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H J Wolfe

Publications and source records attributed to H J Wolfe.

At least 55 records · Page 3Linked to original sources
PubMed1991

Expression of angiogenic growth factor genes in primary human astrocytomas may contribute to their growth and progression.

Astrocytomas are highly malignant brain tumors and are among the most neovascularized solid tumors. We have investigated the expression of the angiogenic growth factors acidic fibroblast growth factor and transforming growth factor-alpha, together with its receptor epidermal growth factor receptor, in 30 primary astrocytomas. Both acidic fibroblast growth factor and transforming growth factor-alpha, together with epidermal growth factor receptor, are found to be greatly overexpressed in these tumors when compared with normal brain. This overexpression of angiogenic growth factors may underlie the intense neovascularization characteristic of astrocytomas.

Angiogenesis Inducing Agents↗
PubMed1990

neu oncogene protein and epidermal growth factor receptor are independently expressed in benign and malignant breast tissues.

The neu oncogene protein, p185, and epidermal growth factor receptor (EGFR) were localized immunohistochemically in benign and malignant human breast tissues using monoclonal antibodies. Both benign and malignant epithelial cells were positive for these oncogene proteins in acetone-postfixed frozen sections. Stromal cells were negative for p185, but occasionally positive for EGFR. Myoepithelial cells were consistently positive for EGFR, and p185 was localized predominantly in duct-lining cells, where the basolateral plasma membrane was the normal expression site of both substances. Paraformaldehyde-prefixed frozen sections were less sensitive for antigen demonstration. Based on the intensity of immunoreactivity, 11 of 37 acetone-postfixed breast carcinomas (30%) were judged neu overexpressors, while none of 24 benign tissues overexpressed neu. Epidermal growth factor receptor was demonstrated in 18 of 36 acetone-postfixed cancer tissues (50%) and was overexpressed in three (8%). At the cellular level, heterogenous expression of p185 and EGFR was occasionally observed in both benign and malignant tissues, and a single case of cancer overexpressing both neu and EGFR showed reciprocal patterns of staining, indicating their independent expression. In some carcinomas, EGFR was localized only in stromal cells. Our findings confirmed mutually independent expression of the two closely related protooncogenes in benign and malignant breast tissues.

Biomarkers, Tumor↗
PubMed1990

Strategies for the analysis of oncogene overexpression. Studies of the neu oncogene in breast carcinoma.

The development of a consistent strategy for the analysis of oncogene expression at the cellular level is essential for understanding the roles of these genes in the development and progression of human neoplasia. Detection of the neu oncogene products in breast carcinoma was selected as a model for analysis of oncogene expression. Fifty-two primary human breast carcinomas were evaluated by quantitation of neu DNA amplification and mRNA expression and by localization of neu mRNA and protein (p 185) at the cellular level by in situ hybridization (ISH) and immunohistochemistry (IHC). The specificity and sensitivity of the molecular and immunologic probes for neu were established with the use of genetically engineered cell lines that overexpressed either neu or epidermal growth factor receptor (EGFR). Twenty-nine percent of breast carcinomas demonstrated neu DNA amplification and mRNA overexpression, and there was close correlation between the level of neu mRNA expression and detection of neu gene products by ISH and IHC. Thirty-two percent of carcinomas demonstrated neu mRNA overexpression by ISH. The immunohistochemical method using TA1 monoclonal antibody for p185 was exquisitely sensitive in acetone-fixed frozen sections and provided an excellent approach for judging overexpression as confirmed by the various molecular analyses. All areas of nonmalignant breast epithelium stained weakly, and a wide range of staining intensity was observed in malignant breast epithelium, with 31% of carcinomas judged to be p185 overexpressors. Heterogeneous expression of p185 was seen in some carcinomas. This study provides a strategic approach for the evaluation of oncogene expression in human tumors.

Antibodies, Monoclonal↗
PubMed1990

Coexpression of platelet-derived growth factor (PDGF) and PDGF-receptor genes by primary human astrocytomas may contribute to their development and maintenance.

The present studies investigated the expression of the two PDGF genes (c-sis/PDGF-2 and PDGF-1) and the PDGF-receptor b gene (PDGF-R) in 34 primary human astrocytomas. Northern blot analysis demonstrated the coexpression of the c-sis/PDGF-2 protooncogene and the PDGF-R gene in all astrocytomas examined. The majority of the tumors also expressed the PDGF-1 gene. There was no correlation between the expression of the two PDGF genes. Nonmalignant human brain tissue expressed the PDGF-R and PDGF-1 genes but not the c-sis/PDGF-2 protooncogene. In situ hybridization of astrocytoma tissue localized the expression of the c-sis and PDGF-R mRNA's in tumor cells. Capillary endothelial cells also expressed c-sis mRNA. In contrast, nonmalignant human brain tissue expressed only PDGF-R mRNA but not c-sis/PDGF-2 mRNA. The coexpression of a potent mitogenic growth factor protooncogene (c-sis) and its receptor gene in astrocytoma tumor cells suggests the presence of an autocrine mechanism that may contribute to the development and maintenance of astrocytomas. The expression of c-sis mRNA in tumor cells but not in nonmalignant brain cells may serve as an additional diagnostic criterion for the detection of astrocytomas in small tissue specimen using in situ hybridization for the detection of c-sis mRNA and/or immunostaining for the recognition of its protein product.

Astrocytoma↗
PubMed1990

Prognostic significance of peritumoral lymphatic and blood vessel invasion in node-negative carcinoma of the breast.

The prognostic significance of intramammary lymphatic and blood vessel invasion was evaluated in a retrospective series of 221 patients with node-negative carcinoma of the breast treated with modified radical mastectomy. To facilitate identification of lymphatic and blood vessel invasion, the tumors were studied with an immunohistochemical technique using antibodies to endothelial markers. Peritumoral lymphatic and blood vessel invasion (PLBI) (encompassing both lymphatic and blood vessel invasion) was an adverse prognostic indicator independent of menopausal status, tumor size, and other histologic variables. Recurrence of disease and death resulting from carcinoma were significantly higher for patients with PLBI-present (+) tumors compared with patients with PLBI-absent (-) tumors (P less than .0001). The risk of recurrence for patients with PLBI+ tumors was 4.7 times that for their PLBI- counterparts. The presence of intratumoral lymphatic and blood vessel invasion (ILBI) is less important because few examples were found without concomitant PLBI. When PLBI was separated into lymphatic invasion and blood vessel invasion individually, the prognostic significance was retained in both groups. The immunohistochemical approach reduced both false-negative and false-positive observations and identified about 40% of PLBI that would have been missed by routine histologic examination alone. The presence of PLBI appears to be a potentially useful discriminant in predicting the outcome of patients with node-negative carcinoma of the breast.

Breast Neoplasms↗
PubMed1990

The detection of Epstein-Barr virus in hairy cell leukemia cells by in situ hybridization.

Epstein-Barr virus (EBV) has been implicated in the pathogenesis of several B-cell lymphoid proliferations. Because patients with hairy cell leukemia (HCL) have a high incidence of seropositivity for EBV antigens, we studied the cells of HCL for evidence of EBV infection using in situ hybridization techniques. EBV mRNA was detected in the tumor cells in four of six cases using a radiolabeled RNA probe. Confirmatory serologic data were available in three cases in which the viral DNA was detected and in one negative case. Our results suggest that EBV infection may have a pathogenetic role in this disorder.

Adult↗
PubMed1988

The clinical outcome of prospective screening for multiple endocrine neoplasia type 2a. An 18-year experience.

An important question facing physicians who care for families with multiple endocrine neoplasia type 2a is whether prospective screening to detect early abnormalities of the thyroid, parathyroid, or adrenal glands favorably influences the ultimate course of the disease. An 18-year study of a large family has allowed us to examine the effect of early treatment on the clinical course of the disease. Of 22 patients who underwent thyroidectomy for early C-cell abnormalities, 19 remained free of detectable medullary thyroid carcinoma according to all criteria, at a mean of 11 years after thyroidectomy. None of the 22 patients had evidence of parathyroid disease either at the time of surgery or after a mean follow-up of 10 years. Prospective screening for adrenal medullary abnormalities by means of measurement of 24-hour urinary epinephrine excretion and the ratio of urinary epinephrine to norepinephrine was predictive of pheochromocytoma in 10 of 11 patients (with a false negative result in one patient) but was not useful in diagnosing adrenal medullary hyperplasia. We conclude that regular, prospective screening and early treatment of the manifestations of multiple endocrine neoplasia can prevent metastasis of medullary thyroid carcinoma and the morbidity and mortality caused by pheochromocytoma.

Adrenal Gland Neoplasms↗
PubMed1988

DNA probes in diagnostic pathology.

Molecular pathology has become firmly established as a distinctive discipline in medicine. It has introduced radical changes in concepts of disease causation and in classification of disease states affecting humans and other organisms. In addition, molecular pathology represents a "new" diagnostic technology with many potentials that have been heretofore untapped. This overview provides a discussion of the use of DNA probes in the study of human diseases. The role of detectable genetic abnormalities in pathogenesis will be considered, as well as their possible impact on nosology and disease classification.

DNA↗
PubMed1988

Gastrin-releasing peptide gene expression in developing, hyperplastic, and neoplastic human thyroid C-cells.

Gastrin-releasing peptide (GRP), the mammalian homolog of bombesin, is often studied as a prototypic neuroregulatory hormone and growth factor, but its own regulation and physiological roles remain to be fully defined. We now demonstrate that the GRP gene is expressed in human thyroidal calcitonin (CT)-containing neuroendocrine cells (C-cells) in an ontogenic pattern similar to its expression in pulmonary neuroendocrine cells and is also expressed at high levels in C-cell hyperplasias and neoplasias (medullary carcinomas of the thyroid). Mean GRP-like immunoreactivity is 20 times higher in 3-week-old to 5-month-old infants than in normal adults, with six of seven infants having GRP levels 6- to 67-fold higher than those in normal adults, the highest levels occurring at 2-2.5 months. CT levels are about 100 times greater than GRP levels at all time intervals, with levels of GRP and CT being linearly correlated (r = 0.98). By RNA blot analysis, GRP mRNAs are increased in neonatal thyroids compared to adult thyroids. In situ hybridization and immunoperoxidase analyses localize GRP mRNAs and peptide to a majority of C-cells in fetuses and neonates, but to only 5-18% of C-cells in normal adults. The majority of developing C-cells have a dendritic morphology, suggesting a paracrine role, although this morphology is not observed in adult C-cells. In addition, for unknown reasons, an increased percentage of C-cells positive for GRP occurs in normal thyroid adjacent to GRP-negative follicular adenomas and papillary carcinomas, an association that we term perineoplastic. We hypothesize that GRP gene expression may play a role in both normal and neoplastic growth processes.

Adenoma↗
PubMed1988

Acute stimulation of chromaffin cell proliferation in the adult rat adrenal medulla.

Susceptible strains of rats develop adrenal medullary hyperplasia and neoplasia after long-term administration of the antihypertensive drug reserpine, or of other pharmacologic agents which alter neuroendocrine function. These proliferative lesions are of potential medical importance as a model for familial multiple endocrine neoplasia syndromes, and are of fundamental interest because they might elucidate mechanisms regulating chromaffin cell proliferation during normal development. To study the initiation of the adrenal lesions, chromaffin cell mitoses were counted in adult male rats injected with reserpine or control solvent for 5 days, with the final injection containing colcemid to arrest cells in mitosis. Rare mitoses were observed in mature-appearing epinephrine and norepinephrine cells in control adrenals. Reserpine caused an 8-fold increase in chromaffin cell mitoses in otherwise histologically normal glands, and the mitotic cells after reserpine administration showed marked granule depletion. Reserpine directly depletes catecholamine stores and reflexively increases neurogenic stimulation of chromaffin cells to increase catecholamine synthesis. The findings suggest that signals regulating function also regulate proliferation of mature chromaffin cells, and that prolongation of these signals or superimposed abnormalities may lead to pathologic proliferative states. The reserpine model may be a useful system for elucidating normal and pathologic mechanisms of signal transduction.

Adrenal Medulla↗
PubMed1987

Peptide YY. Structure of the precursor and expression in exocrine pancreas.

Peptide YY is a 36-residue gastrointestinal hormone which inhibits both pancreatic and gastric secretion. We have isolated a cDNA encoding the peptide YY precursor by screening a rat intestinal lambda gt11 cDNA library with an antiserum directed against the porcine hormone. The nucleotide sequence of the cDNA encodes a 98-residue protein (molecular weight, 11, 121) which has an amino acid sequence identical to that of porcine peptide YY. Rat peptide YY is preceded immediately by a signal sequence and followed by a cleavage-amidation sequence Gly-Lys-Arg plus 31 additional amino acids. Thus the peptide YY precursor is similar in structure to that of two related peptides, pancreatic polypeptide and neuropeptide Y. RNA blot hybridizations reveal that the peptide YY gene is much more actively expressed in pancreas than previously realized. In situ hybridizations localized peptide YY cells exclusively to the exocrine pancreas. The abundance of peptide YY in one of its target organs, the pancreas, suggests a paracrine mechanism for peptide YY in regulating pancreatic enzyme secretion.

Amino Acid Sequence↗
PubMed1987

Hypertrophy of pheochromocytoma cells treated with nerve growth factor and activators of adenylate cyclase.

PC12 pheochromocytoma cells treated with nerve growth factor (NGF) in combination with high concentrations of the activators of adenylate cyclase, forskolin or cholera toxin, become more neuron-like in size than cells treated with NGF or with activators of adenylate cyclase alone. Cells treated simultaneously with NGF plus forskolin or cholera toxin paradoxically show less process outgrowth than cells treated with NGF alone. Addition of forskolin or cholera toxin to cells pretreated with NGF, however, produces enlarged cells with intact processes that are indistinguishable from cultured neurons. One possible implication of these findings is that NGF might act in concert with agents that increase intracellular cyclic AMP to cause neuronal maturation during embryogenesis, and that the proper sequence of exposure to these signals is necessary for normal development. Specific activity of acetylcholinesterase is increased by NGF but is unaffected or slightly decreased by forskolin, suggesting that individual aspects of the developing neuronal phenotype are subject to different types of control.

Adenylyl Cyclases↗
PubMed1987

S-100 protein positivity in breast carcinomas: a potential pitfall in diagnostic immunohistochemistry.

S-100 protein, originally isolated from neural tissues, has also been identified in various normal and neoplastic cells, including malignant melanomas. A systematic immunohistochemical investigation of this antigen was performed on formalin-fixed paraffin-embedded samples of benign and malignant breast tissues with use of the avidin-biotin-peroxidase complex immunoperoxidase technique and a polyclonal antiserum that recognizes both the alpha and beta subunits of S-100 protein. In benign breast tissue, S-100 protein was present in both epithelial and myoepithelial cells of terminal ducts and lobules; the staining was cytoplasmic and sometimes nuclear. Of 100 randomly selected invasive breast carcinomas, 48 per cent contained S-100 protein-positive tumor cells. Lobular and medullary carcinomas (60 per cent and 80 per cent, respectively) were more frequently positive than ductal carcinomas (45 per cent). Dendritic cells, most likely Langerhans' cells, were present in some carcinomas and were also positive for S-100. There was no relationship of S-100 positivity to histologic differentiation, recurrence interval, or the expression of various tumor markers. The presence of S-100 protein positivity in metastatic breast carcinomas may lead to the erroneous diagnosis of malignant melanoma. Our observations underscore the importance of testing for a broad panel of tumor markers rather than relying on single antigens in evaluating metastatic malignancies of undetermined origin.

Adenocarcinoma, Mucinous↗
PubMed1987

Medullary thyroid carcinoma in the Syrian golden hamster: an immunohistochemical study.

Spontaneously occurring thyroid neoplasms exhibiting solid and/or anaplastic growth patterns in the Syrian golden hamster have been thought to be derived from follicular cells. Eight neoplasms of this type have been analyzed immunohistochemically and have been classified as medullary thyroid carcinomas (MTC) on the basis of their content of calcitonin (CT). Well differentiated MTCs in this species were composed of polyhedral cells showing uniform CT immunoreactivity while the poorly differentiated MTCs most often had spindle patterns of growth with marked variation in CT immunoreactivity. Both well and poorly differentiated MTCs contained entrapped follicles which were CT negative. In contrast to MTC in the rat and in humans with familial MTC, the tumors in hamsters were not associated with C-cell hyperplasia. The Syrian golden hamster may, therefore, serve as a useful model to study the factors which are responsible for the development of spontaneous (non-familial) MTC.

Animals↗
PubMed1987

Hyperplastic lesions of the gastrointestinal endocrine cells.

A substantial body of knowledge is presently available on the morphologic, histochemical, ultrastructural, and functional characteristics of both the normal endocrine cell population of the gut and their related endocrine tumors. In contrast to this, we have only recently begun to recognize the existence of hyperplastic proliferations of various endocrine cell types, and information is therefore steadily accumulating on the morphologic criteria for their recognition, their clinicopathologic correlates and the clinical relevance of this morphologic finding. Hyperplastic proliferations of various endocrine cell types most often develop as a secondary phenomenon in a variety of clinical situations, and may modify the clinical course of the associated condition in a manner that underscores the functional interrelationships these endocrine cells have not only with each other but with other cell types as well. However, similar proliferations may also occur as a primary event (e.g. primary antral G-cell hyperplasia) and give rise to clinical and biochemical features attributable to the overproduction of their specific hormonal product (e.g. Zollinger-Ellison Syndrome, type I). This communication provides a broad overview of the current state of our knowledge of hyperplastic lesions of a variety of gut endocrine cell types in humans, their pathophysiologic significance, their relationship (if any) to the subsequent development of endocrine tumors (i.e. the hyperplasia-neoplasia sequence), and the utility of certain experimental models for the study of such proliferations in a variety of animal species.

APUD Cells↗
PubMed1987

Transient elevation of messenger RNA encoding gastrin-releasing peptide, a putative pulmonary growth factor in human fetal lung.

Gastrin-releasing peptide (GRP), the mammalian homologue of the amphibian peptide bombesin, is present in pulmonary neuroendocrine cells and appears to be a growth factor for both normal and neoplastic pulmonary cells. Previously we have reported the cloning of the messenger RNAs (mRNAs) and gene that encode human GRP. We now report that GRP mRNAs are markedly elevated in human fetal lung during the canalicular phase of pulmonary development (from approximately 16 to 30 wk gestation). By RNA blot and in situ hybridization analyses, GRP mRNAs were first detectable in fetal lung at 9-10 wk, plateaued at levels 25-fold higher than in adult lungs from 16 to approximately 30 wk and then declined to near adult levels by 34 wk gestation. By contrast, GRP peptide levels remain elevated until several months after birth. Consistent with this, in situ hybridization and immunohistochemical studies showed that GRP mRNA and peptide consistently colocalized in early gestation lung but that in neonatal lung, many cells that contained GRP peptide no longer contained GRP mRNA. The transient expression of high levels of GRP mRNAs during an approximately 12-wk phase of fetal lung development suggests that the secretion of GRP or its COOH-terminal peptides from pulmonary neuroendocrine cells may play a role in normal lung development.

Cloning, Molecular↗