Biomedical subjects

J B Dekernion

Publications and source records attributed to J B Dekernion.

At least 19 recordsLinked to original sources

PubMed1998

Diagnosis and treatment of prostate cancer.

In the United States, prostate cancer is the most common solid tumor malignancy in men and second to lung cancer as the leading cause of cancer deaths in this group. Even though prostate cancer is responsible for 40,000 deaths per year, screening programs are a matter of controversy because scientific evidence is lacking that early detection decreases morbidity and mortality. Furthermore, treatment decisions are difficult to make because of the generally indolent nature of prostate cancer and because it tends to occur in older men who often have multiple, competing medical illnesses. Depending on the specific situation, radical prostatectomy, radiotherapy or watchful waiting (observation) will be the most appropriate management option. In general, localized cancer is best treated with surgical removal of the prostate gland or radiotherapy. Hormone deprivation therapy is the primary method of controlling metastatic prostate cancer. At present, chemotherapy cannot cure disseminated prostate cancer. Watchful waiting is a reasonable management alternative for prostate cancer in an older patient or a patient with other serious illnesses.

Adult↗

PubMed1995

Prostate tissue specificity of the prostate-specific antigen promoter isolated from a patient with prostate cancer.

We have cloned and characterized a 620-bp fragment of DNA that flanks 5' of the prostate-specific antigen (PSA) gene from a prostate cancer patient. Using DNA transfection, the efficacy of this putative promoter in regulating gene expression was quantitated in several prostate and nonprostate tissue cell lines. Our results demonstrated that the 620-dp DNA fragment actively drives gene expression in LNCaP, a PSA-producing prostate tumor cell line. No promoter activity was detected in the non-PSA-producing prostate tumor lines, DU145 and PC-3, nor in a renal (R11) or breast (MCF-7) cancer cell line. Furthermore, the promoter activity could be regulated in vitro by androgen stimulation. Dihydrotestosterone (DHT) concentrations between 3 and 30 nM induced the highest promoter activity in the transfected LNCaP cells, which parallels the expression profile of the androgen receptor in LNCaP cells. In addition, our PSA promoter exhibited competitive inhibition of the endogenous genomic PSA promoter in transfected LNCaP cells, suggesting that prostate cell-specific DNA-binding proteins are required to activate the PSA promoter. increased its potency four- to five-fold while retaining tissue specificity. Our data suggest that a strong tissue-specific negative regulatory element capable of overriding the nonspecific CMV promoter is present in the PSA promoter and confers its tissue specificity. The use of a highly specific promoter-driven gene vector will allow selective expression of therapeutic genes within PSA-producing prostate cancer cells, providing a unique strategy for prostate cancer gene therapy.

Antigens, Neoplasm↗

PubMed1995

Derivation and application of upper limits for prostate specific antigen in men aged 50-74 years with no clinical evidence of prostatic carcinoma.

OBJECTIVE: To derive age-specific upper limits for prostate specific antigen (PSA) level in men 50-74 years of age with no clinical evidence of prostatic carcinoma, and to test the sensitivity and specificity for cancer detection of these upper limits. SUBJECTS AND METHODS: A total of 6166 men were recruited for a multicentre study of prostate cancer detection and underwent a serum PSA determination and digital rectal examination (DRE). Men considered to be clinically free of prostatic carcinoma were those with a normal DRE and a PSA level < or = 4.0 ng/mL, and men with an abnormality in either parameter who underwent ultrasonography-guided prostate biopsy that revealed no evidence of carcinoma. By these criteria, 5469 men had no evidence of prostatic carcinoma. Dividing the population into 5-year age increments, three statistical methods were assessed to derive upper limits for serum PSA level by age; the mean +2 SD, the 99th percentile, and a 97.5% prediction interval based on linear regression. RESULTS: Newly-derived upper limits calculated by each method in the 50-54 and the 70-74 age group were 3.9 ng/mL and 7.6 ng/mL (mean +2 SD), 5.2 ng/mL and 14.0 ng/mL (99th percentile), and 4.7 ng/mL and 8.2 ng/mL (97.5% prediction interval). The sensitivity of the newly-derived upper limits was tested using receiver operating characteristic curves derived from men with no suspicious findings on DRE and a serum PSA concentration > 4.0 ng/mL. Although the specificity of the test increased with increasing PSA upper limits, no upper limits derived from these three methods yielded adequate sensitivity to detect cancer; sensitivities by age range were from 53 to 94%, using mean +2 SD, from 25 to 50% with the 99th percentile, and from 47 to 64% with the 97.5% prediction interval. CONCLUSION: We do not recommend age-referenced adjustments in upper limits for serum PSA concentration, but recommend that an upper limit of 4.0 ng/mL be used in all men 50-74 years of age.

Aged↗

PubMed1995

Surgery from a US perspective.

Prostate screening has made it possible to detect organ confined prostate carcinoma in men with a life expectancy of 20 years and longer. These clinically significant malignancies may be successfully eradicated by means of anatomical dissection of the prostate, which minimizes both morbidity and mortality. In a retrospective series of patients with clinically localized prostate cancer who were treated with a radical retropubic prostatectomy and lymph node dissection, 5 and 10 year crude survival rates were 96% and 86%. Survival was compromised by penetration of tumour through the prostatic capsule, and even more significantly by involvement of the seminal vesicles. The use of prostate specific antigen (PSA) concentrations to monitor disease progression before any clinical manifestation revealed that disease free survival was less than previously reported. Patients diagnosed and treated more recently had longer disease free survival than the overall group mainly because of earlier detection with PSA, with consequent lower tumour volumes and stage. In addition, 92 +/- 3(SD)% patients with pathologically organ confined tumours, without capsular or seminal vesicle invasion, are clinically disease free with non-detectable PSA at 5 years. Our data therefore show that radical prostatectomy can cure patients with organ confined prostate cancer, with acceptable morbidity. Although the need for cure may be questioned in many patients, young patients with prostate cancer almost certainly benefit from eradication of the malignancy.

Adult↗

PubMed1992

The expression of C-jun and junB mRNA in renal cell cancer and in vitro regulation by transforming growth factor beta 1 and tumor necrosis factor alpha 1.

The proto-oncogene C-jun acts as a transcriptional activator or repressor for numerous cellular genes, and the overexpression of these genes may cause malignant transformation. JunB inhibits c-jun's transforming activities. We investigated the expression of jun genes in renal cell cancer (RCC) and their regulation by cytokines and transforming growth factor beta 1 (TGF-b1). The constitutive expression of c-jun was detected in 39 of 43 fresh frozen RCC, 5 of 10 normal kidneys, and the expression of junB detected in 28 of 34 RCC, 5 of 6 normal kidneys. C-jun was also found expressed in all 10 RCC tumor lines examined and junB was expressed at low levels in 6 of 10 renal tumor lines. TGF-b1 and tumor necrosis factor alpha (TNF-a) have been shown to alter the expression of jun genes in other tissue types. Additionally, TGF-b1, TNF-a, and gamma interferon (g-IFN) were shown to inhibit the growth of RCC. We found that TGF-b1 highly augmented the expression of junB (mean of 34 folds, p less than .05), but did not significantly alter the expression of c-jun, the transforming gene. In contrast, TNF-a significantly enhanced the expression of both c-jun (mean fold enhancement of 2.1, p less than .05) and junB (2.2 folds, p less than .05). Interleukin-2 (IL-2), interleukin-4 (IL-4) and g-IFN did not significantly alter jun expression. The findings presented suggest that c-jun may have a role in inducing malignant transformation in RCC and a novel mechanism by which TGF-b1 may exert its anti-tumor effects, via the activation of junB. Additionally, although TGF-b1, TNF-a, and g-IFN all have anti-proliferative actions on RCC in vitro, they were found to have different effects in altering jun expressions.

Carcinoma, Renal Cell↗

PubMed1991

The effects of interleukin-6 on tumor-infiltrating lymphocytes derived from human renal cell cancer.

Tumor-infiltrating lymphocytes (TIL) are a heterogeneous population of T cells with potent antitumor activity against a wide variety of tumors. TIL from renal cell cancer (RCC) typically exhibit diminished growth and antitumor activity after four weeks in vitro. We have therefore investigated effects of varying doses of interleukin-6 (IL-6) (0, 25, 100 units/ml.) on in vitro expansion, proliferation, cytotoxicity, and expression of cell surface phenotypes of long term renal TIL cultures from three RCC patients. Among the various conditions tested, three of three TIL cultures displayed a mild increase in cell expansion when grown in IL-2 with the addition of 100 units/ml. of IL-6. Two of three TIL cultures grown in IL-2 and 100 U/ml. of IL-6 demonstrated enhanced proliferation as determined by 3H-thymidine uptake. TIL could not be isolated or maintained in vitro when grown in the presence of IL-6 alone without IL-2. IL-6 was also found to enhance the long term non-specific cytotoxicity against an allogeneic nonrenal tumor target. No consistent effect on autologous tumor-specific cytotoxicity was demonstrated. We conclude that IL-6, when used in combination with IL-2, may modestly enhance the long-term growth of RCC-derived TIL.

Carcinoma, Renal Cell↗

PubMed1991

[Adoptive immunotherapy and metastasized cancer of the kidney. Regulator effects of interleukin-4 on tumor infiltrating lymphocytes (TIL)].

Adoptive immunotherapy is a new therapeutic approach of the treatment of advanced renal cell cancer. Experimental studies have shown that the cells with the highest cytolytic activity are tumor infiltrating lymphocytes (TIL). The effects of interleukin-4 (IL-4) on the expansion, proliferation, phenotype and antitumor activity of TIL were studied. Cultures were obtained from three primary renal tumors and one group of tumor invaded, regional lymph nodes. IL-4 induced a significant increase in lymphocytes expansion and proliferation, but the response was dependent of the concurrent dose of IL-2 in culture. TIL grown in the presence of IL-4 significantly reduced the level of non specific, non MHC restricted antitumor activity while exhibiting no effect on the level of autologous killing. The effects of irradiated autologous tumor stimulation on TIL cultures were also evaluated. Addition of autologous tumor increased expansion and proliferation of all cultures and significantly enhanced levels of autologous killing. IL-4 and autologous tumor stimulation are effective growth factors when used in combination with a lose dose IL-2 regimen and may be of significant benefit in the expansion of TIL for clinical trials.

Adenocarcinoma↗

PubMed1988

The effect of bacillus Calmette-Guerin on the urinary system of pigs.

An experimental study was conducted to determine the changes in structure and function of the pig kidney and renal pelvis following intrarenal infusion of bacillus Calmette-Guerin (BCG). Bilateral nephrostomy tubes were inserted in six pigs through a subcostal (flank) retroperitoneal approach. One week later, antegrade pyelograms and renal scans with hippuran I-131 were obtained. The left kidney was then infused weekly for six weeks with two ampules of BCG (Tice strain) dissolved in 75 cc of saline. The right kidney, serving as a control, was infused concomitantly with 75 cc of saline. On week 7, bilateral antegrade pyelograms and renal scans were repeated. Two pigs were sacrificed at four, eight and 12 weeks after completion of BCG therapy. In all pigs, antegrade pyelograms of the left kidney before BCG instillation were identical to those obtained after completion of treatment and to those of the saline infused kidneys. The isotope renal scan in five pigs showed no significant change in image appearance or relative renal plasma flow in the pre-treatment and post-treatment images. In one pig, there was a decrease in the relative clearance of hippuran in the saline infused kidney. In this kidney, an upper pole abscess was found. Microscopic examination of the renal cortex, medulla, pelvis and ureter of the BCG infused kidneys was normal and identical to the saline infused kidneys. The urothelium was intact and no inflammatory changes were noted in the renal cortex or medulla. These results show that direct infusion of BCG into the renal collecting system has no adverse effect on the structure and function of pig kidneys when followed one to three months after treatment.

Animals↗

PubMed1987

Detection of onco-fetal bladder antigen in urine of patients with transitional cell carcinoma.

Studies of antigens associated with transitional cell carcinoma were extended by using murine IgM monoclonal antibody E7, developed earlier by this laboratory. These antibodies react preferentially with human bladder tumors and transitional cell carcinoma (TCC) cell line 647V. We now report that monoclonal antibody E7 detected the presence of antigen in midgestational and third trimester amniotic fluids, and in urine of patients with advanced transitional cell carcinoma. Western blot analysis showed that the antigen present in amniotic fluids consists of a sharp band with molecular weight greater than 200 kdaltons. A similar molecular weight pattern was seen with the solubilized membrane of 647V. A sensitive and convenient sandwich ELISA was developed and the urine of patients with bladder cancer was assayed for the presence of the E7 antigen. Antigen was detected in the urine of patients with advanced transitional cell carcinoma but not in the urine of normal adults or in urine from patients with prostate cancer, renal cell carcinoma, or benign prostate hyperplasia. An inhibition enzyme immunoassay was developed with monomeric forms of the E7 antibody and confirmed the presence of antigen in the urine of patients with TCC. We conclude that the E7 antigen is an onco-fetal antigen expressed in patients with transitional cell carcinoma of the bladder.

Antibodies, Monoclonal↗

PubMed1984

Growth stimulating activity produced by human bladder cancer cells.

Growth promoting properties have been identified in the conditioned serum-free medium from cultures of the human transitional cell carcinoma cell line 647V. This activity appears to reside in a molecule of more than 5000 MW. The factor responsible for 647V growth is distinguished from epidermal growth factor, since it fails to inhibit the specific binding of epidermal growth factor by 647V cells, and 647V cells are not stimulated to grow by epidermal growth factor. It also does not appear to be an insulin-like growth factor-like molecule since it fails to competitively bind with human insulin-like growth factor-carrier protein.

Binding, Competitive↗

PubMed1983

The addition of chemotherapy to hormonal therapy for treatment of patients with metastatic carcinoma of the prostate.

Patients with advanced prostate carcinoma that had been stabilized by orchiectomy (ORCH) or hormone therapy for at least 3 months, were randomized to either diethylstilbestrol (DES) alone or DES plus Cytoxan or DES plus Emcyt. A total of 188 patients were randomized between July, 1976 and February, 1982 of which 161 were evaluable for objective response to treatment. Objective response rates, response duration, or survival experiences were not demonstrably different between treatment arms, either for all patients or within good or poor prognosis groups determined by initial pain or acid phosphatase level. Subjective improvements in performance status were small for each treatment. Pain relief was somewhat greater in the chemotherapy-hormone combinations than in the DES/ORCH, but the advantage was not statistically significant. Side effects were primarily nausea and vomiting and leukopenia, mostly in the DES + Cytoxan arm. The duration of stabilization prior to entry did not influence response overall, although there were opposing trends within each of the two chemotherapy arms. The premise for combining antitumor agents with hormones before hormone failure is still felt to be a more logical approach than waiting for the ultimate hormone failure, and a combination of hormones plus two antitumor agents is being evaluated in a subsequent ongoing trial where a more rigid design limits the duration of the preentry period of hormone stabilization.

Aged↗

PubMed1979

The detection and clinical significance of antibodies to tumor-associated antigens in patients with renal cell carcinoma.

Antibodies against renal carcinoma cells were detected by a microcomplement fixation assay in the sera of 94 per cent of 75 patients with recently resected, localized or metastatic disease, and in 20 per cent of normal controls. Absorption of sera with pooled normal kidney cells abrogated reactivity against normal kidney cells but did not decrease reactivity significantly against the renal carcinoma cells. Analyses of sequential serum samples revealed that after nephrectomy in 9 of 10 patients free of tumor but a high risk for recurrence antibody levels decreased or disappeared by 1 year. However, these levels remained elevated in 2 patients who subsequently were found to have occult persistent tumor. Antibody titers in patients with metastatic renal cell carcinoma declined as the disease progressed. Patients with persistently elevated titers had the longest survival. Although the antibodies detected by this assay may not be specific for renal cell carcinoma, their detection may be of clinical significance with regard to the prognosis of the disease.

Adenocarcinoma↗

PubMed1979

Management of advanced testicular seminoma.

The treatment of seminoma (stages A, B1 and B2) with conventional x-ray therapy can be expected to give satisfactory cure rates. However, the cure rate for patients with advanced stages of B3 and C disease, treated with conventional radiation therapy, is unacceptable (22 per cent). It appears that with a pre-radiation/chemotherapeutic plan consisting of actinomycin D, vincristine and cyclophosphamide survival can be improved dramatically in these patients. After a rest period of 2 to 4 weeks radiation therapy is given to the retroperitoneal, mediastinal and supraclavicular lymph nodes as per standard therapy. If evidence of bulk disease persists or if positive alpha-fetoprotein or beta-human chorionic gonadotropin has been detected then retroperitoneal lymph-adenectomy should be done after completion of the radiation therapy. With adjuvant chemotherapy 5 of 5 patients survive free of disease 18 months to 5 years after therapy.

Cyclophosphamide↗

PubMed1978

The natural history of metastatic renal cell carcinoma: a computer analysis.

Survival factors of 86 patients with metastatic renal cell carcinoma were studied by computer analysis. Cumulative survival was 53 per cent at 6 months, 43 per cent at 1 year, 26 per cent at 2 years and 13 per cent at 5 years. Survival was influenced favorably by confinement of metastases to the lungs, by the absence of local recurrence or persistence of tumor and by a longer interval free of disease after removal of the primary tumor. Medical therapy improved survival during the first year after diagnosis of metastases but no objective regression of tumor was observed. Excision of metastatic foci significantly improved survival for up to 5 years (p less than 0.05 and p less than 0.02) after which most patients died of recurrence. Palliative or adjunctive nephrectomy in patients with metastases was associated with a 6 per cent mortality rate but it increases survival over other patients with metastases at the time of diagnosis of renal carcinoma who did not undergo nephrectomy. This difference was owing to patient selection and survival of those who had adjunctive nephrectomy was no greater than that of the study population as a whole. However, based on the factors that were associated with improved survival palliative nephrectomy may be beneficial when a limited number of metastases treatable by excision or radiation therapy are present, when effective systemic therapy exists or when the primary tumor produces severe symptoms.

Adenocarcinoma↗

PubMed1977

Surgical treatment of Peyronie's disease: a new approach.

We treated 12 patients with intractable Peyronie's disease with a new approach based on simple incision of the fibrotic plaque(s) and stenting of the corpora with penile implants. Infection in 1 case necessitated removal of the prostheses, while the remaining 11 patients had satisfactory functional and anatomical results. The procedure is indicated for patients with 1) Peyronie's disease and impotency, 2) normal potency and extensive disease and 3) normal potency and localized disease in selective cases. In this series insertion of the penile prostheses did not change sexual prowess in previously potent patients.

Adult↗

PubMed1977

The response of metastatic retroperitoneal seminoma to chemotherapy.

Two patients with advanced metastatic seminoma were treated with radiation therapy, triple-drug chemotherapy and radical surgical resection. In 1 patient the seminoma was radiation-recurrent and radiation-resistant, while in the second patient the metastatic seminoma encroached upon both kidneys and could not be irradiated initially for fear of bilateral radiation nephritis. Both tumors were reduced in size markedly by the chemotherapy and the residual mass was excised in each instance. One patient was free of the tumor 18 months after treatment, while the other patient had recurrence in a distant area after 16 months. The marked responsiveness of both tumors to triple-drug chemotherapy emphasizes the importance of an aggressive approach to advanced metastatic seminoma, including radiation therapy, chemotherapy and surgery.

Adult↗

PubMed1976

Immune cytolysis of human renal carcinoma mediated by xenogeneic immune ribonucleic acid.

With a microcytotoxicity assay it was shown that normal, non-immune human lymphocytes were converted to effector cells specifically cytotoxic to human renal carcinoma cells after incubation with xenogeneic immune ribonucleic acids. The ribonucleic acid was extracted from the lymphoid tissues of sheep that had been immunized with human renal carcinoma tissue. Lymphocytes incubated without ribonucleic acid from or with ribonucleic acid sheep immunized with Freund's adjuvant alone did not increase cytotoxicity. Immunotherapy with immune ribonucleic acid increased cytotoxic activity of lymphocytes from a patient with metastatic renal carcinoma. The microcytotoxicity assay may be a useful method to assessing the cellular immune response in patients receiving immunotherapy and seems to correlate with their clinical course.

Adenocarcinoma↗

PubMed1976

Advanced renal cell carcinoma: treatment with xenogeneic immune ribonucleic acid and appropriate surgical resection.

Herein we describe the first clinical treatment of renal cell carcinoma in humans with xenogeneic immune ribonucleic acid. Twelve patients with advanced renal cell carcinoma have been treated by appropriate operations to remove tumor bulk followed by specific passive immunotherapy. Xenogeneic specific immune ribonucleic acid was prepared from the spleen of normal sheep that had received 4 weekly injections of a homogenate of renal cell carcinoma. Results indicate that 1) xenogeneic specific immune ribonucleic acid can safely be given to humans without local or systemic toxicity, 2) there is a suggestion of clinical benefit, since only 2 patients have had progression of known metastases during treatment with immune ribonucleic acid and 3) xenogeneic immune ribonucleic acid can enhance the immune response to renal cell carcinoma, as demonstrated by in vitro lymphocytoxicity tests.

Adenocarcinoma↗