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Biomedical subjects

C E Ehrlich

Publications and source records attributed to C E Ehrlich.

11 recordsLinked to original sources
PubMed1992

Inhibition by tiazofurin of inosine 5'-phosphate dehydrogenase (IMP DH) activity in extracts of ovarian carcinomas.

Cancer cells have an increased ability to synthesize GTP (guanosine triphosphate) because of increased activity of IMP DH (inosine 5'-phosphate dehydrogenase, EC 1.1.1.205). Because IMP DH activity is rate limiting for de novo biosynthesis of GTP, this enzyme was suggested as a sensitive target for chemotherapy. Tiazofurin (2-beta-D-ribofuranosylthiazole-4-carboxamide) is converted in the cells into the active metabolite, TAD, (thiazole-4-carboxamide adenine dinucleotide) which potently inhibits IMP DH activity. By adding TAD to tissue extracts one can determine the extent of inhibition of IMP DH. We applied the IMP DH assay method to extracts of normal ovaries (N = 11) and epithelial ovarian carcinomas (N = 10). The IMP DH activity (mean +/- SE) in ovarian carcinoma was 21.1 +/- 5.8 which was markedly higher than that observed in normal ovaries (2.9 +/- 0.7 nmol/hr/mg protein) (P < 0.05%). The inhibition by TAD of IMP DH activity in ovarian carcinomas (N = 4) was 81%. The results indicate that IMP DH activity is elevated sevenfold in ovarian carcinomas as compared to normal ovary and can be inhibited by exposure to tiazofurin (TAD). Similar high IMP DH activity and inhibition of the activity by TAD was observed in patients with chronic granulocytic leukemia in blast crisis among whom 70 to 80% remissions were reported. Since there is increased IMP DH activity in human ovarian carcinomas and in OVCAR-5 cells and tiazofurin and TAD inhibit IMP DH activity of these cells and the proliferation of human ovarian carcinoma xenografts in the mouse, tiazofurin may merit serious consideration for a Phase II trial for patients with recurrent/refractory epithelial ovarian carcinoma.

Adenocarcinoma↗
PubMed1992

Recurrent squamous carcinoma of the vulva.

OBJECTIVE: This study reviews experience at Indiana University with recurrent squamous carcinoma of the vulva over an 18-year period from 1971 to 1989. The pattern of recurrence, time interval to recurrence, and efficacy of salvage therapy are evaluated in the context of the primary tumor. STUDY DESIGN: This is a retrospective study of 40 patients, 21 of whom underwent primary therapy for invasive squamous carcinoma of the vulva at Indiana University. RESULTS: Vulvar recurrences were observed in 17 patients (43%), the groin was involved in 12 (30%), whereas pelvic and distant recurrences were observed in 2 (5%) and 9 (22.5%) patients, respectively. Salvage surgery and/or radiotherapy were successful in 25 patients (62.5%) alive from 1 to 144 months (median 8 months) from secondary therapy. Survival after retreatment varied significantly by site of recurrence (p = 0.002), tumor grade (p = 0.009), and interval to recurrence (p < 0.001). Best outcomes were in patients with initial stage I or II disease (International Federation of Gynecology and Obstetrics), grade 1 tumors, local failure, and interval to relapse of > 16 months' duration. Two of 12 patients with groin recurrences were salvaged with surgery and radiotherapy. CONCLUSION: Long-term follow-up of patients with vulvar cancer and careful restaging at the time of recurrence are mandatory. Although local and nodal recurrences may be controlled with surgery and/or radiotherapy, regional recurrences are usually fatal.

Adult↗
PubMed1979

Juvenile granulosa cell tumor: a clinicopathologic study of three cases with ultrastructural observations.

We have encountered three cases of a recently recognized form of granulosa cell tumor referred to by Scully as the juvenile type, and we have made ultrastructural observations on one case. This variant is encountered almost exclusively in the first two decades, and is characterized at the optical microscopic level by a macrofollicular or a diffuse, sometime disorderly pattern of growth, often with extensive luteinization and hyperchromatic nuclei. One of our patients developed precocious pseudopuberty. Our ultrastructural observations in this case supported the concept that this tumor is a granulosa cell tumor, and the tumor showed some similarities to previously reported granulosa cell tumors. A spectrum of cells was observed ranging from well differentiated granulosa cells to stromal cells with many intermediate forms present. The stromal cells varied from being fibroblast-like to theca-like. Both granulosa and stromal cells sometimes contained abundant lipid. Evidence of luteinization, i.e. abundant smooth endoplasmic reticulum and tubular mitochondrial cristae, was not noted in either the granulosa or stromal cells. Focal areas of smooth endoplasmic reticulum were found, however, in teh cytoplasm of cells intermediate between granulosa and stromal types. These cells may represent the source of steroid hormone secretion.

Child↗
PubMed1977

Paget's disease of the vulva. A histogenetic study of five cases including ultrastructural observations and review of the literature.

Five cases of extramammary Paget's disease of the vulva were studied by histologic, ultrastructural, and immunologic methods. In one of these cases, the associated invasive adnexal carcinoma was studied in a similar fashion. In all five cases, carcinoma-in situ of the sweat glands was observed. In two cases, the glands were identified as aporcrine. In the other three it could not be determined whether they were apocrine or eccrine. In one case tumor cells were seen extending from a focus of underlying carcinoma-in-situ of sweat glands through the excretory duct into the surface epithelium. The ultrastructural findings indicated that the Paget's cells as well as the cells of the invasive carcinoma were adenocarcinoma cells, but the findings were not conclusive as to whether the cells were apocrine or eccrine. There was no evidence of origin of the Paget's cells from keratinocytes. We believe that the bulk of evidence favors an extraepidermal origin for extramammary Paget's disease. The tumor is most commonly derived from the secretory portion of sweat glands, probably either of apocrine or eccrine types, or the dermal or poral portion of the sweat duct. Some cases of Paget's disease are derived from other types of glands.

Antigens, Neoplasm↗
PubMed1977

Nonpuerperal inversion of the uterus by endometrial stromal sarcoma of the uterine fundus.

Nonpuerperal inversion of the uterus is rare; the 69th such case in the English literature is reported. Although caused most frequently by submucous leiomyoma, nonpuerperal uterine inversion may be caused by carcinoma or, as in this report, a sarcoma of the uterine fundus. For optimal therapy and to reduce surgical complications, the correct preoperative diagnosis of uterine inversion and any concomitant disease is mandatory.

Aged↗
PubMed1977

Mucinous cystadenocarcinoma of the retroperitoneum.

A case of a primary retroperitoneal mucinous cystadenocarcinoma of ovarian type found at laparotomy in the presence of two normal ovaries is described. Careful examination of the tumor showed no evidence of ovarian tissue in the wall. The appearance of this tumor could be traced from areas of benign mucinous cystadenoma, through a mucinous tumor of borderline malignancy to a highly malignant anaplastic tumor containing only occasional mucicarmine positive cells. In areas, the connective tissue of the neoplasm, resembled ovarian stroma in appearance. At autopsy, the retroperitoneum was free of neoplasm, but widespread metastases, consisting of poorly differentiated adenocarcinoma were observed. This neoplasm may have arisen from displaced coelomic epithelium or from a supernumerary ovary.

Cystadenoma↗
PubMed1976

Progesterone binding in human endometrial carcinomas.

By means of dextran-coated charcoal assay, the capacity of various endometrial cytosol preparations for specific binding of 3H-rone was determined. With the use of an arbitrary value of 50 femtomoles of bound 3H-progesterone per milligram of cytosol protein as the breaking point between high and low binding capacities, 19 out of 20 normal endometria had high progesterone-binding capacities. Two out of 11 Grade I, 3 out of 8 Grade II, and 2 out or 4 Grade III endometrial carcinomas showed low binding capacities. All 4 endometrial polyps, 7 out of 9 hyperplastic endometria, and 0 out of 7 nonendometrial gynecologic tumors had high binding capacities. These data suggest a progressive loss of specific progesterone-binding activity from normal endometria to hyperplastic endometria, and from the well-differentiated to the anaplastic forms of endometrial adenocarcinoma. There seemed to be an inverse relationship betweeen age and concentration of progesterone receptors in endometrial adenocarcinomas. All irradiated tumors studied had low progesterone-binding capacity.

Adenocarcinoma↗
PubMed1976

An evaluation of the usefulness of amylase isozyme differentiation in patients with hyperamylasemia.

Amylase assays measure total activity without differentiating the relative contributions of pancreatic- and salivary-type amylase isozymes. Since polyacrylamide electrophoresis allows identification of salivary-and pancreatic-type isoxymes and their respective variants, serum and urine specimens from patients with the clinical diagnoses of mumps (4), pancreatitis (16), or undiagnosed hyperamylasemias (5) were compared with specimens from control subjects. Patients with mumps had elevations of salivary-type isozymes, while those with pancreatitis had elevations of pancreatic-type isozymes. Elevation of salivary-type isozymes was identified in the five patients who had undiagnosed hyperamylasemias; among these, the isozymes of two originated in neoplastic ovarian tissue and those of three, probably in the salivary glands. Amylase isozyme differentiation cannot unamibiguously identify the tissue source of hyperamylasemia. However, in patients whose hyperamylasemia is of unknown etiology or who respond atypically to therapy, amylase electrophoresis provides identification of the elevated isozyme type, thus providing the basis for the rational selection of further diagnostic procedures.

Aged↗