Orhan Bayram

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.

Prognostic value of serum IL-18 and nitric oxide activity in breast cancer patients at operable stage

Interleukin-18 (IL-18) is a multifunctional cytokine that was previously termed interferon-&ggr;-inducing factor. It has been suggested that serum IL-18 level may be used as a prognostic factor in some cancer types. Nitric oxide is a potent biologic molecule involved in the pathogenesis of cancer. In this study, we measured serum IL-18 and nitrate + nitrite levels in 56 patients with nonmetastatic breast cancer and 14 control subjects. Serum IL-18* and nitrate + nitrite** levels were significantly higher in patients with breast cancer when compared to the control subjects (*p < 0.05, **p < 0.001). Serum IL-18 levels were significantly higher in patients whose tumor size was greater than or equal to 5 cm when compared to patients whose tumor size was less than or equal to 2 cm (p < 0.05). Patients who were axillary lymph node negative (ALN) had lower serum IL-18 levels when compared to patients with positive ALN (p < 0.001). Serum IL-18 levels were significantly higher in patients with stage IIB or IIIA when compared to patients with stage I or IIA (p < 0.05). There was no significant difference in serum nitrate + nitrite levels in terms of age, tumor stage, estrogen receptor, and menopausal and ALN status (p > 0.05). In conclusion, serum IL-18 level may be a useful marker to predict prognosis of patients with breast cancer in complete remission after surgery. Long-term follow-up is required to clarify this hypothesis.

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.

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.

Examination of the rescue effects of folic acid on derangement of the tubo-ovarian ultrastructural architecture caused by methotrexate

The purpose of this examination was to observe the effects of folic acid (FA) on methotrexate (MTX)-induced derangements in the fallopian tubes. Investigators in this study sought to explore whether MTX-induced dysfunction in the fallopian tubes would be lessened by the addition of FA to MTX treatment. For this study, 18 albino Wistar rats were randomly divided into 6 groups, each of which comprised 3 rats; 0.1 mg/kg FA, 1 mg/kg MTX + 0.1 mg/kg FA, 5 mg/kg MTX + 0.1 mg/kg FA, 1 mg/kg MTX, and 5 mg/kg MTX were given to groups 2, 3, 4, 5, and 6, respectively; group 1 was the control group. After MTX injection, fallopian tube samples from all groups were prepared for examination under electron microscopy. The findings observed in groups 1 and 2 were similar. The level of cellular destruction was greater with the higher doses of MTX without FA; in particular, loss of cilia in the epithelium was prominent in groups 5 and 6. However, there was less cellular destruction observed in groups 3 and 4 than in groups 5 and 6. As a result, the addition of FA should not be overlooked, even when a single-dose MTX regimen is chosen for the treatment of patients with unruptured ectopic pregnancy

Expression of steroid receptors in intact rat uterus, mammary gland, and liver treated with selective estrogen receptor modulators and conjugated equine estrogens.

The aim of the present study was to determine the effects of conjugated equine estrogens (CEE) and selective estrogen receptor modulators (SERM) (tamoxifen [TAM] and raloxifene [RAL]) on the expression of steroid receptors—estrogen receptor (ER) and progesterone receptor (PR)—in intact rat uterus, mammary gland, and liver. A total of 24 female rats weighing 250 to 300 g were randomized into 4 groups. Groups 1, 2, 3, and 4 were respectively given conjugated equine estrogen, tamoxifen, raloxifene, and vehicle for a 28-day period. ER and PR expression was detected in tissues of the uterus, mammary gland, and liver. Uterine wet weight and serum estradiol levels were established for all groups. No statistical difference was observed between groups in the ER expression of mammary gland and liver and in the PR expression of uterus, mammary gland, and liver, but differences were noted in serum estradiol levels and uterine ER expression. Serum estradiol levels were lower in the TAM-treated group; differences between the TAM-treated group and the other groups were statistically important (P > .05). Uterine ER expression was greater in the CEE-treated group; differences between the CEE-treated group and theTAM and RAL-treated groups were statistically important (P > .05). CEE or SERM versus vehicle treatment in controls did not seem to result in statistically important differences in ER and PR expression in intact rat uterus, mammary gland, and liver. Only ER expression in the uterus was found to be greater in the CEE-treated group than in SERM-treated groups.

Evaluation of hormone replacement therapy which may have an adrenomedullin-mediated protective effect on cardiovascular disorders

Background and aims: This study aimed to determine whether there is an adrenomedullin (AM)-mediated protective effect of postmenopausal estrogen/progestin therapy (HRT) against cardiovascular disorders. Methods: A total of 22 postmenopausal women without hysterectomy undergoing postmenopausal symptoms (aged 43–52) were treated with conjugated equine estrogen (0.625 mg/die) plus medroxyprogesterone acetate (2.5 mg/die) for six months. The flow velocity of the right middle cerebral artery [measured as resistance index (RI) and pulsatility index (PI)], plasma levels of adrenomedullin and endothelin-1 (ET-1), mean baseline ratio of AM to ET-1, and lipid profiles were assessed before and after HRT. Results: A statistically significant difference was found for triglycerides, total cholesterol, AM/ET-1 ratio and right middle cerebral artery PI (p<0.05), without any significant differences in HDL, LDL, AM, ET-1, systolic blood pressure, diastolic blood pressure, a right middle cerebral artery RI (p>0.05) between pre- and post- HRT. Conclusions: Adrenomedullin may be added to other vasoactive peptides as a new potential candidate for HRT-mediated vascular protection. The ratio of AM/ET-1 vs AM or ET-1 alone may be a useful biological marker of this protection.