PURPOSE To investigate the effect and related molecular mechanisms of lapatinib/celastrol combination or single-agent treatment in HER2/neu-overexpressing MDA-MB-453 breast cancer cells. METHODS The effects of treatment with lapatinib, celastrol or their combination on cell growth were determined using MTT assay. Drug synergy was determined using the combination index (CI) methods derived fro...

Purpose:Novel therapeutic regimens are needed to improve dismal outcomes associated with late-stage ovarian cancer. Oncolytic viruses are currently being tested in patients with ovarian cancer. Here, we tested the therapeutic efficacy of combining doxorubicin with 34.5ENVE, an oncolytic herpes simplex virus transcriptionally driven by a modified stem cell–specific nestin promoter, and encoding ...

Oncolytic viruses selectively replicate in cancer cells by exploiting biochemical differences between normal and tumor cells. Treatment with epigenetic modifiers such as 5-Azacytidine, a DNA methyltransferase inhibitor, increases the replication and cytotoxicity of oncolytic viruses in vivo and in vitro. The cotton rat is an attractive animal to study oncolytic viruses, as syngeneic models of b...

Uroporphyrinogen decarboxylase (UROD) catalyzes the conversion of uroporphyrinogen to coproporphyrinogen during heme biosynthesis. This enzyme was recently identified as a potential anticancer target; its inhibition leads to an increase in reactive oxygen species, likely mediated by the Fenton reaction, thereby decreasing cancer cell viability and working in cooperation with radiation and/or ci...

Multimodal therapy is generally more effective than single-agent treatment for cancer. rRp450 is an engineered herpes simplex viral mutant that replicates in and kills tumor cells in a relatively selective fashion. It also expresses, in infected cells, the cyclophosphamide (CPA)-sensitive rat cytochrome P450 2B1 (CYP2B1) and the ganciclovir (GCV)-sensitive herpes simplex virus thymidine kinase ...

BACKGROUND Chemotherapy is one of the antitumor therapies used worldwide in spite of its serious side effects and unsatisfactory results. Many attempts have been made to increase its activity and reduce its toxicity. 5-Fluorouracil (5-FU) is still a widely-used chemotherapeutic agent, especially in combination with other chemotherapies. Combination therapy seems to be the best option for target...

PURPOSE Oncolytic viruses (OV) based on herpes simplex virus type 1 (HSV1) are being used in clinical trials for a variety of cancers. The OV, rQNestin34.5, uses a nestin promoter/enhancer to selectively drive robust viral replication in malignant glioma cells. We have discovered that this promoter becomes extensively methylated in infected glioma cells, reducing OV efficacy. EXPERIMENTAL DES...

There is a clear clinical need for alternative types of non-antibiotic biocides due to the rising global health concern of microbial drug resistance. In this work, a novel antibacterial concept was delineated that utilized hyperosmotic stress (H) in concert with membrane-disrupting nanoemulsions (NEs). The antibacterial effects of either H or a NE, as well as in combination (H+NE), were assesse...

The development of drug resistance remains one of the major hurdles in cancer chemotherapy, particularly so for ovarian cancer. Combination of drugs acting synergistically in combination can offer a means of overcoming drug resistance. In this study, two tumour-active phytochemicals, quercetin and thymoquinone, were combined with two platinum drugs, cisplatin and oxaliplatin, with the aim of pr...

PM01183 is a novel marine-derived covalent DNA binder in clinical development. PM01183 is structurally similar to trabectedin (yondelis, ecteinascidin-743) except for the C subunit, and this modification is accompanied by different pharmacokinetics in cancer patients. We here characterize the interaction of PM01183 with the nucleotide excision repair (NER) pathway in comparison with trabectedin...