Search PubMed⌕ Search

Biomedical subjects

H W Herr

Publications and source records attributed to H W Herr.

At least 199 records · Page 11Linked to original sources
PubMed1984

Potentiation of methylglyoxal-bis-guanylhydrazone by alpha-difluoromethylornithine in rat prostate cancer.

The polyamines, putrescine, spermidine, and spermine, are fundamentally related to both normal and neoplastic cell proliferation. The prostate gland and prostatic tumors in man and rodents contain large amounts of polyamines. This suggests that inhibition of polyamine biosynthetic enzymes, ornithine decarboxylase (ODC) and S-adenosyl-methionine decarboxylase (SAMDC) may retard the growth of prostatic cancer. Since alpha-difluoromethylornithine (DFMO) and methylglyoxal-bis-guanylhydrazone (MGBG) are irreversible and competitive inhibitors of ODC and SAMDC, respectively, they were tested as single agents and in combination on a transplantable rapidly growing and hormone-resistant G subline of the Dunning R-3327 rat prostatic adenocarcinoma. Groups of rats bearing tumors were treated with various regimens of DFMO, MGBG, and DFMO plus MGBG, daily for 21 days. Analysis of differences in tumor growth between treatment groups and controls showed DFMO had no antitumor effect but was well tolerated, MGBG retarded growth rate significantly but resulted in drug deaths in over 50% of the animals, and the combination of DFMO and MGBG resulted in rapid decline in tumor growth rates after 5 to 9 days of treatment with reduced toxicity. At 21 days, or death, 38 of 60 (63%) rats had no viable tumor on histologic study, whereas tumor was present in each of the animals in the other groups. Alpha-difluoromethylornithine increased the intracellular uptake of MGBG and potentiated the antigrowth activity of MGBG on a hormone refractory rat prostatic tumor with less toxicity than MGBG alone.

Adenocarcinoma↗
PubMed1984

Antigrowth effect of polyamine biosynthesis inhibitors on the Dunning R 3327-G prostatic tumor.

alpha-Difluoromethylornithine (DFMO) and methylglyoxal-bis-guanylhydrazone (MGBG), when administered simultaneously, inhibited growth and were highly toxic to the Dunning R 3327-G hormone-resistant prostatic adenocarcinoma transplanted into Copenhagen rats. Neither DFMO (2%) nor MGBG at a nontoxic dose (15 mg/kg) inhibited tumor growth, but total (47% early cure rate) or near total suppression of growth of established tumors was observed in rats receiving both treatments.

Adenocarcinoma↗
PubMed1984

Inguinal lymph node metastases from germ cell testicular tumors.

Between 1948 and 1982, 22 patients were seen with metastasis to the inguinal nodes from testicular germ cell tumors: 8 had a history of unilateral or bilateral orchiopexy with or without herniorrhaphy, 4 had nonsurgically corrected or uncorrected cryptorchidism, 9 had a history of herniorrhaphy, hydrocelectomy or transscrotal orchiectomy and 1 had no history of scrotal, iliac or inguinal surgery, or of tunica vaginalis or scrotal wall involvement by tumor. The histological type was pure seminoma in 5 patients, embryonal carcinoma in 7 and mixed tumor in 10. Treatment was individualized for tumor type and mode of presentation, and varied during the years according to the modalities available. At the time of this report 8 of 22 patients (36 per cent) are alive without evidence of disease from 2 to 29.5 years, 3 (16 per cent) have died without evidence of disease 10 to 17 years after treatment, 10 (45 per cent) have died of metastases 10 months to 6 years after treatment and 1 has been lost to followup. The over-all incidence of groin metastases from testicular carcinoma is low, even with a history of scrotal or inguinal surgery.

Adolescent↗
PubMed1984

Orchiectomy alone in the treatment of clinical stage I nonseminomatous germ cell tumor of the testis.

Forty-five patients with clinical stage I nonseminomatous germ cell tumor of the testis (NSGCTT) were entered in a prospective clinical trial to receive no treatment other than orchiectomy until clinical evidence of relapse. Of this group, 36 patients (80%) have been continuously free of disease for a median duration of 19.5 months after orchiectomy. Nine patients (20%) have relapsed, eight within seven months of orchiectomy. Seven of nine relapsing patients have been rendered free of disease with chemotherapy and/or surgery for a median duration of seven months (range, one to 33 months) after completion of treatment; the other two patients are presently under treatment although one has progressive disease. The relapse rate was higher in patients with embryonal carcinoma than in those with teratocarcinoma, 57% versus 17%. These preliminary results imply that the omission of routine lymphadenectomy or lymph-node irradiation in clinical stage I NSGCTT deserves further trial.

Adolescent↗
PubMed1984

Effects of alpha-difluoromethylornithine and methylglyoxal bis(guanylhydrazone) on the growth of experimental renal adenocarcinoma in mice.

alpha-Difluoromethylornithine (DFMO) and methylglyoxal bis-(guanylhydrazone) (MGBG) were tested against a murine renal adenocarcinoma, because polyamines are necessary for neoplastic cell growth and because human renal adenocarcinomas contain higher levels of spermidine than do normal renal cells; MGBG inhibits spermidine synthesis and has some activity against human renal tumors; DFMO irreversibly inhibits ornithine decarboxylase, the first rate-limiting enzyme controlling polyamine biosynthesis; and DFMO promotes intracellular accumulation of MGBG in experimental tumor models and human leukemia. DFMO (2%) in drinking water, MGBG (15 mg/kg i.p.), or a combination of DFMO and MGBG was administered daily to BALB/c mice (n = 80) with intrarenal transplants of renal adenocarcinoma cells. At 28 days, renal carcinomas weighed 64 and 73% less, respectively, in DFMO- and DFMO-MGBG-treated mice than in control animals (p less than 0.01). MGBG alone had no antigrowth effect. DFMO-MGBG reduced the total metastatic index (total number of metastases/total number of animals) to 1.2 versus 3.6 in control animals (p less than 0.01) and increased survival by 12.3 +/- 1.5 (S.E.) days, from 30.8 to 42.5 days (p less than 0.05). Compared with control, DFMO-, or MGBG-treated animals, DFMO-MGBG exposure reduced tumor growth and the number of metastases, prevented metastases in some animals (47%), and increased survival of mice bearing renal adenocarcinomas. DFMO also appeared to selectively increase the uptake of [14C]MGBG by tumor tissue, which may help to explain the enhanced synergistic antigrowth effect of DFMO and MGBG against this murine renal adenocarcinoma.

Adenocarcinoma↗
PubMed1983

Planned preoperative cisplatin and radiation therapy for locally advanced bladder cancer.

Cisplatin (DDP) is an active agent in the treatment of disseminated bladder cancer. In addition to its direct tumor cytotoxicity, recent animal and clinical data suggest synergism with radiation therapy (RT). Since improved survival with preoperative RT is largely restricted to bladder cancer patients in whom radiation-induced downstaging (P less than T) may be recognized, the authors administered DDP + RT preoperatively to patients with locally advanced (T3, T4) bladder tumors selected for cystectomy. The aim was to evaluate the feasibility of such a combination in relation to surgical and hematologic complications, the immediate effect on tumor downstaging, disease progression, and survival. Two thousand rad (400 rad X 5 days) was delivered to the whole pelvis, followed by cystectomy in 2 days. DDP (70 mg/m2) was given intravenously on day 2 of the RT. Twenty-four patients received preoperative DDP + RT and underwent attempted cystectomy; however, six patients were nonresectable owing to extensive pelvic disease, and an additional five patients had resectable pelvic lymph node metastases. Pelvic complications developed in 3 of 24 (12%) patients, but none required reoperation. No patient had a wound dehiscence. Transient myelosuppression was similar to that induced by 2000 rad preoperative RT alone. Tumor downstaging (P less than T) was seen in 9 of 24 (38%) patients, and in 5 (21%) patients, no tumor was found in the surgical specimen (P0). Distant metastases alone have been detected in 4 of 18 (22%) patients who had a cystectomy (all 4 had nodal metastases). Disease-free survival at a median follow-up of 22 months (range, 12-34 months) is 60% (14/24) for all patients (89% for P less than T and 40% for P greater than or equal to T patients) and 78% (14/18) for the resected patients. Combined preoperative DDP + RT proved to be a safe and feasible regimen which resulted in a possibly greater recognition of radioresponsive bladder tumors, and after cystectomy, an encouraging early survival rate in patients with locally advanced disease.

Aged↗
PubMed1983

Association of depressed mixed lymphocyte reactivity with the development of bladder carcinoma in patients with papillomas.

Patients with bladder papillomas have an excellent overall prognosis, although approximately 10% of such patients develop frank bladder cancer. It is therefore important to devise methods for subclassifying bladder papillomas in an attempt to identify those patients at high risk for progression to carcinoma. The lymphoproliferative responses in 27 patients with bladder papillomas were tested in the mixed lymphocyte reaction (MLR). Patient responses were compared to those of normal individuals tested simultaneously. A relative proliferation index (RPI) was defined as a percent response relative to the mean normal response. A RPI less than 0.5 was defined as a depressed MLR and greater than 0.5 as a normal MLR. All patients were followed at three-month intervals for at least five years for the development of superficial or invasive bladder carcinoma. Of the 27 patients, 12 had a depressed MLR and 10/12 (83%) developed cancer within five years. Of the 15 patients with a normal MLR, only three developed bladder carcinoma. The number of papilloma patients surviving free of bladder carcinoma at five years was 12/15 (80%) with a normal MLR and 2/12 (17%) with a depressed MLR (P less than 0.01). Measurement of the MLR appeared to offer a useful adjunct in the evaluation of staging and biologic potential of bladder papilloma.

Adult↗
PubMed1983

VAB-6 combination chemotherapy in resected stage II-B testis cancer.

Twenty-four patients with resected Stage II-B nonseminomatous germ cell tumors of the testis received adjuvant chemotherapy with the modified VAB-6 regimen for one year. Eighteen patients had nodal category N2B and six nodal category N3 (extranodal extension of tumor). Adjuvant VAB-6 started with two four day inductions at approximately four week intervals. Induction was cyclophosphamide 600 mg/m2 IV, vinblastine 4 mg/m2 IV, dactinomycin 1 mg/m2 IV, bleomycin 30 mg IV on day 1, then bleomycin 20 mg/m2/day by continuous 24 hour infusion for three days, and cis-platinum 120 mg/m2 IV on day 4. Maintenance was vinblastine 6 mg/m2 IV and dactinomycin 1 mg/m2 IV every three weeks. Six patients received a third induction but without bleomycin. All 24 patients remain free of disease with a median follow up of 24 months. Myelosuppression was the major toxicity. Four patients received antibiotics for fever during myelosuppression. In one patient, serum creatinine temporarily rose over 2 mg/dl after cis-platinum. VAB-6 is effective in the prevention of recurrences in resected Stage II-B nonseminomatous germ cell tumors. However, the optimal regimen remains to be defined.

Adolescent↗
PubMed1983

The patient, disease status, and treatment options for prostate cancer: stages B1 and B2.

Prostatic adenocarcinoma palpably confined to the prostate is clinically defined as stage B. Although potentially curable in many, if not most, instances, there is no disputing that the optimal management of patients with stage B neoplasms is one of the most uncertain and controversial issues in modern urologic oncology. The present uncertainty can be related to three major factors: 1) competing causes of death in patients commonly older than 50 years of age; 2) the variable and unpredictable natural course of localized prostatic cancer as reflected by the three, at least in part, independent variables of growth rate, metastatic potential, and therapeutic responsiveness; and 3) the multiplicity and effectiveness of a variety of treatments in producing effects on the tumor favorable to the patient. The relative effectiveness of different treatments has been and remains clouded by a constantly changing array of clinical staging techniques, selection criteria for treatment, and definitions of response, and by the general absence of satisfactory control data. Experiences with patients receiving no treatment, various forms of irradiation, and radical excision have indicated a general similarity in at least 10-year survival rates and clinically manifest local failure rates among comparable substages of stage B prostatic cancer. Since suitable control data are lacking, one may conclude that a variety of treatments offer similar prospects of benefit or that none of the treatments is producing significant beneficial effect and that survivals are a consequence of the natural history of stage B disease. A Possibility that has yet to be evaluated is that different treatments produce benefit in different segments of the stage B prostatic cancer population, and the challenge today is to recognize and define such neoplasms that may respond most appropriately to one form of therapy or another.

Age Factors↗
PubMed1983

Presumptive downstaging from preoperative irradiation for bladder cancer as determined by flow cytometry: preliminary report.

Presumptive tumor downstaging was evaluated in 28 patients with grade II or III, solid, muscle-infiltrating bladder cancer (clinical category T3) treated by integrated irradiation (2000 rad to the whole pelvis in 5 days) and cystectomy (1-14 days later) by comparing the results of flow cytometry (FCM) on barbotage specimens obtained before and after irradiation (at the time of cystectomy) and the results of pretreatment clinical stage (T category) and post cystectomy pathological stage (P category). The patients were divided into three groups: (1) P greater than T, (2) P = T, and (3) P less than T. All of the patients in this study had positive FCM specimens with an aneuploid stemline in the pre-irradiation specimen. A complete radiation response (CRR) was defined by FCM as disappearance of the aneuploid stem cell line. Of the 5 patients in the P less than T group, 4 showed a CRR; of 20 patients in the P = T group, 8 showed a CRR; of the 3 patients in the P greater than T group, none showed a CRR. The proportion of patients in the various T/P groups is consistent with that previously observed in patients receiving integrated irradiation (2000 rad in 5 days) and cystectomy (1-14 days later). The overall downstaging response of 43%, as determined by FCM, correlates well with the pathological downstaging rates of 40%-68% reported by others following high dose (4000-5000 rad) integrated irradiation cystectomy regimens; however, it is more than the 27% rate reported with the low dose short course (2000 rad in 5 days) regimen. The correlation of the FCM findings with clinico-pathological downstaging is consistent with the possibility that FCM may be useful in identifying a favorable radiation response.

Carcinoma, Squamous Cell↗
PubMed1983

Renal cell carcinoma extending into inferior vena cava.

Of 18 patients with renal cell carcinoma extending into the inferior vena cava 16 underwent radical nephrectomy with either venacavotomy and tumor thrombectomy or vena cava resection. Of 8 patients with no evidence of metastasis at the time of surgery 4 (50 per cent) are free of cancer for a mean duration of 93 months. Of 8 patients with known preoperative metastasis 7 died with cancer after a mean survival of 12 months. Operative mortality was 6.2 per cent and morbidity was minimal.

Adenocarcinoma↗
PubMed1983

Bladder carcinosarcoma: histologic variation in metastatic lesions.

Carcinosarcoma is a tumor composed of malignant epithelial and mesenchymal elements, which occurs rarely in the bladder. Although the prognosis of bladder carcinosarcoma is known to be poor the histology of metastatic lesions is not well described. We report 2 cases of bladder carcinosarcoma with pelvic lymph node involvement. Pure sarcomatous metastasis was present in 1 patient and only carcinoma in the other. The histologic composition of metastatic lesions may be of significance in treatment planning in patients with bladder carcinosarcoma.

Aged↗
PubMed1983

Panniculectomy in conjunction with radical cystectomy in the obese patient.

Obesity in the abdominal area causes difficulty not only with the placement of an ileal conduit stoma and conduit length but also with surgical exposure during radical surgery to the pelvis. Such problems may be ameliorated by using a horizontal abdominal dermolipectomy in conjunction with a midline fascial and peritoneal incision and the Turnbull ileal stoma in selected obese patients. The advantages of this technique far outweigh the limited complications which may be encountered.

Abdomen↗