PubMed Health⌕ Search

Biomedical subjects

T E Keane

Publications and source records attributed to T E Keane.

10 recordsLinked to original sources
PubMed1991

The therapeutic impact of dipyridamole: chemopotentiation of the cytotoxic combination 5-fluorouracil/cisplatin in an animal model of human bladder cancer.

Using an in vivo assay of tumor cytotoxicity (the subrenal capsule assay in nude mice), two therapeutic strategies for the treatment of advanced human transitional cell carcinoma have been evaluated: 1) the use of 5-fluorouracil in combination with cisplatin and 2) the ability of the chemosensitizer dipyridamole to augment the cytotoxicity of CDDP and 5FU. A moderate cytotoxic response of human TCC line DU-4284 to single agent CDDP was seen; it was dose dependent at minimally toxic doses [maximal cytotoxicity--27% tumor survival (%TS) relative to control]. Efficacy was further significantly enhanced by the addition of DP [11%TS (p = .008)]. 5FU at minimally toxic doses (100 and 150 mg./kg.) also demonstrated moderate dose-dependent cytotoxic activity (35 and 31%TS, respectively) which was further enhanced by DP [21%TS (p = .03) and 18%TS (p = .05)]. A constant dose ratio of CDDP/5FU when diluted showed dose-dependent cytotoxicity; at the highest dose dilution studied, substantial cytotoxic efficacy (17%TS) was attained. The cytotoxicity of 5FU/CDDP was order independent (p = .95). The addition of DP to this combination (5FU/CDDP) further enhanced efficacy; host toxicity was not substantially enhanced. A multiple regression analysis confirmed a statistically significant effect of DP with both CDDP and 5FU (p = .001 and 0.0001, respectively); tests for trend showed no significant interaction (p = 0.33 for all models). It is concluded that, in this preclinical in vivo model of human bladder cancer, 1) CDDP and 5FU show substantial enhanced efficacy when combined, and 2) DP serves as an in vivo chemosensitizer of both CDDP and 5FU; DP further augments the efficacy of this binary combination. These data would indicate the potential of this ternary (5FU/CDDP/DP) drug therapeutic regimen for clinical trial to treat advanced bladder cancer.

Animals↗
PubMed1990

Characterization of a new model of human prostatic cancer: the multicellular tumor spheroid.

Multicellular tumor spheroids (MTS) provide a closer in vitro correlate to in vivo malignancy than do conventional monolayer cultures; while simulating many parameters of in vivo growth, MTS systems provide those perquisites (i.e., experimental control, economy, expediency) associated with in vitro evaluation of preclinical therapeutic strategies. For these reasons, we exploited the proclivity of the highly metastatic human prostatic carcinoma subline I-LN-PC3-IA to spontaneously assume a spheroid morphology under routine culture conditions. I-LN spheroids demonstrate salient features described in other spheroid systems and exhibit histologic characteristics of human prostate carcinoma. Cells encompassed in the I-LN spheroid format demonstrated functional divergence from their monolayer counterparts with respect to immunoreactivity for prostatic acid phosphatase, positional dependence of prostate-restricted p40 antigen expression, and chemotherapeutic drug response. This new in vitro-in vivo transition model of human prostatic carcinoma should provide a valuable in vitro context to expediently evaluate in vivo correlates of oncolytic protocols on a malignancy that remains refractive to therapy.

Antineoplastic Agents↗
PubMed1990

Enhanced in vivo cytotoxicity of recombinant human tumor necrosis factor with etoposide in human renal cell carcinoma. Evaluation in a pre-clinical model.

The combination of tumor necrosis factor (TNF) and etoposide (ETP) was evaluated for potential cytotoxic efficacy against a human renal cell carcinoma xenograft using an in vivo assay employing an athymic mouse host with tumor implanted a the subrenal capsule site. Both antitumor efficacy (relative survival or RTS) and toxicity (weight loss) of TNF and ETP alone and in combination were evaluated. While TNF and ETP alone were mildly inhibitory (RTS 90% and 71%, respectively), the combination caused marked tumor inhibition (45% of controls). Host toxicity encountered with the combination did not exceed the toxicity associated with ETP alone, suggesting that the therapeutic index may have been augmented. It is concluded that enhanced antitumor activity without substantial augmentation of toxicity is observed with this combination, providing a rationale for further evaluation of tumor necrosis factor-based regimens for the treatment of advanced renal carcinoma.

Animals↗
PubMed1990

Endometrioma. An intra-abdominal troublemaker.

A ten-year review of intestinal and abdominal wall endometriomas is reported. Seven cases of intestinal and two cases of abdominal wall endometriomas are presented. Symptoms were varied but a majority had some gynecologic complaint. In this select group of patients, preoperative investigations did not assist in establishing the diagnosis. All patients underwent surgery and coexisting inflammatory bowel disease was present in two patients. This review suggests that endometrioma of the intestine requires a high index of suspicion for diagnosis and that danazol does not appear to be effective treatment for these patients.

Abdominal Neoplasms↗
PubMed1990

Dipyridamole-cisplatin potentiation: enhanced in vivo cytotoxicity in xenograft models of human testicular and bladder cancers.

The antitumor efficacy and host toxicity of dipyridamole (DP), methotrexate (MTX) and cisplatin (CDDP) alone and combined were evaluated in a nude mouse supported human bladder cancer model. Single agent post treatment tumor volume growth ratio [TGR] values of DP, MTX and CDDP were 97%, 65% and 49% of control. While the MTX/DP combination produced only mild cytotoxic enhancement, CDDP/DP and CDDP/MTX/DP reduced TGR to 20% and 17%, respectively. A second multi-dose evaluation of CDDP/DP using human testicular carcinoma in this model also showed a CDDP dose-dependent response with achievable complete tumor regression. Host toxicity was not substantially increased by DP. DP would appear to be effective in vivo as a chemosensitizer of CDDP; it may enhance the therapeutic efficacy of CDDP in a variety of tumors.

Animals↗