がんの科学と治療

Objective: To study tumor size and tumor stage alteration during the first period of mammography screening three randomized samples of breast cancers were sorted out from 1993, 1995, and 1997 and a control group from 1987 two years before screening was introduced in 1989 in the Stockholm Gotland County. Among 2080 patients 989 representing the screened age 50 - 69 years were analyzed in the two age groups 50-59 and 60-69 years. Women were called for screening every 2 years.
Study Design: Tumor size was divided into three size groups: ≤ 10 mm, 10-20 mm, and > 20 mm. From the numbers counted in each group the percent was calculated and the distribution presented in figure bars and numerically in tables. The development during the three years was followed.
Results: In the 1993 sample a significant reduction in tumor size > 20 mm was observed compared to the control group (P<0.001) and was accompanied by an increase in tumors for intermediate tumor size 10-20 mm in the screened age group 60-69 years (P<0.05). There was a significant increase of more favorable tumor stages (Stage I) (P<0.02) and reduction in Stage IIA (P<0.001). In 1995 a similar but reduced tendency was found and in 1997 the difference found so far was equilibrated but a significant increase in tumors ≤ 10mm appeared for the first time in the screened age group 60-69 years. Conclusion: The reduced numbers of tumors > 20 mm found after start of screening explains that screening has yielded about 50% of such tumors compared to the controls of which most are tumor stage II-III. At the same time as screening continues there is first a transient increase in intermediate tumors size and finally an increasing numbers of small tumors ≤ 10 mm resulting in more favorable tumor stages.

Breast cancer is leading cause of mortality among women, resulting in more than half a million deaths worldwide each year. Unfortunately, the recovery rate of advanced breast cancer by current available drug treatment is till unacceptably low. Chemotherapy is the main stay of cancer treatment and most of the drugs cause general toxicity to any non-proliferating cells, which can severely limit the therapeutic values of these drugs. Tetrahydroisoqinoline derivatives (THIQs) were identified as subtype selective estrogen receptor antagonists/agonists hence, potential therapeutic agents for breast cancer. Substituted THIQs were synthesized and well characterized. Antiproliferative activity against human ER (+) MCF-7 (Breast), ER(-) MDA-MB-231 (breast) and Ishikawa (endometrial) cancer cell lines were studied after 72 hours drug exposure employing CellTiter-Glo assay at concentrations ranging from 0.01- 100,000 nM. The activities of these compounds were compared with Tamoxifen (TAM). In-vitro results indicated that most of the compounds showed better activity than TAM. The most active compounds obtained in this study were 6a, 6b, 6d and 6j (IC50=0.63, 0.23; 0.93, 0.21; 043, 0.01; 0.7, 0.02 μg/ml) against MCF-7 and Ishikawa cell lines, in comparison to Tamoxifen activity (IC50=5.14, 4.55 μg/ml). The newly synthesized molecules were docked in the active sites of the ER-α (PDB: 3ERT) and ER-β (PDB: 3ERT) crystal structures and probable binding modes of this class of molecules were determined.

Introduction: Glucose is a simple sugar that plays an important role in energy production in biological systems. However, it has been linked to many long-term health problems including the risk of heart disease and stroke, erectile dysfunction in men and pregnancy complications in women, and damage to the kidneys, nerves, eye and vision. Also, the underlying mechanisms of diabetic complications are poorly understood.
Methods: In the present study, D-glucose-induced cytotoxic, genotoxic, and apoptotic effects were studied using MCF-7 cells as an in vitro test model. Cell viability was determined by MTT assay. Genotoxic damage was tested by the means of alkaline single cell gel electrophoresis (Comet) assay. Cell apoptosis was measured by flow cytometry assessment (Annexin-V/PI assay).
Results: The results of MTT assay indicated that D-glucose significantly reduces the viability of MCF-7 cells in a dose and time-dependent manner. Similar trend was obtained with the trypan blue exclusion test. Data obtained from the Comet assay indicated that D-glucose causes DNA damage in MCF-7 cells in a dose-dependent manner. The flow cytometry assessment (Annexin V FITC/PI) showed a strong dose-response relationship between D-glucose exposure and annexin V positive MCF-7 cells undergoing early apoptosis.
Conclusion: Taking together, these data provide clear evidence that D-glucose induces cytotoxic, genotoxic, and apoptotic effects on MCF-7 cells. This finding represents the basis for further studies addressing the pathophysiological mechanisms of action of glucose overdose.

Background: Non-small cell lung cancer (NSCLC) in young patients is uncommon and is thought to constitute a distinct oncological entity with characteristic clinicopathological patterns. The objective of our work is to analyze presentation, management and outcome data of NSCLC patients aged less than 45 years and compare them with those of patients over 45 years old.

Materials and methods: We retrospectively reviewed all patients treated for metastatic NSCLC over the period of 5 years (2007–2012) at the Medical Oncology Department of Hassan II University Hospital. The clinicopathological characteristics of patients aged less than and over 45 years old were compared and evaluated for prognostic significance regarding outcome.

Results: The data for NSCLC patients (116), of whom 15 were aged <45, were retrieved. In comparative analysis, there was a trend for an increased proportion of females with lung cancer among the younger individuals (56% in the younger vs 23 % in the older age group, p=0.008). History of smoking was less frequently retrieved in younger patients (40%) than patients aged over 45 (81.2%) (p=0.005).No differences were found for hemoptysis, performance status, histology or number of metastatic sites. More patients in the young group (86.7%) received biotherapy with platinum based regimen than in older patients (50.5%); (p= 0.008).The mean number of cycles was 2.6 per patient. The Progression free survival (PFS) and overall survival (OS) were not significantly different (median PFS: 6.0 vs 5.0 months; p=0.9 and median OS 7.0 vs. 5.0 months, p=0.14).

Conclusion: This retrospective study failed to present strong evidence that NSCLC among young individuals constitutes a distinct clinicopathological entity. The limited number of younger patients treated here, suggests designing other studies to shed light on this controversial subject.

Introduction: Epidemiological evidence shows that variations in estrogen receptor (ER) genes cause alterations in the effect of estrogen in breast tissue, which may explain individual variations in mammographic density. High mammographic density (HMD) is an important risk factor for breast cancer.

Objective: To evaluate the association of clinical features and polymorphism of ERα-(GT)n gene and mammographic density in post-menopause women. Casuistry and method: According to ACR-BIRADS criteria, 463 post-menopause women of ages between 45 and 60 have been prospectively analyzed through computer objective assessment, being 308 with HMD and 155 with non-dense breasts (Control group). The participants had not used hormone therapies 12 months prior to assessments and had no personal history of breast cancer. Risk factors for breast cancer considered by other studies also have been analyzed in this paper. Peripheral blood samples have been obtained to extract DNA and to analyze the presence of polymorphism in the ERα-(GT)n promoter region.

Results: From the risk factors considered for breast cancer, there was association with high mammographic density in: age (p=0.005); waist circumference (p=0.001); number of pregnancies (p=0.007); age at 1st birth (p=0.035); family history (p=0.035); time after menopause (p=0.007), and body mass index (p=0.022). Differences between HMD and controls for distribution of tanden repeats polymorphism genotype STRs-(GT)n (p=0.151) was verified as non-significant.

Conclusion: Our data showed that age, waist circumference, number of pregnancies, age at 1st birth, family history of breast cancer, time after menopause, and body mass index were associated to post-menopause HMD. However, tanden repeats polymorphism (GT)n may not be associated with HMD but it will be necessary studies with a larger number of cases as we have obtained few genotypes (GT)n higher than 17 repeats.