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J B DeKernion

Publications and source records attributed to J B DeKernion.

14 recordsLinked to original sources

Patterns of cytokine release of unselected and CD8+ selected renal cell carcinoma tumor-infiltrating lymphocytes (TIL). Evidence for enhanced specific killing of tumor necrosis factor-secreting/IL-6 nonsecreting TIL in vitro and correlation with complete response in vivo.

Murine systems have demonstrated improved anti-tumor efficacy when tumor-infiltrating lymphocytes (TIL) are combined with interleukin-2 (IL-2). One goal of human adoptive immunotherapy is to identify and expand TIL with specific activity against autologous tumor. In this study we attempted to isolate and characterize such cells by phenotype and cytokine expression pattern. Fourteen unselected (bulk) TIL and 5 CD8+ selected cultures were established from primary renal cell carcinoma. All cultures were grown in the presence of IL-2; triplicate cultures of each TIL culture were grown in IL-2 alone or were intermittently cocultured with irradiated allogeneic or autologous tumor. The in vitro cytotoxicity, phenotype, and cytokine expression pattern as defined by the secretion of tumor necrosis factor-alpha (TNF-alpha), interferon-gamma, granulocyte-macrophage colony-stimulating factor, IL-4, IL-6, and IL-12 were evaluated for each culture. While there was significant heterogeneity among the cultures under differing culture conditions as characterized by cytotoxicity, phenotype, and cytokine secretion pattern, we identified 8 TIL cultures which demonstrated specific enhanced lysis of only autologous tumor upon exposure to irradiated autologous tumor in vitro. These cultures demonstrate a decreased proportion of cells expressing the phenotype CD11b+. More importantly, these cultures were defined by the cytokine secretion phenotype TNF(+)/IL-6(-) upon exposure to irradiated autologous tumor. When utilized in vivo in adoptive immunotherapy of metastatic renal cell carcinoma together with IL-2, complete resolution of all metastatic tumor has only been achieved in patients who received TIL with the cytokine profile TNF(+)/IL-6(-). These findings suggest that tumor-specific renal TIL with enhanced tumor-specific cytotoxicity can be generated in vitro and can be characterized by a specific pattern of cytokine secretion. In addition, patients who receive TIL characterized by the cytokine profile TNF(+)/IL-6(-) may have an improved outcome when receiving immunotherapy.

CD8 Antigens↗

Intraurethral prostaglandin E-2 cream: a possible alternative treatment for erectile dysfunction.

Prostaglandin E-2 (PGE-2) is an oxytocic agent in suppository form with vasodilatory effects similar to prostaglandin E-1 (PGE-1). Because some men find intracavernosal injections disagreeable, we investigated whether intraurethral PGE-2 may provide an alternative method for treating erectile dysfunction. A PGE-2 cream was made using PGE-2 suppositories (20 mg or 40 mg), 10 cc of 2% lidocaine (Xylocaine) jelly, and 40 cc of surgical lubrication. Two cc of the cream was instilled into the urethral meatus using a syringe, the cream was massaged down the urethra, and the urethra was occluded for five minutes. Treatment response was rated as no penile tumescence, partial tumescence, and full tumescence. Overall, 70 percent showed a response and 30 percent had full penile tumescence. Two of 4 men who had no tumescence using PGE-2 had a subsequent full tumescence using intracavernosal PGE-1 (15 mg), while 3 of 4 men with a partial tumescence with PGE-2 had a subsequent full tumescence using intracavernosal PGE-1 (15 mg). These data demonstrate that full penile tumescence may be achieved in impotent men using intraurethral PGE-2 cream. This pilot study supports the necessity for further investigations in a randomized double-blind manner in the use of intraurethral PGE-2 cream as a less invasive treatment alternative for erectile dysfunction.

Administration, Topical↗

Work in progress: transcatheter embolization of renal cell carcinoma with radioactive infarct particles.

Treatment by radioactive infarct implant is advocated for patients who have renal cell carcinoma with distant metastases. The radioactive infarct implants were placed into the primary tumor, and when feasible into metastases, by transcatheter embolization. Metastases to the skeleton, liver, lungs, adrenals, and retroperitoneal muscles were also seeded; metastases to the central nervous system, pancreas, and spleen, as well as most pulmonary metastases, proved inaccessible to this approach. The effectiveness of this treatment modality was shown by improved cumulative survival rates (59% for patients with metastases and at risk at two years and 50% for those at risk at five years). The best results were obtained when treating patients who had skeletal metastases (90% survival of those at risk at two years and 60% at five years). Measurable palliation factors, such as decrease in the size of the primary lesion, weight gain, and control of bleeding and pain, were indicators of treatment response and were observed in the majority of patients. Remissions were signaled by weight gain, normalization of the erythrocyte sedimentation rate, and disappearance or decrease of tumor markers. Some evidence suggests that the salutary results may be based on significant reduction of tumor burden, temporary local control of tumor, and improved general immunocompetence.

Adenocarcinoma↗

Acute scrotal pain and swelling in children: a surgical emergency.

The pediatric patient with acute scrotal pain and swelling can pose a difficult diagnostic problem. The therapeutic approach to these patients, however, need not be difficult. Despite the advent of Doppler ultrasonic equipment and technetium pertechnetate scanning to differentiate torsion of the testes from other causes of acute scrotal pain and swelling, the policy of emergency scrotal exploration in nearly all such pediatric patients seems to be most appropriate. The exception to this rule might be the rare child with frank pyuria and/or urinary tract infection in whom the diagnosis of epididymo-orchitis is suggested by all parameters.

Adolescent↗