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L G Gomella

Publications and source records attributed to L G Gomella.

At least 19 recordsLinked to original sources
PubMed1992

Detection of hematogenous micrometastasis in patients with prostate cancer.

The goal of this study was to determine if patients with stage D0-3 prostatic adenocarcinoma have detectable hematogenous micrometastasis. Polymerase chain reaction amplification of prostate-specific antigen mRNA, which is exclusively expressed by prostatic epithelial cells, was used to detect circulating prostatic cells. Peripheral venous blood was obtained from 17 control and 12 prostate cancer patients with stage D0-3 prostatic adenocarcinoma. Of the 12 cancer cases, four patients (stage D1-3) tested positive for prostate-specific antigen RNA, indicating the presence of circulating micrometastasis. The 17 negative controls all tested negative. Contrary to a long held hypothesis, these data point to the possibility that hematogenous metastasis may be a relatively early event in the natural history of human prostate cancer. These findings may have an important impact on our understanding and treatment of prostate cancer.

Base Sequence↗
PubMed1992

Murine bladder carcinoma cells present antigen to BCG-specific CD4+ T-cells.

Intravesical administration of Bacillus Calmette-Guérin (BCG) is the most effective therapy for superficial transitional cell carcinoma of the bladder although its mechanism of action is not known. To determine if bladder tumors are capable of antigen presentation and thus might interact directly with BCG-specific T-cells, we studied the murine bladder tumor MB49. MB49 (MHC Class II negative) (IA-), when induced to express IA with interferon, presented BCG to specific CD4+ T-cells obtained from bladder-draining lymph nodes following intravesical BCG administration. This interaction resulted in antigen- and IA-dependent interleukin 2 and tumor necrosis factor production. Interferon also induced MB49 IA expression in vivo. This first demonstration of antigen presentation by epithelial tumors supports new approaches to immunotherapy of these malignancies.

Administration, Intravesical↗
PubMed1992

Phase II evaluation of coumarin (1,2-benzopyrone) in metastatic prostatic carcinoma.

The unavailability of effective treatment of metastatic hormone refractory prostatic carcinoma warrants trials of new and promising treatments. Coumarin is an investigational new drug that has produced objective tumor regression in some patients with metastatic renal cell carcinoma and malignant melanoma. Coumarin has shown activity against prostatic carcinoma in the Dunning R-3327 rat prostatic adenocarcinoma model. Forty-eight patients with metastatic hormone naive (5 stage D1 and 10 stage D2) or hormone refractory (33 stage D3) prostatic carcinoma of average age 67.6 years (range 46-86) and ECOG performance status of 2 or better were given 3 grams coumarin daily by mouth and evaluated monthly for toxicity and response by rigid criteria in a multicenter trial. Toxicity was limited to asymptomatic SGOT elevations in 3 patients and nausea and vomiting in 4 patients that required cessation of therapy in 2. Eligibility and protocol violations removed 6 additional patients from response evaluation. There were no complete responses. Partial responses (3 of 40 patients, 8%) occurred in 2 patients with bidimentionally measurable disease and 1 patient with disease evaluable by bone scan and elevated prostate specific antigen and prostatic acid phosphatase. The remaining patients progressed after 1 to 12 (average 4.4) months. Coumarin is a relatively nontoxic drug that may warrant further trials in a subset of patients with prostatic carcinoma.

Adult↗
PubMed1992

Suramin interference with transforming growth factor-beta inhibition of human renal cell carcinoma in culture.

Suramin is a polyanionic compound used clinically for the treatment of trypanosomiasis, which is known to inhibit the action of many protein factors in vitro. Transforming growth factor-beta (TGF-beta) is a multifunctional regulatory protein which inhibits the growth of renal cell carcinoma in culture. While suramin at 50-500 micrograms/ml had no significant effect on the growth of renal cell carcinoma in culture in our experiments, it did partially reverse the growth inhibition induced by TGF-beta in the two cell lines tested. This effect apparently is caused by suramin's direct interference with 125I-labeled TGF-beta's ability to bind to the cell, and not by any effect of suramin on the TGF-beta receptor. Furthermore, suramin dissociates TGF-beta bound to the cell with a t1/2 of less than 30 min. These results are consistent with those previously reported regarding suramin's interaction with other protein growth factors, and suggest that suramin may interact with the TGF-beta protein itself to inactivate it.

Carcinoma, Renal Cell↗
PubMed1991

Analysis of iodine-125 interstitial therapy in the treatment of localized carcinoma of the prostate.

Definitive treatment of localized carcinoma of the prostate has included radical surgery, external beam radiation therapy, and interstitial radiation therapy. The interstitial agent most commonly used is Iodine-125. Forty-eight patients were treated with interstitial radiation therapy using Iodine-125 implants with a median follow-up of 55 months. Forty-three percent of the evaluable patients had progressive disease with approximately 50% progressing at 5 years by Kaplan-Meier analysis. Overall actuarial survival in the group was 80% at 5 years. This and several other studies suggest that control of prostate cancer with Iodine-125 seeds may be suboptimal as compared with other treatment modalities, especially the radical retropubic prostatectomy. Analysis of treatment parameters is presented along with a discussion of the current status and future prospects for treatment of localized carcinoma of the prostate with interstitial radiation therapy.

Actuarial Analysis↗
PubMed1990

Preparative cytoreductive surgery in patients with metastatic renal cell carcinoma treated with adoptive immunotherapy with interleukin-2 or interleukin-2 plus lymphokine activated killer cells.

A total of 63 patients with metastatic renal cell carcinoma with the primary kidney tumor in place was accepted as candidates for immunotherapy at the Surgery Branch of the National Cancer Institute. Of the 63 patients 54 underwent nephrectomy and 9 were treated with the primary kidney tumor in place. Many of the patients underwent associated procedures, such as regional lymphadenectomy (11), venacavotomy with extraction of tumor thrombus (9), hepatic resection (2), pulmonary wedge resection (2), cholecystectomy (2), splenectomy (2), distal pancreatectomy (1), omentectomy (1) and contralateral adrenalectomy (1). Of the 54 patients 20 were not able to enter therapy because of tumor-related (17) or other medical (3) reasons that developed between the operation and therapy, while 34 were able to receive immunotherapy postoperatively. The 20 patients who were treated with either high dose interleukin-2 or interleukin-2 plus lymphokine activated killer cells soon postoperatively (mean 2.1 months) were able to tolerate roughly the same amount of interleukin-2 as the 74 who had undergone nephrectomy before referral to our institute and who were treated for a mean of 22 months after nephrectomy. Further studies, including a prospective, randomized trial, will be required to define the role of nephrectomy in patients with advanced renal cell carcinoma before treatment with interleukin-2 based immunotherapies.

Carcinoma, Renal Cell↗
PubMed1990

Epidermal growth factor receptor gene analysis in renal cell carcinoma.

The epidermal growth factor receptor binds the mitogens epidermal growth factor and transforming growth factor-alpha. Increased expression of the epidermal growth factor receptor has been noted in many types of tumors and is associated with gene amplification in several including epidermoid carcinoma, lung carcinoma, breast carcinoma and glioblastoma. We have recently observed increased expression of the epidermal growth factor receptor messenger RNA in neoplastic tissue relative to normal kidney tissue from patients with renal cell carcinoma. To determine if epidermal growth factor receptor gene amplification was present in renal cell carcinoma, DNA was extracted from renal cell carcinoma cell lines and from normal kidney and renal cell carcinoma tissues derived from radical nephrectomy specimens from thirty patients. DNA was analyzed by Southern blot hybridization. There was no epidermal growth factor receptor gene amplification detected in the renal cell carcinoma samples studied, indicating the increased epidermal growth factor gene expression observed in renal cell carcinoma does not occur through gene amplification. Unlike other tumors with enhanced epidermal growth factor receptor gene expression, amplification of this gene does not appear to be a common feature of renal cell carcinoma.

Adenocarcinoma↗
PubMed1989

Expression of transforming growth factor alpha in normal human adult kidney and enhanced expression of transforming growth factors alpha and beta 1 in renal cell carcinoma.

Normal kidney and renal cell carcinoma tissues from ten patients were studied for mRNA and DNA for both transforming growth factors alpha and beta 1. Northern and Southern hybridizations were conducted on samples extracted from the solid tumor and surrounding normal tissues and two tumor-derived cell lines. Low levels of constitutive expression of TGF-alpha mRNA were detected in all normal kidney tissues; six of the ten patients, however, demonstrated an increased (2- to 8-fold) expression of TGF-alpha in the tumor versus normal kidney as determined by densitometry of RNA blots. All ten patients had elevated mRNA levels for TGF-beta 1 in the tumor (2.5-to 22-fold increase) relative to normal kidney. Two tumor-derived cell lines also expressed TGF-alpha and TGF-beta 1 mRNA. Southern blot hybridization of the DNA extracted from the normal tumor pairs revealed no gene amplification or gross rearrangement for either the TGF-alpha or TGF-beta 1 genes. These results demonstrate the expected constitutive expression of TGF-beta 1 by normal kidney; however, the constitutive expression of TGF-alpha by Northern blot analysis in normal adult human kidney is previously unreported. Enhanced expression of TGF-alpha and TGF-beta 1 mRNA in solid tumor may be related to the development of renal cell carcinoma.

Autoradiography↗
PubMed1989

Renal vein thrombosis presenting as renal mass.

The excretory urogram of patients with acute renal vein thrombosis typically demonstrates symmetric enlargement of the involved kidney. We report a case of renal vein thrombosis that presented as a discrete renal mass on excretory urography and abdominal computerized tomography. The entity of renal vein thrombosis is briefly reviewed along with the computerized tomography findings seen in this setting.

Diagnosis, Differential↗
PubMed1989

Epidermal growth factor receptor gene expression in normal human kidney and renal cell carcinoma.

The epidermal growth factor receptor (EGFr) is a transmembrane glycoprotein detected on many cells and tissues including neoplastic and normal kidney. EGFr binds the mitogenic polypeptide hormone epidermal growth factor (EGF) as well as EGF-related transforming growth factor-alpha (TGF-alpha). Increases in EGFr gene expression and protein production have been implicated in the development of the malignant phenotype for certain cancers. To determine if alterations in EGFr gene expression are present in human renal cell carcinoma, paired samples of normal and neoplastic renal tissue from ten patients with advanced renal cell carcinoma were analyzed for EGFr mRNA content by Northern blot hybridization. The EGFr gene was constitutively expressed in 90% of normal kidney samples. In seven out of nine evaluable patients, tumors expressed 1.7 to 8.4 times more EGFr mRNA than corresponding normal tissue. Two patients showed no elevation of tumor EGFr mRNA and one patient had no identifiable EGFr transcripts in either neoplastic or normal kidney. Expression of EGFr mRNA was also detected in three tumor-derived and two established renal cell carcinoma cell lines. EGFr transcripts were not found in tumor infiltrating lymphocytes (TIL). These findings suggest that overexpression of EGFr mRNA may be associated with malignant transformation in renal cell carcinomas.

Blotting, Northern↗
PubMed1989

Transforming growth factor-beta inhibits the growth of renal cell carcinoma in vitro.

Transforming growth factor-beta (TGF-beta) is a bifunctional growth regulatory hormone which inhibits the growth of many normal and neoplastic epithelial cell lines in monolayer culture. Endogenous and exogenous TGF-beta may influence cell proliferation through autocrine and paracrine binding to specific TGF-beta receptors. Growth effects of TGF-beta on human renal cell carcinoma cell lines have not been thus far described. We have studied the effects of TGF-beta on one renal tumor-derived (UOK-39) and one established (SKRC-7) renal cell carcinoma cell line. Exogenous addition of biologically active TGF-beta to cell cultures at concentrations between two and five ng./ml. inhibited the anchorage-dependent growth of UOK-39 by 75% and SKRC-7 by 44%, relative to controls. Low numbers of high affinity TGF-beta receptors were identified on both cell lines in 125I-TGF-beta binding assays. UOK-39 cells bound radiolabeled TGF-beta with higher affinity than SKRC-7 cells, but had fewer receptor sites, by Scatchard analysis of binding data. These results suggest that TGF-beta inhibits proliferation of renal carcinoma cells in vitro which may be mediated through binding of exogenous TGF-beta to functional TGF-beta receptors on the cell surface.

Carcinoma, Renal Cell↗
PubMed1989

Expression of mRNA for transforming growth factors-alpha and -beta and secretion of transforming growth factor-beta by renal cell carcinoma cell lines.

Transforming growth factors (TGFs)-alpha and -beta are regulatory polypeptides that reversibly confer a transformed phenotype upon normal cultured fibroblasts. TGF-alpha is synthesized primarily by malignant cells and shares many properties with the tissue mitogen, epidermal growth factor (EGF). The expression of TGF-beta mRNA has been demonstrated in a variety of normal and malignant cell types, some of which secrete the mature protein in an inactive form. To investigate the role of TGFs in human renal cell carcinoma (RCC), we used two renal tumor-derived cell lines and one established RCC cell line for analysis of TGF-alpha and TGF-beta mRNA production and for evaluation of TGF-beta protein secretion. By northern blot hybridization, all three RCC cell lines expressed TGF-alpha and -beta mRNA. In addition, TGF-beta activity was found in the conditioned medium from these cells. The secreted TGF-beta protein, however, displayed biological activity only after activation by acid-treatment. These data demonstrate the constitutive expression of TGF-alpha and -beta mRNA by RCC cell lines and, also, the secretion by this tumor of endogenous TGF-beta protein in a latent form.

Carcinoma, Renal Cell↗
PubMed1986

The influence of uremia and immunosuppression on an animal model for ischemic colitis.

Up to 1 percent of renal transplant recipients have been reported to develop ischemic colitis. Immunosuppressive agents and uremia have been implicated in the development of this complication, but their exact relationship remains unclear. A rat model was developed to determine the effects of uremia alone and in combination with immunosuppression on the development of ischemic colitis. Seventy-six animals were included in the study. Uremia and ischemic colitis were induced surgically. The immunosuppressive agents azathioprine and methylprednisolone were administered for 72 hours after a colonic segment was devascularized in chronically uremic rats. One-way analysis of variance (ANOVA) showed that uremia potentiates colonic ischemia significantly (4.09 cm2 vs 1.25 cm2, P less than 0.03). The addition of parenteral steroids (methylprednisolone) or azathioprine alone and in combination did not potentiate or reduce this ischemic process in uremic animals. Each of these factors alone is commonly present in the renal transplant population and can contribute to the development of potentially fatal ischemic colitis.

Animals↗
PubMed1986

Ischemic colitis and immunosuppression. An experimental model.

The incidence of ischemic colitis in renal transplant recipients approaches 1 percent. The mortality in these patients with ischemic colitis is nearly 70 percent. Immunosuppressive agents have been implicated in the development of ischemic colitis. To study the effect of immunosuppressive agents on ischemic colitis, a 4-cm segment of the colon was devascularized in 27 male Fischer rats. The animals were divided into one control and two treatment groups. One treatment group received methylprednisolone and the other, azathioprine, in doses similar to those of renal transplant recipients. Both experimental groups, either separately or combined, showed significantly greater areas of colonic ischemic changes than did the control group. This study demonstrates that systemic administration of immunosuppressive agents may augment the development of ischemic colitis.

Animals↗
PubMed1986

A trial of prophylactic thiotepa or mitomycin C intravesical therapy in patients with recurrent or multiple superficial bladder cancers.

There were 40 consecutive patients with recurrent or multiple superficial stage Ta or T1 transitional cell cancer assigned randomly to receive prophylactic thiotepa or mitomycin C intravesical chemotherapy. Patients received 8 weekly instillations followed by 22 monthly treatments of either 60 mg. thiotepa or 40 mg. mitomycin C. Of 25 patients randomized to receive mitomycin C 4 had recurrence in a total of 337 patient-months (1.19 per 100 patient-months), while disease recurred in 1 of 15 patients randomized to receive thiotepa who were followed for a total of 220 patient-months (0.45 per 100 patient-months). No significant difference in recurrence rate was noted for either drug group (p equals 0.18). Toxicity requiring cessation of therapy was observed in 7 patients (28 per cent) on mitomycin C and none on thiotepa.

Carcinoma, Transitional Cell↗
PubMed1985

The surgical implications of herniation of the urinary bladder.

The urinary bladder is often involved in an inguinal hernia, but herniation of the entire bladder into the scrotum is rare. As many as 4% of inguinal hernias may involve the bladder, usually in the form of a sliding hernia. Most urinary bladder herniations are diagnosed at the time of inguinal herniorrhaphy, and are therefore most commonly repaired through an inguinal incision. If the diagnosis requires amendment, alternative surgical approaches are available. We studied two patients with massive inguinoscrotal herniation of the urinary bladder, commonly referred to as "scrotal cystocele." We reviewed the literature, incidence, causes, diagnosis, and surgical consideration of herniation of the urinary bladder, and gave particular attention to the interrelationship of bladder herniations with inguinal hernias.

Aged↗
PubMed1979

BCLS instruction.

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Education, Medical↗