The numerical probability of carcinogenicity to humans of some pharmaceutical drugs: alkylating agents, topoisomerase inhibitors or poisons, and DNA intercalators

2021 ◽  
Author(s):  
Jose D. Suarez‐Torres ◽  
Camilo A. Orozco ◽  
Carlos E. Ciangherotti
Keyword(s):  
Alkylating Agents ◽  
Pharmaceutical Drugs ◽  
Topoisomerase Inhibitors ◽  
Dna Intercalators

scholarly journals WHO HAS THERAPY-RELATED AML?

2017 ◽  
Vol 9 (1) ◽  
pp. e2017025 ◽  
Author(s):  
Robert Gale ◽  
John M. Bennett ◽  
F. Owen Hoffman
Keyword(s):  
Dna Repair ◽  
Cancer Therapy ◽  
Gene Variants ◽  
Topoisomerase Inhibitors ◽  
Dna Intercalators ◽  
Myeloid Neoplasm ◽  
Anti Cancer ◽  
Topoisomerase 2 ◽  
Or Gene ◽  
Ionizing Radiations

Therapy-related leukemia or therapy-related myeloid neoplasm are widely-used terms to designate leukemia developing in persons who previously received anti-cancer therapy (for example, see references 1, 2), especially if the prior anti-cancer therapy included drugs such as alkylators, DNA-intercalators, topoisomerase-2-inhibitors, purines and/or ionizing radiations.   Sometimes specific genes such as AML1, EVI1, NRAS or MLL are mutated by therapy or gene variants are produced which activate mutagens or interfere with DNA repair, such FANC, NQ01 or AML2. 3-5   But how can we know if AML in someone is a therapy-related?Keywords: Therapy-related leukemia; alkylators; ionizing radiations; Topoisomerase Inhibitors; DNA Repair

scholarly journals Effect of Glutathione Depletion on Antitumor Drug Toxicity (Apoptosis and Necrosis) in U-937 Human Promonocytic Cells

2001 ◽  
Vol 276 (50) ◽  
pp. 47107-47115 ◽  
Author(s):  
Alfonso Troyano ◽  
Carlos Fernández ◽  
Patricia Sancho ◽  
Elena de Blas ◽  
Patricio Aller
Keyword(s):  
Transmembrane Potential ◽  
Reduced Glutathione ◽  
Alkylating Agents ◽  
Glutathione Depletion ◽  
Topoisomerase Inhibitors ◽  
Synthesis Inhibitor ◽  
Dna Topoisomerase ◽  
Antioxidant Agents ◽  
Apoptosis And Necrosis ◽  
Promonocytic Cells

Treatment with the DNA topoisomerase inhibitors etoposide, doxorubicin, and camptothecin, and with the alkylating agents cisplatin and melphalan, caused peroxide accumulation and apoptosis in U-937 human promonocytic cells. Preincubation with the reduced glutathione (GSH) synthesis inhibitorl-buthionine-(S,R)-sulfoximine (BSO) always potentiated peroxide accumulation. However, although GSH depletion potentiated the toxicity of cisplatin and melphalan, occasionally switching the mode of death from apoptosis to necrosis, it did not affect the toxicity of the other antitumor drugs. Hypoxia or preincubation with antioxidant agents attenuated death induction, apoptotic and necrotic, by alkylating drugs. The generation of necrosis by cisplatin could not be mimicked by addition of exogenous H2O2instead of BSO and was not adequately explained by caspase inactivation nor by a selective fall in ATP content. Treatment with cisplatin and melphalan caused a late decrease in mitochondrial transmembrane potential (ΔΨm), which was much greater during necrosis than during apoptosis. The administration of the antioxidant agentsN-acetyl-l-cysteine and butylated hydroxyanisole after pulse treatment with cisplatin or melphalan did not affect apoptosis but attenuated necrosis. Under these conditions, both antioxidants attenuated the necrosis-associated ΔΨm decrease. These results indicate that oxidation-mediated alterations in mitochondrial function regulate the selection between apoptosis and necrosis in alkylating drug-treated human promonocytic cells.

Impact of the type of first-cancer therapy in therapy-related myelodysplastic syndromes outcomes.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e18555-e18555
Author(s):  
Ana Alfonso Pierola ◽  
Guillermo Montalban-Bravo ◽  
Koichi Takahashi ◽  
Elias Jabbour ◽  
Tapan M. Kadia ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Myelodysplastic Syndromes ◽  
Alkylating Agents ◽  
Complex Karyotype ◽  
Topoisomerase Inhibitors ◽  
Previous Therapy ◽  
Hematological Cancers ◽  
Background Therapy ◽  
Poor Outcomes ◽  
The Impact

e18555 Background: Therapy-related myelodysplastic syndromes (t-MDS) are known to have poor outcomes. The impact of the therapy received for the first cancer remains unknown. Methods: 228 t-MDS diagnosed between July 2001 and December 2015 were retrospectively reviewed. Results: Median age at diagnosis of t-MDS was 66 years (range 13-87). Previous malignancies: 54% hematological cancers and 47% solid tumors. 14% had multiple cancers before the t-MDS. Previous therapy received: 119 (52%) chemotherapy (CT), 17 (8%) radiotherapy (RT), or 92 (40%) both (Table). Median time to develop t-MDS was 73 months (range 5-355). According to IPSS, 13 patients (6%) had low-risk, 65 (29%) intermediate-1 risk, 119 (53%) intermediate-2 risk and 29 (13%) high-risk. 124 patients (58%) had complex karyotype. The most frequent cytogenetic abnormalities detected were: -7/7q (n=99; 46%), -5/5q (n=77; 36%), and +8 (n=13; 6%). TP53was observed in 51% (n=21/41). Median OS was 12 months (CI95% = 10-14). Univariate and multivariate analysis revealed that CT vs RT (p=0.028; HR [CI95%] = 1.988 [1.08-3.67]), and higher IPSS risk (low: p=0.027; intermediate-1: p=0.285 HR [CI95%] = 1.48 [0.72-3.01]; intermediate-2: p=0.055, HR [CI95%] = 1.95 [0.99-3.88]; high: p=0.015 HR [CI95%] = 2.59 [1.21-5.55]), had a poor impact in OS. No statistical differences between OS and type of CT received, molecular or cytogenetic alterations were observed. However, complex karyotype (71% vs 51%, p=0.007) and -7/7 abnormalities (61% vs 36%; p=0.001) were more frequent in patients who had received platinum; -7/7q- abnormalities were also associated to alkylating agents (50% vs 27%, p=0.012), antibiotics (74% vs 42%; p=0.003) and topoisomerase inhibitors (60% vs 37%; p=0.002). Conclusions: t-MDS is associated with poor outcomes. Receiving CT vs RT and higher IPSS risk had a poor impact in OS. The type of CT may be associated with specific cytogenetic alterations. [Table: see text]

scholarly journals A Series of 116 Therapy-Related Myeloid Neoplasms (t-MN) Patients from 2 French Comprehensive Cancer Centers

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1322-1322
Author(s):  
Hind Bennani ◽  
Véronique Saada ◽  
Christophe Willekens ◽  
Jacques Vargaftig
Keyword(s):  
Radiation Therapy ◽  
Median Survival ◽  
Primary Tumor ◽  
Alkylating Agents ◽  
Intermediate Risk ◽  
Topoisomerase Inhibitors ◽  
Cancer Centers ◽  
Myeloid Neoplasms ◽  
Comprehensive Cancer Centers ◽  
The Impact

Abstract Background: Cancer patients (pts) who receive chemotherapy and/or radiation therapy for their primary tumor are at risk for developing therapy-related myeloid neoplasms (t-MN). Estimates of t-MN prevalence are mainly derived from retrospective series from hematology departments: they account for 10 to 20% of all AML cases. However this condition is frequently diagnosed in daily practice in comprehensive cancer centers (CCC). This suspected higher frequency might be due to optimized follow-up protocols and improved survival outcomes after tumor remission. The aim of this study was to assess clinical factors associated with t-MN in 2 French CCC focusing on delay of onset, survival, cytogenetically defined prognosis, treatment received for primary tumor and myeloid disease presentation. Methods: We conducted a retrospective study of cancer pts who developed t-MN seen at Institut Gustave Roussy, Villejuif, France and Institut Curie, Saint-Cloud, France between 2004 and November 2014. As defined in the current 2008 WHO classification, t-MN includes therapy-related acute myeloid leukemia (t-AML), myelodysplastic syndrome (t-MDS) and myelodysplastic/myeloproliferative neoplasms (t-MDS/MPN). The study inclusion criteria were development of t-MN after chemotherapy and/or radiation therapy for any primary tumor. Results: 116 patients were retrieved from our records. 86 patients were women (74%) and the median age at t-MN diagnosis was 65 years (range, 25-91 years). The distribution of primary malignancies by site was as follows: breast cancer 46 pts, hematologic malignancy (lymphoma and myeloma) 24 pts, gynecologic cancer 14 pts, head and neck cancer 8 pts, urologic cancer 6 pts, gastrointestinal cancer 4 pts, miscellaneous (sarcoma, neurooncology, neuroendocrinology cancer) 14 pts. The median interval between primary cancer and t-MN was 60 months (range, 12-324). At the time of t-MN diagnosis, 69 (59%) had t-AML, 46 (40%) had t-MDS and 1 (1%) had t-MDS/MPN. Of note, among t-AML pts 15 (13%) had AML with recurrent genetic abnormalities and 14 had AML (12%) with MDS-related changes. Median survival from the diagnosis of t-MN was 6.5 months (5y OS was below 20%). Adverse risk karyotypes were prominent (63 pts, 59%) followed by intermediate risk (32 pts, 30%). Of note 12 pts (10%) had favorable risk karyotype. The impact of karyotype on survival was crucial: median survival was 60 months for favorable risk pts, 14 months for intermediate risk pts and only 6 months for adverse risk karyotypes. 26 pts (22%) were treated by radiation therapy alone. Treatment modality (radiation therapy alone, chemotherapy alone or combined treatment) did not affect survival or delay of onset. Of note, when we isolated pts treated by alkylating agents without topoisomerase inhibitors from those treated by topoisomerase inhibitors without alkylating agents we found that the disease presentation did not differ (same proportion of t-AML vs. t-MDS in each group), an observation in contrast with the classical description of post-alkylating agent t-MDS vs. post- topoisomerase inhibitor t-AML. Conclusion: We report a heterogeneous cohort of 116 pts with numerous primary tumors and treatment protocols. Prominent adverse risk karyotypes are in line with a dismal survival yet favorable risk karyotypes are not uncommon and remain associated with a relatively good prognosis. Disclosures No relevant conflicts of interest to declare.

Design, synthesis and biological evaluation of new oligopyrrole carboxamides linked with tricyclic DNA-intercalators as potential DNA ligands or topoisomerase inhibitors

2007 ◽  
Vol 42 (6) ◽  
pp. 752-771 ◽  
Author(s):  
Marie-Hélène David-Cordonnier ◽  
Marie-Paule Hildebrand ◽  
Brigitte Baldeyrou ◽  
Amelie Lansiaux ◽  
Christoph Keuser ◽  
...  
Keyword(s):  
Biological Evaluation ◽  
Topoisomerase Inhibitors ◽  
Design Synthesis ◽  
Dna Intercalators ◽  
Synthesis And Biological Evaluation

Problems Facing the Arab Pharmaceutical Industry: A Case Study from Yemen

2016 ◽  
Vol 2 (4) ◽  
pp. 234-241
Author(s):  
Mohammed Al-Shakka ◽  
Ebtesam Abood ◽  
Adel Al-Dhubhany ◽  
Sami Abdo Radman Aldubai ◽  
Khaled Said ◽  
...  
Keyword(s):  
Pharmaceutical Industry ◽  
Low Income ◽  
Well Being ◽  
Pharmaceutical Products ◽  
Domestic Market ◽  
Raw Material ◽  
Political Crisis ◽  
Pharmaceutical Manufacturer ◽  
University Graduates ◽  
Pharmaceutical Drugs

Because of the almost-instant connection with the welfare and well-being of individuals, pharmaceutical industry stands prominently as a very important factor for the improvement and progress of a healthy productive nation. These days, pharmaceutical industry thrives as one of the largest and exponentially expanding global industries. Nonetheless, millions of people in low income developing countries, have to suffer from the fatal consequences of the inaccessibility and non-availability of essential drugs. This is also happening in Yemen, where the pharmaceutical manufacturers sector have to face up to many challenges. The Yemen Drug Company (YEDCO) was founded in 1964 by the Yemeni government as it collaborated with private investors. It was endorsed as a company with the expertise in the medicinal drug marketing. YEDCO started its work by taking in drugs from foreign companies and then locally marketing and distributing them. In 1982, YEDCO built the first medicinal factory for drugs in Sana’a. Since then, seven companies were set up to manufacture medicines in Yemen. The expanding population has led to the need to have more pharmaceutical products. It may be understandable that pharmaceutical manufacturer companies are also hit by the political crisis in the country. Inadequate amount of fuel and raw material as well as low security status were some of the underlying factors behind these ill-effects in Yemen. Imported drugs make up about nearly 90% % of the pharmaceutical market compared to 10% drugs from the domestic market. This situation has led to an additional burden being shouldered by the national economy, where Yemen spends about US$263 million annually on pharmaceutical drugs, in reference to the national Supreme Drugs Authority. Although there is a very quick growth in the population and drugs consumption, the pharmaceutical industry has not been very active, where global pharmaceutical products play their role dominantly on the domestic market. The pharmaceutical production necessitates skilled human resources like university graduates. By contrast, the government and the private sector should also motivate the pharmaceutical industry and make use of the local employment

Vaccines for aquaculture overview

2020 ◽  
pp. 42-43
Author(s):  
Andrey S. Khishov ◽  
◽  
Galina I. Burlakova ◽  
Keyword(s):  
Antimicrobial Agents ◽  
Aquatic Organisms ◽  
Animal Husbandry ◽  
Well Being ◽  
Pharmaceutical Drugs ◽  
Short Development Time ◽  
The Creation ◽  
Basic And Applied Research ◽  
North And South America ◽  
Aquaculture Production

Aquaculture production is a promising direction for the development of food production. Like traditional types of animal husbandry, it needs effective medicines for veterinary use, which would ensure not only the well-being of farmed aquatic organisms, but also increase the safety of the fish products and non-fish objects of fishing. The development of measures to control epizootic processes in aquatic organisms is impossible without the creation of new immunological preparations. The development and use of immunobiological drugs will reduce the use of antimicrobial agents. The corresponding set of pharmaceutical drugs was transferred from the traditional veterinary medicine, but due to the peculiarities of the biology of aquatic animals, their immunity and the characteristics of specific pathogens, this could not be done with biological products. The short development time in the aquaculture industry poses current challenges in the form of a lack of basic and applied research for relatively poorly understood groups of new pathogens. The immunological processes associated with the development and intensity of the immune response in aquatic organisms require a detailed study. For domestic aquaculture producers, the analysis and dissemination of the experience accumulated by mankind and the application of advanced developments in this area are even more relevant, since Russia is just beginning its path of intensifying aquaculture production. At the same time, it is clear that the prohibition of the use and monitoring of antimicrobial agents in food products and feed requires a change in the approach to the problem and will lead to the creation of new immunobiological drugs. The market for immunobiological preparations for aquaculture is the most promising for development. In the article, the authors provide data on the development and registration of vaccines for aquaculture in Europe, North and South America.

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