The effects of taurolidine, a novel antineoplastic agent, on human malignant mesothelioma.

Purpose: Malignant mesothelioma (MM) is a cancer with uniformly poor responses to current therapeutic regimens. This study evaluates whether taurolidine, a novel antineoplastic agent, is effective against human MM cell lines and a murine model of human MM.

Experimental Design: Cell growth inhibition and viability assays were performed on REN, LRK, and H28 cell lines after 24-72-h exposure to 0-200 microm taurolidine.

Mechanistic and antineoplastic evaluation of taurolidine in the DU145 model of human prostate cancer.

Taurolidine (TRD) was designed in the 1970s as a broad-spectrum antibiotic and is used clinically at high doses without systemic toxicity. We have found that this agent possesses cytotoxic activity in human tumor cell lines and antineoplastic activity in mice bearing i.p.

Thrombospondin-1 plus irinotecan: a novel antiangiogenic-chemotherapeutic combination that inhibits the growth of advanced human colon tumor xenografts in mice.

Chemotherapy for the treatment of advanced or metastatic colon cancer, utilizing agents such as 5-fluorouracil (5-FU) and irinotecan (CPT-11), produce a 5-year survival of about 10%. Thus, the identification of new, effective, therapeutic regimens to treat this disease remains critically important. To this end, selected antiangiogenic agents, compounds that inhibit neovascularization, have been shown to produce a modest tumor growth-inhibitory effect with little systemic toxicity.

Use of growth factors in the elderly patient with cancer: a report from the Second International Society for Geriatric Oncology (SIOG) 2001 meeting.

Over 70% of the total incidence of cancer recorded in Europe in 1996 was in the elderly population (> or =60 years). Despite such high statistics, elderly cancer patients have often been denied the treatment that younger patients routinely receive. The response of elderly cancer patients to full-dose chemotherapy treatment in several neoplasms is similar to that of younger patients, demonstrating that age should not be a barrier to the administration of potentially curative or palliative chemotherapy.

The antibacterial drug taurolidine induces apoptosis by a mitochondrial cytochrome c-dependent mechanism.

The antibacterial agent taurolidine (TRD) has been used as a lavage antibiotic to prevent development of peritonitis in patients after surgery. We recently showed that TRD induced growth arrest and apoptosis of a variety of cultured cell lines derived from human solid tumors and also significantly inhibited the growth of human ovarian tumors in a mouse model. In this report, we present data to show that TRD, at concentrations below the doses that are used to treat patients in the clinic, induces apoptosis of human leukemia HL-60 cells by a mitochondrial cytochrome c-dependent pathway.

A role for MAP kinase in the antitumor activity of a nucleoside analog.

Nucleoside analogs (NAs) have been used extensively in both antitumor and antiviral therapies. Their general mechanism of action has been postulated to result from incorporation into DNA, leading to disruption of DNA synthesis and DNA polymerase inhibition. To further explore the antitumor mechanisms of NAs we have evaluated ganciclovir (GCV), an NA antiviral agent, in herpes simplex virus thymidine kinase (HSV-TK) gene-modified tumor cells.

Role of p21 in apoptosis and senescence of human colon cancer cells treated with camptothecin.

Treatment of cells with the anti-cancer drug camptothecin (CPT) induces topoisomerase I (Top1)-mediated DNA damage, which in turn affects cell proliferation and survival. In this report, we demonstrate that treatment of the wild-type HCT116 (wt HCT116) human colon cancer cell line and the isogenic p53(-/-) HCT116 and p21(-/-) HCT116 cell lines with a high concentration (250 nm) of CPT resulted in apoptosis, indicating that apoptosis occurred by a p53- and p21-independent mechanism. In contrast, treatment with a low concentration (20 nm) of CPT induced cell cycle arrest and senescence of the wt HCT116 cells, but apoptosis of the p53(-/-) HCT116 and p21(-/-) HCT116 cells.