Ercüment Tekin

Single Nucleotide Polymorphisms in the Hypoxia-inducible Factor-1α (HIF-1α) Gene in Human Sporadic Breast Cancer

BACKGROUND DNA sequence variations in hypoxia-inducible factor-1alpha (HIF-1alpha) gene, which have been demonstrated to be correlated with tumor angiogenesis, may yield changes both in the production outcomes and in the activities of the gene. In this study, we investigated the relationship between three single nucleotide polymorphisms (SNPs) [C1772T and G1790A in exon 12 and C111A in exon 2 of the HIF-1alpha gene] in the HIF-1alpha gene coding regions and development of sporadic breast cancer in the Turkish population. These three polymorphisms result in an amino acid change from proline 582 to serine, from alanine 588 to threonine and from serine 28 to tyrosine, respectively. METHODS Genomic DNA was isolated from 102 sporadic breast cancer patients and 102 healthy female controls. All three HIF-1alpha gene regions were amplified by PCR, and genotypes were determined by RFLP and DNA sequencing. RESULTS There were no significant differences between patients and controls in terms of the distribution of C1772T and G1790A polymorphisms of HIF-1 gene (p >0.05). As for HIF-1alpha C111A polymorphism, we did not find CA and AA variants of the gene in either controls or patients. Multivariable logistic regression analysis was performed between CC and CT + TT genotypes of C1772T polymorphism. No significant differences were found between these two genotypes in terms of clinicopathological characteristics of the patients including age at enrollment, age at menarche and first delivery, number of full-term pregnancies, body mass index, use of oral contraceptives and postmenopausal hormones, family history of breast and ovarian cancers, menopausal status, histopathological features, oophorectomy, smoking habits, and alcohol consumption (p >0.05). CONCLUSIONS Our results suggest that none of the polymorphisms studied in the HIF-1alpha gene influence susceptibility to sporadic breast cancer. The present study is the first case-control study that investigates the association of HIF-1alpha polymorphisms with sporadic breast cancer in the Turkish population.

Outcome and cost comparison of laparoscopic transabdominal preperitoneal hernia repair versus Open Lichtenstein technique.

Laparoscopic hernia repair has all the advantages of a tension free repair. This study compares the laparoscopic transabdominal preperitoneal (TAPP) approach with tension-free open hernia repair in terms of operative time, postoperative pain, hospital stay, complications, and cost. Open and TAPP repairs using polypropylene mesh were performed in two groups of 25 male patients. The difference in operative times between the groups was not significant. Mean pain scores (0-100) for the open group were 54.12 +/- 13.06 at 12 hours and 37.24 +/- 11.38 at 24 hours, significantly higher than the corresponding scores of 38.36 +/- 8.21 at 12 hours and 20.92 +/- 8.73 at 24 hours for the TAPP group (P < 0.05). The mean postoperative analgesic dose was 6.72 +/- 2.72 in the TAPP group, which was insignificantly lower than 7.52 +/- 2.00 in the open group. Mean hospital stay was 2.24 +/- 0.97 days in the open group and 1.52 +/- 0.51 in the TAPP group, which was significant (P < 0.05). Twenty patients (80%) in the TAPP group rated themselves highly satisfied with the surgery as compared to 11 patients (44%) in the open group (P < 0.05). There was no recurrence in either group during a mean followup period of 13.5 months (range, 8-28 months). Laparoscopic hernia repair was significantly more expensive than open (1100 US dollars versus 629 US dollars). TAPP repair is superior to open repair in terms of shorter hospital stay, lower postoperative pain, and better patient satisfaction. It is also safe, with no recurrence in a short-term period. This technique will be the operation of choice for the treatment of groin hernia after long-term results have been established in our center.

Serum YKL-40 levels as a prognostic factor in patients with locally advanced breast cancer.

IntroductionYKL-40 is a growth factor for connective tissue cells; it also stimulates the migration of endothelial cells. YKL-40 is secreted by cancer cells, and elevated serum levels have been associated with poorer prognosis in metastatic breast cancer. In the present study we evaluated the prognostic role of serum YKL-40 levels in patients with locally advanced breast cancer.MethodsYKL-40 levels were measured using ELISA in serum samples obtained from 45 breast cancer patients prior to surgery and chemotherapy. The median follow-up time was 46 months (range, 10–96 months). All patients underwent surgery after chemotherapy. During the follow-up period, 21 patients relapsed and there were 17 deaths.ResultsThe median serum YKL-40 concentration in patients with locally advanced breast cancer was 149.5 μg/l (range, 25.0–1021.3 μg/l). This was higher than levels observed in healthy female controls but the difference was not significant (P=0.44). Serum YKL-40 levels were also higher in patients with tumour size >2 cm and node-positive disease but again the differences were not significant (P>0.05). Tumour volume was correlated with serum YKL-40 levels (r=0.308, P=0.039). High serum YKL-40 levels were associated with shorter disease-free and overall survival although this trend failed to reach significance (P>0.05). Multivariate analysis including tumour size, lymph node status, oestrogen and progesterone receptor status, tumour grade, and serum YKL-40 levels indicated that serum YKL-40 levels were an independent prognostic variable for overall survival (hazard ratio, 1.004; 95% confidence intervals: 1.00, 1.07; P=0.027). Tumour size, lymph node status and oestrogen receptor status were also independent prognostic variables for overall survival (P<0.05).ConclusionOur results show that serum levels of the growth factor YKL-40 may be a useful prognostic indicator of outcome for patients with locally advanced breast cancer. Further studies are required to fully elucidate the biological function of YKL-40 in breast cancer.

Microanatomy of Milk Ducts in the Nipple

The aim of this study was to determine number and diameter of milk ducts in the nipple and to investigate the possible influences of age, breast weight, and diameter of the nipple on the number of ducts. Two hundred and twenty-six carcinoma mastectomy specimens were weighed and the nipple diameters measured. The number of ducts was counted in histological cross sections. Mean diameter of the nipple and mean breast weight were 13.9 mm and 844.6 g, respectively. There was a small but statistically significant positive correlation between nipple diameter and number of milk ducts (rho = 0.158; p = 0.01), but no correlation with breast weight. The mean number of ducts in the nipple duct bundle was 17.5. This is significantly higher than the number of ducts reported to open on the nipple surface. This discrepancy could reflect duct branching within the nipple or the presence of some ducts which do not reach the nipple surface. Smaller breast ducts (diameter <0.5 mm) represent nearly 50% of the nipple ducts and could be a challenge to the ductoscopy technology.

The effect of pentoxifylline on the healing of intestinal anastomosis in rats with experimental obstructive jaundice.

The aims of this study were (1) to investigate the effect of experimental obstructive jaundice on the healing of intestinal anastomosis, and (2) to investigate the effect of pentoxifylline on the healing of intestinal anastomosis in rats with obstructive jaundice. Obstructive jaundice was induced in rats by the ligation and division of the common bile duct. Four days after this operation, either pentoxifylline or isotonic saline solution was administered intraperitoneally to these jaundiced rats and controls, and then intestinal anastomosis was performed. The concentrations of serum tumor necrosis factor α (TNF-α) and serum triglyceride of jaundiced and nonjaundiced rats were measured, and the quality of healing was evaluated by measuring the bursting preasure and hydroxyproline content of the anastomoses on the fifth and tenth days of anastomotic healing. Obstructive jaundice resulted in an impaired wound healing of the intestinal anastomosis in the rats. The administration of pentoxifylline to the jaundiced rats resulted in better anastomotic wound healing. The beneficial effects of pentoxifylline on anastomotic healing in rats with obstructive jaundice was attributed to its inhibitor effect on the endotoxin-induced TNF-α release from macrophages and monocytes, and the stabilizing effect on the neutrophils.

An Investigation into the Serum Thioredoxin, Superoxide Dismutase, Malondialdehyde, and Advanced Oxidation Protein Products in Patients with Breast Cancer

BackgroundReactive oxygen species (free radicals) play an important role in carcinogenesis. Extensive antioxidant defense mechanisms counteract free radicals in mammalian cells. Oxidative stress is a disturbance in the balance between the production of free radicals and antioxidant defenses. There is direct evidence that oxidative stress and lipid peroxidation (LPO) are linked to the etiology of breast cancer. The increasing global incidence of breast cancer emphasizes the need to understand the various mechanisms involved in breast tumorigenesis. The present study was undertaken to investigate the oxidative stress and antioxidant status in the blood samples of patients with breast cancer.MethodsThe present study was based on 23 women who were surgically treated at Gazi University, Faculty of Medicine, Department of General Surgery. The malondialdehyde (MDA) levels as an index of LPO along with the examination of superoxide dismutase (SOD) activities and advanced oxidation protein product (AOPP) and thioredoxin (Trx) levels were determined in the blood samples of 23 patients with breast cancer and 13 healthy controls.ResultsMDA, AOPP, and Trx levels and SOD activities were significantly higher in patients with breast cancer than the controls.ConclusionsThe results showed that oxidative stress may be related to breast cancer and especially some molecules, such as Trx and AOPP, may be useful biomarkers in breast cancer diagnosis and treatment. More detailed knowledge related to the pathophysiology of these molecules could provide valuable information on the origin and development of malignant tumors, such as breast cancer.

Cisplatin plus vinorelbine as a salvage regimen in refractory breast cancer.

Aims and background Breast cancer refractory to known effective agents is one of the major clinical problems frequently encountered in practice. Cisplatin and vinorelbine are known to be active drugs in anthracycline-refractory cases. In this phase II study, the effectiveness and tolerability of cisplatin and vinorelbine was investigated when used in combination as a salvage regimen in the treatment of metastatic refractory breast cancer. Study design Twenty-four patients with advanced refractory breast cancer who had been previously treated with a regimen containing doxorubicin were included in the study. Six of the 24 patients also received taxanes after failure of doxorubicin. Cisplatin at 80 mg/m2 on day 1 and vinorelbine at 25 mg/m2 on days 1 and 8 were given every 3 weeks. Results A total of 98 cycles of chemotherapy was given, with a median of 4/patient. The response rate was 25% (2 [8.3%] complete and 4 [16.7%] partial responses). The median survival rates were 14 months in responders and 5.5 months in nonresponders (P = 0.0282). One complete and one partial response were observed in patients previously treated with paclitaxel (overall response rate, 33%). The median response duration was 12.5 mo (range, 4–21) in complete and 4.5 mo (range, 1.5–13) in the partial response group. Grade 3 and 4 neutropenia occurred in 9 patients, with no toxic deaths. Grade 2-3 nausea and vomiting in 6 patients and grade 1 neuropathy in 1 patient were noted. Conclusions Although the number of cases is insufficient to indicate that the combination will be effective, it is noteworthy in consideration of anthracycline and taxane refractory cases. A combination of cisplatin and vinorelbine seems to be a reasonable and acceptable choice as an alternative salvage regimen in such cases.

The effects of glutamine-enriched feeding on incisional healing in rats

Abstract Glutamine (Gln), which is the most abundant free amino acid in the circulation, and also a primary fuel for rapidly dividing cells, was used to determine its effects on incisional healing. The effect of Gln-enriched feeding was investigated using tensile strength measurement, which reflects the quality and speed of regeneration, and by the measurement of tissue hydroxyproline level which correlate directly with the collagen content of wounds. Forty albino Wistar rats in four equal groups received a special diet 7 days prior to surgery and 7 days after surgery. On the 7th day of study a 5-cm dorsal midline skin incision was made and then closed by interrupted sutures. Group 1 received a normal diet for all 14 days; group 2 received a Gln-enriched diet 7 days prior to surgery and a normal diet 7 days after surgery; group 3 received a normal diet prior to surgery and a Gln-enriched diet after surgery; group 4 received a constant Gln-enriched diet. On the 7th postoperative day, tensile strength measurements and hydroxyproline level analyses were done. A preoperative Gln-enriched diet did not show any significant improvement in the tensile strength and hydroxyproline levels on the 7th postoperative day, but a pre- and postoperative, and a postoperative Gln-enriched diet significantly improved the tensile strength and hydroxyproline levels when compared with the normal diet group (P<0.0001). These findings show that wound healing is better when Gln was added in the postoperative, or both pre- and postoperative periods, but not when only added in the preoperative period.

Neopterin, Catalase and Superoxide Dismutase in Females with Benign and Malignant Breast Tumors

Abstract The aim of the present study was to evaluate the relationship between the levels of neopterin among patients with benign and malignant breast disease and the relation with the stage of the malignant process. In this study, neopterin concentrations and enzyme activities of superoxide dismutase (SOD) and catalase (CAT) were determined in malign (n=30) and benign breast tumor patients (n=30) by high performance liquid chromatographic and spectrophotometric methods, respectively. Results were compared with a healthy control group (n=20). The correlations between neopterin, CAT and SOD were also evaluated in controls and patients. Urinary neopterin level of the control group was (mean value ± S.D.) 128.6 ± 64.6 μmol/mol creatinine. Neopterin concentrations in patients with breast malignancy were 153.6 ± 71.2 μmol/mol creatinine and 107.8 ± 32.1 μmol/mol creatinine in benign disorders patients. The mean neopterin level in the benign group was found to be statistically different from the malign tumor group (p = 0.039). SOD and CAT activities in controls were found as 3.57 ± 0.84 U/mg protein and 2.19 ± 0.20 U/mg protein, respectively. In patients with malignancy, the SOD activity was 3.84 ± 0.73 U/mg protein while CAT activity was 1.03 ± 0.13 U/mg protein. Patients with benign breast disorders, SOD activity was 4.09 ± 1.00 U/mg protein and CAT activity was 1.02 ± 0.18 U/mg protein. Whereas SOD activity did not differ between the groups of patients and controls, the mean catalase level in the control group was higher than in the benign and malign tumor groups (both p <0.001). Urinary neopterin concentration seems to be an important and useful biomarker in diagnosis of breast tumors in clinical practice.

Immune system modulation in patients with malignant and benign breast disorders: tryptophan degradation and serum neopterin

Tryptophan degradation metabolites are known to suppress T-cell function, which is a mechanism of resistance of tumor cells against immune surveillance. The aim of this study was to evaluate tryptophan degradation along with serum neopterin levels in benign and malignant breast disease. Serum tryptophan and kynurenine levels and neopterin concentrations of 30 patients with malignant and 27 patients with benign breast disease were determined by HPLC and ELISA, respectively. The slight increase in tryptophan degradation in a subgroup of cancer patients with higher grade tumors was not statistically significant, but the increased degradation was correlated with higher neopterin concentrations. Neopterin levels in patients with malignant breast disease were significantly higher than in the benign group (p<0.05). Tryptophan degradation positively correlates with the aggressiveness of the tumor because it changes with tumor grade rather than disease stage.