Biomedical subjects

C J Logothetis

Publications and source records attributed to C J Logothetis.

132 records · Page 8Linked to original sources

PubMedDate not supplied

Continuous infusion of vinblastine for advanced hormone-refractory prostate cancer.

Thirty-nine patients with metastatic prostate cancer refractory to hormonal manipulation were treated with vinblastine by continuous infusion. The dose was 1.5 mg/m2 daily for 5 days. A 21% response rate was obtained. Eight patients, two with visceral metastasis, one with nodal disease, and five with osseous metastasis achieved objective response. The median duration of response was 28 weeks. Myelosuppression was the major side effect: the median leukocyte count nadir was 2.8 X 10(3)/ml and the median platelet count nadir was 184 X 10(3)/ml.

Adenocarcinoma↗

PubMedDate not supplied

Antiproliferative effects of cyclocreatine on human prostatic carcinoma cells.

Creatine kinase (CK; EC 2.7.3.2) isoenzymes and their substrates have an important function in cellular energy generation and utilization. The brain isoform (CK-BB) has been implicated in cellular transformation processes involving the oncogenic products of the Ela virus and the p53 tumor suppressor gene. Cyclocreatine, an analogue of creatine, has been previously shown to inhibit the growth of a broad spectrum of cancer cells derived from solid tumors. Results reported herein indicate an increased level of creatine kinase activity in human prostate carcinoma cell lines and inhibitory effects of cyclocreatine alone and in combination with adriamycin on the growth of these cells in vitro and in vivo, in immune-deprived mice. Our results suggest the possible use of cyclocreatine in the treatment of prostatic carcinoma.

Animals↗

PubMedDate not supplied

SMS 201-995 in the treatment of refractory prostatic carcinoma.

The long-acting synthetic somatostatin analog, SMA 201-995, was used to treat patients with advanced hormonal-refractory prostate cancer. Twenty-two of 24 study patients treated are evaluable for toxicity and 20 are evaluable for response. The dose of SMS 201-995 was 100 mg subcutaneously every 8 hours for 6 weeks. Two patients suffered intolerable gastrointestinal complications requiring early cessation of therapy. No patient had objective evidence of tumor regression. After developing a clinical suspicion that tumor growth accelerated with SMS 201-995, we observed 10 patients closely for 2 months before beginning SMS 201-995 treatment and for the first 2 months on the therapy. In these 10 patients, the serum prostatic acid phosphatase level rose at an accelerated rate after 1 to 2 months of treatment. Among the 20 patients treated and evaluable for response, new osseous metastases developed in 12 and new visceral metastases in 4; 1 developed disseminated intravascular coagulation and 2 developed neurologic complications (mean time to objective progression, 5.6 weeks). Six patients received salvage chemotherapy after disease progressed on SMS 201-995 therapy, 5 of whom have achieved objective tumor regressions. We believe SMS 201995 stimulates prostatic tumor growth and may sensitize tumor cells to subsequent chemotherapy.

Acid Phosphatase↗

PubMedDate not supplied

5-Fluorouracil and interferon-alpha in chemotherapy refractory bladder carcinoma: an effective regimen.

Seventy-seven patients with metastatic transitional cell carcinoma of the bladder who were unable to receive primary Cisplatin-based therapy or failed primary chemotherapy received one of three sequential 5-Fluorouracil-based salvage regimens: a) 5-Fluorouracil (1000 mg/m2 B.S.A. x 5 days) and Mitomycin-C (14 mg/m2 B.S.A. 6 week intervals), b) 5-Fluorouracil (750 mg/m2 B.S.A. x 5 days) and a-Interferon (5 miu/m2 B.S.A. daily x 5 then 3 times a week (TIW), c) 5-Fluorouracil (500 mg/m2 B.S.A. x 5 days), a-Interferon (5 miu/m2 B.S.A. x 5 days then TIW) and 13-Cis Retinoic Acid in escalating doses daily. Only 1 (6%) of the patients with regimen A responded, whereas 9 (30%) of the patients with regimen B and 8 (27%) in regimen C responded. Although all responses were partial remissions, responses were seen in patients with advanced and initially refractory transitional cell carcinomas. This data reveals that a-Interferon and 5-Fluorouracil is an effective combination in the treatment of metastatic transitional cell carcinoma and worthy of further study.

Adult↗

PubMedDate not supplied

Growth inhibition of human prostatic carcinoma cell lines by serotonin antagonists.

Neuroendocrine (NE) differentiation within the primary prostate tumor has been correlated with tumor progression and shortened patient survival. Serotonin (5-hydroxytryptamine, 5-HT), a known mitogen, is found in most neuroendocrine cells of the human prostate. We have previously found that human prostatic carcinoma cell lines, PC-3, DU-145 and LNCaP, display certain NE characteristics. In this study, we have examined the effects of several subtype-selective 5-HT receptor antagonists on the growth of the three lines. Of these, the 5-HT1A antagonist pindobind had the most marked antiproliferative effect in vitro. Pindobind also had marked growth-inhibitory effects on the aggressive PC-3 cell line in vivo, in athymic nude mice. Radioligand binding studies indicated the presence of 5-HT binding sites on all three cell lines. Our results suggest that 5-HT is involved in the growth of prostate tumor cells and may serve as a target for treatment.

Cell Division↗

PubMedDate not supplied

Serum calcitonin in small cell carcinoma of the prostate.

Small cell carcinoma (SCC) of the prostate is a rare and recently recognized subtype of prostate cancer. The neuroendocrine component of the prostate carcinoma is becoming more frequently detected in classic adenocarcinoma of the prostate. Clinically, these tumors represent a considerable portion of so called androgen independent prostatic carcinomas. It has been hypothesized that the neuroendocrine cells being admixed with adenocarcinoma is selected and emerges as a hormone refractory carcinoma after the androgen blockade. The SCC shows a spectrum from a mixed adenocarcinoma with SCC component to the extreme case of pure SCC. Characteristically, prostatic SCC shows low measurable serum level of traditional prostate tumor marker, prostatic specific antigen (PSA). Instead, SCC secretes several neural peptides and calcitonin (CT) is one of them. The usefulness of serum CT as a neuroendocrine marker was evaluated retrospectively in 16 patients with SCC of the prostate (5 pure SCCs and II combined adenocarcinoma and SCCs). The serum CT was measured by radioimmunoassay. In all the patients, serum CT level was measured after SCC was diagnosed histologically. All 16 patients presented with advanced tumor with extensive metastasis. Nine (56 percent) out of 16 cases showed elevated serum CT (range 42 approximately 2,654 pg/ml) and chemically supported the diagnosis of SCC. Owing to the retrospective nature of the study, the serum CT was measured only once in most of the cases, and the value of monitoring the disease progress or the responsiveness to the chemotherapy could not be evaluated. Survival analysis by logrank test did not show statistically significant prognostic value of serum CT in SCCs of the prostate. However, patients with extremely high serum CT level tend to have poor survival. Future studies are needed for further evaluation of serum CT as a disease monitor and prognostic marker in SCC of the prostate. Serum CT may have a role as a tumor marker in the early diagnosis of SCC of the prostate, which often is not diagnosed until the advanced stage.

Adenocarcinoma↗