Association of TNF-α and TNF-β gene polymorphism with steroid receptor expression in breast cancer patients

The presence of estrogen and progesterone receptors is correlated with good prognosis in breast cancer. The effect of TNF-α on down-regulation of estrogen receptor and blocking the proliferative response of breast cancer cells to estradiol have been demonstrated. However, the effect of TNFA and TNFB gene polymorphisms on the expression of steroid receptors in breast cancer cells is not well documented. Therefore, 160 breast cancer patients were recruited to investigate the association of TNFA and TNFB gene polymorphism with the level of steroid receptor expression. This association was not found to be significant for TNFA polymorphism and estrogen receptor expression (p=0.07). However, when combined genotypes of TNFA and TNFB polymorphism was considered, homozygous patients for lower TNF-α producer genotypes (TNFA1/A1 and TNFB1/B1) showed significantly higher progesterone receptor expression (p=0.041). Our findings indicate that TNFA and TNFB polymorphisms may be associated with the levels of steroid receptor expression in breast cancer patients. Further studies on a larger group of breast cancer patients are recommended.     

Comparison of serum cortisol level in open heart surgery--morphine versus sufentanil

BACKGROUND AND AIMS: In open-heart surgery, cardiopulmonary bypass (CPB) can cause a rise in the level of stress hormones such as cortisol. Reducing this hormonal response is beneficial in the recovery period. Anesthetic agents and methods used in such operations have different effects on this response. In the present study two agents (morphine and sufentanil) routinely used for the cardiac surgery in Nemazi Hospital were compared regarding their effect on the serum cortisol levels. MATERIALS AND METHODS: Thirty patients undergoing coronary artery bypass grafting (CABG) in Nemazi Hospital were selected and divided into two groups. Group 1 (16 patients received morphine in a dose of 1 mg/kg) and Group 2 (14 patients received sufentanil in a dose of 5 microg/kg). Serum cortisol levels were measured before induction of anesthesia, after tracheal intubation, after initiation of CPB and twelve hours after the termination of operation. RESULTS: Morphine and sufentanil both lowered the serum cortisol level during the operation. However, twelve hours after the operation, cortisol levels in both groups were higher than those taken in the previous set times. CONCLUSION: Neither morphine nor sufentanil in the mentioned doses could reduce the endocrine response in the postoperative period, and thus have no preference, in cardiac surgery.     

Cytotoxic T Lymphocyte Antigen-4 Gene in Breast Cancer

The exon 1 polymorphism (49A/G) of ctla-4 gene corresponds to an amino acid exchange (threonine to alanine) in the leader peptide of the expressed protein. There are reports concerning the higher level of G allele in subjects with various autoimmune diseases, which has resulted in the hypothesis that CTLA-4 may play a role in regulating self-tolerance by the immune system and in the pathogenesis of autoimmune disorders. This study was undertaken to investigate the correlation of exon 1 (49A/G) polymorphism in the ctla-4 gene and breast cancer. The ctla-4 49A/G polymorphism was studied in 197 women with primary breast cancer and 151 age/sex matched normal individuals. The results indicated a significant difference between frequency of ctla-4 genotypes in patients and controls. The frequency of GG genotype was significantly decreased in breast cancer patients compared to controls (4.6% v.s. 12.6%, P = 0.012). There was also a significant positive correlation between tumor size and the existence of AA genotype in patients (P = 0.016). In addition, a positive correlation between AA genotype and lymph node involvement was observed (P = 0.042). The observed decrease in the frequency of GG genotype in the breast cancer patients is contrary to the frequently reported increase of GG genotype in autoimmune diseases. In addition, the data implies that polymorphism of ctla-4 exon 1 contributes in tumor progression.     

Seroprevalence of <Emphasis Type="Italic">Neospora caninum</Emphasis> infection in dogs from rural and urban environments in Tehran,Iran

103 serum samples were taken from owned dogs in Tehran (53 urban dogs and 50 farm dogs) from February to May 2005 and tested for IgG antibody against Neospora caninum using the immunofluorescence antibody test. Urban dogs were selected from apparent healthy dogs referred to the Small Animal Hospital of Faculty of Veterinary Medicine, University of Tehran, for routine operation, and the farm dogs were selected from the sheepdogs in sheep flocks around Tehran randomly. The titer of 1:50 was selected as cutoff. In total, 20 of 103 cases (19.4%) were identified as positive. The infection rate in farm dogs (28%) was higher than in urban dogs (11.3%), and the difference was statistically significant (p < 0.05). The infection rates in different genders and age groups were determined. The differences between seroprevalence of N. caninum infection in different sexes were not significant. A high correlation was observed between the infection rate and age (r ² = 0.97, p < 0.01).     

Polymorphism in the genes of alpha and beta tumor necrosis factors (TNF-alpha and TNF-beta) and gamma interferon (IFN-gamma) among Iranian women with breast cancer

The association of the polymorphism in the genes of TNF-alpha, TNF-beta and IFN-gamma with breast cancer was investigated in the present study. There were no differences in the TNF-alpha and TNF-beta alleles and genotypes frequencies between breast cancer patients (n=223) and control subjects (n=267). The correlations between TNFA or TNFB alleles or genotypes and clinicopathological indices were also insignificant. However, the frequency of IFN-gamma+874 T/T genotype was significantly higher in breast cancer patients compared to those of controls (P<0.002; OR=2.03, 95% CI=1.28-3.2) which indicates that Iranian women carrying the IFN-gamma+874 T/T genotype may be exposed to an increased risk of breast cancer development.     

Epidemiology and mortality of burns in the South West of Iran

Burn injuries still produce a significant morbidity and mortality in Iran. This study was carried out to analyze the epidemiology, mortality, and current etiological factors of 2043 burn patients who were admitted to the burn centers in the Fars province during 4 years (1994-1998). There were two burn centers in the Fars province serving 3817036 people over an area of 124,000 km(2). The overall incidence rates of hospitalization and death were 13.4 and 4.6 per 100000 person-years. The mean age was 21.9 years, and 51% of patients were children under 19-years-old. The highest rates of hospitalization and death were observed in the elderly (80 years). Also young females (20-29 years) had a high rate of hospitalization. Thus, 55% of the patients had BBS less than 40%. Burn injuries were more frequent and larger with higher mortality in females than in males (P<0.0001). There was also statistically significant correlation between age groups, gender, and BBS with mortality rate (P<0.0001). Flame was the most common etiology of burns. There was also significant correlation between age groups and type of burns (P<0.0001). Suicide attempts for all the patients > or = 11 years were the cause of 41.3% (256/620) of the burns involving women and of 10.3% (40/388) of the burns involving men. The overall case fatality rate was 34.4%. The mortality rate was significantly higher for self-inflicted burns (78%) than for accidental burns (26.7%). Most of the lesions requiring hospital admission occurred during the winter months. Factors associated with an increase in mortality were suicidal burns, burn size, age, and flame burns. Most of the burn injuries were caused by domestic accidents and were, therefore, preventable.     

Combined value of apparent diffusion coefficient-standardized uptake value max in evaluation of post-treated locally advanced rectal cancer

AIM: To assess the clinical diagnostic value of functional imaging, combining quantitative parameters of apparent diffusion coefficient (ADC) and standardized uptake value (SUV)max, before and after chemo-radiation therapy, in prediction of tumor response of patients with rectal cancer, related to tumor regression grade at histology.METHODS: A total of 31 patients with biopsy proven diagnosis of rectal carcinoma were enrolled in our study. All patients underwent a whole body ¹⁸FDG positron emission tomography (PET)/computed tomography (CT) scan and a pelvic magnetic resonance (MR) examination including diffusion weighted (DW) imaging for staging (PET1, RM1) and after completion (6.6 wk) of neoadjuvant treatment (PET2, RM2). Subsequently all patients underwent total mesorectal excision and the histological results were compared with imaging findings. The MR scanning, performed on 1.5 T magnet (Philips, Achieva), included T2-weighted multiplanar imaging and in addition DW images with b-value of 0 and 1000 mm²/s. On PET/CT the SUVmax of the rectal lesion were calculated in PET1 and PET2. The percentage decrease of SUVmax (ΔSUV) and ADC (ΔADC) values from baseline to presurgical scan were assessed and correlated with pathologic response classified as tumor regression grade (Mandard’s criteria; TRG1 = complete regression, TRG5 = no regression).RESULTS: After completion of therapy, all the patients were submitted to surgery. According to the Mandard’s criteria, 22 tumors showed complete (TRG1) or subtotal regression (TRG2) and were classified as responders; 9 tumors were classified as non responders (TRG3, 4 and 5). Considering all patients the mean values of SUVmax in PET 1 was higher than the mean value of SUVmax in PET 2 (P < 0.001), whereas the mean ADC values was lower in RM1 than RM2 (P < 0.001), with a ΔSUV and ΔADC respectively of 60.2% and 66.8%. The best predictors for TRG response were SUV2 (threshold of 4.4) and ADC2 (1.29 × 10^-3 mm²/s) with high sensitivity and specificity. Combining in a single analysis both the obtained median value, the positive predictive value, in predicting the different group category response in related to TRG system, presented R² of 0.95.CONCLUSION: The functional imaging combining ADC and SUVmax in a single analysis permits to detect changes in cellular tissue structures useful for the assessment of tumour response after the neoadjuvant therapy in rectal cancer, increasing the sensitivity in correct depiction of treatment response than either method alone.     

The efficacy and safety of neoadjuvant chemotherapy?+/??letrozole in postmenopausal women with locally advanced breast cancer: a randomized phase III clinical trial

This two-arm randomized clinical study aimed to evaluate the efficacy and safety of neoadjuvant concurrent chemotherapy and letrozole in postmenopausal women with locally advanced breast carcinoma. One hundred and one postmenopausal women aged 50-83 years with pathologically proven locally advanced (clinical stage T3, T4 and/or N2, N3) breast cancer were randomly assigned to receive neoadjuvant chemotherapy alone (control arm, n = 51) or neoadjuvant chemotherapy concurrent with letrozole 2.5 mg (study arm, n = 50). Chemotherapy consisted of a median 4 (range 3-5) cycles of intravenous 5-fluorouracil 600 mg/m(2), doxorubicin 60 mg/m(2), and cyclophosphamide 600 mg/m(2), every three weeks. All patients subsequently underwent modified radical mastectomy approximately two weeks after the last cycle of chemotherapy. Pathologic complete response rates were 25.5% and 10.2% in the study and the control group, respectively (P = 0.049). Similarly, clinical complete response rates were 27.6% and 10.2% in the study and the control group, respectively (P = 0.037). In the subgroup analysis of hormone receptor-positive cases, the complete response rates were more prominent in study group compared with control group. Common treatment-related side effects such as nausea, vomiting, bone marrow suppression, and mucositis were similar in both groups, but hot flush was more prevalent in study group compared with control group (P = 0.023). The addition of letrozole concurrently with neoadjuvant chemotherapy provides a higher clinical and pathologic response rates with acceptable toxicity compared with chemotherapy alone in postmenopausal women with locally advanced sensitive breast cancer.     

Elevated Syndecan-1 levels in the sera of patients with breast cancer correlate with tumor size

Background

Breast cancer is the leading type of cancer in Iranian women and affects them at least one decade younger than their counterparts in developed countries. Breast tumor progression and metastasis is accompanied by a decrease in the membranous expression of Syndecan-1 and an increase in its shedding. We measured the level of soluble Syndecan-1 in the sera of Iranian patients with breast cancer.

Methods

The study population included 61 chemotherapy-naïve breast cancer patients and 30 age/sex-matched healthy individuals. Blood was collected by venipuncture method and serum was separated, aliquoted and kept at ?40 °C until used. A commercial ELISA was used to detect Syndecan-1 levels in the sera.

Results

Soluble Syndecan-1 levels were increased in the sera of patients with breast cancer compared to healthy controls (87.89 ± 89.29 vs. 47.57 ± 46.46 ng/ml, p = 0.005). There was a positive correlation between soluble Syndecan-1 levels and tumor size (p = 0.017). The serum level of Syndecan-1 in patients without calcification showed a trend of increase compared to that of patients with calcification (108.80 ± 101.76 vs. 59.82 ± 57.13 ng/ml).

Conclusion

The positive correlation between soluble Syndecan-1 levels and tumor size in the present study highlights the importance of different varieties (cell-bound and soluble) of this molecule in the breast tumor progression and their significance as tumor biomarkers.