Erhan Onuk

Significance of serum vascular endothelial growth factor, insulin-like growth factor-I levels and nitric oxide activity in breast cancer patients

Vascular endothelial growth factor (VEGF) is used to evaluate the angiogenic activity in breast carcinoma. Nitric oxide (NO) and insulin-like growth factor-I (IGF-I) are also implicated in breast tumorigenesis, including angiogenesis. We measured serum VEGF, IGF-I and nitrate+nitrite levels in 38 patients with metastatic and 23 with nonmetastatic breast cancer and in 16 controls. Serum VEGF and IGF-I levels were higher in patients with metastatic disease than in those with nonmetastatic disease or in controls (P<0.001). Serum nitrate+nitrite levels were higher in patients with metastatic and nonmetastatic disease than in controls (P<0.001). Patients with visceral metastasis and local metastasis had higher serum VEGF and nitrate+nitrite levels than patients with bone metastasis (P<0.05). In the metastatic disease group, there was a positive correlation between serum VEGF levels and nitrate+nitrite levels (r=0.436, P<0.05). Within the group with nonmetastatic disease, premenopausal patients had higher serum IGF-I levels than did postmenopausal patients (P<0.001). NO may involve an angiogenic process that is stimulated by VEGF in breast carcinoma. Larger studies are required to clarify these suggestions.

Total thyroidectomy for the treatment of Hashimoto's thyroiditis coexisting with papillary thyroid carcinoma.

The coexistence of Hashimoto’s thyroiditis (HT) and papillary thyroid carcinoma (PTC) is controversial. This study was conducted to evaluate the correlation between HT and PTC and to identify predictive factors for the coexistence of PTC and HT. A total of 922 patients underwent surgery for thyroid disorders between January 2001 and August 2005. In all, 199 patients had been diagnosed with PTC, 37 of whom had coexistent HT; in 689 patients, benign thyroid disease had been diagnosed. Patients’ age and sex, as well as histopathology, tumor size, nodal involvement status, multicentricity, presence of metastasis, and serum thyroglobulin levels, were retrospectively reviewed. A significant correlation was observed between HT and PTC, although no statistical significance was noted between PTC and HT type (nodular or diffuse). Most patients with PTC+HT were female and younger (<40 y old) than those with PTC only. The rate of occult tumor in patients with PTC+HT was higher than that in patients with PTC alone. Data indicate the coexistence of PTC and HT and suggest that PTC may develop even in cases of diffuse HT. Total thyroidectomy is the surgical procedure of choice, especially in young, female patients with HT.

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.

No association between serum levels of insulin-like growth factor-I, vascular endothelial growth factor, prolactin and clinicopathological characteristics of breast carcinoma after surgery.

Abstract

Effect of tamoxifen on serum IL-18, vascular endothelial growth factor and nitric oxide activities in breast carcinoma patients.

Vascular endothelial growth factor (VEGF) is a multi‐functional cytokine that has been suggested to be a major angiogenic factor in breast cancer. Nitric oxide (NO) is a potent biological molecule that partipicates in the multi‐step process of carcinogenesis. Interleukin (IL)‐18 has been shown to have potent anti‐tumour effects. In this study, we investigated the effect of tamoxifen therapy on serum VEGF, NO and IL‐18 activity in breast cancer patients. Serum levels of VEGF, nitrate + nitrite and IL‐18 were measured in 34 postmenopausal breast cancer patients before and 3 months after the tamoxifen therapy. Both serum VEGF and IL‐18 levels decreased after tamoxifen therapy (P = 0·051, P < 0·05, respectively). Serum VEGF levels increased in patients with endometrial thickness, while patients without endometrial thickness had a significant reduction in serum VEGF levels after therapy (P < 0·05). Serum nitrate + nitrite levels increased after the therapy, but this was not statistically significant (P > 0·05). A decrease in serum VEGF levels with tamoxifen therapy may be a reflection of reduced angiogenic activity in patients without endometrial thickness. The negative effect of tamoxifen therapy on IL‐18, which is known to have a potent antitumour activity, may be related to the decreased tumour growth by induction of NO and reduction of VEGF activity as a feedback mechanism.

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.

The effects of indomethacin, NDGA, allopurinol and superoxide dismutase on prostaglandin E2 and leukotriene C4 levels after mesenteric ischemia-reperfusion injury

In this study, the changes of arachidonic acid metabolites after an ischemia-reperfusion (I/R) period are investigated. The cyclooxygenase and lipoxygenase metabolites were found to be significantly increased after a 45 min period of ischemia followed by 5 min of reperfusion. Prostaglandin E2 (PGE2)- and leukotriene C4 (LTC4)-like activities did not change in the ischemic period, but they both increased after reperfusion. A cyclooxygenase inhibitor indomethacin and lipoxygenase inhibitor nordehydroguaretic acid (NDGA) decreased PGE2- and LTC4-like activities, respectively, while allopurinol and superoxide dismutase (SOD) decreased both activities. According to our results, it can be assumed that free oxygen radicals are responsible for the elevation of PGE2- and LTC4-like activities and both of these arachidonic acid metabolites and free oxygen radicals are the main necrotizing agents in ischemia-reperfusion induced damage.