Search results for "anticancer drug"
showing 10 items of 47 documents
GSK3β as a novel promising target to overcome chemoresistance in pancreatic cancer
2021
Pancreatic cancer is an aggressive malignancy with increasing incidence and poor prognosis due to its late diagnosis and intrinsic chemoresistance. Most pancreatic cancer patients present with locally advanced or metastatic disease characterized by inherent resistance to chemotherapy. These features pose a series of therapeutic challenges and new targets are urgently needed. Glycogen synthase kinase 3 beta (GSK3β) is a conserved serine/threonine kinase, which regulates key cellular processes including cell proliferation, DNA repair, cell cycle progression, signaling and metabolic pathways. GSK3β is implicated in non-malignant and malignant diseases including inflammation, neurodegenerative …
Apoptotic effects of thiazolobenzimidazole derivatives on sensitive and multidrug resistant leukaemic cells
2001
We investigated the cytotoxic activity of eight thiazolobenzimidazole derivatives on sensitive HL60 and multidrug-resistant (MDR) (HL60R) leukaemia cell lines. The antitumour effects of these compounds were compared with those of RS-TBZ, a thiazolobenzimidazole derivative, previously described in our reports, that was able to induce apoptosis more markedly in MDR cells than in the parental sensitive cell lines. Only two compounds in this study proved to have interesting effects: (a) the S-enantiomer of TBZ, that was able to induce apoptosis in MDR cells in a slightly more selective manner than TBZ (racemic form); and (b) TBZ-4-OCH3 (TBZ-4-OCH3), that showed cytotoxic and apoptotic effects o…
Beyond cholesterol reduction, the pleiotropic effects of statins: is their use in cancer prevention hype or hope?
2013
ISSN 1758-4299 10.2217/CLP.13.29 © 2013 Future Medicine Ltd Clin. Lipidol. (2013) 8(3), 273–277 Pleiotropic effects of statins Millions of patients worldwide are currently tak ing prescribed statins. Clinical trials have dem onstrated that statins reduce the risk of cardio vascular disease [1]. Statins are well known to reduce cholesterol levels through the inhibition of 3hydroxymethylglutaryl CoA reductase [2]. However, great interest has recently been paid to the mechanisms beyond cholesterol reduc tion (pleiotropic effects) by which statins exert their action. Indeed, statins are associated with plaque stabilization and improvement of endo thelial function, as well as antiinflamm…
Molecular Approaches to Target Heat Shock Proteins for Cancer Treatment
2015
HSP90 was the first molecular target to inhibit the interaction of this heat shock protein (HSP) with client proteins in cancer cells and tissues. The HSP90 inhibition was attempted to liberate from this chaperone the oncogenic fusion proteins, mutated and activated serine/threonine protein kinases, tyrosine kinases, as well as transcription factors with oncogenic activity, in this manner, the free proteins could be recognized by the proteasome system to be degraded. We should remember here that many HSP family members are overexpressed in different kinds of cancer tissues, these molecules act as chaperones of tumorigenesis. In cancer patients, the first generation of HSP90 inhibitors showe…
Prevention and Clinical Management of Cardiovascular Damage Induced by Anticancer Drugs: Need gor Early Biomarkers snd Cardio- snd Vasculo-Protection…
2018
The use of chemotherapy has largely improved the prognosis of cancer patients in the past two decades. However, the advent of more effective anticancer therapies has led to a higher incidence of cardiovascular toxicity that shows an increased incidence and represents a significant determinant of quality of life and mortality during ongoing treatment and in long-term survivors of cancer. In this setting, the primary objective for cardiologists and oncologists is the early identification of patients at high risk for developing cardiovascular toxicity and the identification of the cardiovascular cardiotoxicity in the earliest stages to personalize cancer therapy, arrange preventive interventio…
Timely recognition of cardiovascular toxicity by anticancer agents: a common objective of the pharmacologist, oncologist and cardiologist.
2011
Both conventional and new anticancer drugs can frequently cause adverse cardiovascular effects, which can span from subclinical abnormalities to serious life-threatening and sometimes fatal events. This review examines the principal basic and clinical elements that may be of profit to identify, prevent and treat such toxicities. Clearly, the accomplishment of such objectives requires the strong commitment and cooperation of different professional figures including, but not limited to, pharmacologists, oncologists and cardiologists. The aspect of anticancer drug cardiotoxicity seems to be somehow underestimated, mainly due to inadequate reporting of adverse reactions from oncology drugs in t…
Targeting multiple myeloma with natural polyphenols
2019
Multiple myeloma (MM) is still an incurable hematologic malignancy. Although new therapeutic strategies have been developed to target different pathways in malignant cells, such as proliferation, differentiation, and apoptosis, better survival rates have also been achieved by the introduction of autologous stem cell transplantation (ASCT). Hematopoietic stem cell transplantation and novel targeted agents, such as proteasome inhibitors, monoclonal antibodies, immunomodulatory drugs, check-point inhibitors and epigenetic modulators, have significantly achieved long remission time and increased survival rates. However, most patients relapse, develop resistance, and eventually die because of re…
Multistage rocket: integrational design of a prodrug-based siRNA delivery system with sequential release for enhanced antitumor efficacy.
2018
An integrated peptide-camptothecin prodrug (RSC) system was designed as a nano-sized multistage rocket for the efficient complexation and controlled sequential release of siRNA and anticancer drug under tumor-relevant reductive and esterase-enriched conditions, which facilitated the avoidance of negative interactions and maximized the synergistic effect.
In silico, spectroscopic, and biological insights on annelated pyrrolo[3,2-e]pyrimidines with antiproliferative activity
2013
The in silico COMPARE analysis was performed on 8-[3-(piperidino)propyl]-4,10-dimethyl-9-phenyl-6-(methylsulfanyl)-3,4-dihydropyrimido[1,2-c]pyrrolo[3,2-e]pyrimidin-2(8H)-one, a compound with promising antiproliferative activity, previously synthetized and screened against a panel of 60 human tumor cell lines. The results evidenced that this compound matches the biological properties of Chromomycin A3 and Actinomycin D, known drugs with high DNA binding affinity. Prompted by such results, a thorough spectroscopic investigation of its DNA aqueous solutions was performed, with the aim to verify its DNA-binding properties. DNA groove-binding interaction was assigned by UV-vis spectrophotometri…
Design, synthesis and biological evaluation of new anticancer drugs: FGFR inhibitors
2021
Fibroblast growth factor receptors (FGFRs) constitute a family of tyrosine kinases receptors (RTKs) that exert pivotal physiological functions in human embryonic and adult tissues. Hyperactivated FGFR signaling drives tumorigenesis in multiple cancer types, including lung and brain cancers. Great effort has been laid on the development of new compounds that specifically target the FGFR axis. However, cancer cell- based and microenvironmental resistance mechanisms against FGFR inhibitors often arise and are currently poorly understood. Furthermore, FGFR-targeted therapy often presents different side effects, e due to the broad biological spectrum of the FGFR signaling axis as well as to its …