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Biomedical subjects

F Basolo

Publications and source records attributed to F Basolo.

At least 109 records · Page 6Linked to original sources

Transforming growth factor-alpha expression is enhanced in human mammary epithelial cells transformed by an activated c-Ha-ras protooncogene but not by the c-neu protooncogene, and overexpression of the transforming growth factor-alpha complementary DNA leads to transformation.

MCF-10A cells are a spontaneously immortalized normal human mammary epithelial cell line. MCF-10A cells were transfected with two expression vector plasmids containing either a human point-mutated c-Ha-ras protooncogene or the rat c-neu protooncogene. c-Ha-ras-transfected MCF-10A cells grow as colonies in soft agar, exhibit a 3- to 4-fold increase in their growth rate in serum-free medium, and show a reduced mitogenic response to exogenous epidermal growth factor (EGF) or transforming growth factor-alpha (TGF alpha) as compared to MCF-10A cells. c-Ha-ras-transfected MCF-10A cells express a 4- to 8-fold increase in TGF alpha mRNA levels and secrete 4- to 6-fold more TGF alpha protein as compared to MCF-10A cells. Addition of either an anti-TGF alpha neutralizing monoclonal antibody or an anti-EGF receptor blocking monoclonal antibody to the Ha-ras-transformed MCF-10A cells produces a 50 to 80% inhibition of colony formation of these cells in soft agar. c-neu-transfected MCF-10A cells grown in soft agar and exhibit an increase in their growth rate in serum-free medium at a level comparable to that observed in Ha-ras-transformed MCF-10A cells. Addition of an anti-c-erbB-2 monoclonal antibody inhibits the anchorage-independent growth of these cells in soft agar. However, c-neu-transformed MCF-10A cells show no increase in TGF alpha secretion and no change in their responsiveness to exogenous EGF or TGF alpha. A recombinant retroviral vector containing the human TGF alpha gene was also introduced into MCF-10A cells. TGF alpha-infected MCF-10A cells secrete 15- to 20-fold more TGF alpha protein than MCF-10A cells, form colonies in soft agar, exhibit an enhanced growth rate in serum-free medium, and show a decreased mitogenic response to exogenous EGF or TGF alpha at a level equivalent to Ha-ras-transformed MCF-10A cells. Growth of TGF alpha-infected MCF-10A cells in soft agar is completely inhibited by anti-TGF alpha neutralizing or anti-EGF receptor blocking monoclonal antibodies. These results suggest that TGF alpha is an intermediary in the transformation of human mammary epithelial cells by an activated c-Ha-ras gene, but not by the c-neu gene, and demonstrate that overexpression of this growth factor is able to transform immortalized human mammary epithelial cells which also express a sufficient complement of functional EGF receptors.

Blotting, Northern↗

Somatostatin in medullary thyroid cancer. In vitro and in vivo studies.

The authors evaluated the presence of somatostatin (SRIF) in the plasma and in the tumor tissue of a total of 22 patients with medullary thyroid cancer (MTC) and studied the effect of exogenous SRIF administration on basal and pentagastrin (PG)-stimulated plasma calcitonin (CT) and carcinoembryonic antigen (CEA) levels. Mean plasma SRIF concentrations were significantly higher than those found in normal controls, with five of 15 patients having plasma SRIF levels above the mean + 2 SD of normal controls. High immunoreactive SRIF concentrations were found in the extract of three tumor tissues but not in one follicular thyroid cancer or in one toxic diffuse goiter. By immunoperoxidase staining seven of 11 (63.6%) primary MTC and five of 13 (38.5%) metastases expressed SRIF antigen in a low number of cells and with a weak degree of staining. As expected, CT was expressed in almost 100% of the cases with positivity in most of the cells and strong degree of staining. Patients with positive SRIF staining in the primary tumor had longer survival than SRIF negative patients. Infusion of synthetic SRIF (11 micrograms/minute/45 minutes) produced a significant reduction of plasma CT (but not CEA) levels in 12 of the 15 patients submitted to this test. Maximal percent decrease of plasma CT ranged from 10.8% to 72.7% of the basal value and was usually observed between 30 and 45 minutes from the beginning of the infusion. When infused together with the injection of PG, SRIF was able to significantly (P less than 0.05) inhibit the PG-induced CT release in five of six patients tested. These results demonstrate the following: SRIF is present in a few cells of many primary MTC and less frequently in their metastases; tentatively, the expression of SRIF antigen in the tumor seems to be associated with longer survival; increased SRIF concentrations are found in the plasma of some patients with metastatic involvement; and treatment with exogenous SRIF reduces the basal and PG-induced CT (but not CEA) release from the tumor.

Calcitonin↗

A human monoclonal autoantibody isolated from a patient with infectious mononucleosis reactive with both self antigens and Epstein-Barr virus nuclear antigen (EBNA).

In order to investigate the mechanism(s) by which Epstein-Barr virus (EBV) induces the outcome of autoantibodies during infectious mononucleosis (IM), a human IgM (k) monoclonal antibody to cytoskeletal filaments of epithelial cells has been prepared by EBV transformation of peripheral blood B lymphocytes obtained from a patient with IM. The antibody was also found to react with smooth muscle of frozen sections of human stomach tissue by immunofluorescence, and with the Epstein-Barr nuclear antigen (EBNA) by an enzyme-linked immunosorbent assay. These findings demonstrate at the clonal level the epitope homology between host's cell antigens and EBV-encoded nuclear antigen, which might have relevance in EBV-induced autoimmunity.

Antibodies, Monoclonal↗

Epstein-Barr virus-transformed human B lymphocytes endocytose autologous and heterologous red blood cells.

Epstein-Barr virus (EBV)-transformed B lymphocytes, either isolated from a patient with EBV-induced infectious mononucleosis or obtained by in vitro infection of B lymphocytes of donors in different clinical conditions, have been tested for the ability to endocytose particulate forms of antigens, such as human, sheep or mouse red blood cells. By light and electron microscopy, it has been found that EBV-transformed B cells are able to bind and internalize human autologous and allogeneic erythrocytes, as well as sheep and mouse erythrocytes, independent of the specificity of the secreted immunoglobulins. The ability of EBV-transformed B lymphocytes to endocytose and process particulate forms of autoantigens during infectious mononucleosis might have a role both in the production of heterophile antibodies and in EBV-induced autoimmunity.

Animals↗

Mechanisms other than polyclonal B cell activation possibly involved in Epstein-Barr virus-induced autoimmunity.

In order to verify whether Epstein-Barr virus (EBV)-induced polyclonal B cell activation is the major cause of autoimmunity during infectious mononucleosis (IM), we have investigated, by immunoblotting, the fine specificity of anti-smooth muscle autoantibodies (autoAbs) in the sera of IM patients. Furthermore, we have isolated a number of in vivo infected EBV-positive cell lines from a patient with IM and compared the reactivity of the secreted immunoglobulins (Igs) with that of serum autoAbs. The reactivity of anti-smooth muscle autoAbs was found to be closely restricted to three proteins of approximate molecular weights 54, 52 and 48 kD. Furthermore, none of 48 EBV-positive B cell lines shared any reactivity with serum autoantibodies. Taken together, these results suggest that EBV-induced autoimmunity is not a consequence of a random activation of B cells, but a specific phenomenon, requiring mechanisms other than polyclonal B cell activation.

Antibody Specificity↗

Influence of T and N stages on long-term survival in resectable small cell lung cancer.

The influence of T and N stages on long-term survival was evaluated in 49 patients with small cell lung cancer treated between 1975 and 1982. Adjuvant chemotherapy was administered in 34 patients and consisted of cyclophosphamide, doxorubicin and vincristine or etoposide, while 15 patients were treated with surgery alone. To date, overall median survival is 12 months, with nine patients (18.4%), who received adjuvant chemotherapy, currently alive and disease-free at 60 to 150 months. Survival was statistically influenced by the N stage but not the T stage; patients at the N0 stage had a significant increase when compared to N1 and N2 patients, on both 5-year survival (p less than 0.05 and p less than 0.025, respectively) and long-term survivors (p = 0.006 and p = 0.004, respectively). Results suggest that surgery and adjuvant chemotherapy might be an effective form of treatment in small cell lung cancer for T1, T2 and also T3 tumours without hilar or mediastinal lymph node involvement.

Adult↗

Differences in progression of BALB/cfRIII and BALB/cfC3H mammary hyperplastic alveolar nodules transplanted into the gland-free fat pads of BALB/c mice.

In BALB/cfC3H and BALB/cfRIII virgin female mice, i.e., BALB/c mice carrying milk-transmitted C3H and those carrying RIII murine mammary tumor virus infection, respectively, mammary noduligenesis and tumorigenesis are remarkably different. Focal hyperplastic alveolar changes or hyperplastic alveolar nodules were removed from BALB/cfRIII or BALB/cfC3H breeding female donors and transplanted into the gland-free mammary fat pads of syngeneic BALB/c virgin female recipients with or without hormonal supplementation. The results obtained have shown significant differences in: (a) the morphological type of outgrowths; (b) the incidence of malignant transformations; and (c) the hormonal responsiveness of the tumors arisen after pituitary transplants.

Adipose Tissue↗

Osteosarcoma of the myometrium synchronous with bilateral papillary cystadenocarcinoma of the ovary and papillary adenocarcinoma of the cervix.

We report an extremely rare case of a 60-year-old woman with myometrial osteosarcoma associated with bilateral papillary cystadenocarcinoma of the ovary and papillary adenocarcinoma of the cervix. The uterine osteosarcoma is the seventh case reported in the world, while it is the second case of synchronous triple primary tumors of the upper female genital tract. Clinical and pathological features of previously reported cases of uterine osteosarcoma and triple primary neoplasias of the upper female genital tract are critically reviewed.

Adenocarcinoma, Papillary↗

Multiple organ-reactivity of monoclonal autoantibodies to mouse erythrocytes.

Autoantibodies reacting with bromelain-treated autologous mouse red blood cells (Br-MRBC) are spontaneously produced by normal mice. In order to understand the biological significance of these autoantibodies, anti-Br-MRBC monoclonal autoantibodies have been prepared and studied for reactivity with a panel of frozen tissue sections from organs of normal mice by direct immunofluorescence. It has been found that the anti-Br-MRBC monoclonal autoantibodies are polyspecific, since they react with cells in multiple organs.

Animals↗

Endosonographic staging of rectal carcinoma.

Transrectal ultrasonography (US) scanning facilitates the ultrastructural differentiation of the various histologic layers of the rectal wall. In particular, the muscularis propria is represented by the 4th sonographic layer. Rectal carcinoma appears on US as a low echogenic area that suddenly interrupts the regular sequence of parietal layers. Sixty-five patients suffering with carcinoma of the lower two-thirds of the rectum underwent preoperative linear endosonography for staging. The reliability of such a method in assessing the extrarectal spread was evaluated in our study, at the end of which 55 sonographic/histologic correlations were obtained. Four false-negative and 1 false-positive determinations of the presence or absence of extrarectal spread proved that sonography has a sensitivity and specificity of 91%, with a positive predictive value of 97% and a negative predictive value of 71%. Lower results are obtained in lymph node staging: enlarged lymph nodes are seen in only 11/22 C1/C2 patients (11 false negatives) while we were aware of 3 false positives.

Adult↗

Lung colonization and metastasis of murine mammary tumors: relationship to various characteristics of the primary tumors.

The ability to metastasize via the bloodstream of mammary tumors occurring in Balb/cfC3H and Balb/cfRIII mice (two substrains of identical Balb/c genotype carrying milk-transmitted C3H or RIII murine mammary tumor virus (MuMTV) infection, respectively) has been compared in MuMTV-free Balb/c virgin female recipients given intravenous tumor cell suspensions or subcutaneous solid tumor transplants from mammary tumor-bearing Balb/cfC3H and Balb/cfRIII breeding female donors. Tumor cell suspensions different for MuMTV inducing variant, growth rate, tumor size, and clinical duration, injected intravenously to Balb/c virgin female recipients, have been compared with respect to the foci of lung colonization induced in recipient hosts. The results obtained indicate that MuMTV variant, growth rate and clinical duration of the primary mammary tumor, but not the size of the primary tumor, significantly influence the lung colonization. Similar results were obtained with solid subcutaneous transplants of the same mammary tumors. The significance of these results for the understanding of the general mechanisms of tumor metastases is discussed.

Animals↗

Reciprocal interference between milk-transmitted mammary tumor virus and Friend leukemia viruses in mice: possible role of the interferon system.

We have previously shown that mice simultaneously infected with the murine mammary tumor virus (MuMTV) and with certain slow murine leukemia viruses (MLV) have an increased resistance to the pathological effects of both agents. Here we report that milk-transmitted MuMTV also delays the development of the acute erythroleukemia induced by Friend leukemia virus (FLV), and retards, or prevents in some cases, the development of long-term lymphomas caused by its helper component. This is confirmed by the observation that the average life span of MuMTV-carrying mice infected with FLV or its helper component is prolonged by over 30% as compared to that of MuMTV-free animals infected with the same agents and by the finding that the replication of Friend viruses is reduced in mice neonatally exposed to MuMTV. Since the antibody responses of mice to MuMTV and to FLV were not cross-reactive, we searched for antiviral activity in the tissues of mice exposed to MuMTV, FLV, or the helper component of FLV. Low levels of interferon-alpha/beta were consistently detected in spleen extracts from mice infected with all these agents but could not be demonstrated in the spleens of uninfected BALB/c mice; thus, the chronic production of endogenous interferon is likely to play a major role in the reciprocal interference in vivo between retroviruses belonging to different genera.

Animals↗

Morphology and progression of preneoplastic changes in methylcholanthrene-induced mouse mammary tumorigenesis.

Susceptible BALB/c virgin female mice were treated with 3-methylcholanthrene in almond oil (0.5%) by skin painting and killed at monthly intervals. The mammary glands were prepared as whole mounts for stereoscopic study of the glandular tree with removal of any focal change for histology. The results showed a marked disarrangement in the architecture of the glandular tree, a prevalent ductal tree, and an overcrowding of ducts. Focal hyperplastic changes were frequently observed, including hyperplastic alveolar nodules, hyperplastic ductal nodules, noduloids and intraductal epithelial growths, and their respective rates of malignant transformation observed at histology were 22%, 15%, 7% and 50%. Data suggest a different weight of these preneoplastic changes as sources of malignant transformation and a prevalent ductal origin of the methylcholanthrene-induced neoplasms.

Animals↗

Systemic lymphoid atrophy in coxsackievirus B3-infected mice: effects of virus and immunopotentiating agents.

Adult mice infected with coxsackievirus B3 (CB3) showed a generalized lymphoid involution. This effect was produced by most of the isolates and clones of CB3 and, to a lesser extent, by coxsackievirus B1 but not by other highly pathogenic picornaviruses. While moderate involution of the thymus also occurred in mild CB3 infections, peripheral changes strictly correlated with the severity of disease. The major alteration of the thymus was a massive cortical depletion, whereas the reduction of spleen and lymph node cellularity appeared devoid of selectivity. No histological and ultrastructural signs of CB3 replication in such organs could be detected. Attempts to demonstrate CB3 replication in thymus, spleen, and lymph node cells were unsuccessful. CB3-induced lymphoid atrophy was not prevented by adrenalectomy and was exacerbated by three different immunopotentiating agents. Thus, certain picornaviruses may cause severe stress-independent lymphoid damage in the absence of viral replication in situ. A role for autoreactive mechanisms is suggested.

Adjuvants, Immunologic↗

Factors that affect metastasis in virus-induced mouse mammary tumors.

Two hundred and forty-one mammary tumor-bearing breeding female mice of the BALB/cf C3H and BALB/ cfRIII strains, carrying milk-transmitted murine mammary tumor virus (MuMTV) of C3H and RIII origin, respectively, were studied to evaluate the factors that affect tumor metastasis. Only lung metastases were considered and the following factors taken in account: MuMTV inducing variant (C3H, RIII), number of deliveries, tumor histotype , number of tumors per mouse, clinical duration of tumors, tumor size, and tumor growth rate. Only the number of deliveries, the tumor size and the number of tumors per mouse were found to significantly influence the rate of metastasis. The tumor growth rate affects concurrently with tumor size the metastatic process. In fact, the larger the tumor the higher the tumor growth rate. This direct relationship is significant (P less than 0.01) and, in case of lung metastases at autopsy, there was a prevalence of large tumors (greater than 2 cm) and high growth rate (greater than 0.3 mm/day). The discordance of these data with those concerning mammary tumor metastasis in virgin females of the same two strains, the enhancing effect of pregnancies on metastatic spread of tumors, and the significance of results for the understanding of the general mechanisms of tumor metastasis are discussed.

Animals↗

Lobuloalveolar differentiation and tumorigenesis: two separate activities of mouse mammary tumor virus.

The morphological growth of the mammary glandular tree from 3 to 18 months of age has been quantified in three groups of genetically identical virgin female mice: BALB/c mice free of milk-transmitted mouse mammary tumor virus (MMTV) infection and BALB/cfC3H and BALB/cfRIII mice carrying milk-transmitted MMTV infection of C3H or RIII origin, respectively. Mice were killed at 3-month intervals, and their mammary glands were prepared for stereoscopic examination as whole mounts. Any cluster of alveoli from 0.1 mm in diameter was counted and measured at 0.1-mm intervals. The small clusters of alveoli (less than or equal to 0.3 mm) were used to measure the amount of lobuloalveolar differentiation. The larger clusters of alveoli, the hyperplastic alveolar nodules, and the mammary tumors were used to measure the frequency of tumor cell transformations. Lobuloalveolar differentiation in BALB/c mice was increased significantly by both C3H (p less than 0.001) and RIII (p less than 0.001) MMTV infections. RIII MMTV induced a significantly higher lobuloalveolar differentiation as compared to that induced by C3H MMTV (p less than 0.001). C3H MMTV showed a significantly higher capability in inducing hyperplastic alveolar nodules and mammary tumors as compared to that of RIII MMTV (p less than 0.001). The conclusions were that two different activities are carried out by MMTV, namely, lobuloalveolar differentiation and noduligenesis, and that these two MMTV activities are distinct from each other.

Animals↗

Carbon monoxide binding kinetics in "capped" porphyrin compounds.

The rate constants for CO binding to the five-coordinate ferrous iron complexes of 5,10,15,20-[pyromellitoyl(tetrakis-o-oxyoxyphenyl)]porphyrin and 5,10,15,20-[pyromellitoyl(tetrakis-o-oxypropoxyphenyl)]porphyrin have been measured and compared with the corresponding rate constants for other hemes and hemoproteins. The second-order rate constant is independent of cap size and is comparable to that of high-affinity state hemoglobin (k5 approximately 4 X 10(6) M-1s-1). Therefore, these capped porphyrins provide no steric hindrance to CO binding. In addition, a kinetic scheme involving an unusual seven-coordinate porphyrin species is described.

Carbon Monoxide↗