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Biomedical subjects

C Botti

Publications and source records attributed to C Botti.

At least 19 recordsLinked to original sources

Breast cancer is associated with loss of the c-kit oncogene product.

The proto-oncogene c-kit encodes a tyrosine kinase receptor related to the PDGF/CSF-1 receptors. Mutations of this gene result in impairment of hematopoiesis, melanogenesis and gametogenesis. Using monoclonal antibodies to the c-kit gene product, we have analyzed its expression in normal and transformed human tissues. Unexpectedly, the receptor was found to be expressed in normal mammary epithelium. While in benign breast lesions, the c-kit gene product was detected at variable levels in 82% of the instances, in primary tumors, no product could be identified in 87% of the cases. This phenotype is maintained in metastatic foci. These findings were confirmed by paired Northern blot analysis of RNA preparations from normal and tumor tissues. These results demonstrate that the c-kit receptor may also be involved in the growth control of mammary epithelium and that this function may be impaired following malignant transformation and de-differentiation.

Blotting, Northern

A model-based study of learning and memory following transient global amnesia attacks.

Verbal learning and forgetting were studied in patients one month after an episode of Transient Global Amnesia and in normal control subjects by means of a two-stage stochastic model, which allows independent measurements of encoding, storage and forgetting. We preliminarily ascertained both the necessity and the sufficiency of the model to account for several performance scores of the two experimental groups, and then compared the learning and forgetting functions between groups. In spite of the analytical power of the statistical method adopted. Transient Global Amnesia was not found to entail persistent impairment of encoding and storage, as well as of retaining memory traces and retrieval algorhythm.

Cerebral Cortex

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

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

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

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

[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

[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

The influence of tumor lymphocytic infiltration on long term survival of surgically treated colorectal cancer patients.

Prognostic significance of host-immune response, as gathered by the degree of tumour lymphocytic infiltration (TLI), and its relationship to other prognostic variables were investigated in 361 colorectal cancer patients admitted to our Institution for curative resection from January 1960 to December 1978. The presence of a local immune reactivity was significantly related to a less advanced stage of disease and a better differentiated tumour. A poorer prognosis was detected in patients with minor or no lymphocytic infiltration. TLI was the single most important prognostic parameter, according to the Cox model and to logistic regression analysis. These findings suggest that also TLI should be considered in the current Staging System of colorectal cancer.

Adult

Extracapsular lymphnode metastases in the staging and prognosis of gastric cancer.

The aim of this study was to evaluate the influence of the degree of nodal involvement (extracapsular vs intracapsular) on survival of 121 patients radically resected for gastric adenocarcinoma with nodal metastases at the Department of Clinica Chirurgica I of "La Sapienza" University of Rome. Patients with extracapsular nodal metastases had a worse 10-year survival rate than those with intracapsular nodal involvement (7.9% vs 22.4%). A better prognosis among patients with intracapsular node metastases was observed in each p-TN subgroup. In the multifactorial analysis (3-way ANOVA) survival was correlated with the depth of invasion of the gastric wall and the degree of lymphnode involvement (p less than 0.01) but not with the level of nodal involvement (N1 vs N2). Our results suggest that the degree of nodal involvement is an important independent prognostic factor that should be considered in the current staging system for curative resection in gastric carcinoma.

Adenocarcinoma

[Tracheobronchial carcinoids: current therapeutic trends].

Tracheobronchial carcinoids are relatively uncommon neoplasms potentially curable with surgery. However, the extent of excision which results in the best long term local and distant tumour control is still controversial. A series of 522 patients who underwent surgical treatment for tracheobronchial carcinoids reported by the literature which included 52 cases of tracheobronchial neuroendocrine tumours observed between 1960 and december 1983 at the Institute of I Clinica Chirurgica of Università "La Sapienza" Rome was reviewed. Local recurrence rate range between 1% and 1.8% after major surgery and between 11.8% and 16.7%, after bronchial wall resection and endoscopic treatment respectively. Local recurrences were detected after a mean period of 110.2 month (median = 9 years). 15 years survival rate was above 70%. Long term prognosis was related to the degree of malignancy (typical or atypical forms) and locoregional (N) and distant metastases (M). Factors related to the possibility to obtain free margins by the surgical procedure (pneumonectomy/lobectomy or sleeve resections vs simple bronchial wall resection or endoscopic resection), the degree of bronchial wall involvement (endobronchial, iceberg, peripheral), the biology of primary tumour (atypical vs typical) and the presence of regional and/or distant metastases are of prognostic importance for both local and distant tumour control. The Authors describe their strategy for managing this disease: endoscopic treatment or simple bronchial wall resection are available for endobronchial typical carcinoid tumours. Atypical carcinoid neoplasms or tumours involving bronchial wall or peripheral lung parenchyma need more extended resection and lymphadenectomy.

Bronchial Neoplasms

[Age as a prognostic factor following excisional surgery for colorectal cancer].

On a series of 369 patients with colorectal cancer who underwent curative resections at the I Instituto di Clinica Chirurgica della Università "La Sapienza" of Rome between 1960 and 1980, age was related to survival. All patients were followed for a minimum of ten years; 79 of them were aged over 65 years and 290 under at the time of the operation. The survival was correlated to the age and to other prognostic parameters: post surgical stage (TNM UICC classification) degree of differentiation of the tumour (NG--Black classification), degree of lymphocytic infiltration of neoplasm (LI Black classification) as expression of immunological immune-response of the host. Patients less than 65 years old had a better survival than patients greater than = 65 years old (median survival 72 months and 44 months respectively) (p = 0.006). These differences where true in subgroups with stage 2 of disease (p TNM UICC) and a favourable immunological reactivity (LI greater than = 2). These results suggest a possible independent role of age in defining the outcome of patients with colorectal cancer.

Age Factors

[Immediate breast reconstruction and oncologic criteria: our current definition].

After a review of the literature, the authors attempt at a definition of the oncologically safe candidate to an immediate reconstruction after modified radical mastectomy for breast cancer. The analysis of the natural history of locally recurrent breast cancer indicates that the potential for its masking is negligible. Survival curves of patients submitted to immediate breast reconstruction are similar to those reported for historical controls. The ideal candidate for an immediate reconstruction is a stage I (negative axillary nodes) patient. As immediate breast reconstruction does not alter the prognosis of breast cancer patients nor does it harm the use of adjuvant therapies, the authors believe that even a well motivated stage II (positive axillary nodes) patient should be considered as a candidate for an immediate reconstructive procedure.

Breast