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Thomas E Keane

Publications and source records attributed to Thomas E Keane.

10 recordsLinked to original sources
PubMed2006

Involvement of sphingolipids in apoptin-induced cell killing.

The potential anti-tumor agent Apoptin activates apoptosis in many human cancers and transformed cell lines, but is believed to be less potent in primary cells. Although caspase 3 is activated during apoptin-induced apoptosis, the mechanism of tumor cell killing remains elusive. We now show that apoptin-mediated cell death involves modulation of the sphingomyelin-ceramide pathway. Treating cells with Ad-GFPApoptin resulted in increased ceramide accumulation and enhanced expression of acid sphingomyelinase (ASMase) with a concomitant increase in ASMase activity and decreased sphingomyelin. Using confocal microscopy, ASMase, normally present in the endosomal/lysosomal compartment, was observed to translocate to the cell's periphery. Cotreatment of Ad-GFPApoptin-infected cells with the ASMase inhibitor desipramine (2.5 muM) attenuated (30%; P<0.01) apoptin-induced cell death. Apoptin was also able to induce a significant decline in sphingosine content by inhibition of ceramide deacylation through down-regulation of acid ceramidase at the protein level. Supporting the role of ceramide in apoptin action, treatment of cells with the combination of an exogenous cell-permeable ceramide analog (C6-ceramide) and Ad-GFPApoptin infection yielded a significant increase (P<0.01) in apoptosis over either treatment modality alone. Together, these data suggest that apoptin modulates ceramide/sphingolipid metabolism as part of its mechanism of action.

Adenoviridae↗
PubMed2006

The emergence of radioimmunoscintigraphy for prostate cancer.

The ability to label tissue-specific antibodies has long been of interest for improving detection and guidance for therapeutic applications. The most studied target for prostate cancer is the prostate-specific membrane antigen, which is upregulated in prostate cancer, hormone-refractive disease, and prostate cancer metastases. Investigations using radioimmunoscintigraphy with the radiolabeled 7E11 antibody capromab pendetide have significantly improved sensitivity for prostate cancer detection compared with standard cross-sectional imaging, based on tissue confirmation of pathologic results. Over the past 5 years, significantly greater image resolution from improved camera technology and the use of co-registration to fuse functional and anatomic (computerized tomography and magnetic resonance imaging) images have dramatically enhanced prostate cancer localization. Outcomes data from several sources have spurred a resurgence in interest in this imaging modality.

Journal Article↗
PubMed2005

Fluorescence in situ hybridization for detecting transitional cell carcinoma: implications for clinical practice.

OBJECTIVE: To determine the diagnostic sensitivity of genetic studies using fluorescence in situ hybridization (FISH) for detecting both new and recurrent cases of transitional cell carcinoma (TCC) in a routine clinical practice setting, as bladder cancer has a significant risk of recurrence and progression to invasive disease and thus sensitive surveillance testing is very important. PATIENTS AND METHODS: FISH was performed using the UroVysion kit (Vysis Inc., Downers Grove, IL, USA) Consecutive patients were assessed using FISH, both to evaluate those with a history of TCC or with suspicious symptoms, and the FISH results were compared with concurrent biopsy and cytological assessments. RESULTS: In all, 521 consecutive FISH tests from 300 patients were evaluated; 47% had a history of bladder cancer and 53% had suspicious symptoms. Of the 521 FISH tests, 24% were positive; concurrent cytology was available for 84% of the FISH tests, with a concordance rate of 78% (6% were positive for both and 72% were negative by both tests). For the discordant cases, FISH was positive and cytology negative in 21% of cases, and cytology was positive with a negative FISH for 1%. In all, 99 FISH tests had concurrent biopsy data. Of the 44 cases histologically positive for TCC, 32 were FISH-positive, resulting in an overall sensitivity (95% confidence interval) of 73 (60-88)%. FISH detected 95% of cases with high-grade carcinoma, while only seven of these 17 were positive by concurrent cytological assessment. FISH detected 56% and cytology detected 32% of low-grade lesions. FISH detected all nine new cases with positive histology. Overall, the specificity of FISH was 65 (53-78)%. Of 112 patients with previous TCC, 28 had a recurrence; 22 of these had positive FISH results. CONCLUSION: FISH analysis has a high sensitivity for detecting new cases of TCC, as well as recurrences. From the present data FISH is considerably more sensitive and only slightly less specific than cytology in diagnosing TCC. Therefore, we recommend FISH as a useful initial diagnostic tool in patients suspected of both new and recurrent TCC.

Adult↗
PubMed2005

The present and future for gene and viral therapy of directly accessible prostate and squamous cell cancers of the head and neck.

Gene therapy has been in a continuous evolutionary process since the first approved trial occurred in 1990 at the National Institute of Health. In the USA, as of March 2004, there were 619 approved gene therapy/transfer protocols and 405 of these were for cancer treatment. Another 294 trials are in progress worldwide, with most concentrated in Europe. However, cancer gene therapy is in its relative infancy when compared with the well-established use of chemo-radiotherapy for treating cancer. As the field develops it is becoming clear that using gene therapy in conjunction with established chemo-radiotherapy approaches is yielding the best results. This concept shall be reviewed in the context of the status of the field, and a future direction based on a combination of gene therapy with small molecule modification of sphingolipid metabolism shall be discussed.

Adenoviridae↗
PubMed2004

Community-acquired methicillin-resistant Staphylococcus aureus prostatic abscess.

We present a 43-year-old man with a history of intravenous drug abuse who presented to the emergency department with a 5-week history of lower urinary tract symptoms. On digital rectal examination, a firm prostate with exquisite tenderness was noted. Computed tomography scan of the pelvis with contrast demonstrated a 4.4 by 2.7-cm prostatic abscess in the right lobe. Suppurative fluid was expressed from the right prostatic lobe during transurethral resection of the prostate. Cultures of blood and suppurative prostatic fluid grew methicillin-resistant Staphylococcus aureus.

Abscess↗
PubMed2003

Concomitant intraoperative renal artery embolization and resection of complex renal carcinoma.

BACKGROUND: Renal cell carcinoma, which has the propensity for rapid enlargement and local invasion, may present a surgical challenge, in part because of extensive vascularity. Conventional treatment typically involves staged preoperative renal artery embolization followed by nephrectomy after 1 or 2 days. We evaluated the clinical outcome of concomitant intraoperative embolization and nephrectomy. METHODS: Over 7 years, eight patients with renal cell carcinoma underwent combined intraoperative renal artery coil embolization and nephrectomy. A cohort of 14 patients who underwent staged renal embolization and nephrectomy during the same period served as the control group. Renal tumor embolization was achieved via percutaneous femoral artery approach, followed by coil placement in the distal portion of the main renal artery. Complete renal artery embolization was confirmed with intraoperative angiography. Nephrectomy was performed either concomitantly or after renal artery embolization, dependent on treatment group. Intraoperative data, clinical outcome, and hospital cost were compared between the two groups. RESULTS: Renal artery embolization and nephrectomy were successfully performed in all patients. There was no perioperative mortality. Mean hospital length of stay in the combined and staged treatment groups was 5.6 +/- 1.3 days and 10.2 +/- 3.2 days, respectively. Post-infarction syndrome developed in four patients (36%) in the staged group, compared with no patients in the combined treatment group. Decreased room cost and radiology cost was noted in the combined treatment group compared with the staged group. Mean total hospital cost was significantly less in patients who underwent the combined treatment compared with the staged treatment approach (mean difference, US dollars 9214; P =.02) During mean follow-up of 36 months, six patients (27%) died of unrelated causes. There was no evidence of tumor recurrence in surviving patients. DISCUSSION: In patients with renal cell carcinoma, combined renal embolization and nephrectomy minimizes patient discomfort and post-infarction syndrome associated with traditional staged treatment. Moreover, it is associated with reduced hospital costs, due in part to decreased hospital length of stay. Vascular surgeons with endovascular skills are well suited to perform intraoperative renal artery embolization. Use of adjunctive endovascular techniques to facilitate large open procedures is a growing role for the endovascular-competent vascular surgeon.

Aged↗
PubMedDate not supplied

Camptothecin analogues and vinblastine in the treatment of renal cell carcinoma: an in vivo study using a human orthotopic renal cancer xenograft.

To perform a series of in vivo cytotoxicity studies using a variety of doses of the comptothecin analogues 9-Aminocamptothecin (9-AC) and Irinotecan (CPT-11) with a human RCC xenograft tumor line (DU11983m). Using the subrenal capsule assay (80 nude mice) (NM-SRCA), 9-AC was evaluated at both low and high dosage levels (0.75 mg/kg and 1.25 mg/kg oral x10 doses over 12 days). Following an initial assessment of acute tumor inhibition, the study was extended to a survival assay with some cohorts receiving retreatment boluses on a once or twice weekly basis. CPT-11 was assessed at a dose of 100 mg/kg x3 over 9 days with weekly retreatment and two cohorts received 9-AC combined with Vinblastine (2.7 mg/kg) and Vinblastine alone, respectively. Tumor inhibition: tumor growth inhibition was significant (over 80%) with all cohorts receiving any camptothecin analogue and was virtually complete (>99% tumor inhibition) at the high dose 9-AC (1.25 mg/kg). Vinblastine alone achieved only moderate cytotoxic effect (46%) and induced the largest recorded cohort weight loss (toxicity). Survival analysis: the low and high dose 9-AC single agent cohorts were not significantly different; however, the CPT-11 cohort experienced maximal survival benefit. (P = 0.003) and the addition of Vinblastine did not enhance this survival advantage among the 9-AC cohorts. Control and single agent Vinblastine cohorts had the poorest survival with the treated group still surviving longer (P = 0.02). At 35 days after final assessment of acute tumor inhibition, all animals in both the control and Vinblastine alone cohorts were dead. None of the animals in any of the other cohorts (all of which had experienced a greater than 80% tumor inhibition) had died. No deaths occurred due to surgery or treatment toxicity and all deaths were deemed tumor related. CPT-11 and 9-AC produced a marked survival advantage in an orthotopic model of human advanced renal carcinoma and are identified as agents for further clinical assessment.

Animals↗