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Biomedical subjects

G Nicolò

Publications and source records attributed to G Nicolò.

At least 37 records · Page 2Linked to original sources

A study on macronuclear chromatin structure in Colpoda inflata (Protozoa, Ciliophora) by means of image analysis.

Resting encystment is a reversible cytodifferentiation phenomenon regularly taking place during the life cycle of Colpodidae. The encystment involves regulation of the macronuclear DNA content, accomplished via chromatin extrusion and DNA synthesis mechanisms. An analysis of macronuclear chromatin texture was carried out in Colpoda inflata logarithmically growing cells, pre-cystic cells, and increasingly aging resting cysts after Feulgen staining. Morphometric and densitometric parameters as well as Markovian chromatin texture variables were utilised for image analysis. Moreover, univariate and multivariate analyses were applied both to macronuclei and to their chromatin extrusion bodies. The results show that structural variations in chromatin appear under macronuclear functional activity conditions, suggesting a dynamic state of chromatin texture throughout a long-term resting encystment.

Animals↗

Endoscopic retrograde forceps biopsy and brush cytology of biliary strictures: a prospective study.

BACKGROUND: Nonsurgical pathologic confirmation of malignant bile duct strictures is desirable for defining subsequent treatment and prognosis. Endoscopic retrograde cholangiopancreatography is frequently performed in patients suspected of having pancreaticobiliary obstruction, but there exists no standardized method for defining the nature of obstructing lesions by ERCP. METHODS: We prospectively evaluated the yields of endoscopic retrograde brush cytology and biopsy for the diagnosis of malignant bile duct strictures. Fluoroscopically guided endobiliary biopsy and brush cytology (52) or cytology alone (42) were performed during endoscopic retrograde cholangiopancreatography in 94 consecutive patients, 64 with malignant strictures and 30 with benign strictures. A single cytopathologist classified the results of these studies as positive or negative for malignancy. RESULTS: The sensitivities of the two procedures were identical (53%) and the gain achieved by combining the two techniques (61%) was small. Specificity proved excellent for both methods. One major complication that occurred was perforation of the common hepatic duct with leakage of bile, which was managed by surgical oversewing. This complication was ascribed to biopsy and untimely removal of the nasobiliary drain by the patient herself. CONCLUSIONS: This study indicates that endoscopic retrograde brush cytology alone may be sufficient in daily practice, at least in centers that have access to experienced cytopathologists. We recommend use of forceps biopsy in selected cases where brush cytology is negative.

Adult↗

Cytokine expression in human primary and metastatic melanoma cells: analysis in fresh bioptic specimens.

In recent years, several studies have documented that melanoma cell lines produce various cytokine/growth factors and their receptors. Since cell lines can acquire altered properties, such as changes in growth requirements, we studied constitutive cytokine gene expression in melanoma cells from 20 fresh surgical specimens: seven primary melanomas and 13 metastases (12 lymph-node metastases and one subcutaneous metastasis). After tumour cell isolation by discontinuous gradient, we tested for mRNA expression by means of reverse-transcriptase polymerase chain reaction. Most melanoma cells tested expressed growth factors: basic fibroblast growth factor (bFGF), interleukin (IL)1 alpha, IL-1 beta, IL-6 and IL-8 and, in five cases out of 20, expressed granulocyte-macrophage colony-stimulating factor (GM-CSF) (two out of five were also positive for GM-CSF receptor). Our results do not point to a direct correlation between cytokine expression and clinical stage at the time when the bioptic specimen was obtained. However, they allow us to suggest a possible metastatic tumour cell phenotype, in which autogenous GM-CSF expression could modulate immune response against the tumour cell itself or could potentiate metastatic colonization properties.

Adult↗

Antiproliferative and synergistic effect of interferon alpha-2a, retinoids and their association in established human cancer cell lines.

The effect of 13-cis-retinoic acid (cRA) and all-trans-retinoic acid (tRA) used alone or in combination with interferon alpha-2a (alpha-IFN 2a) was tested on three established human cell lines: KB (epidermoid carcinoma of the oral cavity), SCC-25 (tongue squamous cell carcinoma) and MCF-7 (mammary carcinoma). Both retinoids significantly decreased cell proliferation (growth curves) and colony forming efficiency (CFE) in all cell lines, in a dose-dependent way (at a concentration ranging from 10(-5) to 10(-9) M) and differing from line to line, following the pattern: MCF-7 > SCC-25 > KB. Retinoids at any concentration (already at 10(-7) M) combined with alpha-IFN 2a (ranging from 100 to 500 IU/ml) were more effective in inhibiting cell proliferation than each of the two compounds alone. This was particularly evident with SCC-25 cells. Concerning MCF-7 cells, on the contrary, the effects produced by the association suggested a possible additive more than synergistic amplification of growth inhibition.

Breast Neoplasms↗

Angiosarcoma of the residual breast after conservative surgery and radiotherapy for primary carcinoma.

BACKGROUND: Angiosarcoma of residual breast, arising after conservative surgery and radiotherapy for early breast cancer, is a rare tumor, with only 14 cases having so far been documented. The first was observed in 1987 and 7 of the 14 were reported in 1992 alone. METHODS: Here, we present an additional case developing in residual breast 3.3 years after lumpectomy and radiotherapy. The other fourteen are reviewed. RESULTS: Review of data from this series of patients reveals a higher incidence of breast oedema (67%) than that reported in the literature (4%). Another unusual finding is the shorter mean latency period (time interval from radiotherapy to onset of angiosarcoma) noted here (6 years) compared to the more than 10 years reported for other secondary angiosarcomas. CONCLUSIONS: In view of the widespread use of radiotherapy after breast-conserving surgery, and also its lack of benefit in terms of overall survival, every novel complication should be investigated. Given the apparent rise in incidence of this rare tumor over the last few years, doctors should be aware of the phenomenon in order to recognize and define it.

Aged↗

Primary gastric lymphoma.

The records of 30 patients with primary gastric lymphoma and a minimum of 5 years of follow-up were reviewed and clinical and pathologic prognostic factors analyzed. The overall 5-year survival was 40% (median 23 months). No significant relationship between surgical and patient age, sex, duration of symptoms, macroscopic appearance, or size of the primary lesion or degree of serosal infiltration was demonstrated. Stage of disease and site of primary had an impact on prognosis. Survival was improved in patients with stage I-II disease (P < 0.05) and in patients with primary located in the distal third of the stomach (P < 0.05). Although histology in all three classifications did not correlate well with survival, patients with low-grade lymphoma according to Kiel showed improved outcome (P < 0.05). Five-year survival of 11 patients with positive lymph nodes, 6 of whom were treated with cytotoxic therapy, was 54% and comparable to that of 7 patients (56%) with no nodal involvement who did not receive chemotherapy after surgery.

Adult↗

Expression of different tenascin isoforms in normal, hyperplastic and neoplastic human breast tissues.

Functionally different tenascin (TN) isoforms, containing varying numbers of a 91 amino-acid motif resembling the fibronectin type-III homology repeat, may be generated by alternative splicing of the TN primary transcript. In fact, only the TN isoform containing the alternatively spliced region can induce loss of focal adhesion in cultured cells and seems to be able to facilitate cell migration. We examined the patterns of alternative splicing of the TN primary transcript in normal, hyperplastic and neoplastic breast tissues, and found that, in all the invasive breast carcinomas analyzed, the relative amount of TN mRNA in which the alternatively spliced region was included was about 10 times higher than in RNA from normal breast tissues. A similar result was observed in phyllodes tumors and in those fibroadenomas which showed very high stromal cellularity. Western-blot analysis using different monoclonal antibodies showed the same pattern as that seen in Northern blotting. The data reported here suggest that, in the breast, expression of the high-molecular-mass TN isoform is a marker of stromal element proliferation and that, in invasive breast carcinomas, this TN isoform could play a role in generating a permissive environment for proliferation, invasion and metastasis of neoplastic epithelial cells.

Blotting, Northern↗

Prediction of survival by thymidine labelling index in patients with resistant ovarian carcinoma.

The relationship between tumour proliferative activity, evaluated by thymidine labelling index (TLI), clinicopathological variables and clinical outcome, was analysed in a series of 64 chemotherapy-resistant, ovarian cancer patients. The median TLI of 4.6% (range 0.01-45.7) was used as the cut-off to discriminate rapidly from slowly proliferating tumours. Univariate analyses showed a significant advantage in survival for patients with TLI less than or equal to 4.6 (P = 0.0004), ECOG performance status less than or equal to 1 (P = 0.0001) and residual disease after primary surgery less than or equal to 2 cm (P = 0.019). Multivariate analysis demonstrated that performance status was the only independent prognostic variable, although TLI was the last covariate removed from the Cox's regression model.

Carcinoma↗

Treatment of oral leukoplakia with beta-carotene.

Over the past few years, beta-carotene has progressively gained ground as a drug chosen in the treatment of oral leukoplakias, thus making it possible to reduce the use of 13-cis-retinoic acid, which was shown by many studies to be highly toxic while beta-carotene has proved to have no significant side effects and hence to be much more suitable in oral premalignancy. In 1989, a phase II study of patients showing oral leukoplakias and treated with beta-carotene (90 mg/day) was begun. A total of 23 patients (aged between 17 and 85) were included in the study and 18 (8 male and 10 female) were evaluated. Eight patients (44.4%) had objective responses (6 complete, 2 partial). Four CR and a PR appeared unexpectedly within 2-7 months after the end of the therapy. The lesions were macroscopically and histologically examined at entry; in the evaluated patients, two types of alterations were found: atypical hyperplasia (16 patients) and dysplasia (2 patients). No signs of significant toxicity were detected; only in 1 patient treatment had to be interrupted for 1 week. The results of this study show the fair efficacy of beta-carotene against oral leukoplakias, but further confirmations through controlled clinical studies are needed.

Adult↗

[Efficacy of the combination of nicardipine-enalapril and atenolol in severe hypertension secondary to chronic renal disease].

The antihypertensive efficacy of combination therapy with N-E-A was evaluated during 6 months in 15 patients with hypertension associated with mild to moderate kidney failure. After 6 months a significant reduction of SBP and DBP (p < 0.001), with improvement of creatinine clearance and with no adverse effects on ECG, heart rate and routine laboratory tests test, was observed in 3 patients treated with N 20 mg x 2/d + E 10 mg/d + A 50 mg/d and in 8 patients treated with N 20 mg x 3 + E 10 mg x 2, + A 50 mg x 2. Four patients did not respond to this therapy.

Adult↗

Identification of breast cyst subpopulations: biochemical and morphological features.

The concentration of insulin-like growth factor-I (IGF-I) and its relationship to other biochemical parameters of cyst fluids was investigated in 94 cyst fluids of 86 women with gross cystic breast disease. The relationship between the biochemical parameters and the cytological features of breast fluids (presence or absence of apocrine cells) was also studied. IGF-I was detected in all tested fluids, with a concentration 50 to 100 times lower than that found in plasma. IGF-I concentration was higher in cysts with a Na+/K+ ratio greater than 3 (greater than 3) and was inversely related to both dehydroepiandrosterone sulfate (DHEA-S) and epidermal growth factor (EGF) concentration (p less than 0.001). It is suggested that Na+/K+ greater than 3 cysts have a higher permeability to plasma and extracellular fluids compared to Na+/K+ less than 3 cysts. Apocrine cells were found in 78% of Na+/K+ less than 3 fluids as well as in 53% of Na+/K+ greater than 3 fluids. A well-defined relationship was found between the biochemical parameters of breast fluids, but the presence of either IGF-I or EGF was not related to the morphology of breast cysts as assessed by cytological examination.

Biopsy, Needle↗

Endocervical metastases secondary to breast carcinoma. A case report.

Only 24 cases of breast cancer metastases to the uterine cervix have been reported to date. The present case present secondary cervical involvement in the absence of concomitant extragenital metastases. The patient did not present with abnormal vaginal discharge and the cervical lesion responded to conventional combination chemotherapy for breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗

Invasive activity, spreading on and chemotactic response to laminin are properties of high but not low metastatic mouse osteosarcoma cells.

We have examined the interactions of low (Os43 and OS48) and high (Os50/K8 and Os50/K12) metastatic cell lines derived from osteosarcomas (Os) of the Balb/c mouse with fibronectin (FN) and laminin (LN). All of these cell lines formed osteogenic tumors when transplanted subcutaneously into syngeneic mice. Os43 and Os48 cells gave rise to few metastases while the Os50/K8 and Os50/K12 cells were highly metastatic. In an in vitro chemoinvasion assay only the highly metastatic cells were able to invade a reconstituted basement membrane. Although the interactions of all cell lines with FN were quite similar, their response to LN differed considerably. Within each of the cell lines, chemotactic response to and cell spreading on LN were closely correlated. Highly metastatic Os cells migrated to and spread on LN substrates to a much greater extent than low metastatic cells. Os43 and particularly Os48 showed very much low migration to LN, similar to that of Balb/c 3T3 fibroblasts. They also spread poorly on LN, resembling the behavior of normal human bone cells which were used as a control. Thus, with these assays it is possible to distinguish the LN interactions associated with the metastatic phenotype of Os cells. The acquisition of LN recognition in tumor cells of bone origin may be related to their ability to invade and metastasize. This system may be valuable for the study of LN recognition molecules, their appearance, or changes with the metastatic phenotype.

Animals↗

Expression of tenascin and of the ED-B containing oncofetal fibronectin isoform in human cancer.

Tenascin (TN) and the oncofetal ED-B containing fibronectin isoform (B-FN) have been reported to be stromal markers of a number of malignancies. Here we report on studies of the distribution of TN and B-FN in normal adult tissues and in benign and malignant tumors, as well as on the levels of the B-FN mRNA in cultured fetal and non-fetal human fibroblasts originating from different tissues. B-FN has an extremely restricted distribution in normal adult tissues, is not expressed in benign tumors, but is greatly expressed in a high percentage of malignant tumors. On the contrary, human TN in normal adult tissues is less restricted than what has previously been reported and it is largely expressed in a number of both benign and malignant tumors. Moreover, we observed a great variability in the relative amount of B-FN mRNA among the 17 normal human fibroblast cell lines tested. We found very low levels in non-fetal skin fibroblasts and higher levels in fetal lung fibroblasts. We also found differences in the relative amounts of B-FN mRNA between fibroblast cell lines originating from the skin and the lung of the same subject.

Adult↗

Gamma heavy chain disease associated with Hodgkin's disease. Clinical, pathologic, and immunologic features of one case.

This report describes the clinical, pathologic, and immunologic features of a patient with gamma heavy chain disease (gamma-HCD) associated with Hodgkin's disease (HD). The diagnosis of gamma-HCD was established by serum electrophoresis and immunoelectrophoresis and confirmed by biochemical analysis of patient's serum showing the presence of an incomplete gamma chain, with an approximate molecular weight of 40 kilodaltons. The diagnosis of HD rested upon the presence of systemic lymphadenopathy, the typical histologic pattern and reactivity of Reed-Sternberg cells with the LeuM1-CD15 monoclonal antibody. The two diseases developed independently, in the absence of any immunosuppressive treatment. Furthermore, there was some evidence suggesting that HD tissue was not responsible for the production of the incomplete gamma chain. This and similar cases may provide a model for a better understanding of the events leading to the simultaneous outgrowth of two lymphoid neoplasias in the same patient.

Antibodies, Monoclonal↗

Lymph node biopsy in the diagnostic and prognostic assessment of patients with HIV infection.

Thirty-three anti-HIV positive patients with persistent generalized lymphadenopathy (PGL) who underwent lymph-node biopsy were studied to assess the diagnostic and prognostic relations existing between clinical, histological and laboratory findings. Patients were also examined for known risk factors, laboratory and bacteriological tests, and mononuclear cell surface marker analysis. 4 histological types were identified according to Ràcz's classification. At biopsy, there were 21 cases of LAS (64%), 6 cases of ARC (18%) and 6 cases of AIDS (18%); a clear prevalence of type 1 was evidenced in LAS/ARC patients, while only type 4 was present in the AIDS group. An ARC type 3 patient developed manifest AIDS within 13 months from biopsy. These results suggest that anti-HIV positive asymptomatic patients with PGL apparently do not require lymph node biopsy, as none of them showed histologic findings suggestive of opportunistic infections, malignant lymphoma or Kaposi's sarcoma. On the contrary, lymph node biopsy can play a diagnostic and prognostic role in anti-HIV negative subjects with PGL, and in ARC and AIDS patients.

AIDS-Related Complex↗

Intrapleural natural beta interferon in the treatment of malignant pleural effusions.

Effusion recurrence is a major problem in the palliative care of patients with disseminated cancer. Thirty-two patients with recurrent malignant pleural effusions were treated with intracavitary natural beta-interferon at increasing doses (5-20 million units) for a maximum of three administrations. Among 29 evaluable patients, 11 showed complete (27.6%) or partial (10.3%) remission. No difference in response rate was observed according to sex, age, and histological type. All the responses were observed in patients with an effusion volume less than 1,000 ml (11/16; 68.8%). No side effect was observed. In conclusion, intrapleural beta-interferon is promising as a palliative in the treatment of recurrent malignant effusions.

Adenocarcinoma↗