Era
Zurich Open Repository and Archive University of Zurich Main Library Strickhofstrasse 39 CH-8057 Zurich www.zora.uzh.ch Year: 2009 ACNU-based chemotherapy for recurrent glioma in the temozolomide era Happold, C Abstract: No standard of care for patients with recurrent glioblastoma has been defined since temo- zolomide has become the treatment of choice for patients with newly diagnosed glioblastoma. This has renewed interest in the use of nitrosourea-based regimens for patients with progressive or recurrent dis- ease. The most commonly used regimens are carmustine (BCNU) monotherapy or lomustine (CCNU) combined with procarbazine and vincristine (PCV). Here we report our institutional experience with nimustine (ACNU) alone (n = 14) or in combination with other agents (n = 18) in 32 patients with glioblastoma treated previously with temozolomide. There were no complete and two partial responses. The progression-free survival (PFS) rate at 6 months was 20% and the survival rate at 12 months 26%. Grade III or IV hematological toxicity was observed in 50% of all patients and led to interruption of treatment in 13% of patients. Non-hematological toxicity was moderate to severe and led to interruption of treatment in 9% of patients. Thus, in this cohort of patients pretreated with temozolomide, ACNU failed to induce a substantial stabilization of disease in recurrent glioblastoma, but caused a notable hematotoxicity. This study does not commend ACNU as a therapy of first choice for patients with recurrent glioblastomas pretreated with temozolomide. DOI: https://doi.org/10.1007/s11060-008-9728-9 Posted at the Zurich Open Repository and Archive, University of Zurich ZORA URL: https://doi.org/10.5167/uzh-10588 Journal Article Originally published at: Happold, C (2009). -
Method and Compositions for the Treatment of Tumors Comprising a Calcium Channel Blocker Compound of the Dlhydropyridlne Class and a Platinum Coordination Compound
turopaiscnes patentamt European Patent Office © Publication number: 0 221 382 Office europeen des brevets A1 (2) EUROPEAN PATENT APPLICATION © Application number: 86113897.2 © Int. CI.4: A61K 33/24 , ~ //(A61K33/24,31:44) © Date of filing: 07.10.86 © Priority: 10.10.85 US 786321 © Applicant: THE BOARD OF GOVERNORS OF WAYNE STATE UNIVERSITY © Date of publication of application: 5050 Cass Avenue 13.05.87 Bulletin 87/20 Detroit Michigan 48202(US) © Designated Contracting States: @ Inventor: Honn, Kenneth V. AT BE CH DE ES FR GB IT LI LU NL SE 1889 Stanhope Grosse Polnte Woods, Michigan 48236(US) Inventor: Tayior, John D. 1408 Joliet Place Detroit, Michigan 48207(US) Inventor: Onoda, James M. 212 Baker Street No. 203, Royal Oak, Michigan 48067(US) © Representative: Patentanwalte GrUnecker, Kinkeidey, Stockmalr & Partner Maximllianstrasse 58 D-8000 MUnchen 22(DE) «y Method and compositions for the treatment of tumors comprising a calcium channel blocker compound of the dlhydropyridlne class and a platinum coordination compound. (jy The invention relates to compositions for the vherein R, and R2 are methyl groups, R, and R» are treatment of malignant tumors in a mammal which ilkyi or alkyloxyalkylene groups containing I to 8 comprise: :arbdn atoms and R5 and R« are hydrogen or one or (a) a calcium channel blocker compound of wo electron withdrawing substituents; and the dihydropyridine class selected from the group (b) a platinum coordination compound which ^consisting of las antitumor properties in humans wherein the veight ratio of the calcium channel blocker com- x>und to the platinum coordination compound is >etween I and 1000 and 10 to I. -
Revlimid-INN Lenalidomide
ANNEX I SUMMARY OF PRODUCT CHARACTERISTICS 1 This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 4.8 for how to report adverse reactions. 1. NAME OF THE MEDICINAL PRODUCT Revlimid 2.5 mg hard capsules Revlimid 5 mg hard capsules Revlimid 7.5 mg hard capsules Revlimid 10 mg hard capsules Revlimid 15 mg hard capsules Revlimid 20 mg hard capsules Revlimid 25 mg hard capsules 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Revlimid 2.5 mg hard capsules Each capsule contains 2.5 mg of lenalidomide. Excipient(s) with known effect Each capsule contains 73.5 mg of lactose (as anhydrous lactose). Revlimid 5 mg hard capsules Each capsule contains 5 mg of lenalidomide. Excipient(s) with known effect Each capsule contains 147 mg of lactose (as anhydrous lactose). Revlimid 7.5 mg hard capsules Each capsule contains 7.5 mg of lenalidomide. Excipient(s) with known effect Each capsule contains 144.5 mg of lactose (as anhydrous lactose). Revlimid 10 mg hard capsules Each capsule contains 10 mg of lenalidomide. Excipient(s) with known effect Each capsule contains 294 mg of lactose (as anhydrous lactose). Revlimid 15 mg hard capsules Each capsule contains 15 mg of lenalidomide. Excipient(s) with known effect Each capsule contains 289 mg of lactose (as anhydrous lactose). Revlimid 20 mg hard capsules Each capsule contains 20 mg of lenalidomide. Excipient(s) with known effect Each capsule contains 244.5 mg of lactose (as anhydrous lactose). -
Overcoming the Immunosuppressive Tumor Microenvironment in Multiple Myeloma
cancers Review Overcoming the Immunosuppressive Tumor Microenvironment in Multiple Myeloma Fatih M. Uckun 1,2,3 1 Norris Comprehensive Cancer Center and Childrens Center for Cancer and Blood Diseases, University of Southern California Keck School of Medicine (USC KSOM), Los Angeles, CA 90027, USA; [email protected] 2 Department of Developmental Therapeutics, Immunology, and Integrative Medicine, Drug Discovery Institute, Ares Pharmaceuticals, St. Paul, MN 55110, USA 3 Reven Pharmaceuticals, Translational Oncology Program, Golden, CO 80401, USA Simple Summary: This article provides a comprehensive review of new and emerging treatment strategies against multiple myeloma that employ precision medicines and/or drugs capable of improving the ability of the immune system to prevent or slow down the progression of multiple myeloma. These rationally designed new treatment methods have the potential to change the therapeutic landscape in multiple myeloma and improve the long-term survival outcome. Abstract: SeverFigurel cellular elements of the bone marrow (BM) microenvironment in multiple myeloma (MM) patients contribute to the immune evasion, proliferation, and drug resistance of MM cells, including myeloid-derived suppressor cells (MDSCs), tumor-associated M2-like, “alter- natively activated” macrophages, CD38+ regulatory B-cells (Bregs), and regulatory T-cells (Tregs). These immunosuppressive elements in bidirectional and multi-directional crosstalk with each other inhibit both memory and cytotoxic effector T-cell populations as well as natural killer (NK) cells. Immunomodulatory imide drugs (IMiDs), protease inhibitors (PI), monoclonal antibodies (MoAb), Citation: Uckun, F.M. Overcoming the Immunosuppressive Tumor adoptive T-cell/NK cell therapy, and inhibitors of anti-apoptotic signaling pathways have emerged as Microenvironment in Multiple promising therapeutic platforms that can be employed in various combinations as part of a rationally Myeloma. -
In Relapsed Or Refractory Diffuse
Dührsen et al. Blood Cancer Journal (2021) 11:95 https://doi.org/10.1038/s41408-021-00485-5 Blood Cancer Journal CORRESPONDENCE Open Access Phase I/II trial of lenalidomide, methotrexate, leucovorin, cytarabine, and rituximab (LeMLAR) in relapsed or refractory diffuse large B cell lymphoma Ulrich Dührsen 1, Mareike Tometten2,FrankKroschinsky3, Arnold Ganser4,StefanIbach5, Stefanie Bertram6 and Andreas Hüttmann 1 Dear Editor, ≥2.5 mg/dl, serum aspartate [AST] or alanin amino- Lenalidomide has moderate activity in relapsed or transferase [ALT] >4× upper limit of normal [ULN]), refractory diffuse large B cell lymphoma (r/rDLBCL)1. active hepatitis B or C, human immunodeficiency virus Based on the COMLA regimen used in the 1970s and infection, any other uncontrolled infection, as well as 1980s2, we combined lenalidomide with methotrexate pregnancy and nursing period. All patients gave written (plus leucovorin), cytarabine, and rituximab (LeMLAR) in informed consent. The LeMLAR regimen (Fig. 1) com- a phase I/II trial. Lenalidomide induces apoptosis and cell prised up to six 28-day cycles consisting of lenalidomide cycle arrest in the G0/G1 phase3. After discontinuation, (day 1–21), methotrexate (5–10 min i.v. bolus; day 1, 8, surviving cells start to proliferate and become susceptible 15), leucovorin (four oral 45 mg doses six hours apart, to the S-phase-specific agents methotrexate and cytar- starting 24 h after methotrexate), cytarabine (5-10 min i.v. 1234567890():,; 1234567890():,; 1234567890():,; 1234567890():,; abine administered in the subsequent cycle. Because of bolus; day 1, 8, 15), and rituximab (375 mg/m², day 1). All – low toxicity for immune effector cells4 6, these drugs are patients received prophylactic enoxaparin (40 mg s.c.). -
Repositioning Fda-Approved Drugs in Combination with Epigenetic Drugs to Reprogram Colon Cancer Epigenome
Author Manuscript Published OnlineFirst on December 15, 2016; DOI: 10.1158/1535-7163.MCT-16-0588 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. REPOSITIONING FDA-APPROVED DRUGS IN COMBINATION WITH EPIGENETIC DRUGS TO REPROGRAM COLON CANCER EPIGENOME Noël J.-M. Raynal1,2, Elodie M. Da Costa2, Justin T. Lee1, Vazganush Gharibyan3, Saira Ahmed3, Hanghang Zhang1,Takahiro Sato1, Gabriel G. Malouf4, and Jean-Pierre J. Issa1 1Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, 3307 North Broad Street, Philadelphia, PA, 19140, USA. 2Département de pharmacologie, Université de Montréal and Sainte-Justine University Hospital Research Center, 3175, Chemin de la Côte-Sainte- Catherine, Montréal (Québec) H3T 1C5, Canada. 3Department of Leukemia, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA. 4Department of Medical Oncology, Groupe Hospitalier Pitié-Salpêtrière, University Pierre and Marie Curie (Paris VI), Institut Universitaire de cancérologie, AP-HP, Paris, France. Note: Supplementary data for this article are available at Molecular Cancer Therapeutics Online (http://mct.aacrjournals.org/). Corresponding Author: Noël J.-M. Raynal, Département de Pharmacologie, Université de Montréal , Centre de recherche de l’Hôpital Sainte-Justine, 3175, Chemin de la Côte-Sainte-Catherine, Montréal (Québec), H3T 1C5, Canada. Phone : (514) 345-4931 ext. 6763. Email : [email protected] Running title: High-throughput screening for epigenetic drug combinations Key words: Drug repurposing, Drug combination, High-throughput drug screening, Epigenetic therapy The authors declare no potential conflicts of interest. 1 Downloaded from mct.aacrjournals.org on September 23, 2021. -
Safety and Tolerability of Lenalidomide Maintenance in Post-Transplant
www.nature.com/bmt ARTICLE OPEN Safety and tolerability of lenalidomide maintenance in post-transplant acute myeloid leukemia and high-risk myelodysplastic syndrome ✉ Brian Pham 1 , Rasmus Hoeg1, Rajeev Krishnan2, Carol Richman1, Joseph Tuscano1 and Mehrdad Abedi 1 © The Author(s) 2021 Relapse after allogeneic stem cell transplant in unfavorable-risk acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS) portends a poor prognosis. We conducted a single-center phase I dose-escalation study with lenalidomide maintenance in high-risk MDS and AML patients after allogeneic transplantation. Sixteen patients enrolled in a “3 + 3” study design starting at lenalidomide 5 mg daily, increasing in increments of 5 mg up to 15 mg. Lenalidomide was given for 21 days of a 28-day cycle for a total of six cycles. Most common dose-limiting toxicities were lymphopenia, diarrhea, nausea, and neutropenia. Two patients had acute graft-versus-host disease (GVHD), and five patients developed chronic GVHD. The maximum tolerated dose was 10 mg, after dose-limiting toxicities were seen in the 15 mg group. Two dose-limiting toxicities were seen from development of acute GVHD and grade III diarrhea. Limitations of the study include time to initiation at 6 months post transplant, as many high-risk patients will have relapsed within this time frame before starting maintenance lenalidomide. Overall, lenalidomide was well tolerated with minimal GVHD and low rates of relapse rates, warranting further study. Bone Marrow Transplantation; https://doi.org/10.1038/s41409-021-01444-1 INTRODUCTION mutations, the role for post-transplant maintenance is less clear. Allogeneic stem cell transplantation (allo-SCT) remains the best Hypomethylating agents have been studied for post allo-SCT option for cure in most patients with unfavorable-risk acute maintenance therapy. -
REVLIMID (Lenalidomide) 5 Mg, 10 Mg, 15 Mg and 25 Mg Capsules
® 1 REVLIMID (lenalidomide) 2 5 mg, 10 mg, 15 mg and 25 mg capsules 3 WARNINGS: 4 1. POTENTIAL FOR HUMAN BIRTH DEFECTS 5 2. HEMATOLOGIC TOXICITY (NEUTROPENIA AND 6 THROMBOCYTOPENIA) 7 3. DEEP VENOUS THROMBOSIS AND PULMONARY EMBOLISM 8 9 POTENTIAL FOR HUMAN BIRTH DEFECTS 10 WARNING: POTENTIAL FOR HUMAN BIRTH DEFECTS 11 LENALIDOMIDE IS AN ANALOGUE OF THALIDOMIDE. THALIDOMIDE IS 12 A KNOWN HUMAN TERATOGEN THAT CAUSES SEVERE LIFE 13 THREATENING HUMAN BIRTH DEFECTS. IF LENALIDOMIDE IS TAKEN 14 DURING PREGNANCY, IT MAY CAUSE BIRTH DEFECTS OR DEATH TO AN 15 UNBORN BABY. FEMALES SHOULD BE ADVISED TO AVOID PREGNANCY 16 WHILE TAKING REVLIMID® (lenalidomide). 17 Special Prescribing Requirements 18 BECAUSE OF THIS POTENTIAL TOXICITY AND TO AVOID FETAL 19 EXPOSURE TO REVLIMID® (lenalidomide), REVLIMID® (lenalidomide) IS 20 ONLY AVAILABLE UNDER A SPECIAL RESTRICTED DISTRIBUTION 21 PROGRAM. THIS PROGRAM IS CALLED "RevAssist®." UNDER THIS 22 PROGRAM, ONLY PRESCRIBERS AND PHARMACISTS REGISTERED WITH 23 THE PROGRAM CAN PRESCRIBE AND DISPENSE THE PRODUCT. IN 24 ADDITION, REVLIMID® (lenalidomide) MUST ONLY BE DISPENSED TO 25 PATIENTS WHO ARE REGISTERED AND MEET ALL THE CONDITIONS OF 26 THE RevAssist® PROGRAM. 27 PLEASE SEE THE FOLLOWING INFORMATION FOR PRESCRIBERS, 28 FEMALE PATIENTS, AND MALE PATIENTS ABOUT THIS RESTRICTED 29 DISTRIBUTION PROGRAM. 30 RevAssist® PROGRAM DESCRIPTION 31 Prescribers 32 REVLIMID® (lenalidomide) can be prescribed only by licensed prescribers who are 33 registered in the RevAssist® program and understand the potential risk of teratogenicity if 34 lenalidomide is used during pregnancy. 1 35 Effective contraception must be used by female patients of childbearing potential for at 36 least 4 weeks before beginning REVLIMID® (lenalidomide) therapy, during 37 REVLIMID® (lenalidomide) therapy, during dose interruptions and for 4 weeks 38 following discontinuation of REVLIMID® (lenalidomide) therapy. -
Ovid MEDLINE(R)
Supplementary material BMJ Open Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily <1946 to September 16, 2019> # Searches Results 1 exp Hypertension/ 247434 2 hypertens*.tw,kf. 420857 3 ((high* or elevat* or greater* or control*) adj4 (blood or systolic or diastolic) adj4 68657 pressure*).tw,kf. 4 1 or 2 or 3 501365 5 Sex Characteristics/ 52287 6 Sex/ 7632 7 Sex ratio/ 9049 8 Sex Factors/ 254781 9 ((sex* or gender* or man or men or male* or woman or women or female*) adj3 336361 (difference* or different or characteristic* or ratio* or factor* or imbalanc* or issue* or specific* or disparit* or dependen* or dimorphism* or gap or gaps or influenc* or discrepan* or distribut* or composition*)).tw,kf. 10 or/5-9 559186 11 4 and 10 24653 12 exp Antihypertensive Agents/ 254343 13 (antihypertensiv* or anti-hypertensiv* or ((anti?hyperten* or anti-hyperten*) adj5 52111 (therap* or treat* or effective*))).tw,kf. 14 Calcium Channel Blockers/ 36287 15 (calcium adj2 (channel* or exogenous*) adj2 (block* or inhibitor* or 20534 antagonist*)).tw,kf. 16 (agatoxin or amlodipine or anipamil or aranidipine or atagabalin or azelnidipine or 86627 azidodiltiazem or azidopamil or azidopine or belfosdil or benidipine or bepridil or brinazarone or calciseptine or caroverine or cilnidipine or clentiazem or clevidipine or columbianadin or conotoxin or cronidipine or darodipine or deacetyl n nordiltiazem or deacetyl n o dinordiltiazem or deacetyl o nordiltiazem or deacetyldiltiazem or dealkylnorverapamil or dealkylverapamil