Until a few years ago, growth hormone (GH) and insulin-like growth factor-1 (IGF-1) were considered essential only to the control of linear growth, glucose homeostasis, and for the maintenance of skeletal muscle mass. A large body of evidence recently coming from animal and human studies has unequivocally proven that the heart is a target organ for the GH/IGF-1 axis. Specifically GH exerts both direct and indirect cardiovascular actions. Among the direct effects, the ability of GH to trigger cardiac tissue growth plays a pivotal role. Another direct effect is to augment cardiac contractility, independent of myocardial growth. Direct effects of GH also include the improvement of myocardial energetics and mechanical efficiency. Indirect effects of GH on the heart include decreased peripheral vascular resistance (PVR), expansion of blood volume, increased glomerular filtration rate, enhanced respiratory activity, increased skeletal muscle performance, and psychological well-being. Among them, the most consistently found is the decrease of PVR. GH may also raise preload through its sodium-retaining action and its interference with the hormonal system that regulates water and electrolyte metabolism. Particularly important is the effect of GH on skeletal muscle mass and performance. Taking into account that heart failure is characterized by left ventricular dilation, reduced cardiac contractility, and increase of wall stress and peripheral vascular resistance, GH may be beneficial for treatment of heart failure. Animal studies and preliminary human trials have confirmed the validity of the GH approach to the treatment of heart failure. Larger placebo-controlled human studies represent the main focus of future investigations.

Animals↗

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Abnormalities in cell cycle control in cancer and their clinical implications.

Recent studies indicate that the functions of several genes that control the cell cycle are altered during the carcinogenic process and that these changes perturb both cell proliferation and genomic stability, thus promoting cell transformation and enhancing the process of tumor progression. The purpose of this paper is to review current information on the role of cyclins and related genes in the control of the mammalian cell cycle, the types of abnormalities in these genes found in human tumors and the possible clinical implications of these findings.

Animals↗

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Biological characterization of central and peripheral primary non small cell lung cancers (NSCLC).

BACKGROUND: Non Small Cell Lung Carcinomas (NSCLC) comprise 90% of all lung carcinomas. Studies have demonstrated a preferential central (bronchus-derived) localization for squamous cells, whereas adenocarcinomas are frequently peripheral (bronchiolo-alveolus derived). It has been suggested that exposure to carcinogenic insults including cigarette smoke, may induce different types of tumors in different locations. MATERIALS AND METHODS: Forty one NSCLC patients staged according to WHO and TNM were considered for localization and biological parameters (p53 expression, cell ploidy and S-phase). RESULTS: p53 overexpression was found more frequently in central than in peripheral tumors (69% vs 39%) (p = 0.074). Central tumors were more aneuploid (69%) than peripheral ones (46%) (p = 0.03) No difference in smoking habit was observed in the two groups. CONCLUSIONS: Our results suggest that there is no apparent biological difference between these two groups of NSCLCs, and that the smoking does not play a role in either histotype determination or biological behavior.

Adenocarcinoma↗

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Analysis of 4-ABP-DNA adducts and p53 alterations in urinary bladder carcinoma.

BACKGROUND: Activated intermediates of 4-aminobiphenyl (4-ABP) are able to covalently interact with DNA to form adducts. There is a large body of evidence indicating that carcinogen-DNA adduct formation can be one of the cancer initiating mechanisms. MATERIALS AND METHODS: (4-ABP)-induced DNA damage in association with p53 overexpression and mutations were evaluated in specimens of urothelial bladder cancers from 106 patients. RESULTS: 4-ABP-DNA adduct levels resulted higher in smokers compared to non smokers, with a borderline statistical value. p53 nuclear overexpression was related to tumor grading, while no significant correlation with stage, 4-ABP-DNA adducts, smoking habit, and disease recurrence could be observed. Concerning molecular analysis, p53 point mutations were found in 17 of 106 cases (16%) and mutational pattern was significantly associated both with higher grade and stage, but no correlation was found with disease recurrence. CONCLUSIONS: These results suggest that other sources, in addition to tobacco smoke, may contribute to 4-ABP-DNA adducts formation in bladder tissue and that p53 expression/mutation cannot be considered a prognostic factor in bladder cancer.

Aminobiphenyl Compounds↗

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Evaluation of 8-hydroxydeoxyguanosine in human oral cells: the importance of tobacco smoke and urban environment.

The DNA adduct 8-hydroxydeoxyguanosine (8-OHdG) has been widely used as a sensitive biomarker for oxidative damage. To investigate the role of environmental factors on oxidative DNA damage formation, the level of 8-OHdG was determined in oral cells from 109 healthy volunteers by an immunohistochemical method. A statistically significantly higher content of 8-OHdG was detected in oral cells from smokers (111 +/- 55, n = 38) compared with non smokers (78 +/- 48, n = 71), (p < 0.01). Moreover, subjects living in an urban area showed a higher level of oxidative damage with respect to those living in a countryside-suburban area (99 +/- 53, n = 58 vs. 78 +/- 51, n = 51), (p = 0.03). No significant association was detected between 8-OHdG in oral cells and other variables such as passive smoke, oral infections, alcohol or vitamin intake and grilled food consumption. This work suggests that tobacco smoke and environmental exposure to pollutants lead to a measurable increase of oxidative damage in oral cells and confirms that the immunoperoxidase method is an appropriate approach for epidemiological analyses.

8-Hydroxy-2'-Deoxyguanosine↗

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Lead inhibits growth and induces apoptosis in normal rat fibroblasts.

The effects on normal rat fibroblasts of lead supplementation (as lead acetate) in the medium were examined. The amount of lead acetate ranged from 0.078 microM to 320 microM, at 14 concentrations. The normal level of lead in the medium was 0.060 microM, and the normal concentration of lead in the fibroblasts was 3.1 +/- 0.1 ng/10(7) cells: these represented the control conditions. On studying fibroblast proliferation and survival after incubation for 48 hours, a lead acetate dose-dependent inhibition of cell proliferation was observed, the results being shown to be significant by ANOVA (p < 0.01), and suggesting a significant dose-response relationship. Apoptosis, evaluated by quantifying cytoplasmic DNA fragments, differs significantly between the lead levels tested. The distribution in the cell cycle, evaluated by using a fluorescence-activated cell sorter, showed a dose-dependent accumulation of cells in the G0/G1 phase, with a compensatory decrease in the percentage of cells in the S phase. Moreover, the occurrence of a subdiploid peak confirmed that apoptosis was more evident when the medium was supplemented with lead acetate at concentrations of 5-20 microM. The inhibition of cell growth is probably due to a direct inhibition of cell proliferation.

Animal Testing Alternatives↗

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Diagnosis of T1 bladder transitional cell carcinoma by denaturing gradient gel electrophoresis urinalysis.

OBJECTIVE: The diagnosis and follow-up of patients with T1 bladder cancer relies invasive procedures. We developed a non-invasive method for detection of T1 bladder cancer based on a feasible non-radioactive molecular approach. MATERIALS AND METHODS: Urine DNA samples were collected from 24 patients with T1 transitional cell carcinoma (TCC) of the bladder and were processed by denaturing gradient gel electrophoresis (DGGE) analysis. Urine samples obtained from 10 individuals with no clinical evidence of genitourinary malignancy were used as controls. RESULTS: Ten patients out of 24 (41%) had p53 mutations in their tumor samples. Seven of these presented the same mutation in matched urine samples. The p53 mutation pattern found in urine was always identical to that identified in the primary tumor. Decision diagnostic criteria showed that molecular screening by DGGE of amplified DNA from urine sediment had 69.2 % sensitivity, 100% specificity, 95.8 % accuracy, 100% prediction of positive result and 95.4 % prediction of negative result, respectively. No p53 mutation was found in the urine from control subjects. CONCLUSION: DGGE analysis of urine samples could be a useful tool for the early detection of T1 bladder cancer or its recurrence, potentially leading to a reduction in the frequency of invasive procedures used for the management of this disease.

Aged↗

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[4'-epidoxorubicin: its cardiotoxicity. Possible cardiac protection with gallopamil, a drug with calcium-antagonist action].

The 4'-EPI-doxorubicin (4'-EDX) has shown antitumoral activity against a broad spectrum of human tumors. The same clinical reports have shown therapeutic activity comparable to doxorubicin (adriamycin), but a lower cardiac toxicity. 4'-EDX cardiotoxicity appears after highest cumulative doses: 935 mg/m2 bs for 4'-EDX vs 550 mg/m2 bs for adriamycin. Moreover we have observed a protective action of the calcium antagonist gallopamil. We have found an improvement in ventricular performance after using gallopamil, and a reduction of 4'-EDX cardiotoxicity. Cardiac function was evaluated by EKS, STI, echography, myocardial scintigraphy course. Our result indicates the possibility of treating tumors without serious cardiotoxic by 4'-EDX and gallopamil.

Adult↗

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[The problem of the residual cavity in postoperative bronchial fistulas].

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Bronchial Fistula↗

PubMedDate not supplied

New prognostic factors in oncology.

The relevant role played by reliable prognostic factors in oncology, at times more determining and useful than therapy, is stressed. The possibilities offered by the present biological, cellular and molecular information in this rapidly evolving field, are then considered. Factors that can play a prognostic role, dependent on the identification of oncogenes and tumor suppressor genes (TSG) hyperexpression, mutation or deletion and factors related with the determination of some parameters of cell kinetics in the neoplastic tissue (DNA index, phase S), are examined. Based on some instances, the relevance of factors examined in clinical oncology, is evaluated.

Biomarkers↗

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Immunohistochemical analysis of 4-aminobiphenyl-DNA adducts in oral mucosal cells of smokers and nonsmokers.

BACKGROUND: The "biologically effective dose markers", DNA and protein adducts, are a direct index of carcinogen induced cell damage and an indirect one of genetic susceptibility. This study aimed to examine the dose-response relationship for 4-Aminobiphenyl-DNA adducts in oral cells of smokers and non smokers. MATERIALS AND METHODS: An immunoperoxidase method with the monoclonal 3C8 antibody, which recognizes 4-Aminobiphenyl-DNA, has been used for detecting DNA damage in oral cells of 12 smokers and 12 non smokers. RESULTS: Higher staining for 4-Aminobiphenyl-DNA was detected in the cells of smokers (187 +/- 42) vs. non smokers (135 +/- 35) (p = 0.004), with a twofold range in relative staining for both groups, suggesting individual differences relevance in metabolizing carcinogens and/or repairing DNA damage. CONCLUSIONS: This non invasive method requiring small cell amounts is a tool for monitoring large groups of subjects at risk in primary prevention programs.

Adult↗