[Increase risk of ovarian and breast cancers in women with polycystic ovarian syndrome: a review]

Polycystic ovarian syndrome [PCOS] is the most common endocrinopathy among women of reproductive age. In addition of fertility problems, there are numerous potential mechanisms which could promote neoplastic disease, including breast and gynecological cancers [endometrial and ovarian cancers], in women with PCOS. PCOS patients have a higher prevalence of obesity and consequently higher risk of metabolic syndrome. Also, hyper and rogenism, as one of the main symptoms of PCOS, is the result of endocrine alterations like increased presence of androgens and estrogens secreted abnormally. Obesity and fertility disorders caused by PCOS are two important risk factors for various cancers such as ovarian cancer. There is some evidence, which suggests that PCOS may be assumed as a factor in the increased risk of ovarian cancer. Also, androgen levels, weight gain and obesity are the main risk factors for the onset and progression of breast cancer. Related articles in English were searched in PubMed, Google Scholar, Elsevier, Wiley Online Library. Accordingly, PCOS could be known as a cause of estrogen-dependent tumors that have receptors for steroid hormones, such as breast and ovarian cancer. Despite the on going extensive research aiming to determine the relationship between PCOS and increased risk of developing breast and ovarian cancers, limited information has been obtained to confirm this relationship

[The study of peripheral blood mononuclear cells activity of women with polycystic ovary syndrome [PCOS] by co-culture with breast cancer cell lines compared with the healthy controls]

Introduction: polycystic ovary Syndrome [PCOS] is one of the most prevalent endocrinology disorders in women, in whom the state of systemic inflammatory cytokines, especially TNF-alpha is the main reason for immunological disturbances. Some PCOS manifestations such as infertility, hyperandrogenism, obesity and chronic inflammation are considered as risk factors for breast cancer. The risk of developing breast cancer in women with PCOS is being investigated in some epidemiological studies. In this research, the ability of peripheral blood mononuclear cells [PBMCs] of women with PCOS to develop antitumor response was studied and evaluated using an experimental co-culture approach between PBMCs and breast tumor cell lines

Materials and Methods: PBMCs were isolated from 50 heparinized venous blood samples [patient and healthy groups] by density gradient centrifugation byficoll. Breast cancer cell lines [MDA-MB-468 and MCF-7] were incubated as two target cells and were cultured adjacent to PBMCs in a transwell co-culture system. At different time intervals [48 and 72 hours] after co-culture, the proliferation rate of the effectors cells was evaluated by the BrdU cell proliferation assay. Determination of T CD3+CD8+ lymphocytes was determined by flow cytometry

Results: the proliferation of PBMCs after 48 hours of co-culture with MDA-468 [P=0.002] and MCF-7 [P=0.021] was significantly higher in the PCOS group compared to healthy controls. No pronounced differences were observed in T CD3+CD8+ cell numbers between the PCOS group and healthy controls [P>0.05] although T CD3+CD8+ percentage increased after 72 hours of co-culture in most samples. There was no statistically significant difference between MDA-468 and MCF-7 co-cultures in any of the tests

Conclusion: the stimulation threshold for mononuclear cells was reduced in women with PCOS. Differences between proliferation responses of PCOS and control groups may be caused by a chronic inflammatory condition in these patients

[Effects of nulliparity and multiparity on probability of breast tumor incidences: a review]

Breast cancer is the most common malignancy in women. Despite much progress in its identification, advanced surgical techniques and chemotherapies, physicians have not been successful in the control and inhibition of its metastasis. The aim of this study is notification fertility specialist and stakeholders of malignant disease to inform the role of normal pregnancy, which support immunological response of mothers, special anti-tumor and anti-metastatic mechanism against breast cancer in women. Epidemiological studies in the field of cancer associated with pregnancy history show that pregnancy has a dual impact, short-and long term, on the development of breast cancer; the first, a transient effect the after delivery, stimulates the growth of cancer cells in the early stages of transformation and increases risk of cancer, a result of a short-term effect of pregnancy. In addition, the increased differentiation of stem cells that are capable of forming tumors in the breast due to pregnancy and hormonal changes, reduce the risk of cancer, a phenomenon related to the long-term effect of pregnancy. The immune system of multiparous women due to multiple chimerism that occur as a result of the contact of the maternal immune system with common tumor antigens and embryonic cells, is more powerful and resistant against breast tumors than their nulliparous counterparts

[ study of cell proliferation, TNF-alpha cytokine production and expression of CD8 marker in peripheral blood lymphocytes of women with polycystic ovary syndrome [PCOS] by co-culture with ovarian tumor cell lines [SKOV3, A2780]]

Introduction: Polycystic ovarian syndrome [PCOS] is a proinflammatory state that underpins the development of metabolic aberration and ovarian dysfunction in the disorder. Chronic inflammation and increased levels of androgens in these patients and their impact on the immune system, may be able to disrupt antitumor activity and thus increase the risk of developing malignancies including ovarian cancer

Materials and Methods: Peripheral blood mononuclear cells of 50 patients with PCOS and healthy controls were purified by Ficoll density gradient centrifugation. We then measured cell proliferation and concentrations of cytokines TNF- alpha at different time intervals [48 and 72 hours] after co-culture of ovarian [SKOV3, A2780] and breast [MCF-7, MDA-468] tumor cell lines with PBMC in indirect contact of trans well system

Results: Proliferative response of executive cells during stimulation with tumor cell lines after 48 hours was not statistically significant between patients and healthy controls. Between the 2 groups, proliferation rates at the end of 72h were significantly higher than after 48h [P<0.01]. The production of TNF- alpha in co-culture of A2780 cell lines significantly increased in the patient group in time compared to the controls [P<0.05]

Conclusion: Our findings confirmed that, compared to healthy individuals low levels of chronic inflammation in patients with PCOS exhibit increased proliferative response of immune cells and TNF- alpha levels. An increased risk of cancers in patients with PCOS however requires investigation of other aspects of anti-tumor responses in vitro, with larger sample sizes

Gene regulation of pteridine reductase 1 in leishmania promasti-gotes and amastigotes using a full-length antisense construct

Pteridine metabolic pathway is unusual features of Leishmania, which is necessary for the growth of parasite. Leishmania has evolved a complex and versatile pteridine salvage network which has the ability of scavenging a wide area of the conjugated and unconjugated pteridines especially folate and biopterin. In this study, we focus on the inhibition of ptr1 gene expression. L. major ptr1 gene was cloned into pcDNA3 and digested using KpnI and BamHI. The gene was subcloned so that antisense will transcribe and called pcDNA-rPTR. Leishmania major was cultured and late logarithmic-phase promastigotes were harvested. The promastigotes were divided into two groups. One group was transfected with 50 micro g of pcDNA-rPTR, whereas the other group was transfected with pcDNA3. Transfected cells were cultured and plated onto semi-solid media. Mouse pritonean macrophages were transfected using pcDNA-rPTR-tansfected promastigotes. Western blotting was performed on mouse transfected pritonean macrophages and extracts from transfected promastigotes of L. major using a L. major ptr1 antibody raised in rabbits. The PTR1 protein was not expressed in pcDNA-rPTR- tansfected promastigotes and mouse macrophage transfected with pcDNA-rPTR- tansfected promastigotes. This approach might be used to study the pteridine salvage pathway in Leishmania or to assess the possibility of using gene expression inhibition in the treatment of leishmaniasis.

[Effect of low - level helium - neon laser irradiation on proliferation rate of cultured human fibroblasts in high glucose medium]

This study aimed to evaluate the effects of low level laser on human fibroblasts which were cultured in high glucose cultures. The human skin fibroblasts were maintained in Dulbecco's Modified Eagle's Medium [DMEM] in a humidified air-5% CO[2] atmosphere. The cells were cultured. Irradiation was carried out with Helium-Neon [He-Ne] laser unit with power output of 1.5 mW and the diameter of irradiating beam of 1.7 cm on the case groups. In the next step the cells were cultured in high glucose culture medium [15mM/L] for one week before laser irradiation. The irradiation was carried out with the same laser unit with power output of 1.5 mW and the diameter of irradiating beam of 1.7 cm on the case groups. Control cells did not receive laser. The cells were irradiated with three doses of 0.5, 1 and 2 J/cm[2] on three consecutive days. Cell proliferation was evaluated by dimethylthiazol-diphenyltetrazolium bromide [MTT] assay. Data were analyzed by student t test or Mann-Whitney-U test. Laser treatments of 0.5 [p-value=0.002] and 1 [p-value=0.046] had a stimulatory effect and three irradiations of 2 J/cm[2] had a negative effect [p-value=0.011] on proliferation rate of fibroblasts which were cultured in normal culture medium compared to non irradiated cells. All three doses of 0.5 [p-value=0.042], 1 [p-value=0.00] and 2 J/cm[2] [p-value=0.00] had a stimulatory effect on proliferation rate of fibroblasts which were cultured in culture medium with high glucose concentration [15mM/L] in comparison with hyper glycemic non irradiated cells. Low level laser irradiation with helium-neon unit on cultured human fibroblasts in normal and high glucose mediums increased their growth and proliferation

Seroprevalence of acanthamoeba antibodies in rheumatoid arthritis patients by IFAT, Tehran, Iran 2007

This preliminary study was conducted to discriminate the prevalence of Acanthamoeba antibodies in rheumatoid arthritis [RA] patients and healthy controls to analyze the correlation between these two groups. From October 2006 to August 2007 a total of 121 serum samples from RA patients attending the Rheumatolgy Department at Shariati Hospital in Tehran were obtained and stored at -20°C until using by indirect fluorescent-antibody test [IFAT]. RA was diagnosed according to the American Collage of Rheumatology classification criteria. The organism used in this study was isolated from various water resources in Tehran, Iran cultured axenically and then went on a PCR assay based on 18S rRNA to identify the genus Acanthomoeba. Indirect immunofluorescence antibody [IFA] staining of serum samples was carried out to detect anti Acanthomoeba antibodies. In culture, out of 22 samples, 13 [59%] were grown in xenic but only two in axenic medium. PCR amplified a 904bp fragment, specific for Acanthamoeba. Of examined serum samples, Acanthamoeba antibodies were present in 70 [57.8%] and 52 [41.2%], respectively. The highest titer of antibodies [1:320] was detected in one patient with RA. Our study supports the hypothesis that some parasitic microorganisms can involve and contribute toward the development of rheumatoid syndromes

[Cytological radiotoxicity of radioiodine therapy in patients with differentiated thyroid carcinoma]

Cytological radiation damage to lymphocytes can result in augmentation of cells with micronuclei. In this study we investigated Cytological radiation damage to peripheral blood lymphocytes using the micronuclei assay [MNA] method. Considering the value of Iodine-131 in diagnostic and therapeutic nuclear medicine and high absorbed dose of I131 radioiodine in comparison with gamma emitters and the effect of type of radiation, dose and species on radiosensitivity of patients, this study was conducted. To evaluating the Cytological radiotoxicity of therapeutic radiotracers such as radioiodine I131. We studied 22 patients with differential thyroid carcinoma who were referred for treatment with 100 or 150 mci I131. Before and one weak after treatment the peripheral lymphocytes were harvested and isolated by a Cytological method and assayed for frequency of micronuclei as a marker of Cytological radiotoxicity. The means of micronuclei in one hundred binuclear lymphocytes were 6.3 +/- 2.2 before treatment and 9.6 +/- 3.1 after treatment, differences in the number of micronuclei being statistically significant [p value <0.05]. High doses of radioiodine therapy used after surgery for differentiated thyroid carcinoma can increase micronuclei among peripheral lymphocytes as an indirect marker of chromosomal aberrations and cytotoxic radiation damage

effect of glycation of culture medium on phagocytic and respiratory burst of peritoneal macrophages from balb/c mice

Elevated levels of intracellular and extracellular carbohydrates or even in vitro can cause cellular dysfunction that may lead to death. This disorder in diabetic and galactosemic patients paves the way for systemic immune dysfunction and made the patients susceptible for infections. The present study was conducted to determine the effect of glycation of culture medium on phagocytic and respiratory burst of peritoneal macrophages from Balb/c mice. It was an experimental study. Macrophages were obtained from peritoneal cavity lavage of the pure Balb/c mice. Cells were harvested in complete tissue culture medium including different levels of glucose and galactos [5mM to 30 mM] while control group lack any sugar in the medium. E.coli has been used to study the rates of ingestion and killing activity of the cells under these conditions. The adhesion of macrophages was assessed by the average adhered cells in some microscopic fields and also the morphological changes were evaluated. The oxidative and respiratory burst were measured with NBT reduction test. With the counting of the E.coli ingested in cells and also with the numbering of the cells ingested the E.coli, the rate of ingestion, was determined. In order to study the killing activity of the macrophages, after incubation of the macrophages and E.coli with some stimulators, the number of E.coli left in the culture medium was determined by two different ways: Standard mc farland tubes and colony counting. Reduced adhesion and phagocytic morphogenesis were found in media with 15 and 30mM of galactose as compared with other media and control group [p < 0.05]. Meanwhile, number of ingested bacteria was significantly differed in media with concentration of 30mM and the control group. Elevated levels of carbohydrates significantly impaired the bactericidal activities [ingestion and killing], however, respiratory burst of the cells were not changed. Increased concentration of glucose and galactose cause impairment of the morphological changes and adhesion of the macrophages, whereas, respiratory burst function remains unchanged. Recurrent infections in diabetic and galactosemic patients may be explained by this phagocytic impairment

Tissue uptakes of 67Ga-bleomycin and carrier free 67Ga in fibrosarcoma - bearing mice

67Gallium-bleomycin complex [67Ga-BLM] was prepared using Thakour method. Radio-thin-layer-chromatography of prepared complex showed A2 and B2 radiopeaks with Rf at 0.7 and 0.4 respectively with a purity of above% 95. Tissue uptake of 67Ga-BLM and 67GaCl3 in twelve tissues including tumor, blood, liver, lung, spleen, muscle, skin, heart, kidney, colon, colon content,bladder and the total body were counted by well counter at 1, 2, 4, 24 and 48 hours post injection of radiopharmaceuticals. Uptakes of tissues are expressed as percent injected dose per gram of tissue. The clearance rate of 67Ga-BLM was 1.75-1.95 times faster than 67GaCl3 at all time intervals. Bladder uptakes of 67Ga-BLM were highest among twelve tissues at 1,2 and 4 hours after injection, then falling rapidly after 24 and 48 hours. Blood uptake of 67Ga-BLM was lower than 67GaCl3 in all time intervals. Colon content uptake of 67Ga-BLM was highest among twelve tissues at 2 and 4 hours post injection. Tumor to tissue activity ratios were also calculated, showing an increase of tumor to blood and muscle ratios. Tumor to blood ratio increased from 0.3 at 1 hour to 5.3 at 48 hours. Activity ratio of muscle increased from 0.5 at 1 hour to 5.5 at 48 hours. Whole body counting of animals showed that effective half lives of 67Ga-BLM and 67GaCl3 were about 1 and 15 hours respectively, which renders faster excretion of 67Ga-BLM complex. Biodistribution data clearly indicates that prepared complex in comparison with carrier free 67Ga [67GaCl3] has two main advantages: 1] high tumor to soft tissue uptake ratio that make it suitable for tumor imaging, 2] faster excretion specially at first three hours post injection. In addition complex is stable in vitro and in vivo