M Castagna

Università di Pisa, Pisa, Tuscany, Italy

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Publications (41)137.82 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Adjuvant therapy in colorectal cancer has evolved to become the standard of care, whereas the tumor capability of activating effective mechanisms of defence against both chemical and physical cytotoxic agents represents a serious obstacle to the successful therapy of human tumors. Therefore, the possibility to have an assay useful to measure the drug sensitivity of tumor cells has a great importance. A number of cytotoxicity assays are currently available, each of them using a specific approach to detect different aspects of cell viability, such as cell integrity, proliferation and metabolic functions. The purpose of this study is to compare, under identical experimental conditions, three common cytotoxicity assays (ATP-lite, MTT and CCK-8 assays) in the assessment of the anti-proliferative effects of 5-fluorouracil (5-FU) and oxaliplatin (OHP) on three colon cancer cell lines (WiDr, SW620 and HT-29). Regarding 5-FU, the three assays were found to be significantly correlated with a moderate or high correlation coefficient, whereas in the case of OHP we found different outcomes among the assays. Our study demonstrates that the CCK-8 is the most sensitive assay for detecting changes of cell viability, suggesting that the viability measured in cells after drug exposure depends on several parameters like the drug used, the biological characteristics of the target cell and the specific approach employed by the method to detect distinct cell growth and metabolic functions.
    Journal of biological regulators and homeostatic agents 01/2013; 27(1):275-284. · 2.41 Impact Factor
  • Child s Nervous System 11/2011; 28(2):297-303. DOI:10.1007/s00381-011-1626-3 · 1.16 Impact Factor
  • Neuropathology and Applied Neurobiology 02/2008; 34(5):564-8. DOI:10.1111/j.1365-2990.2007.00934.x · 4.97 Impact Factor
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    ABSTRACT: Subependymoma was first described by Scheinker in 1945; it frequently occurs in the ventricles and rarely in the spinal canal representing 0.7% of all central nervous system tumours. Most of these intraventricular tumours are subclinical entities, remaining of small size and discovered at autopsy with 0.4%incidence. We report a case of subependymoma with a completely exophytic growth from the foramen of Luscka: only a similar one has been described in the literature but with a lesser cysternal involvement. Neuroradiological and anatomopathological features of subependymoma are discussed.
    Journal of neurosurgical sciences 07/2007; 51(2):81-4. · 0.78 Impact Factor
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    ABSTRACT: Prostaglandins regulate various functions throughout the gastrointestinal system. Their biosynthesis depends on cyclooxygenase isoforms, named COX-1 and COX-2. The initial hypothesis that COX-2 is an inducible enzyme has been challenged and its constitutive expression in the stomach has been established. In this study, an immunohistochemical analysis was performed to evaluate the distribution and cellular localization of COX-2 in normal human colon. Colonic surgical specimens were processed for COX-2, protein HuC/HuD, neurofilament, S-100 protein and CD117/c-kit immunodetection. COX-2 protein was found to be constitutively expressed in the colonic wall: detectable amounts were localized in mucosal, submucosal and muscular layers, mainly in the neuromuscular compartment. In particular, COX-2 was expressed in muscularis mucosae, submucosal ganglia, longitudinal muscle layer and myenteric ganglia, the neurons of which displayed different degrees of immunostaining. Intramuscular interstitial cells of Cajal, regarded as important sites for the regulation of enteric neuromuscular activity, were also partly COX-2 immunoreactive. This study provides a detailed mapping of COX-2 expression in human colon, and allows better understanding of the roles played by this isoenzyme in gut physiology.
    Neurogastroenterology and Motility 09/2006; 18(8):654-62. DOI:10.1111/j.1365-2982.2006.00795.x · 3.42 Impact Factor
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    ABSTRACT: This study describes a case of autochthonous neurocysticercosis in a non endemic region where a differential diagnosis with more frequent single parenchymal lesions must be carried out. The patient presenting generalized seizures and coma status under the suspicion of cerebral neoplasia was admitted to the neurosurgery division. MRI showed the presence of an ovoidal cystic lesion in right-frontotemporal region. After right fronto-temporal osteoplastic bone flap elevation and usual dural tacking and opening, trans-scissural subaracnoid access was made possible by microsurgical strumentation in right Sylvian fissure. A cystic, translucid lesion was identified in the deep Sylvian fissure, involving the distal segment of the fissure and the frontal lobe, the cystic lesion was removed surgically. Pathological examination showed a typical picture of neurocysticercosis. After both surgical and chemotherapeutic treatment with albendazole the outcome was successful. The diagnosis of neurocysticercosis should be taken into account in the presence of generalized seizures possibly due to single parenchymal lesions, even in non-endemic regions for this parasitic infection.
    Pathologica 09/2006; 98(4):229-31.
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    ABSTRACT: This study was designed to determine the debated prognostic significance of reverse transcriptase-polymerase chain reaction (RT-PCR) positivity in melanoma patients' sentinel lymph node (SLN) negative by conventional histopathology (PATH). Patients with primary stage I-II cutaneous melanoma underwent radioguided sentinel lymphadenectomy. Their SLNs were assessed for tyrosinase (Tyr) and melanoma antigens recognized by T-cells (MART-1) mRNA expression using RT-PCR, in parallel with hematoxylin and eosin staining and immunohistochemistry. Tyr and MART-1 expression in the SLNs were correlated with PATH assay results, standard prognostic factors, time to progression and overall survival. Twenty-three of the 124 patients (18.5%) had positive SLNs by both PATH and RT-PCR (PATH+/PCR+). Sixteen patients (13%) were negative by PATH and positive by RT-PCR (PATH-/PCR+). Eighty-five patients (68.5%) had SLNs that were negative by both PATH and RT-PCR (PATH-/PCR-). At a median follow-up of 30 months, recurrence rates among the three cohorts were statistically different (PATH+/PCR+, 60%; PATH-/PCR+, 31%; PATH-/PCR-, 9.4%). Seven of 23 (30%) and two of 16 (12.5%) patients died in the PATH+/PCR+ and PATH-/PCR+ SLN groups, respectively, whereas no patient died in the PATH-/PCR- SLN group. RT-PCR is more sensitive than PATH to detect SLN metastases and it is a reliable predictor of disease relapse in stage I-II melanoma patients.
    Annals of Oncology 12/2005; 16(11):1832-40. DOI:10.1093/annonc/mdi372 · 6.58 Impact Factor
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    ABSTRACT: In this study we report the presence of peripheral benzodiazepine receptors (PBRs) in human parathyroid glands and describe the effect of their benzodiazepine type ligands on parathyroid cell function. PBR binding features in normal parathyroid tissue were characterized and compared to parathyroid adenoma, using a specific and selective ligand for PBR, [3H] 1-(2-chlorophenyl)-N-methyl-N-(1-methyl-propyl)-3-isoquinoline-carboxamide ([3H]PK11195). Affinity and density of [3H]PK11195 binding sites in homogenate membrane preparations from adenomatous and normal tissues were determined. Parathyroid adenoma showed a statistically significant 2.2 fold increase of [3H]PK11195 binding sites, while the affinity remained unchanged. Our results represent the first evidence of PBRs in parathyroid glands and suggest for them a role in influencing PTH release. A clear trend of PBR up-regulation in parathyroid adenoma was also found.
    Journal of endocrinological investigation 11/2004; 27(9):826-31. DOI:10.1007/BF03346276 · 1.55 Impact Factor
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    ABSTRACT: In the 1990s, the introduction of the Guglielmi detachable coil (GDC) system in clinical practice was followed by extensive clinical use of this endovascular device in the treatment of brain aneurysms. This technology is based on electrothrombosis and electrolytic detachment of platinum coils. Despite the extensive use of this treatment technique, the role of electrothrombosis has not been fully investigated and clarified. An in vitro electron microscopic study of human blood was performed to elucidate the role that electrothrombosis might play in triggering the biologic response of thrombosis of the aneurysmal sac. Human blood from five patients was used to fill plastic containers in which GDCs had been deposited. These five patients had subarachnoid hemorrhage and were similar in age and clinical presentation. Electron microscopic studies were performed on GDCs that had been electrically charged and on GDCs that had not. All electron microscopic studies revealed that the electrically charged GDCs were covered by blood elements and fibrin adherent to the surface of the coil. Noncharged GDCs did not have deposits or adhesions of these blood constituents. These findings demonstrated that passage of electric current through the GDC induces attraction of blood constituents. This attraction may trigger a thrombotic reaction on the surface of the coil. The greater the time of current application, the more pronounced the cellular reaction and the deposition of fibrin and blood cells on the GDC.
    American Journal of Neuroradiology 11/2001; 22(9):1757-60. · 3.68 Impact Factor
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    ABSTRACT: Thyroid hormone is essential for maintaining normal neurological functions both during development and in adult life. Type III-iodothyronine deiodinase (D3) degrades thyroid hormones by converting thyroxine and 3,5,3'-triiodothyroinine (T3) to inactive metabolites. A regional expression of D3 activity has been observed in the human central nervous system (CNS), and a critical role for D3 has been suggested in the regulation of local T3 content in concert with other enzymes. This study was undertaken to further characterize D3 activity in human CNS and to understand its role in the local regulation of T3 content. Autoptic specimens from various areas of human CNS were obtained 6--27 h postmortem from 14 donors who died from cardiovascular accident, neoplastic disease or infectious disease. D3 was determined by measuring the conversion of T3 to 3,3'-diiodothyronine. The T3 content was measured by radioimmunoassay in ethanol extracts, using a specific antiserum. High levels of D3 activity were observed in hippocampus and temporal cortex, lower levels being found in the thalamus, hypothalamus, midbrain cerebellum, parietal and frontal cortex, and brain stem. An inverse relationship between D3 activity and T3 content in these areas was demonstrated. We have concluded that D3 contributes to the local regulation of T3 content in the human CNS.
    European Journal of Endocrinology 07/2001; 144(6):577-83. DOI:10.1530/eje.0.1440577 · 3.69 Impact Factor
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    ABSTRACT: A case of neuroglial tumor in a 18-year-old man is presented. The neoplasm was composed by two cell types. One type showed features typical of neuronal cells, while the other resembled glial cells. The diagnosis was confirmed by immunohistochemistry results.
    Pathologica 03/2001; 93(1):57-60.
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    ABSTRACT: 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. 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. 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. 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.
    Annali italiani di chirurgia 01/2001; 72(3):323-7. · 0.68 Impact Factor
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    ABSTRACT: 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. 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. 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. 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.
    Tumori 01/2001; 87(3):179-86. · 1.09 Impact Factor
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    ABSTRACT: The presence of lymph node metastases is the best prognostic factor for predicting relapse or survival in melanoma patients. It has been demonstrated that melanoma metastases spread through the first lymph node(s) draining the tumor (sentinel lymph node, SN) to the lymphatic system and that detection of melanoma cells in peripheral blood directly correlates with prognosis in melanoma. To identify lymph node metastases and circulating melanocytes, we developed a single-step reverse transcriptase-polymerase chain reaction assay (RT-PCR) for detection of two melanoma-specific markers: the tyrosinase gene, which encodes an enzyme associated with melanin synthesis, and melanoma antigen-related T-cells, which are present in tumor infiltrating T-lymphocytes. This method detects two tumor cells in a background of 10(7) lymphocytes. Thirty patients with stage I-IV cutaneous melanoma entered the study. Blood samples were taken preoperatively, one month after excision of the primary melanoma lesion and the SN or total lymphadenectomy, and before the start of chemotherapy and every three months thereafter in metastatic patients. SNs were collected from 22 patients, bisected and analyzed by RT-PCR and routine pathological and immunohistochemical tests. The preliminary results indicate that RT-PCR for melanoma markers is a sensitive and valuable method for the detection of micrometastases and for early diagnosis and staging of melanoma.
    Tumori 01/2000; 86(4):336-8. · 1.09 Impact Factor
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    ABSTRACT: Histologic findings after Guglielmi detachable coils endovascular embolisation have been studied in experimental aneurysms. Few reports describe histopathologic reactions to platinum coils in humans. In this report we describe gross, light microscopic pathology and scanning electron microscopy study of a ruptured basilar tip artery aneurysm in a patient who died 16 hours following coiling.
    Interventional Neuroradiology 09/1999; 5(3):257-60. · 0.73 Impact Factor
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    Rosalba Ciranni, Maura Castagna, Gino Fornaciari
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    ABSTRACT: Goiter is still a frequent pathological condition of the thyroid gland. Goiter consists of an enlargement of the gland caused by several physiopathologic events, the most important of which is deficient intake of iodine. A series of eighteenth-century mummies housed in the church of Santa Maria della Grazia in Comiso includes one individual showing a pathological condition, with a very large swelling in the antero-inferior region of the neck. X-rays showed small scattered radiopaque foci. Routine histology showed a large number of circular follicles immersed in fibrous tissue. Finally, immunohistochemistry revealed a strong reactivity for thyroglobulin. The data confirmed the nature of the tissue as thyroid, and the macroscopic diagnosis is that of thyroid goiter.
    American Journal of Physical Anthropology 04/1999; 108(4):427-32. DOI:10.1002/(SICI)1096-8644(199904)108:4<427::AID-AJPA4>3.0.CO;2-7 · 2.51 Impact Factor
  • Melanoma Research 01/1997; 7(Supplement 1):S120. DOI:10.1097/00008390-199706001-00418 · 2.10 Impact Factor
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    ABSTRACT: An immunohistochemical study with two rabbit polyclonal antibodies I-AR76 and CA-08-351 against Endothelin-1 (ET-1) was performed in 133 human thyroid specimens: 5 normal thyroids, 30 multinodular goiters (15 toxic and 15 nontoxic), 20 Graves' diseases, 5 Hashimoto's thyroiditis, 26 adenomas (6 Hürthle cell, 16 toxic and 4 nontoxic), 30 classic papillary carcinomas, 3 minimally invasive follicular carcinomas, 1 widely invasive follicular carcinoma, 3 undifferentiated carcinomas and 10 medullary carcinoma. All normal thyroids, non toxic multinodular goiters and non toxic adenomas, 4 (66%) Hürthle cell adenomas, 3 (15%) Graves' diseases, 1 (33%) case of minimally invasive follicular carcinoma showed rare follicular cells with weak cytoplasmic immunoreactivity. Many immunoreactive follicular cells, with or without oxyphilic changes, were observed in all specimens of Hashimoto's disease, while the lymphocytic infiltrate was always negative. Twenty-seven (90%) classic papillary carcinomas were positive. Immunoreactivity was intracytoplasmic, weak in 14 cases and intense in 13. The cells of toxic adenoma and toxic multinodular goiter were negative, whereas the acellular stroma was intensely positive in both cases. Medullary and undifferentiated carcinomas were negative. These results show ET-1 immunoreactivity in normal and pathological human thyroids. In particular, the high content of this peptide in the thyroid papillary carcinoma suggests that ET-1, whose mitogenic role has recently been emphasized, could be involved in the growth of this tumor.
    Journal of endocrinological investigation 06/1995; 18(5):336-40. DOI:10.1007/BF03347834 · 1.55 Impact Factor
  • P. Viacava, M. Castagna, G. Bevilacqua
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    ABSTRACT: Some human breast carcinomas show features of neuroendocrine differentiation. The histogenesis of these tumours is debated especially because of the difficulty in locating neuroendocrine cells in normal mammary glands. The aim of this study was to search for neuroendocrine cells in two series of adult and fetal normal mammary glands.Eight female fetus breasts of gestational age between 24 and 37 weeks and 27 cases of normal adult breast tissues were investigated. Paraffin sections of formalin fixed samples were studied by Grimelius stain and immunohistochemistry using the monoclonal antibody anti-chromogranin A. An ultrastructural study was performed on a fetal mammary gland at the 37th week of gestation.Our results showed no histochemical, immunohistochemical and ultrastructural evidence of neuroendocrine differentiation in normal cells of fetal and adult mammary glands. The absence of neuroendocrine cells during mammary gland development indicates that the neuroendocrine part of a mammary cancer does not originate from a normal counterpart but that it is the result of a neuroendocrine differentiation during neoplastic progression.
    The Breast 06/1995; 4(2):143-146. DOI:10.1016/0960-9776(95)90012-8 · 2.58 Impact Factor
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    ABSTRACT: This pharmacokinetic study was performed in order to assess the potential usefulness of the murine monoclonal antibody (MoAb) AR-3-IgG1 as an immunoscintigraphy agent for pancreatic cancer. This MoAb, which defines a mucin-like antigen (CAR-3) expressed by a large fraction of pancreatic cancers, shows in fact favourable in vivo localizing properties in the experimental animal model of human tumor xenograft. 131I-AR-3-IgG1 was injected i.v. into 5 patients with suspected pancreatic cancer. Whole-body maps and spot views of the abdominal area were recorded with a computerized gamma-camera, and specific regions of interest drawn over the liver and spleen helped to define the kinetics of activity in these organs. Blood samples taken from 0.1-144 hours post-injection and daily urine collections over the same interval served to define the kinetics of plama distribution and removal of activity from the body. Different multicompartmental models were tested to fit the experimental data, assuming as the starting hypothesis that there was to be significant nonspecific tracer accumulation in the liver, spleen and bone marrow, as already observed for the majority of radioiodinated murine MoAbs injected into humans. Surgery confirmed pancreatic cancer in 3 out of the 5 patients (chronic pancreatitis and periampullary cancer in one each); in all these 3 patients immunostaining with the MoAb AR-3 demonstrated the presence of the CAR-3 antigen (with a cytoplasmic and endoluminal/secretory pattern of distribution). Nonspecific radioactivity accumulation in the liver, spleen and bone marrow was extremely low, linked essentially to the blood pool effect of circulating activity in these organs.(ABSTRACT TRUNCATED AT 250 WORDS)
    Journal of nuclear biology and medicine (Turin, Italy: 1991) 01/1995; 38(4 Suppl 1):145-50.