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Biomedical subjects

G R Prout

Publications and source records attributed to G R Prout.

At least 37 records · Page 2Linked to original sources
PubMed1989

Long-term experience with flutamide in patients with prostatic carcinoma.

Fifty-two patients with previously untreated metastatic carcinoma of the prostate were treated with flutamide 250 mg tid. Response was classified according to objective and subjective criteria, and duration of response and total survival were chosen as endpoints. Disease manifestations at presentation and tumor burden were studied to determine their relationship, if any, to treatment response and outcome. Total survival was longest in 26 patients who had objective responses (mean 50 months). Patients who failed to respond (n = 13) and those who had subjective responses (n = 13) survived an average of eleven and 17.2 months, respectively. Tumor burden was correlated with response to treatment and total survival; those judged to have a minimum tumor burden had objective responses and survived an average of sixty months. Sixteen other patients who had been previously treated with diethylstilbestrol were also studied. Nine of these had cardiovascular complications while taking diethylstilbestrol, and tolerated flutamide without further complications. Those in remission stayed in remission, and sexual potency returned to 5 patients.

Adenocarcinoma↗
PubMed1989

Renal cortical tumors. Cytogenetic characterization.

The authors examined three cortical tumors (adenomas) of the kidney and found a consistent chromosome pattern. A combination of chromosome abnormalities (+7, +7, +17, -Y) was shared by these tumors. In contrast, none of them showed alterations of chromosome 3p and 5q, the most common changes in renal cell carcinomas. The chromosome abnormalities in these patients may define a subgroup of renal tumors, so-called adenomas, that cannot be distinguished easily from adenocarcinomas in histopathologic examination.

Adenoma↗
PubMed1988

Photodynamic effect in an experimental bladder tumor treated with intratumor injection of hematoporphyrin derivative.

Photodynamic therapy (PDT) is an experimental treatment modality for malignant tumors. It is based on the principle that a photosensitizer, such as hematoporphyrin derivative (HPD), is retained in higher concentrations in tumors than in surrounding nonmalignant tissues and that photoactivation of the sensitizer can be used to evoke tumor destruction. However, retention of the systemic injection of HPD is not limited to malignant tissues. This lack of specific tumor localization thus reduces the therapeutic ratio of the treatment and causes skin photosensitivity and possible systemic toxicity. Injection of HPD directly into the tumor, on the other hand, has been shown to yield higher levels of the drug in the tumor and lower levels in normal tissues, in comparison with systemic administration. In this study, we examined the photodynamic effect on s.c. implanted mouse bladder tumors subjected to intratumor (i.t.) and i.p. HPD injections. Tumor cell killing, measured by cell survival, was observed in both the it. and i.p. groups and was dependent on fluence and HPD dosage. However, no significant enhancement of cell killing was observed in the i.t. injected tumors, despite the higher porphyrin levels in these tumors. Histological examination of the effect of PDT on the blood vessels indicated that while cell death accompanied severe hemorrhage in the i.p. injected tumors, in the i.t. tumors there was much less hemorrhage and intact blood vessels remained. This observation suggests that with i.t. administration, direct photodynamic action may play a significant role in the tumor cell killing, in contrast to systemic administration, in which destruction of the blood vessels is believed to be the main cause of tumor destruction.

Animals↗
PubMed1988

Involvement of chromosomes 3 and 5 in renal cell carcinoma.

Clonal chromosome abnormalities in short-term cultures were found in 18 of 51 nonfamilial renal cell carcinomas. The breakpoints on chromosome 3 in seven specimens clustered in region 3p11-3p24.2, confirming its importance in the genesis of renal cell carcinoma. An i(5p) and involvement of band 5q21 were other frequent structural chromosome changes. Two additional nonrandom karyotype changes, the gain of one chromosome 7 and the loss of one sex chromosome, were also observed.

Carcinoma, Renal Cell↗
PubMed1988

Invasive bladder carcinoma: preliminary report of selective bladder conservation by transurethral surgery, upfront MCV (methotrexate, cisplatin, and vinblastine) chemotherapy and pelvic irradiation plus cisplatin.

Methotrexate, Cisplatin, and Vinblastine (MCV) was followed by Cisplatin plus radiation therapy in 19 patients with muscle-invading clinical Stage T2-4NXM0 transitional cell carcinoma of the urinary bladder (including cystectomy candidates), to achieve local control and prevent distant metastases. Radical cystectomy was recommended for all patients who failed to reach a complete response (CR = biopsy negative and cytology not positive) following MCV and Cisplatin X 2 plus 4000 cGy. Completely responding patients, and those partially responding patients unsuited for cystectomy, were selected for bladder conservation treated with additional irradiation to the bladder tumor volume (total 6,480 cGy) plus one additional Cisplatin treatment. Dose reductions were required for stomatitis in 26%, mild bone marrow depression in 58%, and renal toxicity in 5% of the patients. During the Cisplatin/4000 cGy, mild dysuria occurred in 68% of patients and 36% had mild bowel hyperactivity. Serious complications have occurred in two patients to date. One patient had recurrent pulmonary emboli, marked reduction in bladder capacity, and diarrhea. A second had bladder perforation during cystoscopic evaluation after MCV and a small bowel obstruction after Cisplatin and 4000 cGy. There was no treatment-related sepsis. Three patients had initial complete transurethral resection of their tumors and therefore 16 patients are evaluable for tumor responsiveness to this protocol. Four patients (25%) were biopsy negative and cytology negative, whereas three additional patients (19%) were biopsy negative but cytology positive following initial MCV. Six patients (38%) were biopsy negative and cytology negative whereas three additional patients (19%) were biopsy negative and cytology positive following MCV and Cisplatin X 2 plus 4000 cGy pelvic radiation. Of the entire group, 9 patients were treated with full-dose radiotherapy. All of these patients are alive without evidence of tumor on rebiopsy of the original tumor site, but one has a persistent positive cytology. Seven patients had a radical cystectomy and 6 are disease free. The treatment of 3 patients deviated from the protocol. Overall, only one patient has developed distant metastases and currently 84% of the patients are disease-free, although follow-up is short. To date, this feasibility study has been clinically practical and well tolerated. The proportion of CR's suggests that this program may prove to be an organ-sparing and curative approach for a significant number of patients, but more experience and follow-up are required.

Adult↗
PubMed1988

Establishment and characterization of a doxorubicin-resistant human bladder cancer cell line (MGH-U1R).

A doxorubicin-resistant bladder cancer cell line has been established. This was accomplished by exposing an established human bladder tumor cell line, MGH-U1, to progressively higher concentrations of doxorubicin over a period of 12 months. The resistant cells, MGH-U1R, are nine times more resistant to doxorubicin and 30 times more resistant to daunorubicin than the parent cells. The MGH-U1R and the MGH-U1 cells have identical isozyme phenotypes. Compared to the parent cells, the resistant cells have a slower growth rate, lower confluent density, are more heterogeneous morphologically, and exhibit more chromosomal aberrations and rearrangements. The resistant cells may now be used as an experimental system for the search of means to overcome drug resistance in human bladder cancer.

Cell Division↗
PubMed1988

Detection of tumor cells in bladder washings by a monoclonal antibody to human bladder tumor-associated antigen.

We have conducted two studies to evaluate the efficacy of using a specific monoclonal antibody (McAb) to detect exfoliated tumor cells in bladder washings. This is a preliminary step toward the development of immunological methods to improve the cytologic detection of bladder carcinoma. In this study, McAb 3G2-C6 was used. The McAb reacts to a bladder tumor-associated cell-surface antigen expressed in bladder tumors of various grades. Bladder washings from patients with and without carcinoma were stained with the McAb using two different indirect immunofluorescence methods (Methods A and B). The results of the immunological studies were compared with those obtained from the cytology laboratory and these in turn, were evaluated against the histopathological diagnosis of respective patients at the time the samples were taken. Immunofluorescence method A detected positive cells in 87% (56/64) of specimens from bladder cancer patients, including 18 of 19 from patients with grade 1 tumor. This method also had a low false-positive rate; only one of 17 specimens from patients with other urinary disorders had positively reacting cells. Immunofluorescence method B, evaluating a second group of specimens, detected positive cells in 68% (15/22) of specimens from patients with carcinoma, and in only one of 17 controls. However, it also identified positive cells in specimens from patients with chronic cystitis and urinary calculi. Overall the results of these studies indicate that the McAb method is superior to the routine cytology in detecting tumor cells in bladder washing specimens. More work must be done, however, to improve the specificity of the method before it can be used as an aid for routine tumor detection.

Antibodies, Monoclonal↗
PubMed1988

Intratumor injection as a more effective means of porphyrin administration for photodynamic therapy.

Photodynamic therapy (PDT) with hematoporphyrin derivative (HpD) as the photosensitizer is a promising new cancer treatment. The major drawback of this procedure is the resulting skin photosensitivity. Patients must remain in subdued light for four to six weeks to avoid cutaneous phototoxicity. In this study, we examine the possibility of reducing the skin photosensitization while maintaining the tumor phototoxic effect by administering the drug directly into the tumor. A subcutaneously implanted mouse bladder tumor (MBT-2) was used. HpD was administered either intraperitoneally (I.P.; 20 mg./kg. b.w.) or by intratumor injection (I.T.; 0.4 mg./cc tumor). The concentrations of HpD in tumor and various tissues (skin, muscle, liver, spleen, kidney, bladder and whole blood) were analyzed at various times after the injection, by 3H-HpD method and by a fluorometric method. Results indicated that at three to 96 hours after the administration, porphyrin levels in tumor were about three to 15 times higher by I.T. than by I.P. injection, while the concentrations in skin and other tissues were 1.3 to 10 times lower. Consequently, at 24 hours after injection ratios between tumor to skin porphyrin were 14 to 92 times higher for I.T. than I.P. injection. Higher porphyrin levels in tumor and lower in normal tissues would indicate lower skin photosensitivity, systemic cytotoxicity and possible greater tumor photosensitivity. This method of porphyrin administration may be useful for the PDT of certain single lesions that are accessible for direct injection.

Animals↗
PubMed1988

Further evidence that renal oncocytoma has malignant potential.

We report a case of bilateral renal oncocytoma. The right tumor infiltrated the renal capsule focally, and the left tumor penetrated through the capsule into the surrounding perinephric fat and extended into the left renal vein. Karyotyping of the left oncocytoma showed loss of chromosomes 1 and Y (-1,-Y). These karyotypic anomalies, along with the capsular, perinephric fat and renal vein involvement, indicate that renal oncocytomas, despite similar gross and microscopic pathological characteristics, are a heterogeneous group of tumors, some of which have malignant (local invasiveness) potential.

Adenoma↗
PubMed1988

Radiation therapy for localized prostate carcinoma: experience at the Massachusetts General Hospital (1973-1981).

The success following irradiation in 370 patients with clinically localized prostate carcinoma was measured by overall patient survival as well as the cumulative incidence with time of treated patients who developed either local tumor regrowth or progression with distant metastases. With a minimum follow-up of 5 years in living patients, we evaluated the cumulative frequency curves using both univariate and multivariate (Cox) analyses. Overall patient survival and probability of progression with distant metastases were significantly influenced by initial tumor stage and the degree of histologic differentiation. The results at 8 years are significantly better for patients with T2 (B) tumors (local regrowth in 8%, distant metastases in 18%) than for patients with T3-T4 (C) tumors (local regrowth in 28%, distant metastases in 60%). Patient tolerance of external-beam radiation therapy was carefully analyzed in 121 consecutively treated patients in 1980 and 1981 for subsequent radiation-related sequelae. Minor transient intestinal and urologic sequelae were observed in 21% and 23% of the patients, respectively. These mild to moderate symptoms resolved in all but 7% of the patients who are continuing with mild symptoms. One patient had a major complication, i.e., a cystectomy required for persistent bleeding. Erectile potency has been maintained in 63% of potent patients. No specific benefit or detriment in outcome was seen in the minority of 51 patients who were irradiated by iodine-125 implantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗
PubMed1987

Photodynamic therapy with hematoporphyrin derivative in the treatment of superficial transitional-cell carcinoma of the bladder.

Photodynamic therapy involves light-induced destruction of tumors containing a photosensitizer such as hematoporphyrin derivative. We conducted a collaborative study to evaluate the efficacy of this form of therapy in treating superficial transitional-cell carcinoma of the bladder. Thirty-seven patients were evaluated and 20 were selected for treatment. A total of 50 papillary tumors and 3 areas of carcinoma in situ were treated. All except two tumors were smaller than 2.5 cm. Assessments for treatment response and toxicity were carried out three months after treatment. The initial diagnosis of one patient was revised after the biopsy material was reviewed, and this patient was not included in the analysis. Complete eradication of all tumors was observed in 9 of 19 patients (47 percent), including those with carcinoma in situ. In the remaining 10 of these 19 patients, 13 tumors could not be eradicated (the overall eradication rate was 37 of 50 tumors [74 percent]), but 9 of the 10 patients had a reduction in tumor size, number, or both of 50 percent or more. We conclude that photodynamic therapy is useful in the treatment of superficial transitional-cell carcinoma of the bladder, but controlled trials will be required to define its place in the treatment of cancer.

Adult↗
PubMed1987

Intraoperative radiation therapy in patients with bladder cancer. A review of techniques allowing improved tumor doses and providing high cure rates without loss of bladder function.

Conventional external beam irradiation, using modern megavoltage techniques and doses that do not harm bladder function, will permanently eradicate local bladder cancer in 30% to 50% of patients, compared with 70% to 90% with cystectomy. In appropriately chosen patients, open surgery can safely provide excellent exposure for the selective delivery of more radiant energy directly to the tumor and less to the uninvolved portion of the bladder. Intraoperative radiation therapy, by either a removable radium or iridium implant or a large single dose of electrons, has been reported to be safe and can permanently cure the bladder of cancer and also preserve bladder function in more than 75% of patients with solitary tumors that invade into but not beyond the bladder muscle. With the increasing interest in and availability of intraoperative radiation therapy in the US, this curative and bladder-sparing treatment for operable patients with bladder cancer invading the trigone is appropriate for careful clinical trial.

Brachytherapy↗
PubMed1987

Treatment of invasive bladder cancer by cisplatin and radiation in patients unsuited for surgery.

Seventy patients with muscle-invading bladder carcinoma (clinical stages T2 to T4) who were not candidates for cystectomy were treated with combined cisplatin and full-dose external-beam radiation on a multi-institutional prospective protocol from 1980 through 1985. Thirty-six patients are alive, all but three without evidence of cancer. The complete response rate is 77% in the 62 patients completing planned irradiation and 70% for all patients. Among the complete responders, 73% are currently maintained, and this group has a significantly higher four-year survival than those not having a complete response and those with recurrence of disease--57% vs 11%. The observed high complete response rates in patients in all stages and the high survival rates suggest irradiation plus cisplatin therapy offers an important therapeutic gain over radiation therapy alone for invasive cancer of the bladder. These results encourage further evaluation of combining cisplatin-based, multidrug chemotherapy with irradiation in patients with locally very-advanced bladder tumors who are not suited for surgery.

Aged↗