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Biomedical subjects

C Rubini

Publications and source records attributed to C Rubini.

At least 73 records · Page 4Linked to original sources
PubMed1991

The value of necropsy in oncology.

The effectiveness of diagnostic procedures in cancer patients was evaluated by comparing clinical with necropsy findings. Necropsy and clinical records of 102 patients were reviewed for primary site and histology of tumour, metastatic sites, presence of second neoplasms, associated non-neoplastic diseases, terminal illness and cause of death. Major discordances between clinical and postmortem findings were found in 34 (33%) cases: in 10 of these a correct clinical definition of site and histology of the primary tumour would have resulted in a change of management and prognosis; in 4 cases in which a major non-neoplastic pathology had been responsible for death, correct diagnosis might have resulted in prolongation of survival. Spread of disease was generally underestimated, even for metastases in clinically accessible organs. Even more disappointing were the clinical data related to terminal illness and cause of death (43% overall concordance).

Autopsy↗
PubMed1990

Percutaneous intrathoracic aspiration biopsy.

An analysis of 617 percutaneous intrathoracic aspiration biopsies (PIAB) performed on 587 patients with pulmonary and mediastinal lesions between 1954 and 1985 are presented. The effectiveness of the procedure between 1954 and 1980 and between 1981 and 1985 with a positivity of 71.6% and 84.9%, respectively, was compared. These results are statistically significant and reflect improvement in the technique employed. A greater positivity was found where the lesion measured 2 to 3 cm in diameter. Complications for this series were 7.8%. In diffuse infiltrating lesions, the positivity is less than that obtained for the whole series, and the risk of developing a pneumothorax is greater. The false-negative cases include those in which an inadequate sample was obtained for diagnosis (13.9% of the total series) and samples containing elements of the chest wall or blood (5.2%).

Adolescent↗
PubMed1989

Morphometric study of chromatin pattern in freeze-fractured rat liver nuclei during malignancy evolution.

Computerized image analysis was performed on freeze-fractured nuclei isolated from normal rat liver and rat liver with diethylnitrosamine induced hepatocarcinomas. Chromatin particles belonging to heterochromatin and interchromatin nuclear regions were measured, distributed into histograms and statistically processed. The ratio between nucleosome filaments (5-10 nm range diameter) and solenoid fibres (25-35 nm range) and Tukey's fitting line were calculated. The N/S ratio shows an inverse trend in treated nuclear samples with respect to the controls indicating that the malignancy progression is accompanied by characteristic derangement of the chromatin arrangement which can be evaluated by morphometric analysis.

Animals↗
PubMed1986

Transforming activity of DNA extracted from BKV-transformed hamster cells after passages in culture.

Primary fetal rat fibroblasts (FRF cells) were transfected with DNA extracted from BKV-transformed hamster kidney cells at low passage after transformation (HKBKlp cells) and at high passage after transformation (HKBKhp cells). Two transformed rat cell lines were obtained, FRF-DNA-HKBKlp cells and FRF-DNA-HKBKhp cells, transformed by DNA extracted from HKBKlp cells and HKBKhp cells, respectively. They were characterized by a number of biological properties and by tumorigenicity and metastatic ability in newborn hamsters. The two transformed FRF cell lines exhibited exactly inverted properties in comparison with HKBK cells, in particular FRF-DNA-HKBKlp cells showed a low level of nuclear T antigen and a diffuse appearance of TSTA at the cell surface, whereas FRF-DNA-HKBKhp cells demonstrated a high level of T antigen and the capping of TSTA in the cell membrane. The tumorigencity and the metastatic ability were greater with FRF-DNA-HKBKlp cells, while FRF-DNA-HKBKhp cells appeared to be less tumorigenic and metastatic in newborn hamsters.

Animals↗
PubMed1983

Isolation and characterization of cell lines derived from hamster kidney cells transformed by BK virus, and transforming activity of their DNA.

Eight cell lines obtained from BK virus-transformed hamster kidney cells were characterized by some biological parameters as presence of BKV T antigen, growth properties and tumourigenicity. The transforming ability of their DNA on primary foetal rat fibroblasts was then studied, and transformed rat cells were characterized by the same biological parameters as above. Transformed hamster cells showed no correlation among presence of virus, growth properties and tumourigenicity; DNA from normal hamster kidney cells and from two BKV-transformed cell lines induced transformation on rat fibroblasts, but presence of BKV T antigen was detected only in one DNA-transformed rat cell line. The role of cellular and viral genes on neoplastic transformation is discussed.

Animals↗
PubMedDate not supplied

Correlation between tumour antigens and malignancy in BKV-transformed hamster cells.

Hamster kidney cells transformed by BK virus (HKBK cells) were studied in order to correlate the membrane tumour antigens to the metastatic capability. The presence of the tumour associated surface antigen (TASA) on the surface of HKBK cells was detected by the immunofluorescence test on live cell suspensions. The metastatic ability was investigated by inoculating HKBK cells subcutaneously (s.c.) into newborn hamsters, s.c., intraperitoneally (i.p.) and in the foot pads into adult hamsters, and s.c. into adult hamsters previously immunized with surface antigens extracted from HKBK cells. The results indicate that there is a correlation between the appearance of tumour antigens on the cell surface and the metastatic ability: HKBK cells at low passage (about 30 subcultures after transformation) showed the capping of TASA in the cell membrane and low metastatic ability, whereas HKBK cells at high passage (about 130 subcultures after transformation) exhibited a diffuse appearance of TASA in the cell surface and were highly metastatic.

Aging↗
PubMedDate not supplied

Cyclooxygenase-2 expression in oral squamous cell carcinoma.

Cyclooxygenase (COX), the key enzyme in prostaglandin cascade, is expressed in two isoforms: the constitutive COX-1 and the inducible COX-2. Hyper-expression of COX-2 has been implicated in the pathogenesis of colon-rectal cancer in humans but it appears to play a significant role as a tumour progression factor also in other forms of human cancer, including oral cancer. The aim of this study was to analyze the expression of COX-2, at the protein level, in 45 cases of oral squamous cell carcinoma. Standard immunohistochemical streptavidin-biotin peroxidase analysis was carried out with highly specific antibody against human COX-2 and cell specific markers, in 45 oral squamous cell carcinomas. Our study revealed a moderate to high COX-2 expression in 35 out of the 45 oral squamous cell carcinoma specimens (77.8%). COX-2 expression appeared particularly abundant in the superficial ulcerated layers of relatively well differentiated carcinomas. However, we were unable to assess any statistically significant association between COX-2 hyper-expression and tumor site, tumor grading, tumor size, presence of lymph node metastases, tumor stage and age at onset, respectively. Interestingly, COX-2 expression was detected not only in areas of epithelial dysplasia adjacent to the primary layers (86% of the cases) but also in normal-appearing epithelium at the boundaries of squamous cell carcinoma (77%), indicating a possible involvement in tumour progression by the apparently normal tissue surrounding the lesion. Moreover, intense COX-2 staining was observed in endothelial cells of intra-tumour vessels and extra-tumour vessels adjacent to the tumour nests, in a high proportion of cases (82%). COX-2 positivity was associated with CD34 and VEGF positivity, indicating that these vessels were probably neo-formed ones. From this study as well as from other works, it appears that indeed COX-2 is over-expressed in this important human malignancy. However, further studies are necessary to understand the exact magnitude of this over-expression and, mostly, the possible role of COX-2 in the pathogenesis and progression of oral cancer.

Aged↗
PubMedDate not supplied

Potential markers of tongue tumor progression selected by cDNA microarray.

Squamous cell carcinoma (SCC), the most frequent malignant tumor of the oral cavity, generally exhibits a poor prognosis and metastases are the main cause of death. This tumor often arises from pre-malignant lesions. To date, it is difficult to predict if and which pre-malignant lesions may progress into oral SCC using traditional methods. For these reasons, several studies are trying to identify markers useful in the progression of pre-malignant lesions and tumors. To define the genetic expression profile of tongue tumor progression we compared 9 dysplasias (DS), 8 tumors without metastasis (TWM), 11 metastasizing SCCs (MT) of the tongue, and a baseline of 11 normal tissues by using cDNA microarray containing 19.2 K clones. We initially applied hierarchical agglomerative clustering based on information from all 6026 clones. Results were obtained by performing a two steps analysis: a Significance Analysis of Microarray (SAM) and a Gene Ontology search. One hundred and five clones have statistically significant different expression levels (FDR < 0.01) between DS and TWM, whereas 570 genes have statistically significant difference expression levels between TWM and MT (FDR < 0.01) as detected by SAM. By filtering with FatiGo only 33 genes were differentially expressed in TWN, respect to DS, whereas 155 genes were differentially expressed in MT respect to TWM. We detected some genes which encode for oncogenes, transcription factors and cell cycle regulators as potential markers of DS progression. Examples are BAG4, PAX3 and CCNI, respectively. Among potential markers of metastases are some genes related to cell mobility (TSPAN-2 and SNTA1), intercellular adhesion (integrin alpha 7) or extracellular matrix components (ADAMTS2 and cathepsin O). Additionally, under-expressed genes encoded apoptosis-related proteins (PDCD4 and CASP4). In conclusion, we identified several genes differentially expressed in tumor progression which can potentially help in better classifying pre-malignant lesions and tongue SCCs.

Adult↗
PubMedDate not supplied

Bone marrow histopathological and molecular changes of small B-cell lymphomas after rituximab therapy: comparison with clinical response and patients outcome.

This study correlates bone marrow changes after Rituximab (RTX) treatment with the clinical characteristics and outcome of 26 patients with small B-cell lymphomas. The percentage, phenotypic profile and clonality pattern of bone marrow lymphoid infiltrate were analysed before and after RTX treatment. Clinical, histological and molecular responses to RTX were correlated to the clinical outcome of the patients. Sixteen out of twenty-six patients obtained a complete clinical remission (CR). A favourable histology--follicular lymphoma (FL), hairy cell leukaemia (HCL) and marginal zone lymphoma (MZL)--was associated with a higher frequency of clinical CR and histological remission (HR), in comparison with mantle cell lymphoma (MCL), chronic lymphocytic leukaemia (CLL) and lymphoplasmacytic lymphoma (LPL). Two patterns of bone marrow HR were observed: 1) complete lymphoid cell disappearance (9 patients); or 2) nodular/interstitial T-cell infiltration (10 patients). Three histological persistence (HP) patterns were observed: 1) persistence of CD20+ small lymphoid cells in 1 patient with MCL; 2) loss of CD20 antigen expression in 4 patients with CLL; or 3) persistence only of clusters of monotypic plasma cells in 2 patients with LPL. CR and HR were strongly correlated. The percentage of lymphomatous infiltrate after RTX was higher in patients who subsequently died of the disease. Molecular response showed no correlations with the further clinical course in 12 patients achieving a complete clinical remission. In conclusion, bone marrow morphological and immunohistochemical analysis with a restricted panel of antibodies is useful to avoid 42% false positive and 85% false negative interpretations. Persistence of monoclonality after RTX might have a role in evaluating the molecular pattern of CD20-negative clones that can emerge after RTX as a tumoral escape to therapy.

Adult↗
PubMedDate not supplied

Genetic analysis of oral squamous cell carcinoma by cDNA microarrays focused apoptotic pathway.

We investigated mRNA expression of the genes involved in the apoptotic mechanism in oral squamous cell carcinoma (OSCC) by cDNA microarray. The aim of this study was to identify genes mainly involved in tumorigenesis, comparing the difference of gene expression in neoplastic and non-neoplastic tissues. Eight frozen samples of OSCC and the corresponding normal oral mucosa were treated to obtain mRNA. The mRNA extracted from these specimens was converted into cDNA and analyzed with SuperArray GEArray Q Series Human Apoptosis Gene Array kit. Our results showed that in OSCC there is a different expression of CRADD, FADD, ATM and APAF-1 genes compared to normal mucosa. Real-Time PCR, and Western blot analysis were performed on a separate cohort of patients in order to confirm the results obtained by DNA microarray. Our analysis of apoptotic process through microarray technology confirmed that different molecules could be responsible or favour the imbalance of apoptosis in cancer tissues. Microarray technology has made it possible to analyze the expression of multiple genes in a single experiment. However, most commercial array kits, designed to include as many genes as possible, produce a vast amount of data that often is difficult to interpret. In addition, the cost of equipment is often prohibitive. In contrast, the focused kit used was a complete, affordable and effective method to improve knowledge of molecular specific pathways.

Apoptosis↗
PubMedDate not supplied

Expression of bcl-2 in oral squamous cell carcinoma: an immunohistochemical study of 90 cases with clinico-pathological correlations.

Apoptosis is a genetically determined process playing an active role in tissue size regulation, morphogenesis and removing damaged cells that could be potentially dangerous for their host. Several agents involved in apoptosis regulation, such as the bcl-2 family components, act as oncogenes and are involved in oral carcinogenesis. Aim of this study is to explore bcl-2 immunoreactivity in oral cancers and to assess its potential clinico-pathological implications. Ninety oral squamous cell carcinoma and 10 normal mucosal formalin-fixed, paraffin-embedded samples were analysed for bcl-2 expression by immunohistochemistry. Normal oral mucosa showed a cytoplasmic pattern of bcl-2 immunoreactivity in the basal cell layers. Seventy-four cases of carcinoma (83%) showed no immunoreactivity, at variance with 16 cases (17%) manifesting consistent cytoplasmic positivity. Overall, the peripheral cells of differentiating epithelial tumour islands were intensely stained, with decreasing immunoreactivity toward the centre of the neoplastic nests. Fully keratinised tumour cells showed inconspicuous or absent bcl-2 immunoreactivity. No statistically significant correlations could be demonstrated between bcl-2 immunoreactivity and the sex of the patients, tumour size and with the occurrence of lymph node metastases. Though a direct correlation was found between bcl-2 immunoreactivity and increasing tumour stage, this did not reach statistical significance. Furthermore, G1 and G3 tumours displayed higher percentages of bcl-2-positive cells in comparison with G2 neoplasms and the different distribution of bcl-2 immunoreactivity in G2 and G3 was statistically significant (p<0.05). Finally, patients with absent or low (scores 0 and 1) bcl-2 immunoreactive tumours manifested poorer overall survival rates in comparison with patients with moderate or high (scores 2 and 3) bcl-2 immunoreactive tumours but the difference was not statistically significant. In normal oral mucosa bcl-2 protein is selectively present in the basal cell layers and possibly participates in the control of the terminal keratinocytes differentiation. The study of bcl-2 immunoreactivity possibly may be useful for better characterising and predicting the prognosis of oral SCC but cooperative studies are needed to assess its applications in the clinical practice.

Aged↗
PubMedDate not supplied

Immunocytochemical detection of hMSH2 and hMLH1 expression in oral melanoma.

BACKGROUND: The DNA mismatch repair system (MMR) plays an important role in the maintenance of genomic stability. To date few studies have been performed on hMSH2 and hMLH1 expression and melanoma of the head and neck region. A study of two cases revealed no mutations of the mismatch repair genes hMSH2 and hMLH1. MATERIALS AND METHODS: To verify the possibility of implication of hMSH2 and hMLH1 alterations in melanocytic cancerogenesis, the authors examined the protein expression pattern of hMSH2 and hMLH1 by immunohistochemistry in 9 paraffin-embedded oral melanoma. RESULTS: One case (11%) showed nuclear positivity for hMSH2, 3 cases (33%) showed cytoplasmic positivity, and five cases (55%) showed no staining in the tumoral cells, even if normal squamous epithelium available in this section showed a nuclear positivity. Four cases (44%) showed no hMLH1 staining in the tumoral cells, even if normal squamous epithelium available in this section showed a nuclear positivity. Two cases (22%) showed nuclear positivity, and three cases (33%) showed cytoplasmic positivity. CONCLUSIONS: The analysis of mismatch repair genes can be a new molecular diagnostic tools for the detection of patients at high risk of developing melanoma and other neoplasia, or metastasis and recurrences.

Adaptor Proteins, Signal Transducing↗
PubMedDate not supplied

The human multidrug resistance gene (MDR-1): immunocytochemical detection of its expression in oral SCC.

A large number of oral cancer patients show poor or partial response to chemotherapy and the mechanisms are poorly understood. At present, an MDR-1 product, the P-170 glycoprotein, is the best known of the P-170 family and is involved in resistance to natural product-based chemotherapeutics, including taxanes, anthracyclines, vinca alkaloids, podophyllotoxins and camptothecins. Although several reports suggest that P-170 is clinically relevant in haematological malignancies, its role in solid tumours is not well understood. Its overexpression has been found to be correlated with the poor outcome observed in patients treated with chemotherapy and presenting drug resistance. The aim of this study was to detect the protein expression patterns of MDR-1 product by immunohistochemistry in formalin-fixed-paraffin-embedded tissues. For these reasons, 30 oral SCC and 6 healthy oral mucosa specimens were tested with anti-P-170 antibodies using standard streptavidin-biotin-peroxide technique. Immunohistochemistry demonstrated that 4 cases (66.6%) of normal oral mucosa and 24 cases (80%) of oral SCC showed positivity. Four cases (13.4%) showed strong positivity in tumour areas and complete negativity in normal epithelial cells adjacent to the tumour. No staining was observed in stromal structures, with the exception of the lymphocytic compartment that showed a strong staining as reported in literature for CD56+ and CD8+ cells. Four G1 tumours (33%) and 2 G3 tumour (33%) showed strong positivity in areas with a higher degree of differentiation. P-170 positivity in normal epithelial cells of smoker patients, in differentiated area of neoplasia and negativity or zonal positivity in undifferentiated area of tumour suggested that activation of the MDR-1 gene or selection of intrinsically multidrug resistance neoplastic cells may occur at early stages of tumorigenesis of oral cancers, before the real evidence of cellular transformation. Thus the contact with possible chemical carcinogens, such as those of tobacco smoke, may induce activation of MDR-1 gene. This study was conducted only on untreated carcinomas so for this reason it cannot indicate the real incidence of acquired multidrug resistance. The data of MDR-1 product expression by immunohistochemistry in oral SCC might suggest that an overexpression of this protein could constitute a hallmark of potential more aggressive phenotype for this type of neoplasia and a rapid method for pre-screening tumours for a constitutive multidrug resistance in order to orientate the cancer treatment.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMedDate not supplied

Microvessel density (MVD) and vascular endothelial growth factor expression (VEGF) in human oral squamous cell carcinoma.

BACKGROUND: Carcinogenesis is thought to be dependent on neovascularization. Vascular endothelial growth factor (VEGF) is a glycoprotein that has the capability of increasing vascular proliferation and permeability. VEGF has been found to be expressed in several different types of tumours and it may contribute to the progression of malignant tumours. Increased microvessel density (MVD) has been described in oral squamous cell carcinoma (OSCC) and seems to be related to patient prognosis. MATERIALS AND METHODS: Fifty-two cases of OSCC were evaluated in the present study. Immunostaining for VEGF and Factor-VIII was performed. The MVD was evaluated in G1, G2 and G3 tumours. RESULTS: The differences between these 3 groups were statistically significant (p = 0.0331). MVD was also evaluated in lymph-node negative and lymph-node positive cases: the differences between these two groups were statistically significant (p < 0.0001). VEGF expression was evaluated in G1, G2 and G3 tumours. The differences between the 3 groups were not statistically significant (p = 0.289), even if an increasing trend in the VEGF positivity was evident from G1 to G3. The difference of VEGF expression between tumours with and without lymph node metastases was not significant (p = 0.196). No correlation was present between intensity of VEGF positivity and histological grading or lymph-node status and between VEGF and MVD. CONCLUSION: Our data showed that MVD was correlated with grading and lymph-node status, while no similar correlation was found for VEGF.

Adult↗