Search PubMed⌕ Search

Biomedical subjects

N L Block

Publications and source records attributed to N L Block.

At least 55 records · Page 3Linked to original sources

Malignant fibrous histiocytoma of spermatic cord.

Malignant fibrous histiocytoma occurs rarely in the genitourinary organs, and is exceptional in the spermatic cord. The prognosis of deep malignant fibrous histiocytoma not occurring in subcutaneous tissue or fascia is generally poor. We report a case, of malignant fibrous histiocytoma giant cell type, arising around the spermatic cord. The patient is alive without metastasis ten years after initial therapy. To our knowledge, this is the longest reported survivor of this disease. Radical inguinal orchiectomy along with wide en bloc local resection is the therapy of choice.

Adult↗

Mature testicular teratoma with vena caval invasion presenting as pulmonary embolism.

We report a case of mature testicular teratoma with invasion and thrombosis of the inferior vena cava that presented as recurrent pulmonary embolism. Treatment included radical orchiectomy, chemotherapeutic cytoreduction and, finally, resection of a massive retroperitoneal tumor with en bloc resection of the inferior vena cava using cardiopulmonary bypass and deep hypothermic circulatory arrest. Management is discussed and the literature is reviewed.

Adult↗

Isolation of a prostate carcinoma cell proliferation-inhibiting factor from human seminal plasma and its similarity to transforming growth factor beta.

Human seminal plasma (SP) has been known to contain both growth-inhibitory and -stimulatory factors. We attempted to identify a factor that inhibited DNA synthesis in some metastatic prostate cancer cell lines. The SP factor was sensitive to digestion by trypsin, but its activity increased after boiling or dialysis against 1 M acetic acid, by 3- to 4-fold. The SP factor was partially purified using a cation-exchange resin. Apparent molecular mass determination by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed it to be a M(r) 25,000 protein, and M(r) 13,000 after reduction. This protein strongly inhibited DNA synthesis in two metastatic androgen-independent human prostatic carcinoma cell lines (PC3 and DU145) and the Dunning R3327G rat prostatic adenocarcinoma. It was ineffective on androgen-dependent LNCaP cells. The proliferation-inhibiting activity of this SP protein was specifically and completely abolished by a neutralizing anti-transforming growth factor beta (TGF-beta) antiserum. Furthermore, immunoblot analysis using the anti-TGF-beta antiserum showed the similarity of this protein to TGF-beta. The maximum concentration of this protein in SP was 165 +/- 11.7 ng/ml (mean +/- SD), of which only one-fourth may be present in active form under normal conditions. Identification of a TGF-beta-like protein in SP might also explain the variety of growth and immune modulation properties of human SP.

Adult↗

Metastatic prostate cancer presenting as obstructive jaundice.

Metastatic cancer of the prostate, presenting with carcinomatous obstruction of the common bile duct as a cause of jaundice and abnormal liver function tests is very unusual. The literature suggests an association between abnormal liver function tests and poor survivability in those patients with liver parenchymal metastases. This case illustrates that patients with abnormal liver function tests on the basis of extrahepatic ductal obstruction may have a better prognosis than those with hepatic disease.

Aged↗

Small bowel perforation associated with intraperitoneal and extraperitoneal bladder perforation caused by stab wound to the penis.

We report an unusual case of small bowel and bladder perforation caused by a stab wound to the penis with preservation of intact corporeal penile bodies and urethra. Diagnosis of bladder perforation was made by the urethrogram and diagnosis of small bowel perforation was made by clinical signs even though the initial physical examination suggested neither of these conditions.

Adult↗

Zoladex versus orchiectomy in treatment of advanced prostate cancer: a randomized trial. Zoladex Prostate Study Group.

We report preliminary results for the first 164 patients enrolled in a multicenter study comparing the endocrine effects, efficacy, and safety of 3.6 mg of goserelin acetate (Zoladex) and orchiectomy in patients with Stage D2 prostate cancer. Eighty-one patients were randomly allocated to receive Zoladex and 83 to orchiectomy. The median follow-up time for all patients was two hundred ten days. Median serum levels of testosterone were reduced to castrate levels (less than 50 ng/dL) within four weeks in both groups and remained suppressed for up to sixty weeks. An objective response according to modified criteria of the National Prostatic Cancer Project was observed in 81 percent and 78 percent of patients in the Zoladex and orchiectomy groups, respectively. There were no statistically significant differences between treatment groups in the distributions of time to treatment failure or time to disease progression. The most commonly reported adverse events in both treatment groups were hot flashes, cancer-related pain, unspecified pain, and urinary symptoms. These results suggest that Zoladex may offer an alternative to orchiectomy in the treatment of advanced prostate cancer.

Acid Phosphatase↗

Aneuploidy of glandular epithelial cells in histologically normal prostate glands.

The percentage of aneuploidy in normal prostate glands from subjects 13-38 years old and 45-66 years old ranged from 0-78% and 0-63%, respectively. In contrast to adults, aneuploidy was absent in fetal and postnatal prostates. It is concluded that aneuploidy is a fundamental attribute of histologically normal adult prostate glands.

Adolescent↗

Interaction of irradiation and microwave-induced hyperthermia in the Dunning R3327G prostatic adenocarcinoma model.

The interaction of radiation and hyperthermia was systematically studied in the Dunning R3327G prostatic adenocarcinoma, the preeminent animal model for human prostatic cancer. Subcutaneous tumors (produced by injection of 10(7) cells) were treated when they had reached a volume of about 1 cm3, which occurred about 3 weeks after implantation. With the use of a randomized complete factorial design, four factors were examined. Each agent was used at one of three dose levels. For radiation, these were 5, 15, and 25 Gy; for hyperthermia, 42 degrees C for 15 minutes, 43 degrees C for 30 minutes, and 44 degrees C for 60 minutes. Two sequences (hyperthermia plus irradiation and irradiation plus hyperthermia) and five time delays between agents (0, 12, 24, 48, and 120 hours) were used. The growth delay (the time it took for the initial tumor volume to double) of subcutaneously implanted tumor served to quantitate treatment effect. Significant (P less than .05) statistical interactions were observed for several combinations of factors and individual factors. Hyperthermia plus irradiation was more effective than irradiation plus hyperthermia except at the delay time between treatments of 0 hours. Peak growth delay occurred when the time between treatments was 0-24 hours and depended on agent doses. Many combinations produced therapeutic synergy.

Adenocarcinoma↗

Measurement of cell-cycle phase-specific cell death using Hoechst 33342 and propidium iodide: preservation by ethanol fixation.

We developed a rapid technique for preservation of Hoechst 33342/propidium iodide-stained cells, using ethanol as a fixative. Combined staining with these dyes makes possible analysis of cell-cycle phase-specific cell death. The technique relies on exclusion of propidium iodide from the viable cells, whereas Hoechst stains all of the cells. The bivariate histograms resulting from the flow cytometric analysis contain the equivalent of two single-parameter DNA histograms, one of the living and the other of the dead cell population. Preservation of staining involved addition of 25% ethanol in PBS after propidium iodide staining and before Hoechst staining. The separation between the living and the dead cell populations was maintained for over 3 days at 4 degrees C. This technique will be valuable for quantitative evaluation of the cell-cycle phase-specific effects of cytostatic or cytotoxic agents, particularly in situations where a lag period between staining and analysis is unavoidable.

Benzimidazoles↗

DNA patterns in parathyroid disease predict postoperative parathyroid hormone secretion.

Flow cytometric analysis of the nuclear deoxyribonucleic acid (DNA) content of parathyroid glands excised from patients with hypercalcemic hyperparathyroidism has identified three distinct DNA patterns. The most frequent pattern showed a high percentage of cells with tetraploid DNA, which indicated an increase in the G2 and M phase of the cell cycle. Thirty-four patients were found to have abnormal tetraploid DNA content. One patient had a normal diploid pattern, and seven were found to have an aneuploid DNA population in their excised parathyroid glands. This unexpected finding of aneuploid DNA appears to be an unique feature of these endocrine glands because they have no histologic or clinical characteristics of malignant change. All patients have remained normocalcemic and clinically well after excision of only grossly enlarged glands. Postoperative parathyroid hormone (PTH) levels were correlated in 17 patients with DNA analyses of biopsy specimens from 30 normal-sized glands which were left in situ. Seven patients with elevated PTH postoperatively had high tetraploid or aneuploid DNA in all 13 glands from which biopsy specimens had high tetraploid or aneuploid DNA in all 13 glands from which biopsy specimens had been taken. In 10 patients with normal PTH levels, six had normal diploid patterns, whereas four had high tetraploid DNA in their gland biopsy specimens. DNA content present in biopsy specimens of normal-sized, in situ glands was predictive (p less than 0.042) of parathyroid gland secretory activity. These findings suggest that the stimulus for parathyroid gland hyperfunction often affects more than a single enlarged gland and persists after clinical cure, as shown by a more rapid cell turnover in some remaining glands and continued hypersecretion of hormone.

DNA↗

Systematic investigation into interaction of ionizing radiation and doxorubicin in the Dunning R3327G prostatic adenocarcinoma model.

The interaction of doxorubicin and radiation has been systematically studied in the Dunning R3327G prostatic adenocarcinoma, the preeminent animal model for human prostatic cancer. Subcutaneous tumors (produced by injection of 10(7) cells) were treated when about 1 cm3 in volume (19-22 days postimplant). Each modality was used at 1 of 3 dose levels; 2, 4, and 9 mg/kg for doxorubicin; and 5, 15, and 25 Gy for radiation. Single treatment with each agent was combined, in both sequences and five delay times (0.5, 12, 24, 48, and 120 hr) between agents. Growth of individual tumors was fit to a quadratic exponential growth model which was solved for the growth delay and growth rate at twice initial volume. Analysis of variance identified significant interactions for doxorubicin and radiation (due to drug toxicity), sequence and delay, and sequence and radiation, in addition to the four factors individually. The effect on the tumor of combined doxorubicin and radiation is basically additive. Sequence and delay are important in overall tumor control.

Adenocarcinoma↗

A technique for localized tumor hyperthermia in small animals.

Hyperthermia, the intentional elevation of tissue temperature above 41 degrees C, is being intensely researched as a therapeutic modality for cancer, especially when used in combination with radiation therapy and/or chemotherapy. A serious impediment to laboratory progress in this area has been the lack of affordable equipment providing control and reproducibility when faced with highly variable factors including tumor size and shape, blood flow, heat conduction, and tissue dielectric discontinuity. Our solution has been the development of a laboratory microwave hyperthermia system, dedicated to the treatment of small, superficial tumors. This system uses a 2.45-GHz microwave generator and custom applicator to noninvasively heat a mass of tissue about 2 cm in diameter and 1.5 cm in depth. Tissue temperature at up to four locations is measured using miniature. Teflonencased thermocouples. The microwave generator and the thermometry are interfaced to a personal computer which provides fully automated hyperthermia treatment reproducible to +/- 0.2 degrees C.

Animals↗

Small cell carcinoma of the prostate gland with inappropriate antidiuretic hormone secretion: morphological, immunohistochemical and clinical expressions.

Small cell carcinomas of the prostate gland are rare, and their histogenesis and clinical behavior remain poorly defined. We report a case with antidiuretic hormone secretion, which demonstrates direct transformation of the adenocarcinoma into the small cell component. The adenocarcinoma reacted positively for prostatic antigen, and negatively for carcinoembryonic antigen and neuron specific enolase, whereas the small cell component was negative for prostatic antigen, and positive for carcinoembryonic antigen and neuron specific enolase. At biopsy this was interpreted as denoting 2 separate tumors: one of prostatic and the other of nonprostatic origin. The clinical course was rapidly fatal but otherwise manifested the metastatic pattern of prostatic carcinoma. We caution that immunohistochemical reactions may be misleading if not interpreted in the context of other findings in the case. This case is labeled as a small cell carcinoma rather than a poorly differentiated adenocarcinoma of the ordinary type because the tumor exhibited morphological, immunohistochemical and biological features typical for that neoplasm.

Adenocarcinoma↗

Cell kinetic effects of incorporated 3H-thymidine on proliferating human lymphocytes: flow cytometric analysis using the DNA/nuclear protein method.

Phytohemagglutinin-stimulated human peripheral blood lymphocytes incorporating high concentrations of 3H-thymidine accumulate in G2 and show a consequent reduction in the number of cells entering M (division delay). The simultaneous flow cytometric analysis of DNA content (propidium iodide fluorescence) and nuclear protein content (fluorescein isothiocyanate fluorescence) allows for the accurate quantitation of these events; G2 and M are separated in the bivariate distributions. A good correlation was observed between mitotic indices, quantitated by manually counting mitotic cells, and integration of the M area in DNA/nuclear protein histograms. Moreover, significant differences in G2 nuclear protein levels were found between untreated and 3H-thymidine-treated lymphocytes. In order to characterize this effect, G2 was empirically divided into low nuclear protein (G2A) and high nuclear protein (G2B) compartments. 3H-thymidine caused an initial accumulation of lymphocytes in G2A, followed within 3-6 h by a gradual movement of some cells into G2B, with a subsequent accumulation of cells in G2B. The results suggest that the distribution of cells in G2 (G2A and G2B), the average nuclear protein content of G2B cells, and the proportion of cells in M are parameters that when used in combination provide a unique description of radiobiological effects.

Cell Cycle↗

Tumor progression in serial passages of the Dunning R3327-G rat prostatic adenocarcinoma: growth rate response to endocrine manipulation.

Serial passages of the poorly differentiated, androgen-sensitive R3327-G prostatic adenocarcinoma were used to study the progressive changes that occur in tumor growth rate and androgen sensitivity. Different in vivo transplant generations (21st to 28th) were compared. The tumor doubling and animal survival times resulting from the implantation of the 21st to 22nd generation (21-22G) tumor cells in intact male rats were significantly greater than those resulting from the implantation of 23-28G tumor cells. The most dramatic difference between early (21-23G) and late (26-28G) tumor generations, however, was in androgen sensitivity. The 26-28G tumors displayed androgen sensitivity only when implanted into animals castrated 2 to 7 days previously. Tumors grown in the pretreated castrates grew at a significantly slower rate than those in intact rats and the pretreated castrates had longer survival times than the intact rats. When 26-28G tumors were allowed to grow in intact rats to approximately 1 cu cm and then the rats were castrated, no significant difference in the growth rate between these tumors and tumors grown in intact rats was observed. In contrast, the androgen sensitivity of 21-23G tumors could be demonstrated, regardless of whether treatment was started before or after implantation. The fact that androgen sensitivity was still evident under certain conditions in late-generation R3327-G tumors demonstrates that the basic mechanism involving androgen response was still present, although functioning at a much reduced level.

Adenocarcinoma↗

Control of growth, morphology, and alkaline phosphatase activity by butyrate and related short-chain fatty acids in the retinoid-responsive 9-1C rat prostatic adenocarcinoma cell.

The actions of butyrate and related short-chain fatty acids were analyzed on the 9-1C retinoid-responsive rat prostatic adenocarcinoma cell. The 9-1C cells, which are inducible for alkaline phosphatase (AP) by retinoic acid, were also inducible for the enzyme by three- to six-carbon fatty acids. The most effective inducer was the four-carbon acid, butyrate, which caused an essentially linear increase in AP activity in the concentration range of 2 to 10 mM. A comparison of AP induction by butyrate and retinoic acid showed the retinoid to be a more potent inducer of the enzyme by several orders of magnitude. Butyrate and related short-chain fatty acids also suppressed 9-1C cell growth, an effect which is not mediated by retinoic acid in these cells. Total growth suppression was achieved at butyrate concentrations of 5 mM and above; 1.5 mM caused 50% inhibition. As in the case of AP induction, all three- to six-carbon fatty acids suppressed growth to some extent, although butyrate was the most effective. The order of carbon chain length effectiveness for both AP induction and growth suppression by the fatty acids was 4 greater than 5 greater than 3 greater than 6. Butyrate appeared to be unique among the various fatty acids in causing an increase in cell protein. The protein content of 9-1C cells cultured in the presence of 4 mM butyrate for 72 h was more than 4-fold greater than that of control cells. This observation paralleled observations on cell volumes analyzed by forward-angle light-scatter flow cytometry, which showed a concentration-related increase in the cross-sectional areas of 9-1C cells following butyrate treatment. This effect has also been shown, in a recent study, to be mediated by retinoids. One of the most striking effects of butyrate treatment was on cellular morphology. The fatty acid caused 9-1C cells, which normally grow in a disorganized array with no apparent affinity for each other, to spread out and become organized into parallel tracts through the monolayer.

Adenocarcinoma↗