OBJECTIVE This study aims to investigate biological behavior changes in a murine lung cancer cell characterized by acquired resistance to sunitinib, a potent inhibitor of multiple-targeted receptor tyrosine kinase. METHODS A lung cancer cell line resistant to sunitinib (LL/2-R) was developed from its parental cell line (LL/2-P). Differences in biological characteristics and associated molecul...

We have demonstrated that spontaneous mam mary adenocarcinomas in mice are resistant to chemotherapeutic agents that are effective inhibi tors of firstand second-generation transplants of the same tumors (12, 14). In the present work we have continued the comparative study with addi tional compounds selected either on the basis of reports by other workers of high activity against one or more ki...

Cell lines and tumors with defined genetic alterations provide ideal systems in which to test the molecular mechanisms of tumor sensitivity to pathway-targeted therapy. We have generated mouse ovarian epithelial tumor cell lines that contain various combinations of genetic alterations in the p53, c-myc, K-ras and Akt genes. Using both in vitro and in vivo approaches, we investigated the effect ...

PURPOSE Non-small cell lung cancers carrying activating mutations in the gene for the epidermal growth factor receptor (EGFR) are highly sensitive to EGFR-specific tyrosine kinase inhibitors. However, most patients who initially respond subsequently experience disease progression while still on treatment. Part of this "acquired resistance" is attributable to a secondary mutation resulting in th...

Today, development of resistance to anticancer drugs (including cisplatin) is noticed as a major problem. Recently several studies demonstrated that palladium complexes showed remarkable cytotoxic effects against K562 cell line and could be used efficiently for treatment of many human cancers including leukemia. Hereof, K562 cells were made resistant to cisplatin using increasing concentration ...

In the embryonal carcinoma cell line Tera and its 3.7-fold cis-diamminedichloroplatinum(II) (CDDP)-resistant subline, Tera-CP, parameters were studied that might have changed in relation to induction of CDDP resistance. Phenotypes of both lines were embryonal carcinoma. Karyotypes were related with a decreased mean number of chromosomes and fewer copies of the short arm of chromosome 12 in Tera...

PURPOSE A subpopulation of pancreatic ductal adenocarcinoma (PDAC) cells is thought to be inherently resistant to chemotherapy or to give rise to tumor cells that become resistant during treatment. Here we determined the role of CD44 expression and its isoforms as a marker and potential target for tumor cells that give rise to invasive and gemcitabine-resistant tumors. EXPERIMENTAL DESIGN RT-...

Insulin receptor substrates 1 and 2 (IRS1/2) mediate mitogenic and antiapoptotic signaling from insulin-like growth factor 1 receptor (IGF-IR), insulin receptor (IR), and other oncoproteins. IRS1 plays a central role in cancer cell proliferation, its expression is increased in many human malignancies, and its upregulation mediates resistance to anticancer drugs. IRS2 is associated with cancer c...

The standard chemotherapy for brain tumors is temozolomide (TMZ), however, as many as 50% of brain tumors are reportedly TMZ resistant leaving patients without a chemotherapeutic option. We performed serial screening of TMZ resistant astrocytoma cell lines, and identified compounds that are cytotoxic to these cells. The most cytotoxic compound was an analog of thiobarbituric acid that we refer ...

Triple negative breast cancer (TNBC) is a that aggressive with short survival rate. In comparison to other subtypes, TNBC tumors are bigger, more chemo resistant, highly proliferative, and usually abundant in stem immune cells. These modifications functionally dependent on high-quality endoplasmic reticulum mitochondrial pool. Endoplasmic health monitored enhanced regular basis via dynamics. Th...