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W D Lawrence

Publications and source records attributed to W D Lawrence.

At least 37 records · Page 2Linked to original sources
PubMed1996

Ovarian neuroendocrine carcinomas of non-small-cell type associated with surface epithelial adenocarcinomas. A study of five cases and review of the literature.

Five primary ovarian carcinomas composed of a high-grade neuroendocrine tumor of non-small-cell type and a surface-epithelial-stromal tumor are reported. The five tumors presented in women aged 36 to 77 (mean, 57) years with abdominal distension or a palpable mass in three cases, right lower quadrant pain with tenderness and fever in one case, and a cervicovaginal smear showing a high estrogen effect in one postmenopausal patient. The tumors were unilateral, 9 to 30 (mean, 16) cm in greatest dimension, and had solid and cystic components. Three tumors were stage I; one, stage II; and one, stage III. Two patients who received chemotherapy died of tumor 8 and 36 months postoperatively, another who refused chemotherapy but later received radiation died of tumor after 19 months, a fourth was lost to follow-up, and a fifth was treated recently. Microscopically, the neuroendocrine components of all the tumors were composed predominantly of sheets, closely packed islands, cords, and trabeculae of epithelial cells with little intervening stroma. The tumor cells in the neuroendocrine areas were medium-sized to large compared with the cells of small cell carcinoma, and they contained scanty to moderate amounts of cytoplasm and hyperchromatic nuclei with coarse chromatin clumping in three cases and abundant cytoplasm and vesicular nuclei with single, large eosinophilic nucleoli in the other two. In all the cases, areas of necrosis and single-cell necrosis were extensive, and mitotic figures were abundant. Positive argyrophil and argentaffin reactions were observed in occasional to many cells in all cases. The glandular components of the tumors were grade 1/3 endometrioid adenocarcinoma (one case), grade 2/3 mucinous adenocarcinoma (2 cases), and mucinous borderline tumor with small foci of mucinous adenocarcinoma (two cases). Numerous enterochromaffin cells were identified in hematoxylin and eosin sections of the borderline mucinous components of two tumors; occasional nonargentaffin argyrophilic cells were present in the endometrioid and mucinous carcinoma components. Luteinized stromal cells were present focally in two cases, including the case in which there was evidence of a high estrogen level. Immunohistochemical studies in five cases showed staining of most cells in the solid components for cytokeratin and chromogranin A and some to most cells for serotonin and neuron-specific enolase. Neuropeptides that were detected in the solid component of one or more of the cases included vasoactive intestinal peptide, somatostatin, gastrin, and glucagon; negative results were obtained for pancreatic polypeptide and insulin. Flow cytometry in four tumors revealed that the neuroendocrine component was aneuploid in two, suspicious for aneuploidy in one, and diploid in one. Tumors of the type described are distinct pathologically from primary ovarian carcinoid tumors and small cell carcinoma of pulmonary type. Although experience with this type of tumor is limited, the prognosis appears to be poor.

Adenocarcinoma↗
PubMed1996

Effects of long-term cocaine exposure on spermatogenesis and fertility in peripubertal male rats.

PURPOSE: This study was conducted to investigate the effects of long-term administration of cocaine on spermatogenesis and fertility in adult male rats. MATERIALS AND METHODS: Thirty-day-old male Sprague-Dawley rats were given cocaine hydrochloride (15 mg./kg. body weight, corresponding to an average single dose for a heavy cocaine user) either daily or twice weekly (weekend group, cocaine given on Saturday and Sunday) and mated with pregnancy-proven female rats after 100 and 150 days of exposure to the drug. Pregnancy rates and litter birth weights were evaluated. Serum testosterone, follicle stimulating hormone and luteinizing hormone levels were measured in all adult rats. Morphologic analysis of the testis entailed the evaluation of quantitative and qualitative histologic parameters to assess the effect of cocaine on various stages of spermatogenesis. RESULTS: After 100 days of treatment, the rats receiving daily cocaine had a pregnancy rate of only 33% versus 86% for the controls (p < 0.05). In rats exposed to cocaine for 150 days the pregnancy rate was 50% compared with 100% for controls (p < 0.05). The birth weights of offspring from the group receiving daily cocaine was 10% less than that of controls (p < 0.05). The weight of the testis and epididymis was not affected by cocaine exposure. Morphometric analysis showed significant differences between the cocaine-treated groups (both the daily cocaine and twice weekly cocaine groups) and their respective controls. The mean diameter of seminiferous tubules in the daily and twice weekly cocaine groups was reduced when compared with their respective controls. These differences between treated groups and their controls were statistically significant (p < 0.05). Similarly the thickness of the germinal epithelium was less in the cocaine-treated groups than in the controls (p < 0.05). Degenerating cells were more numerous in both daily and twice weekly cocaine groups than the controls. Furthermore, the number of step VII spermatids was reduced in both daily and twice weekly cocaine groups, a difference that was statistically significant (p < 0.05). CONCLUSION: Our findings demonstrate that chronic administration of cocaine to peripubertal male rats has a profound effect on their testicular function. Even with twice weekly administration there was a significant adverse effect on spermatogenesis although this was not manifested by diminished fertility in this group. These findings confirm that chronic administration of cocaine to male rats can have a deleterious effect on spermatogenesis and fertility.

Animals↗
PubMed1996

Ectopic pregnancy. A recent five-year study and review of the last 50 years' literature.

OBJECTIVE: To compare the past and current clinical and pathologic factors that are responsible for ectopic pregnancy (EP). STUDY DESIGN: We performed a retrospective chart and histopathologic specimen review of 740 cases of EP during a recent, five-year period. Products of conception, as well as 240 cases of concomitant endometrial biopsies, were examined. RESULTS: The mean age at presentation, proportion of patients with a history of pelvic inflammatory disease, voluntary interruption of pregnancy (VIP), previous surgery and laterality (right side) of the tubal EP were similar to rates reported in previous studies. Ninety-four percent of the EPs were tubal, and 90% of the tubes exhibited some pathologic changes, including chronic salpingitis (49.5%) and follicular salpingitis (10%), among others. Gestational endometrial patterns were seen in 44% of cases. The corpus luteum of pregnancy was contralateral in 30% of cases in which an ovarian biopsy was performed. CONCLUSION: The factors classically associated with EP remained similar over a period of about 50 years, although the association with VIP still appears to be controversial. Endometrial curettage alone cannot be used to exclude an EP. Ovum transmigration may play a role in the genesis of EP.

Adolescent↗
PubMed1995

The borderland between benign and malignant surface epithelial ovarian tumors. Current controversy over the nature and nomenclature of "borderline" ovarian tumors.

In the early 1970s, the International Federation of Gynecology and Obstetrics (FIGO) and the World Health Organization (WHO) adopted the terms "borderline malignancy" and "carcinoma of low malignant potential" in their classifications of surface epithelial tumors of the ovary in order to denote a subset of patients with a significantly more favorable prognosis than those with the "usual" surface epithelial carcinomas. Subsequently, a considerable clinicopathologic body of literature has arisen concerning borderline tumors, particularly the serous and mucinous types. Some of them, particularly advanced stage borderline tumors, have been purported to cause significant illness and death. However, some investigators have impugned their malignant nature, especially in Stage I disease, and blame the suggested poor prognosis in advanced cases on a paucity of accurate morbidity and mortality data and ambiguity in current histopathologic terminology; to address the latter, they have proposed to remove any connotation of malignancy by replacing the aforementioned terms with designations such as "atypical proliferating (serous or mucinous) tumor." Another soon-to-be proposed classification will use the terminology "borderline tumors" as a generic group without destructive invasion but with subdivisions into tumors with "epithelial atypia" and those with "intraepithelial carcinoma." The clinical and therapeutic implications of accurate diagnosis of ovarian borderline tumors mandate additional investigation to elucidate their true prognosis; indeed, further dialogue is necessary to arrive at a nosologic system to reflect that biologic behavior. However, until a consensus has been reached, the pathologic diagnosis should reflect, at some point, the currently sanctioned FIGO/WHO classification of surface epithelial ovarian tumors to obviate any misunderstanding that could lead to patient mismanagement.

Female↗
PubMed1995

Inhibition of breast and ovarian carcinoma cell growth by 1,25-dihydroxyvitamin D3 combined with retinoic acid or dexamethasone.

This study examined the growth inhibitory effects of combining 1,25-dihydroxyvitamin D3 (calcitriol) with retinoic acid or dexamethasone against cultured breast and ovarian carcinoma cells. Retinoic acid (12.5-50 nM) increased the effectiveness of calcitriol (12.5-50 nM) against MCF-7 and NIH:OVCAR3 cells, with synergistic interactions at two of the three ratios tested. Dexamethasone augmented calcitriol effects, with synergism at 0.05 and 0.1 nM dexamethasone in MCF-7 cells and 5 nM in Caov-4 ovarian cells. This study showed favorable interactions for calcitriol-retinoic acid and calcitriol-dexamethasone combinations in breast and ovarian cancer cell lines.

Antineoplastic Agents↗
PubMed1995

Surface epithelial changes in endometrial adenocarcinoma: diagnostic pitfalls in curettage specimens.

A total of 161 uteri removed for endometrial cancer were studied in order to characterize the histopathologic features of the endometrial surface epithelium. Of these, 116 had endometrioid endometrial adenocarcinoma, and 45 had other endometrial cancers. A total of 57 (49%) of the endometrioid endometrial adenocarcinomas showed the following surface epithelial changes: seven had a conspicuous microglandular pattern simulating cervical microglandular hyperplasia; 17 had syncytial aggregates of relatively bland-appearing eosinophilic cells, frequently with papillary or squamoid differentiation simulating papillary syncytial change or other endometrial epithelial metaplasias; and 33 had mixed patterns. The surface epithelial changes varied in extent from rare foci to extensive surface replacement and were largely confined to FIGO grade I and II tumors. Cytologic atypicality varied from mild to moderate and was consistently less than that of the underlying carcinoma. Similar changes were present in some of the prior curettings; in some scanty curettings an unequivocal diagnosis of carcinoma was not possible. Consequently, further clinical investigation is indicated if these changes are present in scanty curettings from postmenopausal women.

Adenocarcinoma↗
PubMed1995

Evaluation of chromosome 12 copy number in ovarian granulosa cell tumors using interphase cytogenetics.

Trisomy 12 is frequently observed in karyotypes of ovarian sex cord-stromal tumors, including adult and juvenile granulosa cell tumors (AGCTs and JGCTs). We assessed the ability to detect this abnormality in deparaffinized tissue sections of 19 ovarian GCTs (17 AGCTs, two JGCTs) and in one fibrothecoma by simultaneous in situ hybridization with fluorescent-labeled centromeric probes to chromosomes 12 (fluorescein isothiocyanate conjugated) and 17 (rhodamine conjugated). In order to quantitate the artifact introduced by nuclear slicing, such analyses were performed both on intact tissue sections and on cytospins of nuclei prepared by enzymatic dissociation from the corresponding tissue block. The series was also evaluated for numerical abnormalities of chromosome X, a less common cytogenetic finding in GCT. Twelve of 19 cases (63%) displayed evidence of trisomy 12 (defined as signal gain in > or = 10% of nuclei) in the intact section, the cytospin, or both. Trisomy for chromosome 17 was present in one case, and trisomy X was present in two cases. In tissue sections the incidence of signal gain for the chromosome 12 probe varied from 0-45% of nuclei (mean 19%). In cytospin preparations, the percentage signal gain for chromosome 12 ranged from 0 to 84% (mean 33%). This study supports the presence of trisomy 12 as a common, but not defining, cytogenetic anomaly in ovarian GCTs. Its presence, however, within only a minority of tumor cells may be partly explained by slicing artifact associated with intact tissue sections, although partial involvement of intact nuclei suggests that trisomy 12 may also be encountered as a heterogeneous abnormality within neoplastic populations of GCTs.

Adult↗
PubMed1995

Insulin resistance in a patient with ovarian stromal hyperthecosis and the hyperandrogenism, insulin resistance and acanthosis nigricans syndrome. Report of a case with a possible endogenous ovarian factor.

Insulin resistance is a common feature of ovarian stromal hyperthecosis and is usually accompanied by hyperandrogenemia. A patient had ovarian stromal hyperthecosis, and her hyperandrogenemia resolved, possibly due to the development of a type of ovarian fibrosis similar to so-called ovarian fibromatosis, without a concomitant improvement in her insulin resistance. The insulin resistance improved markedly, however, after bilateral oophorectomy.

Acanthosis Nigricans↗
PubMed1994

Association between HLA-DQB1 alleles and risk for cervical cancer in African-American women.

Squamous-cell carcinoma of the cervix and its precursor lesions are associated with human papillomavirus (HPV) infection. Epidemiological studies indicate that HPV infection in itself is not sufficient for cervical-cancer induction, suggesting that other factors contribute to carcinogenesis. We have investigated the potential role of host genetic background as one such factor. We screened a series of squamous-cell carcinomas of the cervix for HLA-class-II DQB1* alleles by the polymerase chain reaction and site-specific oligonucleotide probe hybridization and for HPV type from African-American women using a local, ethnically matched control panel. Statistically significant associations for increase in relative risk for cervical cancer were seen for DQB1*0303 and DQB1*0604. DQB1*0201 and the heterozygote DQB1*0301/*0501 showed a decrease in relative risk for cervical cancer. HPV typing revealed no association between virus type and DQB1 alleles. Our results confirm other studies showing an increase in relative risk for cervical cancer associated with HLA-DQ3 alleles in Caucasians.

Adult↗
PubMed1994

Angiogenesis in breast carcinoma--clinicopathologic relevance and potential use as a quantifiable surrogate endpoint biomarker.

Although stochastic acquisition of structural genetic aberrations has become the dominant paradigm for progression of solid tumors, the process of tumor cell invasion and metastasis in large part represents a cooperative interaction with host tissues. Such interactions occur at multiple levels and include the exchange of cytokines/growth factors, the induction of neovascularization (angiogenesis), proteolytic degradation and synthetic alterations of the native extracellular matrix, and fibroblast/inflammatory cell chemotaxis. Many classical histologic and mammographic features of breast carcinoma, such as desmoplasia, are a direct reflection of these tumor-host relationships. Further, sustained growth is not possible without a coordinated interaction between diverse neoplastic and native cell populations. In recent years, quantifiable parameters of tumor-host interaction, such as protease elaboration, have been shown to correlate with intrinsic properties of neoplastic cells and to predict clinical outcome. It is thus reasonable to propose that functional cellular alterations imposed by chemopreventive agents may be reflected in tumor-host interaction parameters. The objective of this review is to briefly summarize the literature addressing one parameter of tumor-host interaction--angiogenesis--emphasizing its applicability as a quantifiable biomarker in breast neoplasia.

Biomarkers, Tumor↗
PubMed1993

Uterine mixed embryonal rhabdomyosarcoma and fetal rhabdomyoma.

A polypoid uterine tumor, occurring in a 31-year-old woman, with histopathologic features of both embryonal rhabdomyosarcoma and fetal rhabdomyoma is reported. The clinical and pathologic differences between pure fetal rhabdomyoma and embryonal rhabdomyosarcoma are detailed and theories concerning the histogenesis of such a mixed, or intermediate, tumor are discussed. Most likely, this neoplasm represents one example in a spectrum of tumors with varying proportions of immature and mature skeletal muscle elements. Its good prognosis is in keeping with that of uterine (cervical) embryonal rhabdomyosarcomas in general, although the presence of mature skeletal muscle elements may signify an even better prognostic group of tumors.

Adult↗
PubMed1993

Additive inhibition of RL95-2 endometrial carcinoma cell growth by carboplatin and 1,25 dihydroxyvitamin D3.

Responses of stage III/IV endometrial adenocarcinomas to cytotoxic agents have been partial and of short duration, results which indicate a need for new agents and therapeutic strategies. This study was undertaken to determine the effects of carboplatin and the active metabolite of vitamin D, 1,25 dihydroxyvitamin D3 (calcitriol), on the growth of RL95-2 endometrial carcinoma cells. Carboplatin is a second-generation platinum-based cytotoxic agent. Calcitriol is a biologic agent that has activity against multiple solid tumors, including ovarian carcinomas. Carboplatin inhibited the growth of RL95-2 cells in a concentration-dependent manner with maximal inhibition (78%) at 200 micrograms/ml. Calcitriol also inhibited RL95-2 growth in a concentration-dependent manner. Maximal inhibition (29%) was elicited by 80 nM calcitriol. Addition of 10-50 nM calcitriol to 5-20 micrograms/ml carboplatin resulted in improved growth inhibition. The degree of interaction between carboplatin and calcitriol was assessed using isobolographic analysis and was found to be additive at all drug concentrations and ratios examined. These results suggest that carboplatin and calcitriol each inhibit the growth of RL95-2 endometrial carcinoma cells and that the combination of these two agents acts additively to inhibit the growth of RL95-2 cells. These agents merit further investigation for their utility against endometrial carcinomas.

Adenocarcinoma↗
PubMed1993

Thyroid hormone stimulates release of calmodulin-enhancing activity from human erythrocyte membranes in vitro.

1. Thyroid hormone (L-thyroxine, 10(-10) mol/l) incubated in vitro with human erythrocyte membranes induced the release of a soluble calmodulin-like material, the 3':5'-cyclic nucleotide phosphodiesterase-stimulating activity of which was at least six-fold greater than its concentration measured by a specific calmodulin radioimmunoassay. 2. The material had the characteristics of calmodulin in that it stimulated both phosphodiesterase and erythrocyte Ca(2+)-ATPase activities, cross-reacted with and was neutralized by anti-calmodulin antibody, was adsorbed by phenothiazine-Sepharose and was heat-stable. Control supernatant from the incubation of membranes in the absence of thyroxine contained calmodulin, the bioactivity of which was not enhanced beyond that predicted from radioimmunoassay. Subsequent addition of thyroxine did not increase calmodulin bioactivity. Calmodulin-agarose removed calmodulin-enhancing activity from the supernatant. 3. Thus, the enhancing factor(s) appears to interact directly with calmodulin. These observations indicate that thyroid hormone promotes the release from human erythrocyte membranes of a soluble factor (or factors) which binds to calmodulin and significantly increases its bioactivity. This enhancing activity is similar to that of a calmodulin activator described in a rat model of hypertension (S.-L. Huang et al., J Clin Invest 1988; 82: 276-81).

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1993

Inhibition of c-myc in breast and ovarian carcinoma cells by 1,25-dihydroxyvitamin D3, retinoic acid and dexamethasone.

The role and regulation of the c-myc protooncogene in breast and ovarian neoplasms is receiving increased attention. The downregulation of the c-myc protooncogene by 1,25-dihydroxyvitamin D3 (calcitriol), retinoic acid (RA) and dexamethasone (Dex) is closely associated with growth inhibition in leukemic cells. Calcitriol, RA and Dex have anti-proliferative activity in breast and gynecologic carcinoma cells; however, the regulation of c-myc by these agents in breast and ovarian cancers is mostly unknown. We have addressed the regulation of c-myc in these cancers using an adaptation of a novel method which employs an immunohistochemical procedure to detect c-myc protein followed by quantification of c-myc staining with computerized image analysis. This system represents an alternative to protein product assay by Western blotting and is straightforward, rapid (1 day), can be carried out on a small scale and provides a sample size that readily facilitates statistical analysis of assay data. In MCF-7 human breast cancer cells, c-myc was suppressed 29% by 0.5 nM Dex, 45% by 0.01 nM RA and 54% by 100 nM calcitriol after 24 h of drug treatment. At the same hormone concentrations, growth was inhibited 18% by Dex, 18% by RA and 39% by calcitriol after 3 days of treatment (p < 0.05 for all hormones). Similar patterns of growth and c-myc inhibition were seen in T47D human breast cancer cells and NIH:OVCAR3 human ovarian cancer cells, with the exception of Dex in T47D cells, which caused no inhibition of c-myc or growth.(ABSTRACT TRUNCATED AT 250 WORDS)

Blotting, Western↗
PubMed1993

Pharmacokinetics and pharmacodynamics of granulocyte-macrophage colony-stimulating factor and zidovudine in patients with AIDS and severe AIDS-related complex.

Granulocytopenia is a complication of human immunodeficiency virus disease, as well as a toxic manifestation of zidovudine therapy. To evaluate pharmacokinetic and pharmacodynamic relationships, 11 AIDS-AIDS-related complex patients who had developed zidovudine-associated granulocytopenia (mean absolute neutrophil count, 1,077/mm3) were examined after addition of granulocyte-macrophage colony-stimulating factor (GM-CSF) to zidovudine. GM-CSF was administered as a daily (1.0 or 0.3 micrograms/kg) or every-other-day (0.3 micrograms/kg) subcutaneous dose over a 28-day period. Zidovudine was continued at the same daily dosage as was previously being administered. Of 11 patients, 7 (1.0 micrograms/kg, n = 5; 0.3 micrograms/kg, n = 2) had a pharmacologic response to GM-CSF with an increase to a mean absolute neutrophil count of 3,189 cells per mm3 at 4 weeks (P < 0.05). The peak concentration of GM-CSF in plasma ranged from 11.5 to 84.4 pg/ml, and the time to peak ranged from 1 to 3 h. No correlation between GM-CSF disposition and hematologic response was noted. A decreased plasma zidovudine-glucuronide/zidovudine ratio was noted after 1 week of GM-CSF, and an increase in the area under the plasma concentration-versus-time curve for zidovudine was found in three patients after 4 weeks. Low doses of GM-CSF can raise the granulocyte count in patients with zidovudine-induced neutropenia. The use of GM-CSF and zidovudine may represent a viable treatment option for persons with human immunodeficiency virus infection who develop neutropenia while receiving zidovudine but do not tolerate alternative nucleoside analogs. Further studies are needed to assess the complex interaction between these two agents.

AIDS-Related Complex↗
PubMed1992

Receptors for 1,25-dihydroxyvitamin D3 in gynecologic neoplasms.

To determine if gynecologic malignancies are candidates for 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) therapy we measured vitamin D receptor (VDR) levels in 11 tumor specimens using a radiolabeled ligand-binding assay. VDR was demonstrated in 3 of 6 ovarian tumors and 1 of 1 uterine sarcomas, but not in endometrial tumors (2), cervical tumors (1), or Krukenberg tumors (1). Scatchard plots revealed that [3H]1,25(OH)2D3 was bound to a single class of high-affinity (Kd = 0.3 to 0.6 nM), saturable sites characteristic of authentic 1,25(OH)2D3 receptors. Specificity of binding activity for 1,25(OH)2D3, the active vitamin D3 metabolite, was demonstrated by failure of 25-hydroxy- and 24,25-dihydroxyvitamin D3 to compete effectively against 1,25(OH)2D3 binding in total cellular tumor extracts. The ovarian carcinoma cell line NIH:OVCAR3 was shown to possess VDR (binding capacity = 137 fmol/mg protein, Kd = 0.48 nM). A 3-day incubation of NIH:OVCAR3 cells with 100 nM 1,25(OH)2D3 resulted in 49% inhibition of cell growth. The growth inhibition of an ovarian carcinoma line and the observation that 36% of gynecologic tumors assayed were shown to be VDR-positive suggest that further study is warranted to delineate the mechanism and possible therapeutic aspects of 1,25(OH)2D3 action in gynecologic tumors.

Calcitriol↗