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Biomedical subjects

V A Memoli

Publications and source records attributed to V A Memoli.

At least 55 records · Page 3Linked to original sources
PubMed1990

Reevaluation of pulmonary neoplasms resected as small cell carcinomas. Significance of distinguishing between well-differentiated and small cell neuroendocrine carcinomas.

The clinicopathologic features of 50 cases of surgically resected small cell carcinoma were reevaluated (doubly blinded). Two pulmonary carcinomas were excluded because neuroendocrine features could not be demonstrated; two additional cases also were excluded because the tumors grossly invaded the chest wall and their pulmonary origin was not substantiated. Thirty-four tumors were confirmed to be small cell neuroendocrine carcinoma (SCNC). Only seven of 11 (64%) patients with T1N0,T2N0 tumors survived more than 1 year; one of 11 (9%) patients survived more than 2 years. In 12 cases, the diagnosis was changed to well-differentiated neuroendocrine carcinoma (WDNC). Of these, nine of nine (100%) patients with T1N0,T2N0 tumors survived more than 1 year; six of eight (75%) patients survived more than 2 years. These observations strongly indicate that a significant number of long-term survivors with the diagnosis of small cell carcinoma may, in fact, have a distinctly less aggressive type of pulmonary neuroendocrine carcinoma. It was concluded that the distinction between small cell and well-differentiated types of neuroendocrine carcinomas has significant prognostic and therapeutic implications.

Adult↗
PubMed1990

Abnormal regulation of coagulation/fibrinolysis in small cell carcinoma of the lung.

Components of coagulation and fibrinolysis reactions were identified in situ by immunohistochemical staining in fresh frozen sections of small cell carcinoma of the lung tissue. Tumor cells stained positively for tissue factor, a protein that is capable of activating the extrinsic pathway of coagulation (the components of which have been seen within small cell carcinoma of the lung [SCCL] tissue), and for proteins C and S antigens. Fibrin was seen in a focal distribution at the host-tumor interface, indicating that thrombin had acted upon the fibrinogen found throughout the tumor stroma. Staining with a neoepitope-specific antibody, which does not discriminate between fibrinogen fragment D and fibrin fragment D-dimer, was similar to that of the fibrin antibody. High molecular weight urokinase-type and tissue-type plasminogen activators were seen in vascular endothelium, but neither existed within the tumor. Low molecular weight urokinase was found in rare isolated foci of tumor cells primarily adjacent to areas of necrosis. Plasminogen activator inhibitor-3 occurred in tumor cell cytoplasmic blebs and in necrotic tumor cells, but plasminogen activator inhibitors 1 and 2 were not seen. Our data suggest a mechanism for thrombin generation and fibrin formation within SCCL tissues that could support cell proliferation, stroma formation, and preservation. These features could be conductive to perpetuation of this tumor and conceivably could form the basis of the beneficial effects of antithrombotic therapy seen in SCCL.

Blood Coagulation↗
PubMed1990

Malignant melanoma. Interaction with coagulation and fibrinolysis pathways in situ.

Immunohistochemical techniques applied to fresh frozen sections of metastatic malignant melanoma tissue revealed abundant fibrinogen (or fibrin I) in perivascular areas throughout the tumor connective tissue stroma. Fibrin was readily detected in a focal distribution in the connective tissue around nodules of viable tumor. Staining for D-dimer of cross-linked fibrin (using an antibody that cross-reacted with fragment D of fibrinogen) coincided with staining for fibrin. Diffuse staining of tumor cell bodies was observed for Factor X, and Factor XIII ("a" subunit) was detected in scattered areas of connective tissue throughout the tumors. Factor VII was not detected, and only rare tumor cells stained for tissue factor. These results support the concept that a tumor cell-associated, thrombin-generating pathway exists in situ in malignant melanoma tissue that includes Factor X but neither tissue factor nor Factor VII. By contrast, tumor cell staining was observed rarely for urokinase and to a variable extent for tissue plasminogen activator.

Antibodies, Monoclonal↗
PubMed1990

Hyperplasia and tumors of the islets of Langerhans in mice bearing an elastase I-SV40 T-antigen fusion gene.

Transgenic mice bearing a fusion gene consisting of rat elastase I 5' flanking DNA fused to the early-coding (T-antigen) region of the SV40 genome (ELSV mice) develop carcinomas of the acinar cells of the exocrine pancreas. Histopathological examination of pancreatic tissue from 79 such animals revealed that, in addition to acinar cell neoplasms, ELSV mice develop two distinct lesions of the islets of Langerhans. By the age of 26 weeks, 36% of the mice had developed insulinomas. Starting at 8 weeks of age, the mice also developed D (somatostatin)-cell hyperplasia, which began at the periphery of the islets but which in advanced cases resulted in nearly complete replacement of other islet cell types by D-cells. By 26 weeks of age, 85% of the mice examined demonstrated the D-cell abnormality. Both the insulinomas and D-cell lesions were negative by immunohistochemistry for T-antigen, which was, however, demonstrated in acinar cell neoplasms using a monoclonal antibody against a C-terminal T-antigen epitope. Insulinomas have been described in other SV40 transgenic mice, particularly when the SV40 enhancer is not included in the transgene, suggesting that the presence of native SV40 enhancer may ordinarily suppress the expression of T-antigen in pancreatic beta-cells. The somatostatin-cell lesion is unique to the ELSV model; it may be neoplastic or represent a response to the growth and neoplastic changes occurring simultaneously in the exocrine pancreas.

Adenoma, Islet Cell↗
PubMed1989

Indirect activation of blood coagulation in colon cancer.

Systemic activation of the coagulation mechanism is known to exist in patients with colon cancer. The mechanism of such activation was investigated using immunohistochemical techniques applied to fresh frozen sections of resected primary colon cancer specimens. Tumor cells stained for tissue factor, factor V, and urokinase-type plasminogen activator. Perivascular and intercellular areas stained for fibrinogen and the "a" subunit of factor XIII. Staining was minimal or absent for protein C, protein S, plasminogen activator inhibitors 1-3, factor VII, factor X, and fibrin (the antigenic site on the amino-terminal portion of B beta chain that is exposed following thrombin cleavage of fibrinopeptide B was not detected). The lack of an intact thrombin-generating pathway in situ associated with viable colon cancer cells is consistent with the findings of others that coagulation activation in colon cancer may be triggered by a soluble tumor product that exerts its effect at sites distant from the tumor. These results may explain the absence of clinical responsiveness of colon cancer to antithrombotic drug therapy and may clarify therapeutic strategies for this common tumor.

Blood Coagulation↗
PubMed1989

Antioxidants vs carotenoids. Inhibitors or promoters of experimental colorectal cancers.

The organospecific, 1,2-dimethylhydrazine-induced murine tumor model was used to test the effects on tumor formation of the following dietary supplements: (1) ascorbic acid, 7% per weight; (2) alpha tocopherol, 1% per weight; (3) beta carotene, 1% per weight; and (4) canthazanthin, 1% per weight. Following a four-week dietary acclimation, a 16-week 1,2-dimethylhydrazine induction, and a four-week hiatus, the animals were killed, underwent autopsies, and tumor formation was recorded. The antioxidant supplements of ascorbic acid and alpha tocopherol resulted in a significant decrease in tumor formation when compared with control groups. In contrast, the beta carotene group showed no difference in tumor formation, and canthazanthin, a non-provitamin A carotenoid, resulted in an increase in tumor formation when compared with controls. In addition, the K-gel powder control diet (a carrier medium for alpha tocopherol acetate) had a significantly higher rate of tumor formation than the regular chow and placebo beadlet control diets. In sum, ascorbic acid and alpha tocopherol demonstrated a clear chemopreventive effect, whereas beta carotene had no effect, and canthazanthin appeared to function as a promoter in this organospecific tumor model.

1,2-Dimethylhydrazine↗
PubMed1988

A novel monoclonal antibody, SCCL 175, with specificity for small cell neuroendocrine carcinoma of the lung.

The murine monoclonal antibody SCCL 175, which is one of several monoclonal antibodies directed against small cell neuroendocrine carcinoma developed by one of us (E.D.B.), was studied for its immunohistochemical reactivity against normal human tissues and a spectrum of bronchopulmonary and metastatic carcinomas using the avidin-biotin complex technique. SCCL 175 reacted with 40 of 44 small cell carcinomas including both primary and metastatic sites and was distributed both on the cell surface and intracytoplasmically. Staining was seen in fresh frozen tissues, cytology preparations, and in a limited number of paraffin-embedded tissue sections after trypsin pretreatment. It was nonreactive with all non-small cell lung carcinomas, neuroendocrine carcinomas from other primary sites, and nonpulmonary carcinomata studied to date. Its distribution in normal adult human tissues was limited to some hypothalamic neurons and the apical membranes of renal proximal tubular epithelium. Cytotrophoblastic and syncytotrophoblastic cells from placental tissue demonstrated variable SCCL 175 immunoreactivity. Of choriocarcinomas studied, one of three demonstrated focal staining. These findings demonstrate the diagnostic utility of SCCL 175 in phenotyping small cell carcinoma of lung, and its specificity suggests a potential role in the therapy of this disease.

Antibodies, Monoclonal↗
PubMed1988

Metastatic islet cell amphicrine carcinoma of the pancreas. Association with an eosinophilic infiltration of the skin.

Nodular skin lesions consisting of eosinophilic cell infiltrates developed in a 45-year-old man with metastatic islet cell amphicrine carcinoma of the pancreas. These infiltrates did not fit previously described eosinophilic skin conditions. Although the tumor responded to conventional chemotherapy, the skin lesions did not. They did, however, respond completely to radiation therapy. This clinical constellation has not been reported previously and may represent a new paraneoplastic syndrome.

Adenoma, Islet Cell↗
PubMed1988

Thrombin-specific sites of fibrinogen in small cell carcinoma of the lung.

Thrombin-generated cleavage sites of human fibrinogen have been identified adjacent to viable tumor cells in fresh frozen sections of small cell carcinoma of the lung (SCCL) by means of immunohistochemical techniques using mouse monoclonal antibodies to the N-terminal peptides of the fibrinogen alpha and beta chains. These results indicate that thrombin is generated in situ in this tumor type. Based on previous evidence for the existence of an initiator of coagulation together with coagulation factor intermediates associated with viable SCCL tumor cells in situ, and also for the favorable effects of anticoagulant therapy with warfarin in SCCL, we postulate that local tumor cell-induced thrombin formation may contribute to self-regulated progression of SCCL through deposition of fibrin and stimulation of cell proliferation. These results suggest novel treatment strategies for this particular tumor type and justify efforts to identify other tumor types in which similar mechanisms exist.

Antibodies, Monoclonal↗
PubMed1988

Well differentiated and small cell neuroendocrine carcinomas of the lung. Two related but distinct clinicopathologic entities.

Twenty-two resected pulmonary well differentiated neuroendocrine carcinomas (WDNC) were re-evaluated histologically as were 28 resected intermediate-small cell neuroendocrine carcinomas (IC-SCNC). WDNC were distinguishable from IC-SCNC by their consistently recognizable organoid architecture, and by the absence or limited extent of necrosis. Furthermore, WDNC could be subclassified into 3 subsets based upon the degrees of pleomorphism, local and vascular invasion, and stromal fibrosis, the mitotic count, and the extent of tumor necrosis. Whereas all those parameters were important in discriminating between WDNC and IC-SCNC, the quality of the organoid architecture, and the extent and pattern of necrosis emerged as the most significant. WDNC with the more aggressive histologic features (subset III) had, as a group, a distinctly worse clinical course that those displaying blander features (subsets I and II). Nevertheless, even subset III of WDNC had, as a group, a longer survival than similarly treated Stages I and II IC-SCNC. We conclude that the histologic spectrum of WDNC is broader than generally recognized. Moreover, 3 subsets of WDNC are definable based on conventional histologic criteria provided sufficient, well preserved samples are examined. Even the most aggressive subset of WDNC can be thus histologically discriminated from IC-SCNC, and, given comparable stages, has a better prognosis than the latter.

Adult↗
PubMed1987

Occurrence of blood coagulation factors in situ in small cell carcinoma of the lung.

Through immunohistochemical techniques, blood coagulation factors were identified in situ in fresh frozen sections of small cell carcinoma of the lung. Prothrombin/thrombin, factor VII, factor X, and antithrombin III were present in intercellular spaces and associated with tumor cells. Factor IX, factor XI, prekallikrein, and high molecular weight kininogen were identified as being associated with tumor cells but did not exist in intercellular spaces. Variable connective tissue staining but no tumor-related staining was observed for factor V, factor VIII-related antigen, factor XII, the B subunit of factor XIII, alpha 1-antitrypsin, alpha 2-macroglobulin, or alpha 2-antiplasmin. Neither consecutive tissue nor the tumor manifested platelet Ib and IIbIIIa surface glycoproteins. These divergent staining patterns suggested that the detected clotting factors had not merely diffused from permeabilized blood vessels, but were selectively localized in situ. While conditions may exist within tumor tissue that both retard and promote thrombin generation, we propose that interactions between the observed coagulation factors ultimately lead to local thrombin formation, which is responsible for the conspicuous fibrin deposits already described in small cell carcinoma of the lung. Thrombin formed locally might contribute to progression of this tumor. Inhibition of local thrombin formation by warfarin therapy could explain the beneficial effects of warfarin therapy in treating small cell carcinoma of the lung.

Antigens↗
PubMed1986

Chemoprevention of colorectal neoplasms. Ascorbic acid and beta-carotene.

The organospecific, 1,2-dimethylhydrazine-induced rat tumor model was used to test tumor formation in groups of animals receiving regular chow, powdered chow with 7%/wt ascorbic acid supplement, pelleted chow with 1%/wt beta-carotene supplement, and pelleted chow with placebo beadlets. Following a 16-week induction period, animals were killed and tumor formation was recorded. Tumor formation in the ascorbic acid supplement group was found to be significantly less than the control group. The beta-carotene group showed no difference in tumor formation compared with the placebo-beadlet control group. Tumor incidence was generally the same between the two control groups, and the ascorbic acid group had significantly fewer tumors than the beta-carotene group. In sum, ascorbic acid supplements in high doses significantly decreased tumor formation, whereas beta-carotene supplements in moderately high doses had no effect on tumor formation in this model.

1,2-Dimethylhydrazine↗
PubMed1986

Malignant neoplasms associated with orthopedic implant materials in rats.

The carcinogenic potential of 22 orthopedic prosthetic materials was studied by implantation in bone in Sprague-Dawley rats and evaluated by complete autopsy examination performed at the time of death or at the end of the 30 month experimental period. When the number of malignancies in these rats was compared with control and sham-operated animals, a small increase in sarcomata was observed in animals bearing metal alloy implants containing high contents of cobalt, chromium, or nickel. An increased incidence of lymphomata with bone involvement was also observed in rats bearing metal implants when compared with control and sham-operated animals.

Animals↗
PubMed1986

Effects of ethinyl estradiol and tamoxifen on liver DNA turnover and new synthesis and appearance of gamma glutamyl transpeptidase-positive foci in female rats.

We investigated possible mechanisms associated with promotion of hepatocarcinogenesis by the synthetic estrogens mestranol (M) and ethinyl estradiol (EE). Our first objective was to determine whether chronic EE treatment was associated with hepatotoxicity accompanied by regenerative hyperplasia. Female Sprague-Dawley (SD) rats were partially hepatectomized and their liver DNA prelabeled with [3H]thymidine. Two weeks later the rats were treated with EE at three doses or M (using timed-release tablets implanted s.c.) or with 0.05% phenobarbital (PB) in the diet. The rats were killed 6 weeks later and the amount of [3H]thymidine remaining in liver DNA determined. The results showed that none of the promoters caused hepatotoxicity as detected by the loss of prelabeled DNA. EE but not M or PB caused a dramatic dose-dependent enlargement of the pituitary. Subsequent experiments were carried out to define the dose-time response of liver DNA synthesis to treatment with EE, M and PB. Female SD rats were treated with these agents and [3H]-thymidine incorporation into DNA was determined at various times thereafter. The results showed that EE at 2.5 micrograms/day and PB (0.05%) caused a rapid increase in liver DNA synthesis which peaked between 24 and 72 h and remained elevated for at least the next 7 days. Dose-response experiments with EE- and M-treated rats demonstrated that 24 h after beginning treatment, significant increases in liver DNA synthesis could be detected at an EE dose as low as 0.1 microgram/day; DNA synthesis was also significantly increased by M. The anti-estrogen tamoxifen (T), did not cause increased liver DNA synthesis. However, T at 15 micrograms/day did inhibit the induction of DNA synthesis caused by EE and M at 2.5 micrograms/day but not by PB (0.05%). The effect of T on promotion by EE of the appearance of gamma glutamyl transpeptidase (GGT)-positive foci was determined. Female SD rats were initiated with a single i.p. dose of diethylnitrosamine at 20 mg/kg given 24 h after partial hepatectomy. One week later the rats were treated with EE (5 micrograms/day), T (15 or 50 micrograms/day) or EE plus T at both doses using timed-release tablets. The rats were killed after 4 months and the incidence, number and size of the GGT foci determined. The results revealed that, as expected, EE enhanced the appearance of GGT foci. Unexpectedly, T alone at both doses also enhanced the appearance of the foci.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1986

Herpes without vesicles: limited, recurrent genital lesions in an immunodebilitated host.

We have reported a case of herpes genitalis in a man with acquired immunodeficiency syndrome (AIDS), who was receiving chemotherapy for Hodgkin's disease. The herpes infection was recurrent but limited, without vesicles or the progressive lesions usually seen in AIDS. Studies excluded known causes, and the unusual character of the infection long obscured and delayed diagnosis. Even atypical, culture-negative penile ulcers in immunodebilitated patients may be herpetic. Retrospective study of our patient's penile biopsy specimen using immunoperoxidase reaction was positive for herpesvirus. The existence of effective treatment mandates vigorous pursuit of the diagnosis.

Acquired Immunodeficiency Syndrome↗