The continuous exposure of antimicrotubule drugs to tumors often results in the emergence of drug-resistant tumor cells with altered expression of several beta-tubulin isotypes. We found that Vinca alkaloid enhanced expression of class II beta-tubulin isotype (mTUBB2) in mouse B16F10 melanoma cells via alteration of the tumor suppressor p53 protein. Vincristine treatment stimulated an increase ...

BACKGROUND New treatment models are needed for the management of advanced stage head and neck carcinomas (HNSCC). Vinflunine is a novel vinca alkaloid which has shown remarkable improvement in efficiency and reduced side-effects in both in vitro and in vivo studies. Better locoregional control and prevention of distant metastasis in advanced HNSCC would be welcome and, with this new efficient c...

The plasticity and instability of the cancer genome is impressive and is characterized by gene amplifications and deletions, rearrangements, and many silent and active mutations. Although targeted therapeutics have had effect in some diseases, there remains a large role for new cytotoxic agents that have the potential to be broadly active across multiple cancers. Platinum-based regimens are the...

Antibodies reactive with human epidermal growth factor receptor (EGFr), such as 225 IgG1 (Masui et al., Cancer Res., 44: 1002-1007, 1984), are effective tumor-suppressive agents in xenograft models. In the present study an additional antibody reactive with EGFr was made and compared to 225 IgG1 for antitumor activity as an unmodified antibody or as a drug immunoconjugate. This IgG1 clone, desig...

Microtubule targeting drugs like taxanes, vinca alkaloids, and epothilones are widely-used and effective chemotherapeutic agents that target the dynamic instability of microtubules and inhibit spindle functioning. However, these drugs have limitations associated with their production, solubility, efficacy and unwanted toxicities, thus driving the need to identify novel antimitotic drugs that ca...

Drug resistance is a major problem in the successful treatment of cancer. Resistance to one drug is often associated with cross-resistance to other anticancer agents. This is commonly seen with the "natural product" anticancer drugs such as the Vinca alkaloids and anthracyclines. In experimental systems, specific changes in plasma membranes characterize this "multiple drug resistance." The most...

Farnesyl transferase (FTase) is an enzyme responsible for post-translational modification in proteins having a carboxy-terminal CaaX motif in human. It catalyzes the attachment of a lipid group in proteins of RAS superfamily, which is essential in signal transduction. FTase has been recognized as an important target for anti cancer therapeutics. In this work, we performed virtual screening agai...

Antibody-drug conjugates (ADC) are an emerging drug class that uses antibodies to improve cytotoxic drug targeting for cancer treatment. ADCs in current clinical trials achieve a compromise between potency and physicochemical/pharmacokinetic properties by conjugating potent cytotoxins directly to an antibody at a 4:1 or less stoichiometric ratio. Herein, we report a novel, polyacetal polymer-ba...

Poor reproducibility of cytotoxicity tests with Vinca alkaloids has fre quently been reported. A commonly presumed light sensitivity of the drugs could not be confirmed. However, we found that they are photo sensitized by riboflavin (vitamin li.i, an obligatory component of cell culture media. Light of wavelengths below 500 nm triggered rapid photoreactions of riboflavin with vinblastine, \ im ...

Catharanthus roseus is a medicinal herb found in many tropical and subtropical regions around the world. This plant produces a diverse array of secondary metabolites that are pharmaceutically important like vinblastine and vincristine used as chemotherapeutic agents in the treatment of several types of cancers. Low yield of these vinca alkaloids from the plant in vivo and the challenges to meet...