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Biomedical subjects

C Botti

Publications and source records attributed to C Botti.

At least 73 records · Page 4Linked to original sources
PubMed1992

Changes in expression of alpha 6/beta 4 integrin heterodimer in primary and metastatic breast cancer.

The alpha 6/beta 4 integrin complex has been shown to be expressed in murine tissues at the basolateral aspect of most epithelial cells including the mammary epithelium, thus suggesting that this heterodimer may interact with components of the basement membrane. Because transformation of mammary epithelium frequently results in disappearance of basement membranes and loss of cell polarisation we have analysed in the present study whether expression of the alpha 6/beta 4 complex is altered in human breast tumours. The results of the present study confirm that in human mammary gland alpha 6 and beta 4 subunits colocalise at the basolateral aspect of the epithelium. While in benign breast lesions this distribution pattern remains mostly unchanged, in primary carcinomas the expression of both chains is either redistributed over the cells surface or significantly reduced. This altered pattern of expression is paralleled by the lack of detection of basement membrane laminin and collagen type IV. In metastatic lesions the expression of the heterodimer is maintained in most of the lymphnodal foci, but less frequently detected in metastasis localised in the pleural cavity and in parenchymal tissues. These findings indicate that in breast epithelium expression of the alpha 6/beta 4 heterodimer is modulated by the presence of basement membrane and is possibly influenced by microenvironmental factors as suggested by the different pattern of alpha 6/beta 4 expression in nodal and extranodal metastatic foci.

Antibodies, Monoclonal↗
PubMed1992

Hyperthermic antiblastic perfusion for the treatment of soft tissue limb sarcoma.

Eighty patients with locally advanced, high grade soft tissue sarcoma of the extremities were studied prospectively in order to determine the efficacy of hyperthermic antiblastic perfusion (H.A.P.) as the first step of a combined multimodality therapy. All of the patients have been evaluated in terms of functional results, loco-regional control and survival according to the different treatment schedules adopted. The first clinical trial employed H.A.P., followed by surgery alone. Because the results obtained were unsatisfactory, the protocol was modified to include a continuous intra-arterial (i.a.) infusion of doxorubicin (dx) or radiotherapy before surgery. The best results have been obtained with the radiotherapy-including protocol showing a conservative surgery rate of 100% and a 94% rate of loco-regional control. The disease-free, distant disease-free and overall survival rates were 68%, 75% and 70%, respectively. The importance of the treatment protocol has been confirmed in a multivariate analysis which demonstrated that the treatment protocol adopted is one of the prognostic factors with an independent value (p = 0.06).

Chemotherapy, Cancer, Regional Perfusion↗
PubMed1991

Comparative analysis of the expression of the extracellular matrix protein tenascin in normal human fetal, adult and tumor tissues.

Tenascin (TN) is a high-molecular-mass oligomeric glycoprotein of the extracellular matrix (ECM) endowed with a programmed expression in embryonic life and a neo-expression in the interstitium of some malignancies. Using monoclonal antibodies (MAbs) which identify human tenascin, we have conducted an extensive immunohistochemical analysis of TN expression in normal fetal and adult human tissues as well as in a wide variety of human tumors. Results of this study demonstrate that TN (1) is detectable in embryonic and fetal tissues at least from the 10th week of gestation; (2) is present in the interstitium of a variety of adult tissues of different embryonic origin; (3) may be neo-expressed in the stroma of benign and malignant tumors; (4) has the ability to accumulate in a highly variable manner in the ECM of tumors of the same and of different histotypes.

Adult↗
PubMed1991

Local recurrence after curative resection for colorectal cancer: frequency, risk factors and treatment.

Analysis of 498 patients with colorectal carcinoma was retrospectively reviewed to evaluate the incidence, risk factors and therapy of local recurrent carcinoma following curative resection. Complete follow-up information was obtained in all but four patients (99.2%). After a median follow up of 42 months, 64 out of 469 (13.6%) patients developed local recurrence (LR). The incidence of LR was higher in rectal than in colon cancer patients (18.3% vs 8.9%) (P less than 0.005). Separate univariate and Cox analyses for rectal patients showed tumor site (P less than 0.02). Dukes stage (P less than 0.002), and adjuvant radiotherapy (P = 0.05) determined risk of LR. For colon cancer patients risk of LR was determined by histological tumor grade (P less than 0.01). Out of 64 patients, 5 (7.8%) underwent radical excision of LR. Forty percent of these survived at 5-year (P less than 0.08). Palliative treatment (radio-chemotherapy) obtained a 5-year survival of 15.3%, with no survivors in no-treatment group. These results suggest that local recurrent colorectal carcinoma remain a difficult treatment problem. More effective combinations of surgery and adjuvant therapy are therefore mandatory to reduce the incidence of local failure in high risk colorectal patients.

Adenocarcinoma↗
PubMed1987

Prognostic significance of flow cytometry in lung cancer. A 5-year study.

Flow cytometrically determined cellular DNA content has been measured on specimens from 101 patients affected by lung cancer (40 epidermoid cell carcinoma, 22 adenocarcinoma, 21 large cell carcinoma, 11 small cell carcinoma, and seven undifferentiated carcinoma), and one by mesothelioma. Ninety-eight of 102 (96%) patients with neoplastic disease evidenced the occurrence of at least one cytometrically aneuploid cell subpopulation. Fifty-five of 102 (54%) cases evidenced the occurrence of multiclonality, that is, the presence of more than one aneuploid stem cell line. However, the incidence of multiclonality in lung carcinoma was statistically different in surgical cases (where multiple site sampling from the primary and lymph nodes was possible) in comparison to the nonsurgical ones (e.g., bronchial washing): 48/77 (62%) and six of 24 (25%), respectively. Therefore, only the 77 surgical patients were used for further analysis. The cases were classified according to the DNA index (DI) in the following way: Group A (tumors with one or more stem lines with DI ranging from 1 to 2) and Group B (tumors with at least one stem line with DI less than 1 or greater than 2). A significant correlation has been found between the cytometric ploidy condition so defined (Groups A and B) and the tumor mass doubling time (DT), Group B being associated with fast growing tumors (DT lower than 90 days). A statistically better 12-month survival rate (5-year maximum follow-up) was observed in Group A (88%) in respect to Group B (47%) and is evident in the patient survival time course. A better prognostic indication can be achieved by stratifying the patients according to both the cytometric ploidy condition and the tumor DT. Flow cytometric data can usefully contribute to the prognostic assessment of lung carcinoma provided that representative cellular material is collected by multiple site sampling.

Actuarial Analysis↗
PubMed1983

A new multiparametric classification in lung cancer patients - S.M.I.G.

The classification of bronchogenic carcinoma as a function of the prognosis is still an open field. The evaluation of stage, by use of the TNM system, and histologic cell type is not sufficient to guarantee a correct prognosis. The growth rate of the neoplasm is another important parameter. We propose a classification that takes into account the stage (S), histologic cell type (M), immune status (I) and the growth rate of the primary tumor (G): S.M.I.G. We studied 90 lung cancer patients according to the S.M.I.G. classification and we observed that their prognoses were directly correlated with their S.M.I.G. scores (the higher the score, the higher the 10-month mortality rate). The mortality rates within the first 10 months of follow-up were respectively 0%, 0%, 36.36%, 68%, 90.9% for the 5 groups obtained by S.M.I.G. The difference is statistically significant (P less than 0.0075) and there is a linear correlation between the mortality rate and the score assigned to each group (R = 0.943; P less than 0.05). The S.M.I.G. classification can predict the prognosis more efficiently than the usual classification (TNM) and histological cell type.

Adenocarcinoma↗
PubMed1983

Non-small-cell lung carcinoma: tumor characterization on the basis of flow cytometrically determined cellular heterogeneity.

Some 150 tumor specimens from 49 patients with non-small-cell carcinoma of the lung (23 epidermoid, 14 adenocarcinoma, 12 large-cell carcinoma) and three with nonneoplastic lung disease were analysed for cellular DNA content by flow cytometry. Monodispersed cells were stained with ethidium bromide and mithramycin. Normal specimens and samples from patients with nonneoplastic disease constantly yielded a single cell population with diploid DNA content. Twenty of 23 epidermoid carcinomas exhibited one or more than one aneuploid subpopulation. Ten of 12 large-cell carcinomas were characterized by one aneuploid clone and 2/12 by two aneuploid clones. Adenocarcinoma exhibited multiclonal cell subpopulations (one to five aneuploid clones). Further information has been obtained on the differential presence of clones in various tumor areas and in infiltrated lymph nodes. These tumors appear characterized by a remarkable degree of cellular heterogeneity. The cytometric ploidy level(s) and the cell population multiclonal structure yield, in comparison with, and in addition to, pathology, indications of possible clinical interest. A correlation between the clonal DNA content and a prognostic parameter such as the tumor mass doubling time has been demonstrated.

Adenocarcinoma↗
PubMed1978

[Rheologic, coagulative parameters and study of fibrinolysis in patients with coronary heart disease before and after aorto-coronary by-pass (author's transl)].

A study has been made of 31 patients with coronary heart disease where diagnosis had been clearly ascertained both from a clinical and strumental point of view. All patients had undergone aorto-coronary by-pass surgery. The controls of the parameters under observation (whole-blood and plasmatic viscosity, hematocrit, fibrinogen, euglobulin lysis, T protothrombin, T of partial thromboplastin, thromboelastogram antithrombin III, plasminogen, alfa2-macroglobulin and fractions C'3c, C'3c, C'4 of the complement) were carried out as follows: basic sample taken, I control (8th-10th day), II control (15th-20th day), III control (45th-50th day), IV control (85th-90th day) after surgical operation. A global examination of our results showed significant changes in the rheologic coagulative and fibrinolytic parameters after an aorto-coronary surgical operation. The slight tendency toward hypercoagulability met with in the basic blood sample (slight increase of whole-blood viscosity, hyperfibrinogenemy, inhibition of fibrinolytic activity) does not change significantly after surgical operation. This seems to indicate that the coronary by-pass does not in any way alter the evolution of arteriosclerosis.

Adult↗
PubMed1977

[Evaluation split renal function and compensatory hypertrophy using a radio-isotopic technique].

Using a new method for the determination of split renal function with a radio-isotopic technique (FG Hipaque I131 and PRP Hippuran I131) we sought to determine residual renal function with pre-operative studies, especially in preparation for nephrectomy, and secondly with postoperative studies of compensatory renal hypertrophy after total or partial nephrectomy and the restoration of function in the kidneys following surgery of the urinary tract. A total of 20 cases was studied. We noted marked compensatory hypertrophy after total and partial nephrectomy and the prompt return of function after procedures involving the urinary tract, on condition that any acute infection be prevented.

Adult↗
PubMedDate not supplied

The application of hyperthermia in regional chemotherapy.

To evaluate the role of hyperthermia combined with chemotherapy in the loco-regional treatment of tumors, a retrospective analysis was done with 228 limb melanoma patients treated with hyperthermic antiblastic perfusion (HAP). A series of treatment- and tumor-related prognostic factors was analyzed to establish their influence on tumor response, loco-regional control, and survival. Concerning tumor response, the logistic model showed that the number of lesions and the minimal tumor temperature (min T) maintained their individual predictive values (P < 0.000001 and P = 0.04, respectively). For loco-regional control, only the number of lesions had a significant predictive value. No direct correlation was found between the treatment-related variables and loco-regional control. However, the 5-year survival rate was significantly higher for patients who achieved a complete response (CR) (51.5%, P = 0.0033) as compared to those who did not (33.3%), providing indirect evidence of the role of the treatment. Multivariate analysis showed that both disease-free and overall survival are strongly influenced by numerous clinical variables and the min T always maintained its significance. When analyzing the subgroup of 119 patients evaluable for tumor response, the Cox model selected the tumor response as the dominant factor for both disease-free and overall survival. These data seem to demonstrate that the optimization of treatment parameters is crucial in determining the CR rate, which, in turn, positively affects the disease outcome. HAP is the treatment of choice for recurrent limb melanoma, and hyperthermia plays an important role in exploiting the efficacy of this technique.

Antineoplastic Agents, Alkylating↗
PubMedDate not supplied

Development of an objective and manual technique to study the human sperm morphology.

The aim of the present paper is to present results of sperm morphology using an objective and manual technique by video image. Experiment 1:252 spermatozoa heads were measured in a microscope and in a monitor by each of three independent observers. The results allowed the calibration of an acetate overlay according to the WHO guideline and following the strict criteria. Experiment 2: 10 morphology slides from normal and abnormal patients were studied. These slides were evaluated by three independent observers, each counting at least 200 cells using the calibrate acetate overlay. In the first experiment the calculation of the regression out-put was: constant: 0.24, standard error of Yc: 0.04, R squared: 0.96, X coefficient: 0.36, and standard error of the coefficient: 0.03. In the second experiment, it can be seen that the differences among the operators are not statistically significant and therefore the experiment is independent from the operator. In conclusion, the methodology developed in this paper for the evaluation of morphology would be a good tool for the evaluation of human sperm morphology.

Cytological Techniques↗
PubMedDate not supplied

Uptake of tritiated thymidine, deoxyglucose and methionine in three lung cancer cell lines: deoxyglucose uptake mirrors tritiated thymidine uptake.

[(18)F]-fluorodeoxyglucose and [(11)C]-methionine are tracers which are widely used in oncological positron emission tomography. This study has been designed to assess the deoxyglucose and methionine uptake behaviour in three cell lines from different lung cancer histotypes. Tracer uptake was compared with proliferative activity as determined by growth curves and tritiated thymidine uptake. Deoxyglucose paralleled thymidine in all cell lines, peaking in the lag phase, decreasing throughout the exponential phase, and reaching its minimum in the plateau phase. The correlation was statistically verified and Spearman's rho ranged from 0.79 to 0.99. The absolute methionine uptake was always highest and always peaked on day 2, followed by a quite rapid decrease. However, besides the delay in maximum uptake, methionine incorporation was also related to proliferation, although the statistical correlations were weaker. These results show for the first time a clear correlation between deoxyglucose uptake and cell proliferation in a model comparing tracer uptake in different growth phases. Although delayed, methionine uptake was also related to cell growth and its greater intensity could be of interest for clinical use.

Carcinoma, Non-Small-Cell Lung↗
PubMedDate not supplied

Biochemical characteristics and recent biological knowledge on prostate-specific antigen.

Since its identification in seminal fluid in 1971, much new information has been obtained about the biology and expression of prostate-specific antigen (PSA). PSA is a glycoprotein composed of 93% amino acids and 7% carbohydrates, with a molecular weight of about 30,000 Da. Functionally and structurally PSA is a kallikrein-like serine protease, and its physiologic role is degradation of the major proteins of seminal coagulum (semenogelin I and II, fibronectin), which leads to semen liquefaction. The PSA gene is located on the 13q region of chromosome 19, and it has a high degree of homology (more than 80%) with genes of the human glandular kallikrein (hKGK1). PSA production and expression are preferentially but not exclusively associated to the normal, benign hyperplastic and cancerous tissues of the prostate. In fact, it has been demonstrated that PSA is also present in accessory male sex glands and breast cancer. It was recently reported that PSA was also present in milk of lactating women. Many factors may influence PSA synthesis and production, and among them the most important are androgen, retinoic acid and growth factor stimulation. Significant advances have been recently made as regards the molecular isoforms of PSA. In the seminal fluid PSA seems partially bound to a serpine (protein C inhibitor), whereas in serum it is predominantly associated to alpha-1-antichymotrypsin and in a small quantity to alpha-2-macroglobulin. These new findings will have implications for the clinical application of PSA as a tumor marker for prostate cancer.

Humans↗
PubMedDate not supplied

Structure, function and gene expression of epithelial mucins.

In this review the main characteristics, i.e., structure, function and gene expression, of the different mucins are discussed. Mucin-type molecules consist of a core protein moiety (apomucin) where a number of carbohydrate chains are attached to serines and threonines by glycosidic bonds. O-linked carbohydrates form up to 80% of the molecule and the length of the glucidic side chains varies from one to more than 20 residues. At least eight mucin-like genes have been isolated so far, and the main characteristic is the presence of a central domain composed of a variable number of "tandem repeats". The sequence homology of the central domain among the different members of the mucin-type family is limited, indicating that this internal domain is unique for each mucin. Thanks to the integrated results of genetic, immunological and biochemical studies, it is now possible to identify eight apomucin genes, namely MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC5B, MUC6 and MUC7. MUC1 is the best characterized mucin and it is expressed on the apical surface of most polarized epithelial cells. The MUC1 gene has been cloned and sequenced. The MUC2 gene encodes a typical secretory gel-forming mucin which represents the predominant form in human intestinal and colon tissues. Another intestinal mucin is MUC3. The MUC4, MUC5AC and MUC5B genes have been isolated from a bronchial tissue cDNA library. The MUC4 and MUC5AC genes are mainly expressed in the respiratory tract, in gastric and reproductive mucosa, while MUC5B is highly detectable only in the bronchial glands. The MUC6 gene is expressed by gastric tissue and, recently, MUC7 has been cloned and sequenced using a salivary cDNA library.

Amino Acid Sequence↗