peplomycin and Salivary-Gland-Neoplasms

We have recently isolated TSC-22 (transforming growth factor-beta-stimulated clone-22) cDNA as an anticancer, drug-inducible (with vesnarinone) gene in a human salivary gland cancer cell line, TYS. We have also reported that TSC-22 negatively regulates the growth of TYS cells and that down-regulation of TSC-22 in TYS cells plays a major role in salivary gland tumorigenesis (Nakashiro et al, 1998). In this study, we transfected TYS cells with an expression vector encoding the TSC-22-GFP (green fluorescent protein) fusion protein, and we established TSC-22-GFP-expressing TYS cell clones. Next, we examined (a) the subcellular localization of the fusion protein, (b) the sensitivity of the transfectants to several anticancer drugs (5-fluorouracil, cis-diaminedichloroplatinum, peplomycin), and (c) induction of apoptotic cell death in the transfectants by 5-fluorouracil treatment. The TSC-22-GFP fusion protein was clearly localized to the cytoplasm, but not to the nucleus. Over-expression of the TSC-22-GFP fusion protein did not affect cell growth, but significantly increased the sensitivity of the cells to the anticancer drugs (p < 0.01; one-way ANOVA). Furthermore, over-expression of the TSC-22-GFP fusion protein markedly enhanced 5-fluorouracil-induced apoptosis. These findings suggest that over-expression of TSC-22-GFP protein in TYS cells enhances the chemosensitivity of the cells via induction of apoptosis.

Topics: Antineoplastic Agents; Apoptosis; Cell Adhesion; Cell Division; Cell Survival; Chromatin; Cisplatin; Fluorouracil; Green Fluorescent Proteins; Humans; Luminescent Proteins; Peplomycin; Recombinant Fusion Proteins; Salivary Gland Neoplasms; Transcription, Genetic; Transfection; Transforming Growth Factor beta; Tumor Cells, Cultured

In patients with head and neck carcinoma, fixed enlarged metastatic lymph nodes (LNs) are sometimes inoperable and carry an increased risk of mortality. To control metastatic LNs, we attempted intranodal injection of anticancer agents.. Fifteen patients with squamous cell carcinoma arising in the gingiva (8), tongue (3), floor of the mouth (1), or maxillary sinus (3) were enrolled. These patients consisted of two groups, those in the early era in which the fixed LNs of six patients were treated with 60Co (RA group) and those in the late era in which both radiation and intranodal injection of anticancer agents were administered to nine patients (IN group). Intranodal injection consisted of peplomycin, 5-fluorouracil, and cis-diamminedichloroplatinum.. In the IN group, LNs regressed from about 40% to nearly 100%, although two patients showed no appreciable response. The LNs treated by combination therapy regressed considerably while LNs in the same patients treated with 60Co alone showed a minor response or grew gradually. In three patients, the LNs regressed sufficiently to be extirpated safely. The good clinical response in the locally injected LNs was histologically associated with distinct evidence of tumor cell degeneration. In the RA group, none of the LNs responded to radiation with 60Co; one LN exhibited slight regression, but the others enlarged during and soon after the radiation. Compatible with the clinical effects, many patients in the IN group demonstrated a good prognosis; three are alive without disease, and four survived for prolonged periods. However, all patients in the RA group died due to progression of the positive LNs or pulmonary complication within 10 months.. These results indicate that intranodal injection of anticancer drugs is useful for the management of fixed enlarged LNs.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Evaluation Studies as Topic; Female; Fluorouracil; Humans; Injections, Intralymphatic; Lymphatic Metastasis; Male; Middle Aged; Mouth Neoplasms; Neck; Patient Selection; Peplomycin; Salivary Gland Neoplasms

Four kinds of cultured human tumor cell lines sensitive or resistant to bleomycin (BLM) were examined for the effect of filipin, a polyene antibiotic, on peplomycin (PEP)-induced cell killing. Although PEP was more effective than BLM against BLM-resistant HeLa cells (HeLa-BLMr), neoplastic cells derived from salivary gland (HSG) and melanoma cells (MEC), these three cell lines were still at least ten times more resistant to PEP than epidermoid carcinoma cell lines including HeLa cells by comparison of IC50, and showed lower cellular accumulation of 3H-PEP as compared with HeLa cells. When these lines were pretreated with filipin, 3H-PEP accumulation by the cells was increased 1.33-, 2.34-, 1.91- and 1.14-fold in HeLa, HeLa-BLMr, HSG and MEC cells, respectively. Combination use of PEP and filipin resulted in a remarkable enhancement of cytocidal effect in HeLa-BLMr and HSG cells (100- and 25-fold decrease of IC50, respectively), and a slight enhancement in HeLa cells, but not in MEC cells. It is therefore suggested that there are differences among cell types in the potentiation of PEP-induced cell killing by filipin.

Topics: Bleomycin; Cell Division; Cell Line; Cell Survival; Cells, Cultured; Drug Synergism; Filipin; HeLa Cells; Humans; Melanoma; Neoplasms; Peplomycin; Polyenes; Salivary Gland Neoplasms