Adipose derived stem cells exert immunomodulatory effects on natural killer cells in breast cancer

Objective: Adipose derived stem cells [ASCs], as one of the important stromal cells in the tumor microenvironment, are determined with immunomodulatory effects. The principle aim of this study was to evaluate the immunosuppressive effects of ASCs on natural killer [NK] cells

Materials and Methods: In this experimental study, we assessed the expressions of indolamine 2, 3-dioxygenase [IDO1], IDO2 and human leukocyte antigen-G5 [HLA-G5] in ASCs isolated from breast cancer patients with different stages as well as normal individuals, using quantitative reverse transcriptase-polymerase chain reaction [qRT-PCR]. Immunomodulatory effects of ASCs on the expression of CD16, CD56, CD69, NKG2D, NKp30, NKG2A and NKp44 was also assessed in peripheral blood lymphocytes [PBLs] by flow-cytometry

Results: Our result showed that IDO1, IDO2 and HLA-G5 had higher mRNA expressions in ASCs isolated from breast cancer patients than those from normal individuals [P>0.05]. mRNA expression of these molecules were higher in ASCs isolated from breast cancer patients with stage III tumors than those with stage II. The indirect culture of ASCs isolated from breast cancer patients and normal individuals with activated PBLs significantly reduced NKG2D+ and CD69+ NK cells [P<0.05]

Conclusion: Results of the present study suggest more evidences for the immunosuppression of ASCs on NK cells, providing conditions in favor of tumor immune evasion

Incidence of breast cancer in Fars province, southern Iran: a hospital-based study

Breast cancer is still considered as one of the most common female cancers worldwide regardless of the countries' level of development. This study determines the incidence of breast cancer in Fars Province, Southern Iran. This study used patients' records from Shiraz University of Medical Sciences Cancer Registry Centre, which is a Hospital- Based Registry of Nemazee Hospital. Data were recorded based on International Classification of Diseases for Oncology [ICD-O] and compromised all invasive cancers in ICD-10 categories of C- 00 to C-80. The findings were shown as the number of cases by site [ICD-10] and gender, with crude incidence [CRs], agespecific incidence and age-standardized incidence rates [ASRs] per 100,000 persons per year, performed by direct method using the world standard population. The age group of 40-49 years had the highest rate of breast cancer and naturally most cases were post-menopause ones. Most cases were diagnosed in moderate differentiated state with an increasing trend. Early diagnosis of in situ neoplasms has not increased over time in comprised with malignant cases. The number of diagnosed cases has sharply increased after year 2004 especially during post-menopause period. As the number of diagnosed cases has increased during postmenopausal period, screening and health programs seem necessary for menopause women

Status of estrogen and progesterone receptors in various phases of the menstrual cycle in breast cancer

Expression of hormone receptors is routinely evaluated in predicting tumor response to hormone therapy in breast cancer patients. Normal female genital organs show cyclic changes in the expression of estrogen and progesterone receptors. This study was designed to assess variations in estrogen and progesterone receptor expression rates in breast cancer patients, who were operated in different phases of the menstrual cycle. From 2001 through 2004, 161 premenopausal patients with breast cancer, who were operated on, were enrolled into this study. Immunohistochemistry for the expression of estrogen and progesterone receptors was performed on their tumor paraffin blocks, using antibodies against estrogen and progesterone receptors. Estrogen receptor expression was seen in 24 out of 30 cases [80%] in early luteal phase, which was significantly higher than that of those operated in early follicular [53%], late follicular [51%] and late luteal [49%] phases [P < 0.05]. Progesterone receptor expression also showed a rising trend in the early luteal phase [87%], as compared with the other phases [P = 0.09]. Expression of estrogen/progesterone receptor shows cyclic changes in breast cancer patients, being highest in the early luteal phase of the menstrual cycle. This variation implies that this phase of the cycle could be the golden time for evaluation of estrogen/progesterone receptor status

Interleukin-10 promoter polymorphisms and breast cancer risk in Iranian women

IL-10 is an anti-inflammatory cytokine which is involved in tumorigenesis. Over production of IL-10 and elevated number of IL-10 generating mononuclear cells in breast tumor tissue has already been shown. To determine the association of IL-10 promoter polymorphisms with increased risk of breast cancer and its association with breast cancer prognostic factors. Peripheral blood samples from 275 female breast cancer patients and 320 cancer free controls were used to detect three single nucleotide polymorphisms in IL-10 promoter region [-1082, -819, -592] by PCR method. The frequency of genotypes and alleles of three mentioned regions of IL-10 promoter and their haplotypes [GCC, ATA, and ACC] showed no statistically significant difference between patients and controls. In the case of prognostic factors, progesterone receptor [PR] status exhibited significant relation with -1082 genotypes [P=0.03] and haplotypes [P=0.02]. -1082 AA genotype was associated with negative PR expression whereas AG and GG genotypes of this site were positively associated with PR expression. Similarly GCC haplotype correlated with positive PR expression and ATA and ACC with negative PR expression. The data of this study showed that IL-10 promoter gene polymorphisms may not be considered as one of the risk factors for breast cancer in Iranian patients

Serum level of HER 2 extracellular domain in Iranian patients with breast cancer: a follow up study

A soluble form of HER-2/neu extracellular domain [sHER-2] is reported to be released in the sera of metastatic breast cancer patients. To measure the level of sHER-2 in sera of 115 breast cancer patients. Serial samples of 27 patients with metastasis, 18 non-metastatic patients, 15 patients in stage 0/I and 14 patients with accompanying benign breast disease were also included in this study. No significant difference was observed between sHER-2 level in the pre-operative sera of breast cancer patients and that of healthy individuals. Only 8 out of 27 patients whom later developed metastasis showed elevated levels of sHER-2 in their first serum sample. However, a trend of increase in the level of sHER-2 was observed in 14 [51.8%] of 27 metastatic sera before clinical diagnosis of the metastasis. A significant association between sHER-2 positive status and vascular invasion of the tumor was observed [P = 0.02]. In addition, significant correlation of sHER-2 level with CEA [highest r = 0.74] and CA 15.3 [highest r = 0.74] tumor marker levels in the serial sera were observed. The mean time from sHER-2 positivity to tumor metastasis was calculated to be 98 days [range = 29-174]. Our results indicate that a relatively high percentage of Iranian patients with breast cancer show an elevated level of sHER-2 in their sera before clinical diagnosis of the tumor metastasis. Therefore, measuring the level of this oncoprotein, not only helps physicians in monitoring the patients during HERCEPTINTM therapy, but also can be helpful in choosing more aggressive treatments at the early satges of tumor metastasis