Hybrid Inorganic Complexes as Cancer Therapeutic Agents: In-vitro Validation.

A series of novel mixed transition metal-Magnesium tartarate complexes of general formulation [MMg(C4H4O6)2 .xH2O] (where M = Mn, Fe, Co, Ni, Cu and Zn) is prepared with bidentate tartarate ligand. The synthesized complexes (C1 to C6) are characterized by various analytical techniques such as Elemental analysis, Thermo gravimetric analysis, FT-IR Spectroscopy, X-ray Diffraction, Magnetic susceptibility study etc. All complexes exhibit the composition MMgL2 where M = Mn(II), Fe(II), Co(II), Ni(II), Cu(II) and Zn(II) and L = bidentate tartarate ligand. Analytical data reveals all complexes possesses 1:1 (metal: ligand) ratio. FT-IR spectral study shows that bidentate tartarate ligand coordinate with metal ion in a bidentate manner through two oxygen atoms. Thermo gravimetric analysis of all complexes shows that degradation curves of complexes agrees with recommended formulae of the complexes. X-ray diffraction technique suggests that all complexes (C1 to C6) are polycrystalline in nature. All newly synthesized metal tartarate complexes and ligand were screened in vitro for their anticancer activity against human breast cancer (MDA-MB-231) cell line. The bioassays of all these complexes showed C3 (Co) and C5 (Cu) Mg-tartarate complexes contains maximum antiproliferative activity at 200 µg/ml concentration on MDA-MB-231 cells as compared to other complexes. MDA-MB-231 cells treated with C3 (Co) and C5 (Cu) Mg-tartarate complexes also showed inhibition in cell migration.

The Biology and Therapeutic Implications of Tumor Dormancy and Reactivation.

Advancements in the early detection of cancer coupled with improved surgery, radiotherapy, and adjuvant therapy led to substantial increase in patient survival. Nevertheless, cancer metastasis is the leading cause of death in several cancer patients. The majority of these deaths are associated with metastatic relapse kinetics after a variable period of clinical remission. Most of the cancer recurrences are thought to be associated with the reactivation of dormant disseminated tumor cells (DTCs). In this review, we have summarized the cellular and molecular mechanisms related to DTCs and the role of microenvironmental niche. These mechanisms regulate the dormant state and help in the reactivation, which leads to metastatic outgrowth. Identification of novel therapeutic targets to eliminate these dormant tumor cells will be highly useful in controlling the metastatic relapse-related death with several cancers.

Involvement of topoisomerase mutations and qnr and aac(6')Ib-cr genes in conferring quinolone resistance to clinical isolates of Vibrio and Shigella spp. from Kolkata, India (1998-2009).

OBJECTIVES: Quinolone antibiotics have been widely used to treat diarrhoeal diseases caused by bacterial agents such as those belonging to the genera Vibrio and Shigella. As these pathogens are accumulating quinolone resistance, treating infections caused by them has become complicated. METHODS: In this study, Vibrio and Shigella spp. isolates obtained from diarrhoeal patients from Kolkata, India, over a period of 12 years (1998-2009) were analysed for quinolone resistance. A total of 27 Vibrio spp. (9 Vibrio cholerae, 11 Vibrio fluvialis and 7 Vibrio parahaemolyticus) and 10 Shigella spp. isolates (7 Shigella flexneri, 2 Shigella dysenteriae and 1 Shigella sonnei) showing reduced susceptibility to quinolones were studied to unravel the genetic factors responsible for quinolone resistance. RESULTS: Antimicrobial susceptibility testing showed a wide spectrum and varying degree of resistance to different generations of quinolones. Genotypic characterisation revealed the involvement of GyrA(S83I) and ParC(S85L) mutations in V. cholerae and V. fluvialis, whereas Shigella spp. isolates showed the mutations S83L and/or D87N/Y in GyrA and S80I or E84K in ParC. Analysis of plasmid-mediated quinolone resistance genes showed that qnrVC5 was detected in three V. fluvialis isolates, aac(6')-Ib-cr in one V. fluvialis isolate and qnrS1 in a S. flexneri isolate. CONCLUSIONS: These results emphasise that quinolone resistance is widespread and therefore quinolones should be used prudently. To the best of our knowledge, this is the first study where resistance to various generations of quinolones in Vibrio and Shigella spp. has been examined in terms of detailed genotype-phenotype correlation.