がんの科学と治療

This study investigated whether exercise associated to shark liver oil supplementation (1 g/kg b.w./day) affects tumor growth, cachexia, lipid peroxidation and proteins expression involved in cell death in Walker 256 tumorbearing rats. Animals were divided into 4 groups: sedentary tumor-bearing (W), sedentary tumor-bearing shark liver oil supplemented (WSL), exercised tumor-bearing (EW) and exercised tumor-bearing shark liver oil supplemented (EWSL). Training sessions consisted of 6 bouts, 30 seconds each with 50% body-weight load attached to the trunk followed by 1 minute of resting (jump training). Five minutes after the finish jump training the exercise groups were subjected to 30 minutes of continuous swimming with a load equivalent to 6% of body weight, 4 times a week during 8 weeks. Tumor cells were injected at the 6th training week and all groups were killed 15 days post inoculation. Tumor weight (g) in W group was of 26.50 ± 1.79 and in the WSL, EW and EWSL was of 14.08 ± 0.91, 15.60 ± 0.55 and 12.60 ± 1.07, respectively. The group W showed hypoglycemia (68.67 ± 2.12 mg/dl), hyperlactacidemia (1.49 ± 0.06 mmol/L), hypertriacylglycerolemia (161.4 ± 9.4 mg/dl) and body weight reduction (13.21 ± 2.25 g) characterizing cachexia state. The groups WSL, EW and EWSL presented reduction of tumor cells proliferation ex vivo, and the production of hydroperoxide and apoptosis was increased. Bax/Bcl-2 expression ratio was increased only in the exercised groups. Shark liver oil supplementation and exercise alone were able in to avoid the installation of cachexia state and also reduced tumor growth, but the association of both cause further effect only in the tumor growth.

Objective: CD133 is a pentaspan membrane protein expressed by the so-called cancer stem cells (CSC) in the majority of human cancers. The aim of this study was to analyze CD133 expression levels in specimens of oral cancer and to evaluate its relation with disease evolution.
Methods: Expression of the CD133 protein was evaluated by immunostaining in a series of oral squamous cell carcinoma (OSCC) and its relation with traditional prognostic indicators and the clinical outcome of patients was analyzed.
Results: CD133 expression was highly variable amongst different samples with a median percentage of positive cells of 5 (range 0 - 80; mean = 11) and CD133 staining was not detectable in tumor cells in 29 (43%) cases. No correlation was observed with age at diagnosis, gender and grading while a significant correlation was observed with tumor stage. Kaplan-Meier curves of disease-free survival displayed a significant separation between the negative and positive groups of patients (p = 0.001 by log-rank test) but CD133 staining did not confirm to be an independent predictor of clinical outcome in a multivariate analyses.
Conclusion: Expression of CD133 was detectable in the majority of OSCC samples and correlated significantly with tumor stage and the clinical outcome of patients in terms of disease-free survival. Further studies are warranted on a larger series of cases to elucidate the role of CD133 in the development and progression of OSCC and its suitability as a prognostic biomarker.

Background: Conventional methods for evaluation of cervix cytology show reproducibility problems. To solve this, there was developed a diagnostic methodology based on fractal and euclidean geometry, mathematically differentiating normality, L SIL and H SIL.
Objective: The aim of the present work is to confirm the clinical applicability of such diagnostic in a blind study.
Methods: The clinic diagnosis of 15 normal cells, 15 ASCUS, 15 L SIL and 15 H SIL was masked. Cellular nucleus and cytoplasm were evaluated calculating fractal dimension, number of spaces occupied by the frontier and number of pixels occupied by the surface of each object. The mathematical diagnosis was established and compared with the conventional diagnosis, calculating specificity, sensibility, negative likelihood ratio and Kappa coefficient.
Results: It was found that simultaneous measures of the nuclear surface and the subtraction between the frontiers of cytoplasm and nucleus, lead to differentiate normality, L SIL and H SIL. Both sensibility and specificity values were of 100 percent. Kappa coefficient was 1 and negative likelihood ratio was zero. 4 ASCUS showed mathematical measures of normality, while the remaining 11 showed values of L-SIL cells.
Conclusion: The mathematical diagnostic prove to be useful for clinical evaluation of cervix cytology, differentiating normality, L SIL and H SIL, quantifying how close it is the cell to a higher severity stage, and clearing up the undetermination of the ASCUS cells.

Relationships between the expressions of immunoglobulins by cancer cells and those of toll-like receptors were investigated through comparative gene regulation studies to understand their roles and mechanisms of action in cancer immunology. RP215 is a monoclonal antibody generated in 1987 and found to recognize the carbohydrate-associated epitope which is detected preferentially in the heavy chains of immunoglobulins expressed by cancer cells, but not in normal immune cells. In this report, RP215 was used to study interactions of cancerous immunoglobulins with toll-like receptors in the innate immunity of cancer cells. From gene regulation studies, with OC-3-VGH ovarian and C-33A cervical cancer cell lines, it was demonstrated that the expressions of cancerous toll-like receptors (TLR-2, -3, -4, -6, -7 and -9) are strongly influenced by the incubation of cancer cells with RP215 or antibodies against human IgG. For example, both RP215 and anti-human IgG were found in high correlation to up-regulate TLR-3 expressions by 2.5 and 3.5 fold, respectively, whereas those of TLR-4 and TLR-9 were downregulated by 50% to 80% of the untreated. Based on these studies, it is reasonable to postulate that cancerous immunoglobulins are highly involved to modulate the innate immunity of cancer cells to allow the growth/proliferation of cancer cells within the human body.

Objective: To examine whether chronic low level arsenic (As) exposure (11-50 μg/L) from drinking water elicits inflammation and oxidative stress.

Methods: Never-smoking pre-menopausal women (n=267) from Nadia district, West Bengal, India, were enrolled into two groups (i) control (n=122, median age 39 yr) from villages with <10 μg/L of As in groudwater, and (ii) exposed (n=145, median age 38 yr) from the same district where the groundwater As was 11-50 μg/L. As in water was measured by atomic absorption spectrophtometry with vapour generation assembly. Sputum cytology and hematology were done by standard procedures. Enzyme-linked immunosorbent assays were used to measure tumor necrosis factor-alpha (TNF-α), interleukin-6, 8, 10, 12 (IL-6, IL-8, IL-10, IL-12) and C-reactive protein (CRP) in plasma and cortisol in serum. Serum nitric oxide (NO) was measured colorimetrically, myleperoxidase (MPO) and neutrophil elastase by spectrophotometry, reactive oxygen species (ROS) by flow cytometry, and inducible nitric oxide synthase (iNOS) by immunocytochemistry.

Results: As level in groundwater was higher in endemic areas (28.32 ± 13.51 vs. 2.72 ± 1.18, p<0.05), and exposed women had lower hemoglobin, leukocyte and erythrocyte levels but elevated platelet count than control and their sputum contained increased number of alveolar macrophages and inflammatory cells. In addition, they had elevated levels of TNF-α, IL-8, IL-6, IL-12, CRP, cortisol and NO but depleted level of IL-10 with excess generation of ROS and increased expression of iNOS in the airways. Neutrophils of As-exposed subjects had elevated levels of MPO and elastase. After controlling education and family income as potential confounders, the rise in pro-inflammatory mediators in blood and excess generation of ROS in the airways were positively associated with as levels in ground water.

Conclusion: Drinking of water contaminated with low level of as for long causes pulmonary and systemic inflammation and generates excess ROS in the airways.

The spontaneous regression of cancer is still a mysterious phenomenon but an understanding of it, at least partially, could lead to new and better cancer treatment. On the basis of new data concerning cancer energy biochemistry, the authors here present a hypothesis to understand and explain the phenomenon of the spontaneous regression of cancer, together with its implications for new approaches to cancer treatment. Such treatment involves the manipulation of the energy metabolism and/or redox status of cancer cells.