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Biomedical subjects

M Castagna

Publications and source records attributed to M Castagna.

120 records · Page 7Linked to original sources

Immunohistochemical study of 49 cutaneous melanomas: p53, PCNA, Bcl-2 expression and multidrug resistance.

AIMS AND BACKGROUND: Thickness and level of invasion are the main morphological elements for an approximate but not sufficiently sensitive prognostic evaluation of cutaneous melanomas. By using immunohistochemical methods it is possible to detect biological markers related to prognosis. We have studied p53, PCNA, Bcl-2 and P-gp expression in 49 primary cutaneous melanomas. MATERIALS: We used the immunophosphatase APAAP immunohistochemical method. The percentage of labeled cells (according to four classes of positivity: <5%; 5-25%; 25-50%; >50%) and the localization of immunoreactivity were expressed for each marker. Statistical analysis was performed to determine the correlations between markers and level or thickness of melanomas. RESULTS: We found a good correlation between p53 expression and melanoma thickness (P <0.005), PCNA and P-gp expression. No relationship was observed between Bcl-2 expression and the different variables considered or other markers. CONCLUSIONS: Our data seem to indicate an unfavorable prognostic role of higher nuclear p53 expression. However, we believe that our results need to be integrated with patients' clinical follow-up and with the study of the expression of these markers in benign melanocytic lesions to gain more accurate information about their prognostic significance.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Mammary fetal gland: identification of new oncofetal antigens by monoclonal antibodies B72.3, MM1.80 and 4.36.

AIMS AND BACKGROUND: The B72.3, MM1.80 and 4.63 monoclonal antibodies directed against tumor-associated antigens react in human breast also with metaplastic, preneoplastic and metastatic cells, whereas they do not react with normal adult mammary tissue. The aim of our study was to point out the expression of these antigens during mammary gland development, since tumor-associated antigens are known to represent antigens of differentiation. STUDY DESIGN: Fifty female fetal breasts between 20 and 40 weeks of gestational age were studied. RESULTS: Mammary tissue was identified only in 15 cases. B72.3, MM1.80 and 4.36 monoclonal antibodies reacted with epithelial antigens and maintained the same location and intensity in the various gestational ages. Immunoreactivity was weak, cytoplasmic and widespread for the 4.36 monoclonal antibody, intense and cytoplasmatic in a large number of cells for the B72.3 monoclonal antibody, and intense and luminal for the MM1.80 monoclonal antibody. CONCLUSIONS: Such data further support the hypothesis that the normal process of development and differentiation can occur during tumor progression processes. Identification of these new oncofetal markers could offer a new perspective able to recognize the different phases of neoplastic progression and could be useful for prevention.

Antibodies, Monoclonal↗

Bilateral synchronous testicular involvement in multiple myeloma. Case report and review of the literature.

The authors describe a case of synchronous bilateral involvement of the testes in a 70-year-old patient seven years after the onset of an IgG k IIIA multiple myeloma. Ultrasonographic and postoperative immunohistochemical studies were performed. A complete review of the literature shows the rarity of testicular plasmacytoma. The present one is the second reported case of syncronous involvement of the testes.

Aged↗

Functional and clinical changes in upper limb spastic patients treated with botulinum toxin (BTX).

Spasticity is a motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes (muscle tone) with exaggerated tendon jerks. In order to study the usefulness of botulinum toxin type A (BTX) as a therapy for spasticity, we studied 15 patients affected by spasticity secondary to stroke. Tests included: clinical evaluation of tone (Ashworth scale); active angles of extension and flexion at elbow and wrist; Hmax/Mmax ratio from flexor carpi radialis (FCR); Hreflex presynaptic inhibition from FCR during vibration; Task score; and video recording. Patients were injected with BTX into one or more muscles with total doses not exceeding 200 International Units (IU). The tests were performed immediately prior to injection and repeated 2 weeks afterwards. Furthermore, in eight patients, testing was also performed one month after BTX injection. Between two weeks and one month after BTX there were no statistically significant differences. A statistically significant difference in the Task and Ashworth scores before and after treatment emerged (p < 0.0014), but only 6 patients showed a clear improvement in motor performance. Overall, we observed an improvement in the angle of active extension and flexion at the wrist and elbow. There were no significant changes in the Hmax/Mmax ratio and the Hreflex presynaptic inhibition during vibration. All the patients reported a subjective improvement. The results suggest that subjective benefits can be gained from the use of BTX in patients affected by spasticity, and that the degree of motor improvement seems to depend on the motor recovery obtained before treatment.

Adult↗

[Clinical significance of a carcinogenesis model of colorectal carcinoma].

OBJECTIVE: Carcinoma of the rectal colon begins as a small neoplastic polyp which gradually increases in size and, after passing through various degrees of dysplasia, develops into an overtly malignant carcinoma. Clinical experience suggests that patients may be divided into subgroups based on the aggressivity of the tumour. The genetic mutations associated with colorectal cancer have been studied and it is known that the genes primarily responsible for biological changes in the tumour cell, in the early stages, are APC, hMSH2, k-ras2 and, in particular, p53. Indeed, the mutation at the level of gene p53 has been recognized as the most common mutation in tumour cells. The aim of this study was investigate the role of p53 and CD34 in colorectal cancer. METHODS: We studied p53 positivity using immunohistological methods and compared our results with the site, stage (using the TNM system) and histological grade of the tumour. We evaluated CD34 positivity using the same methods in order to detect and quantity the presence of angiogenesis in colorectal cancer. RESULT: P53 was found to be markedly raised in the T3 stage of colorectal cancer, while its expression was decreased in stage T2 and stage T1 carcinomas and it was not detectable in adenomas. These results suggest a close correlation between the tumour stage and the expression of p53. An analogous correlation was found between CD34 expression and angiogenesis. CONCLUSION: The overexpression of p53 in epithelial cells and raised angiogenesis (as reflected in CD34 levels) in stromal cells could represent useful prognostic factors in the management of colorectal cancer.

Aged↗

Characterization of monoclonal antibody 436 recognizing the Arg-Pro-Ala-Pro sequence of the polymorphic epithelial mucin (PEM) protein core in breast carcinoma cells.

Epithelial mucins have obtained increasing clinical relevance since they were found in the serum of cancer patients and were shown to be elevated in metastatic disease. We report here the characterization of the monoclonal antibody (MAb) 436 which recognises the protein core of the polymorphic epithelial mucin (PEM) of the human breast. MAb 436 was generated by immunizing Balb/c mice with membrane-enriched fractions prepared from metastatic lesions in the axillary lymph nodes. The antigenic determinant recognized by the MAb 436 is expressed on the surface of breast cancer cells and was measured by ELISA on all of 50 cytosol preparations of primary breast tumors. Immunohistochemistry showed 98% of primary and 100% of metastatic breast cancer lesions to be positive with the 436 antigenic determinant expressed both in the cytoplasm and at the plasma membrane level of the tumor cells. Moreover, the antigen was expressed in a homogeneous fashion (80-100% of the total number of tumor cells) in more than 60% of the tumors. Reactivity with normal tissues was rare and scattered and restricted to glandular structures particularly at the luminal border level except for the distal and collecting tubules of adult and fetal kidney, where a cytoplasmic 436 antigen distribution was observed. Other cancers proved positive but the reactivity was always variable and heterogeneous. The antigen recognized by MAb 436 appears in Western Blotting as a M(r) of more than 200,000 daltons protein resolved in two bands. Epitope mapping experiments using overlapping octapeptides in the repeat unit of the PEM identified in the RPAP (Arg-Pro-Ala-Pro) sequence the binding site of the 436 antigen.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

[Epidemiologic study of epilepsy in the population of Este-Montagnana (U.L.S.S. 22-Veneto Region)].

Epidemiological data of the U.L.S.S. n. 22 of Este-Montagnana (PD) show a prevalence of Epilepsy of 5.94%. These data are referred to an observation period of ten years (1978-1987) and confirm the results of major epidemiological trials in U.K. and U.S.A. Distribution by sex and types of crises is the same. The Authors underline the importance of alcohol-related crises; however this is not yet confirmed by precise parallel data.

Adolescent↗

Different susceptibility of lung cell lines to inhibitors of tumor promotion and inducers of differentiation.

Histologically distinct lung tumor and normal cell lines were treated with a variety of potential inhibitors of cell growth such as inducers of cell differentiation, inhibitors of protein kinase C and inhibitors of tumor promotion. The response was assessed by 3H thymidine incorporation and cloning efficiency. Both phorbol retinoate acetate and mezerein stimulated growth in lung normal cell lines (human fibroblastic PEH cells and rat epithelial TP9 cells) while inhibiting growth in lung tumor cell lines (human small-cell cancer-derived cell line IRSC-10M and adenocarcinoma-derived cell line A549). Likewise, the hydrophobic peptide melittin did not inhibit growth and cloning efficiency of normal cells at 1 microM, a concentration which prevented proliferation in tumor cells. Protein kinase C inhibitors, chlorpromazine, trifluoperazine and 1-(5 isoquinolinylsulfonyl) 2-methylpiperazine, were much more effective on proliferation of IRSC-1OM than of A549 cells. In contrast, the latter cells were more susceptible to anti-promoters such as glycyrrhetic acid, an anti-inflammatory agent, and 3,4',2', 4'-tetrahydroxychalcone or 2,3,5-trimethyl-6 (12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone, two inhibitors of lipoxygenase, a key enzyme in arachidonate metabolism. Our results provide evidence that small-cell carcinoma-derived cells, in contrast with adenocarcinoma-derived cells, are growth-inhibited by protein kinase C inhibitors and poorly dependent on the arachidonate metabolism. This difference in responsiveness suggests that different growth signalling pathways are preferentially triggered in these histologically distinct lung tumor cell lines. As a consequence, the proper susceptibility of tumor cells to phenotype modifiers has to be taken into account in cancer therapy.

Arachidonic Acid↗

Calcitonin and somatostatin containing C cells in rat and human thyroid. Immunohistochemical study by a double-staining method.

C cells of the thyroid probably exert a paracrine control on follicular cells through secretion of peptides such as calcitonin and somatostatin. The aim of the present study was to investigate the expression of different peptides produced by C cells in rat thyroid and in the different morphological and pathological conditions of the human thyroid. Therefore we employed the immunohistochemical double-staining method using anti-calcitonin and anti-somatostatin antibodies. The results of this study show the presence of C cells containing calcitonin and C cells containing somatostatin exclusively in the rat and the human thyroid. This distinction with prevalence of one peptide on the other is maintained in the different morphological and pathological conditions of the human thyroid.

Animals↗

[Concentration of C cells in the thyroid of rats treated with mercaptoimidazole or levo-thyroxine].

Concentration of C cells in the thyroid of rats treated with Mercaptoimidazole or Levo-thyroxine. The aim of the present study was to elucidate the possible functional relationship between follicular and parafollicular cells of the thyroid gland; therefore we have investigated the behaviour of calcitonin producing cells and serum calcitonin concentration in rats both in resting and hyperstimulation conditions of follicular cells. Our results showed that with regard to follicular mass the concentration of the C cells was reduced in the two groups of rats treated compared to control rats. C cell concentration decrease was associated with reduced serum calcitonin concentration. In conclusion C cell activity is independent of TSH and thyroid hormones circulating levels.

Animals↗

[Immunohistochemical study of the enteric glia in chronic intestinal inflammatory disease].

Enteric glial cells, strictly associated with enteric neurons to build up enteric ganglia, belong to the enteric nervous system (ENS), which coordinates many bowel functions. The ENS is spread throughout the gut in myenteric and submucosal plexuses. In our research work, we studied immunohistochemically the ENS in two typical chronic inflammatory bowel diseases, Crohn's disease (CD) and ulcerative colitis (UC), by using specific antibodies against gliocyte (S-100) and neuronal (neurofilaments, NF) markers. We found high S-100 immunoreactivity within the submucosal and muscular layers in samples from CD patients, but not as such in those from UC patients; similar results were also achieved using anti-NF antibodies. Moreover, immunohistochemistry has pointed out that alterations of the ENS are associated, in CD more than in UC, with the expression of major histocompatibility complex class II antigens on components of the ENS, especially on enteroglial cells. These data suggest that histopathological differences exist between CD and UC also within the ENS, especially as far as the glial cells are concerned. Such ENS changes might significantly contribute to the immunopathogenesis and immunopathophysiology of chronic inflammatory bowel diseases.

Colitis, Ulcerative↗