Targeting the Mitochondrial Metabolic Network: a Promising Strategy in Cancer Treatment
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LYSODREN Safely and Effectively
HIGHLIGHTS OF PRESCRIBING INFORMATION -----------------------WARNINGS AND PRECAUTIONS------------------------ These highlights do not include all the information needed to use • Central Nervous System (CNS) Toxicity: Plasma concentrations LYSODREN safely and effectively. See full prescribing information for exceeding 20 mcg/mL are associated with a greater incidence of toxicity. LYSODREN. (5.2) • Adrenal Insufficiency: Institute steroid replacement as clinically LYSODREN® (mitotane) tablets, for oral use indicated. Measure free cortisol and corticotropin (ACTH) levels to Initial U.S. Approval: 1970 achieve optimal steroid replacement. (5.3) • Embryo-Fetal Toxicity: Can cause fetal harm. Advise women of WARNING: ADRENAL CRISIS IN THE SETTING OF SHOCK OR reproductive potential of the potential risk to a fetus and use of effective SEVERE TRAUMA contraception. (5.4, 8.1, 8.3) See full prescribing information for complete boxed warning. • Ovarian Macrocysts in Premenopausal Women: Advise women to seek medical advice if they experience gynecological symptoms such as In patients taking LYSODREN, adrenal crisis occurs in the setting of vaginal bleeding and/or pelvic pain. (5.5) shock or severe trauma and response to shock is impaired. Administer hydrocortisone, monitor for escalating signs of shock and discontinue -------------------------------ADVERSE REACTIONS------------------------------ LYSODREN until recovery. (2.2, 5.1) Common adverse reactions (≥15%) include: anorexia, nausea, vomiting and diarrhea; depression, dizziness or vertigo; and rash. (6) ---------------------------INDICATIONS AND USAGE---------------------------- LYSODREN is an adrenal cytotoxic agent indicated for the treatment of To report SUSPECTED ADVERSE REACTIONS, contact Bristol-Myers inoperable, functional or nonfunctional, adrenal cortical carcinoma. (1) Squibb at 1-800-721-5072 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. -
Methods for Predicting the Survival Time of Patients Suffering from a Lung Cancer
THETWO TORTOITUUSN 20180252720A1ULLUM HOLATIN ( 19) United States (12 ) Patent Application Publication ( 10) Pub . No. : US 2018 / 0252720 A1 DIEU -NOSJEAN et al. (43 ) Pub. Date : Sep . 6 , 2018 (54 ) METHODS FOR PREDICTING THE Publication Classification SURVIVAL TIME OF PATIENTS SUFFERING (51 ) Int . Ci. FROM A LUNG CANCER GOIN 33 /574 ( 2006 .01 ) (71 ) Applicants : INSERM (INSTITUT NATIONAL ( 52 ) U . S . CI. DE LA SANTE ET DE LA CPC .. GOIN 33 /57423 (2013 . 01) ; GOIN 2800/ 52 RECHERCHE MEDICALE ) , Paris ( 2013 . 01 ) (FR ) ; UNIVERSITE PARIS DESCARTES , Paris ( FR ) ; SORBONNE UNIVERSITE , Paris (57 ) ABSTRACT (FR ) ; UNIVERSITE PARIS DIDEROT - PARIS 7 , Paris ( FR ) ; The present invention relates to methods for predicting the ASSISTANCE survival time of patients suffering from a lung cancer . In PUBLIQUE -HOPITAUX DE PARIS particular , the present invention relates to a method for (ADHP ) , Paris (FR ) predicting the survival time of a subject suffering from a lung cancer comprising the steps of i) quantifying the ( 72 ) Inventors: Marie - Caroline DIEU - NOSJEAN , density of regulatory T ( Treg ) cells in a tumor tissue sample Paris (FR ) ; Wolf Herdman obtained from the subject, ii ) quantifying the density of one FRIDMAN , Paris ( FR ) ; Catherine further population of immune cells selected from the group SAUTES - FRIDMAN , Paris ( FR ) ; consisting of TLS -mature DC or TLS - B cells or Tconv cells , Priyanka DEVI, Paris (FR ) CD8 + T cells or CD8 + Granzyme - B + T cells in said tumor tissue sample , iii ) comparing the densities quantified at steps (21 ) Appl. No. : 15/ 754 , 640 i ) and ii ) with their corresponding predetermined reference values and iv ) concluding that the subject will have a short ( 22 ) PCT Filed : Aug . -
EDP & Mitotane Protocol
THE CLATTERBRIDGE CANCER CENTRE NHS FOUNDATION TRUST Systemic Anti Cancer Treatment Protocol EDP + mitotane PROCEDURE REF: MPHA HANEDP (Version No: 1.0) Approved for use in: Symptomatic treatment for advanced (unresectable, metastatic or relapsed) adrenocortical carcinoma ECOG performance status of 0 - 2 All possible tumour tissues should be surgically removed from large metastatic masses before mitotane administration is instituted. This is necessary to minimise the possibility of infarction and haemorrhage in the tumour due to a rapid cytotoxic effect of mitotane Exclusion criteria: Previous complete cumulative doses of anthracyclines Decompensated heart failure (ejection fraction <50%) Unstable angina, uncontrolled cardiac arrhythmias, MI or revascularisation procedure within last 6 months Dosage: Drug Dosage Route Frequency Etoposide 100mg/m2 IV Daily on days 2, 3 and 4 of each cycle Doxorubicin 40mg/m2 IV Once only on day 1 of each cycle Cisplatin 40mg/m2 IV Daily on days 3 and 4 of each cycle Variable, max Continuous, started a week prior to IV Mitotane PO 6g daily chemotherapy if not already taking With cycles repeated at 28 day intervals until disease progression Supportive treatments: Domperidone 10mg oral tablets maximum 3 times a day or as required Issue Date: May 2017 Page 1 of 8 Protocol reference: MPHAHANEDP 1 Authorised by: Drugs & Therapeutics Author: Helen Flint Committee & Dr D Husband Version No: 1.0 THE CLATTERBRIDGE CANCER CENTRE NHS FOUNDATION TRUST Extravasation risk: Doxorubicin is a vesicant and must be observed during administration. Follow the procedure for anthracycline extravasation. Erythematous streaking (a histamine release phenomenon) along the vein proximal to the site of injection has been reported, and must be differentiated from an extravasation event. -
Lonidamine Induces Apoptosis in Drug-Resistant Cells Independently of the P53 Gene
Lonidamine induces apoptosis in drug-resistant cells independently of the p53 gene. D Del Bufalo, … , A Sacchi, G Zupi J Clin Invest. 1996;98(5):1165-1173. https://doi.org/10.1172/JCI118900. Research Article Lonidamine, a dichlorinated derivative of indazole-3-carboxylic acid, was shown to play a significant role in reversing or overcoming multidrug resistance. Here, we show that exposure to 50 microg/ml of lonidamine induces apoptosis in adriamycin and nitrosourea-resistant cells (MCF-7 ADR(r) human breast cancer cell line, and LB9 glioblastoma multiform cell line), as demonstrated by sub-G1 peaks in DNA content histograms, condensation of nuclear chromatin, and internucleosomal DNA fragmentation. Moreover, we find that apoptosis is preceded by accumulation of the cells in the G0/G1 phase of the cell cycle. Interestingly, lonidamine fails to activate the apoptotic program in the corresponding sensitive parental cell lines (ADR-sensitive MCF-7 WT, and nitrosourea-sensitive LI cells) even after long exposure times. The evaluation of bcl-2 protein expression suggests that this different effect of lonidamine treatment in drug-resistant and -sensitive cell lines might not simply be due to dissimilar expression levels of bcl-2 protein. To determine whether the lonidamine-induced apoptosis is mediated by p53 protein, we used cells lacking endogenous p53 and overexpressing either wild-type p53 or dominant-negative p53 mutant. We find that apoptosis by lonidamine is independent of the p53 gene. Find the latest version: https://jci.me/118900/pdf -
Effect of Lonidamine on Systemic Therapy of DB-1 Human Melanoma Xenografts with Temozolomide KAVINDRA NATH 1, DAVID S
ANTICANCER RESEARCH 37 : 3413-3421 (2017) doi:10.21873/anticanres.11708 Effect of Lonidamine on Systemic Therapy of DB-1 Human Melanoma Xenografts with Temozolomide KAVINDRA NATH 1, DAVID S. NELSON 1, JEFFREY ROMAN 1, MARY E. PUTT 2, SEUNG-CHEOL LEE 1, DENNIS B. LEEPER 3 and JERRY D. GLICKSON 1 Departments of 1Radiology and 2Biostatistics & Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, U.S.A.; 3Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, PA, U.S.A. Abstract. Background/Aim: Since temozolomide (TMZ) is stages. However, following recurrence with metastasis, the activated under alkaline conditions, we expected lonidamine prognosis is poor. Mutationally-activated BRAF is found in (LND) to have no effect or perhaps diminish its activity, but 40-60% of all melanomas with most common substitution of initial results suggest it may actually enhance either or both valine to glutamic acid at codon 600 (p. V600E) (3). Overall short- and long-term activity of TMZ in melanoma xenografts. survival is approaching two years using agents that target this Materials and Methods: Cohorts of 5 mice with subcutaneous mutation (4, 5). MEK, RAS and other signal transduction xenografts ~5 mm in diameter were treated with saline inhibitors, in combination with mutant BRAF inhibitors, have (control (CTRL)), LND only, TMZ only or LND followed by been used to deal with melanoma resistance to these agents TMZ at t=40 min (time required for maximal tumor (6). Treatment with anti-programmed death-1 (PD-1) acidification). Results: Mean tumor volume for LND+TMZ for checkpoint inhibitor immunotherapy currently produces the period between 6 and 26 days was reduced compared to durable response in about 25% of melanoma patients (7-10). -
Nath, K., Guo, L., Nancolas, B., Nelson, D. S., Shestov, A. A., Lee, S- C., Roman, J., Zhou, R., Leeper, D
Nath, K., Guo, L., Nancolas, B., Nelson, D. S., Shestov, A. A., Lee, S- C., Roman, J., Zhou, R., Leeper, D. B., Halestrap, A. P., Blair, I. A., & Glickson, J. D. (2016). Mechanism of antineoplastic activity of lonidamine. Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, 1866(2), 151-162. https://doi.org/10.1016/j.bbcan.2016.08.001 Peer reviewed version License (if available): CC BY-NC-ND Link to published version (if available): 10.1016/j.bbcan.2016.08.001 Link to publication record in Explore Bristol Research PDF-document This is the accepted author manuscript (AAM). The final published version (version of record) is available online via Elsevier at http://dx.doi.org/10.1016/j.bbcan.2016.08.001. Please refer to any applicable terms of use of the publisher. University of Bristol - Explore Bristol Research General rights This document is made available in accordance with publisher policies. Please cite only the published version using the reference above. Full terms of use are available: http://www.bristol.ac.uk/red/research-policy/pure/user-guides/ebr-terms/ Mechanism of Antineoplastic Activity of Lonidamine Kavindra Nath1, Lili Guo2, Bethany Nancolas3, David S. Nelson1, Alexander A Shestov1, Seung-Cheol Lee1, Jeffrey Roman1, Rong Zhou1, Dennis B. Leeper4, Andrew P. Halestrap3, Ian A. Blair2 and Jerry D. Glickson1 Departments of Radiology1 and Center of Excellence in Environmental Toxicology, and Department of Systems Pharmacology and Translational Therapeutics2, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA, School of Biochemistry3, Biomedical Sciences Building, University of Bristol, BS8 1TD, UK. -
BC Cancer Benefit Drug List September 2021
Page 1 of 65 BC Cancer Benefit Drug List September 2021 DEFINITIONS Class I Reimbursed for active cancer or approved treatment or approved indication only. Reimbursed for approved indications only. Completion of the BC Cancer Compassionate Access Program Application (formerly Undesignated Indication Form) is necessary to Restricted Funding (R) provide the appropriate clinical information for each patient. NOTES 1. BC Cancer will reimburse, to the Communities Oncology Network hospital pharmacy, the actual acquisition cost of a Benefit Drug, up to the maximum price as determined by BC Cancer, based on the current brand and contract price. Please contact the OSCAR Hotline at 1-888-355-0355 if more information is required. 2. Not Otherwise Specified (NOS) code only applicable to Class I drugs where indicated. 3. Intrahepatic use of chemotherapy drugs is not reimbursable unless specified. 4. For queries regarding other indications not specified, please contact the BC Cancer Compassionate Access Program Office at 604.877.6000 x 6277 or [email protected] DOSAGE TUMOUR PROTOCOL DRUG APPROVED INDICATIONS CLASS NOTES FORM SITE CODES Therapy for Metastatic Castration-Sensitive Prostate Cancer using abiraterone tablet Genitourinary UGUMCSPABI* R Abiraterone and Prednisone Palliative Therapy for Metastatic Castration Resistant Prostate Cancer abiraterone tablet Genitourinary UGUPABI R Using Abiraterone and prednisone acitretin capsule Lymphoma reversal of early dysplastic and neoplastic stem changes LYNOS I first-line treatment of epidermal -
Drug Name Plate Number Well Location % Inhibition, Screen Axitinib 1 1 20 Gefitinib (ZD1839) 1 2 70 Sorafenib Tosylate 1 3 21 Cr
Drug Name Plate Number Well Location % Inhibition, Screen Axitinib 1 1 20 Gefitinib (ZD1839) 1 2 70 Sorafenib Tosylate 1 3 21 Crizotinib (PF-02341066) 1 4 55 Docetaxel 1 5 98 Anastrozole 1 6 25 Cladribine 1 7 23 Methotrexate 1 8 -187 Letrozole 1 9 65 Entecavir Hydrate 1 10 48 Roxadustat (FG-4592) 1 11 19 Imatinib Mesylate (STI571) 1 12 0 Sunitinib Malate 1 13 34 Vismodegib (GDC-0449) 1 14 64 Paclitaxel 1 15 89 Aprepitant 1 16 94 Decitabine 1 17 -79 Bendamustine HCl 1 18 19 Temozolomide 1 19 -111 Nepafenac 1 20 24 Nintedanib (BIBF 1120) 1 21 -43 Lapatinib (GW-572016) Ditosylate 1 22 88 Temsirolimus (CCI-779, NSC 683864) 1 23 96 Belinostat (PXD101) 1 24 46 Capecitabine 1 25 19 Bicalutamide 1 26 83 Dutasteride 1 27 68 Epirubicin HCl 1 28 -59 Tamoxifen 1 29 30 Rufinamide 1 30 96 Afatinib (BIBW2992) 1 31 -54 Lenalidomide (CC-5013) 1 32 19 Vorinostat (SAHA, MK0683) 1 33 38 Rucaparib (AG-014699,PF-01367338) phosphate1 34 14 Lenvatinib (E7080) 1 35 80 Fulvestrant 1 36 76 Melatonin 1 37 15 Etoposide 1 38 -69 Vincristine sulfate 1 39 61 Posaconazole 1 40 97 Bortezomib (PS-341) 1 41 71 Panobinostat (LBH589) 1 42 41 Entinostat (MS-275) 1 43 26 Cabozantinib (XL184, BMS-907351) 1 44 79 Valproic acid sodium salt (Sodium valproate) 1 45 7 Raltitrexed 1 46 39 Bisoprolol fumarate 1 47 -23 Raloxifene HCl 1 48 97 Agomelatine 1 49 35 Prasugrel 1 50 -24 Bosutinib (SKI-606) 1 51 85 Nilotinib (AMN-107) 1 52 99 Enzastaurin (LY317615) 1 53 -12 Everolimus (RAD001) 1 54 94 Regorafenib (BAY 73-4506) 1 55 24 Thalidomide 1 56 40 Tivozanib (AV-951) 1 57 86 Fludarabine -
Case Report: Exceptional Response to Second Line Temozolomide Therapy in a Patient with Metastatic Adrenocortical Carcinoma
CASE REPORT published: 22 April 2021 doi: 10.3389/fendo.2021.674039 Case Report: Exceptional Response to Second Line Temozolomide Therapy in a Patient With Metastatic Adrenocortical Carcinoma † † Deborah Cosentini 1 , Antonella Turla 1 , Ornella Carminati 2, Salvatore Grisanti 1, Vittorio Domenico Ferrari 1, Marta Laganà 1, Giovanni Rosti 3, Sandra Sigala 4 and Alfredo Berruti 1* 1 Medical Oncology Unit, Azienda Socio Sanitaria Territoriale (ASST) Spedali Civili, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia, Italy, 2 Medical Oncology, Department of Edited by: Oncology and Hematology, Azienda Unità Sanitaria Locale (AUSL), Romagna, Ravenna, Italy, 3 Medical Oncology, Barbara Altieri, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy, 4 Section of Pharmacology, Department of Molecular and Translational University Hospital of Wuerzburg, Medicine, University of Brescia, Brescia, Italy Germany Reviewed by: Background: In a recently published retrospective case series, Temozolomide was found Peter Igaz, Semmelweis University, Hungary active as second line approach in advanced ACC patients. The disease control rate obtained, Jaydira Del Rivero, however, was short-lived. We report here an ACC patient with extensive metastatic disease National Cancer Institute (NIH), who obtained a remarkable long lasting response with this alkylating agent. United States *Correspondence: Case Presentation: a 22-year-old female patient with ACC presented at our Medical Alfredo Berruti Oncology Department in poor general condition due the presence of extensive metastatic [email protected] pulmonary involvement. The disease had progressed to etoposide, doxorubicin and † These authors have contributed cisplatin plus mitotane therapy. Second line temozolomide therapy was prescribed equally to this work and share first authorship leading to a progressive improvement of patient general conditions. -
Supplementary Table 1 Mean Viability Values for Each Cell Line for Each Compound Tested in the Small Molecule Screen
Supplementary Table 1 Mean viability values for each cell line for each compound tested in the small molecule screen. A value of "1" represents a hypothetical, perfectly flat line (no effect). Drug GTL-16 GTL-16_A GTL-16_B GTL-16_C GTL-16_D GTL-16_E GTL-16_F GTL-16_G GTL-16_H GTL-16_I GTL-16_J GTL-16_K (S)-Citalopram Oxalate 0.94311374 0.98629332 0.95815778 0.9297682 0.94129628 0.97543865 0.92876703 0.94308692 0.97087634 0.92498189 1.03652668 2-Ethyl-2-thiopseudourea, HBr 0.9926737 1.02483487 1.04627788 1.01238942 1.01124644 0.99179834 1.03981841 1.03206468 1.07888484 0.95669609 1.03375137 1.00257194 2-methoxyestradiol 0.95743567 1.02442777 0.96874416 0.95701057 0.96000141 0.9319331 0.96175575 0.98632097 0.97543859 1.07065523 0.9810608 1.00528908 3-Isobutyl-1-methyl-xanthine 1.07753563 0.90621853 0.91486669 0.88967401 1.00929224 0.87712008 0.86304086 0.84795183 0.8218478 0.80844665 0.86385089 0.88111275 5-FU 0.5692879 0.58485568 0.59111845 0.66370136 0.60502565 0.52588075 0.61204398 0.55819142 0.57166713 0.44119668 0.61203408 0.61352444 6-aminonicotinimide 0.67580861 0.74962443 0.74297309 0.78548056 0.69875711 0.76253933 0.72148764 0.75038254 0.72102743 0.74534333 0.77091813 A-1331852 0.93531603 0.90417945 0.94313675 0.92505068 0.94545311 0.96834266 0.88789237 0.93844146 0.94623333 0.95265883 0.84359944 0.98073947 a-cyano-4-OH-cinnamate (CHCA) 0.9952172 0.98906165 0.99838293 1.01442099 0.99624294 1 0.98471749 1.0049547 1.02723098 0.9742409 0.9819023 1.0257504 A922500 0.87694919 0.97097522 0.94563395 0.96351612 0.90027344 0.97543859 0.95685369 -
For Health Professionals Who Care for Cancer Patients
November 2014 Volume 17, Number 11 For Health Professionals Who Care For Cancer Patients Inside This Issue: . Editor’s Choice – New Programs: nab-Paclitaxel and . Provincial Systemic Therapy Program – Reformat of Gemcitabine for Pancreatic Cancer, Neoadjuvant Paclitaxel BCCA Policy on Prevention and Management of and AC for Breast Cancer, Chlorambucil plus Rituximab for Extravasation of Chemotherapy Lymphomas, Chemotherapy plus Mitotane for . Drug Update – Enzalutamide Patient Assistance Adrenocortical Cancer Program . Cancer Drug Manual – Revised: Filgrastim, Gemcitabine, . List of New and Revised Protocols, Provincial Pre- Oxaliplatin, Paclitaxel, nab-Paclitaxel, Dexamethasone Printed Orders and Patient Handouts – New: . Medication Safety – Improving Website Clarity for Protocol BRLATACG, BRLATWAC, UGIPGEMABR, GUEDPM, Selection LYCHLRR Revised: BRAVEVEX, UCNBEV, GICIRB, . Benefit Drug List – New: BRLATACG, BRLATWAC, GIFFIRB, UGIFFOXB, UGIFIRINOX, GOCXCRT, GOENDH, UGIPGEMABR, GUEDPM, LYCHLRR Revised: ULYRMTN GUPLHRH, GUSCPE, HNAVP, LYIVACR, HNLAPRT, Deleted: BRLAACTW ULKATOATRA, ULKATOP, ULKATOR, ULUAVAFAT, LYABVD, LYCHOP, LYCHOPR, LYCHOPRMTX, LYRMTN . Continuing Professional Development – Workshop on Deleted: BRLAACTW Education in Palliative and End of Life Care for Oncology . Website Resources and Contact Information EDITOR’S CHOICE NEW PROGRAMS The Provincial Systemic Therapy Program has approved the following programs effective 1 November 2014: nab-Paclitaxel (ABRAXANE®) and Gemcitabine for Locally Advanced and Metastatic Pancreatic -
2015 Antiemesis.Pdf
NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Antiemesis Version 2.2015 NCCN.org Continue Version 2.2015, 09/22/15 © National Comprehensive Cancer Network, Inc. 2015, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®. Printed by Alexandre Ferreira on 10/25/2015 6:12:07 AM. For personal use only. Not approved for distribution. Copyright © 2015 National Comprehensive Cancer Network, Inc., All Rights Reserved. NCCN Guidelines Version 2.2015 Panel Members NCCN Guidelines Index Antiemesis Table of Contents Antiemesis Discussion David S. Ettinger, MD/Chair † Steve Kirkegaard, PharmD Σ Eric Roeland, MD The Sidney Kimmel Comprehensive Huntsman Cancer Institute UC San Diego Moores Cancer Cancer Center at Johns Hopkins at the University of Utah Center Michael J. Berger, PharmD/Vice Chair, BCOP Σ Dwight D. Kloth, PharmD, BCOP Σ Hope S. Rugo, MD † ‡ The Ohio State University Comprehensive Fox Chase Cancer Center UCSF Helen Diller Family Cancer Center - James Cancer Hospital Comprehensive Cancer Center and Solove Research Institute Ruth Lagman, MD £ Mayo Clinic Cancer Center Bridget Scullion, PharmD, BCOP Jonathan Aston, PharmD, BCOP, BCPS Σ Dana-Farber/Brigham and Women’s Vanderbilt-Ingram Cancer Center Dean Lim, MD † Cancer Center | Massachusetts City of Hope Comprehensive Cancer Center General Hospital Cancer Center Sally Barbour, PharmD, BCOP, CCP Σ Duke Cancer Institute Cynthia Ma, MD, PhD † John Timoney, PharmD, BCOP † Siteman Cancer Center at Barnes-Jewish Memorial Sloan Kettering Cancer Philip J. Bierman, MD † ‡ Hospital and Washington University School Center Fred & Pamela Buffet Cancer Center of Medicine Barbara Todaro, PharmD Σ Debra Brandt, DO Belinda Mandrell, PhD, RN † Roswell Park Cancer Institute Yale Cancer Center/Smilow Cancer Hospital St.