Research advances in tumor radiosensitization mediated by topoisomerase inhibitors / 中华放射医学与防护杂志

As anticancer drugs,topoisomerase inhibitors have been widely used in clinical practice,and their radiosensitivity has been gradually recognized.Many topoisomerase inhibitors are currently in pre-clinical and clinical studies.Several studies have shown that some topoisomerase inhibitors may be potential ideal radiosensitizers.However,the physico-chemical properties,toxicity and sensitization effects should be further investigated.

Differential in vitro activity of the DNA topoisomerase inhibitor idarubicin against Trypanosoma rangeli and Trypanosoma cruzi

In this study the effect of eight DNA topoisomerase inhibitors on the growth Trypanosoma rangeli epimastigotes in cell culture was investigated. Among the eight compounds tested, idarubicin was the only compound that displayed promising trypanocidal activity with a half-maximal growth inhibition (GI50) value in the sub-micromolar range. Fluorescence-activated cell sorting analysis showed a reduction in DNA content in T. rangeli epimastigotes when treated with idarubicin. In contrast to T. rangeli, against Trypanosoma cruzi epimastigotes idarubicin was much less effective exhibiting a GI50 value in the mid-micromolar range. This result indicates that idarubicin displays differential toxic effects in T. rangeli and T. cruzi. Compared with African trypanosomes, it seems that American trypanosomes are generally less susceptible to DNA topoisomerase inhibitors.

Antioxidant and antitopoisomerase activities in plant extracts of some Colombian flora from La Marcada Natural Regional Park

Many plants have been used to treat some diseases and infections since time immemorial, and this potential has been exploited by the pharmaceutical industry in the search of new analgesic, anticarcinogenic and antimicrobial agents, among other active agents. in order to contribute with bioprospection studies on the Colombian flora, 35 extracts from 13 plant species belonging to seven families (Apocynaceae, Cactaceae, Costaceae, Eremolepidaceae, Passifloraceae, Solanaceae and Urticaceae) were collected from La Marcada Natural Regional Park (LMNRP), Colombia. Dichloromethane, n-hexane and aqueous-methanol crude extracts were prepared and evaluated for their activity against Saccharomyces cerevisiae RS322N, R52Y and RS321 strains in the yeast mutant assay and their antioxidant capacity through the DPPH test. The dichloromethane extract from Myriocarpa stipitata (Urticaceae) showed moderate inhibitory activity against the three S. cerevisiae strains tested. The capacity of the dichloromethane extract from M. stipitata to inhibit the enzyme topoisomerase I and to cause DNA damage was inferred from these results. In the DPPH assay, the n-hexane crude extract from Costus sp. (Costaceae) showed good antioxidant activity (48%); in addition, the crude dichloromethane and aqueous-methanol extracts from Rhipsalis micrantha (Cactaceae) showed moderate antioxidant activity with percentage of 29 and 21%, respectively. Rev. Biol. Trop. 59 (3): 1089-1097. Epub 2011 September 01.

Desde tiempos inmemoriales, muchas plantas han sido usadas para el tratamiento de varias enfermedades e infecciones, este potencial ha sido explotado por la industria farmacéutica en la búsqueda de nuevos agentes analgésicos, anticancerígenos y antimicrobianos, entre otros. Consientes con esto, se evaluó la actividad de 35 extractos de 13 especies de plantas recolectadas en el Parque Regional Natural La Marcada (PRNLM, Colombia) contra las cepas mutadas de Saccharomyces cerevisiae RS322N, R52Y y RS321 en el ensayo de la levadura mutada y la capacidad antioxidante de los extractos a través del método del DPPH. El extracto crudo de diclorometano de Myriocarpa stipitata (Urticaceae) presentó actividad moderada contra las tres cepas de S. cerevisiae evaluadas. Lo cual permitió inferir la capacidad del extracto de diclorometano de esta especie para inhibir la enzima topoisomerasa I y causar daño al ADN. Además, en el ensayo del DPPH, el extracto de n-hexano crudo de Costus sp (Costaceae) mostró actividad antioxidante buena (48%), mientras que los extractos de diclorometano y acuoso metanólico crudos de Rhipsalis micrantha (Cactaceae) tuvieron actividad antioxidante moderada, con valores del 29 y 21%, respectivamente.

Therapy related myelodysplastic syndrome: A case report and review of literature.

Therapy related myeloid neoplasm is directly related to previous cytotoxic chemotherapy or radiation therapy. We present a 47-year-old lady who developed therapy related myelodysplastic syndrome (MDS) 2.5 years after she received four cycles of chemotherapy and local radiation therapy for carcinoma breast. She presented with bicytopenia with trilineage dyspoiesis in the peripheral blood, bone marrow aspirate and biopsy. Fluorescent in-situ hybridization studies did not reveal any of the common abnormalities associated with MDS. A diagnosis of therapy related MDS was rendered. Different studies have shown that patients treated with alkylating agents and ionizing radiation present as MDS with a latent period of 3-10 years. Our patient developed MDS within 2.5 years of starting chemotherapy and radiotherapy and did not reveal any of the conventional cytogenetic abnormalities. It highlights the importance of simple tests like a complete blood count and peripheral blood smear examination in follow-up of the patients treated with chemotherapy.

Therapy-related acute leukemia in breast cancer patients: twelve cases treated with a topoisomerase inhibitor / 대한혈액학회지

BACKGROUND: Therapy-related myeloid neoplasm (t-MN) is a distinct class of acute myeloid leukemia (AML) in the World Health Organization (WHO) classification. Both AML and acute lymphoblastic leukemia (ALL) may develop after treatment for primary cancer. Topoisomerase inhibitors are commonly used to treat breast cancer patients and are well-known for their effect on leukemogenesis of therapy-related acute leukemias (t-AL). METHODS: We retrospectively evaluated bone marrow test results, chromosomal findings, and clinical characteristics of 12 patients who received topoisomerase inhibitors for breast cancer treatment and later developed acute leukemia. RESULTS: Fourteen patients (0.2%) developed t-AL after treatment for breast cancer. Topoisomerase inhibitors were administered to 12 patients. Among them, 9 patients (75%, 9/12) were diagnosed with therapy-related AML (t-AML) and 3 patients (25%, 3/12) with therapy-related ALL (t-ALL). Eight patients (67%, 8/12) showed translocation involving 11q23 and 3 different partner genes, 19p13.1 (37.5%, 3/8), 9p22 (37.5%, 3/8), and 4q21 (25%, 2/8). The median interval between completion of chemotherapy for breast cancer and occurrence of t-AL was 25 months. Patients with 11q23 translocation showed markedly poorer event-free survival than the group without involvement of 11q23. CONCLUSION: The incidence rate of t-AL after treatment for breast cancer was 0.2% in a tertiary hospital in Korea. Translocation involving the MLL gene was frequently found in t-AL caused by a topoisomerase inhibitor and was related to poor prognosis.