Figen Doran

G-308A TNF-α polymorphism is associated with an increased risk of hepatocellular carcinoma in the Turkish population: case-control study.

BACKGROUND Tumor necrosis factor-alpha (TNF-alpha) is a pro-inflammatory cytokine that may act as an endogenous tumor promoter. A genetic polymorphism of TNF-alpha gene at position -308 promoter region is involved in the regulation of expression level and has been found to be associated with susceptibility to various types of cancer. METHODS To determine the association of the TNF-alpha gene G-308A polymorphism on the risk of hepatocellular carcinoma (HCC) in a Turkish population, a hospital-based case-control study was designed consisting of 110 diagnosis subjects with hepatocellular carcinoma and 110 cancer-free control subjects matched on age, gender, smoking and alcohol status. The genotype frequency of this polymorphism was determined by using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. RESULTS The distribution G-308A genotype was significantly associated with the risk of HCC (p<0.001, odds ratio [OR]=4.75, 95% confidence interval [CI]=2.25-9.82 for -308 AA/GA genotypes versus GG genotype). CONCLUSION We suggested that the presence of the high producer allele -308A in the TNF-alpha gene appears to be associated with an increased risk for the development of HCC in Turkish population.

Interleukin (IL)-6, Interleukin (IL)-8 Levels and Cellular Composition of the Vitreous Humor in Proliferative Diabetic Retinopathy, Proliferative Vitreoretinopathy, and Traumatic Proliferative Vitreoretinopathy

Purpose: To investigate the interleukin (IL)-6 levels, IL-8 levels, and cellular composition of the vitreous humor in patients with proliferative diabetic retinopathy (PDR), proliferative vitreoretinopathy (PVR), and traumatic PVR. Methods: Vitreous samples from 14 patients with PDR, 10 patients with PVR, and 10 patients with traumatic PVR were analyzed. Fifteen cadaver eyes were used as controls. Cytokine levels were measured by ELISA. Results: Elevated IL-6 levels were detected in the vitreous of 12 (85.7%) of the PDR patients, eight (80%) of the PVR patients, and all (100%) of the traumatic PVR patients. None of the control IL-6 results were elevated. Vitreous IL-8 levels were elevated in 12 (85.7%) of the PDR patients, six (60%) of the PVR patients, all (100%) of the traumatic PVR patients, and one (6.7%) of the control eyes. Cytological examination of the vitreous specimens revealed a predominance of macrophages (50%) in the PDR samples and a predominance of retinal pigment epithelial (RPE) cells (60%) in the PVR samples. In contrast, neutrophils predominated (88%) in the traumatic PVR samples. Conclusion: The findings suggest that IL-6 and IL-8 may be involved in the pathogenesis of PDR, PVR, and traumatic PVR. High proportions of RPE cells and macrophages are associated with elevated IL-6 and IL-8 levels in the vitreous of PDR and PVR patients; however, the fact that these cells are not predominant in traumatic PVR suggests that different immune response mechanisms may be active in the pathogenesis of these disorders.

A Possible Central Antinociceptive Effect of Dipyrone in Mice

The antinociceptive effect of dipyrone, a nonsteroidal and inflammatory drug, was studied in a series of experiment employing tail-flick and hot-place models and the abdominal constrictor test. The drug was given via intracerebroventricular (i.c.v.), intrathecal (i.t.) or subcutaneous (s.c.) routes. Dipyrone exhibited no analgesic activity in the tail-flick and hotplate tests while it inhibited the number of stretches in a dose-dependent manner. The antinociceptive effect of dipyrone administered by the i.c.v. and i.t. routes was almost complete reversed by naloxone treatment. The same procedure attenuated but not completely inhibited the dipyrone action induced by s.c. administration. Histopathological examination revealed that i.t. dipyrone application produces no significant lesion in the spinal cord. The results suggest that dipyrone may exert a central antinociceptive action reversed by naloxone.

Pheochromocytoma of the urinary bladder

The case of a 65‐year‐old male with pheochromocytoma arising in the urinary bladder is presented. Clinical evaluation included ultrasonography, intravenous pyelography and computerized tomography (CT) scan. Transurethral resection of an exophytic tumor 1 cm in diameter was performed. The histological diagnosis was pheochromocytoma of the bladder. The evaluation and management of this type of tumor is discussed.

Protective Effect of L-Arginine Intake on the Impaired Renal Vascular Responses in the Gentamicin-Treated Rats

The purpose of this study was to investigate the effect of gentamicin (100 mg/kg/day, i.p.) treatment on endothelium-dependent and -independent vasodilation in isolated perfused rat kidney, and the effect of amino acid L-arginine (in the drinking water, 2.25 g/l) on renal dysfunction induced by gentamicin. When gentamicin-treated groups were compared with the control group, it was observed that BUN and creatinine levels increased significantly. Also, the relaxant responses induced by acetylcholine, sodium nitroprusside and pinacidil decreased. Histopathological examination indicated acute tubular necrosis in this group. In animals treated with gentamicin together with L-arginine, there was a significant amelioration in the BUN and creatinine levels. The vasodilator responses were similar to those of the control group. Histopathological examination indicated only hydropic degeneration in tubular epithelium of kidney. Co-administration of L-NG-nitroarginine methyl ester (L-NAME) (112.5 mg/l), an inhibitor of nitric oxide synthase, and L-arginine to rats treated with gentamicin did not change the protective effect of L-arginine. In rats receiving L-NAME alone, the level of BUN and creatinine and vasodilation to acetylcholine were not significantly different when compared to those of the control group, while relaxant responses to sodium nitroprusside and pinacidil were increased. These results suggest that gentamicin leads to an impairment in vascular smooth muscle relaxation in addition to acute tubular necrosis in the rat kidney. Supplementation of L-arginine has an important protective effect on gentamicin-induced nephropathy.

Effect of tempol (4‐hydroxy tempo) on gentamicin‐induced nephrotoxicity in rats

We investigated the effects of tempol (4‐hydroxy tempo), a membrane‐permeable radical scavenger, on gentamicin‐induced renal failure in rats. The rats were given gentamicin (100 mg/kg/day, i.p., once a day); and gentamicin (100 mg/kg/day, i.p.) and tempol (3.5, 7 or 14 mg/kg/day, i.p., once a day). At the end of 7 days, the gentamicin group produced the remarkable nephrotoxicity, characterized by a significantly decreased creatinine clearance and increased serum creatinine, blood urea nitrogen (BUN) and daily urine volume when compared with controls. In control the BUN value was 21.2 ± 0.07 (mg/100 mL); in comparison, it was 96.9 ± 6.03 in gentamicin group (P < 0.05). Renal histopathologic examination confirmed acute tubular necrosis in this group. In rats treated with gentamicin and tempol a partial improvement in biochemical and histologic parameters was observed. BUN values were 96.9 ± 6.03 and 36.3 ± 2.39 in gentamicin, and gentamicin plus tempol (14 mg/kg) treated groups, respectively (P < 0.05). These results suggest that the administration of tempol may have a protective effect on gentamicin‐induced nephrotoxicity in rats.

The effects of ureteral obstruction on Cajal-like cells in rats.

OBJECTIVE To determine the changes in number and morphology of interstitial cells of Cajal (ICC)-like cells (ICC-LC) at the ureteropelvic junction (UPJ) of rats after experimental distal ureteral obstruction. MATERIALS AND METHODS Of a total of 109 rats, 20 served as controls (C), 20 underwent sham-operations (SH) and 69 were in the study (S) groups. The UPJs were extracted initially in the C and SH groups, and 7, 14, 30, 60 and 90 days after ligation of the distal ureter in the study groups (S1, S2, S3, S4 and S5, respectively). The sections stained by c-kit anticore were studied under a light microscope. RESULTS The mean number of ICC-LC was 4.55+/-2.21 in C, 5.15+/-3.51 in SH, 7.40+/-6.88 in S1, 21.16+/-19.03 in S2, 12.63+/-8.16 in S3, 10.40+/-5.09 in S4, and 10.9+/-6.33 in S5. There was a statistically significant increase in ICC-LC in the study groups, except S1, compared to the C and SH groups. No significant difference was detected in Cajal cell morphology and distribution pattern between groups. CONCLUSIONS Based on the changes in number of ICC-LC at the UPJ after obstruction of the distal ureter compared with the limited data available in the literature, we suggest that ICC-LC have a close relationship with motility of the ureter.

Correlation of serum adiponectin levels and hepatic steatosis in hepatitis c virus genotype 1 infection

Steatosis is an important cofactor in hepatitis C virus (HCV) because it is associated with fibrosis and reduces early and sustained virologic response. Recent studies suggest that HCV genotype 1 is not steatogenic if additional risk factors are not present. Because hypoadiponectinemia was found to be a feature of nonalcoholic steatohepatitis (NASH) independent of insulin resistance, its level in patients with hepatitis C genotype can reveal the optimal therapeutic strategy. This study was conducted to determine the role of the relationship between steatosis and serum adiponectin levels in the progression of liver damage in HCV genotype 1 without known risk factors for NASH. Patients (n=50) with biopsy-proven chronic hepatitis C (CHC), positive HCV RNA, and raised alanine aminotransferase were enrolled. They were carefully selected to rule out possible confounding factors for the presence of steatosis and additional systemic or liver disease. Associations between serum adiponectin levels and grade of steatosis, histologic activity index (HAI), fibrosis grade of liver biopsies, patient age, HCV viral load, and serum transaminase activities were studied. Also, adiponectin levels were compared with those of a control group of 30 healthy volunteers with normal ultrasound findings of the upper abdomen who had no known NASH risk factors. The investigators found that adiponectin levels in patients with CHC genotype 1 were similar to those in healthy subjects. No significant association was found between adiponectin levels and severity of steatosis, HCV RNA levels, HAI, transaminases, and fibrosis. Steatosis was present in 41 patients (82%) with CHC. Multivariate analysis of data on 50 patients revealed that severity of steatosis was independently related to age alone (P=.03). A correlation between HCV RNA load and HAI was observed (P=.02; r=0.712). HAI also was associated with stage of fibrosis (P=.00;r= 0.612). In cases of chronic HCV genotype 1 hepatitis, steatosis is a common histologic feature, although no risk factors are known. Results presented here cannot establish an association between adiponectin and severity of steatosis when risk factors for steatosis are unknown. Additional studies are needed to discover a metabolic treatment that would seek to improve the progression of hepatic steatosis in CHC infection.

A randomised trial of two cisplatin-containing chemotherapy regimens in patients with Stage III-B and IV non-small cell lung cancer

Seventy-four newly diagnosed patients with histologically proven Stage III-B and IV non-small cell lung cancer were randomized to receive either cisplatin: 20 mg/m2 x day x 5, ifosfamide: 1.8 g/m2 x day x 5, mesna: 1.2 g/m2 x day x 5, etoposide: 100 mg/m2 x day x 5 (ICE) or cisplatin: 20 g/m2 x day x 5 and etoposide: 100 mg/m2 x day x 5. Response rates were 59% in the ICE and 40% in the CE arm with a significant advantage in response duration and overall survival in the ICE receiving patients (P = 0.03, P = 0.0008). As we used granulocyte colony stimulating factor (G-CSF) very frequently, myelotoxicity remained substantial but acceptable.

Neurofibromatosis type 1, gastrointestinal stromal tumor, leiomyosarcoma and osteosarcoma: Four cases of rare tumors and a review of the literature

BACKGROUND Neurofibromatosis type 1 (NF1) is a genetic syndrome that predisposes patients to benign and malignant tumor development. Patients with NF1 develop multiple neurofibromas that can transform into aggressive sarcomas known as malignant peripheral nerve sheath tumors. In contrast, malignant tumors unrelated to the nervous system rarely coexist with neurofibromatosis. The aim of this article was to present four cases of adult NF1 patients with malignant tumors unrelated to the nervous system as well as a bibliographic search for papers describing these tumors in NF1, focusing on osteosarcomas, gastrointestinal stromal tumors (GISTs), leiomyosarcomas and somatostatinomas and their genetic alterations in NF1. METHODS Search engines such as PubMed and MEDLINE were browsed for English-language articles since 1989 using a list of keywords, as well as references from review articles. Search terms were NF1, osteosarcoma, leiomyosarcoma, somatostatinoma and GIST. Data were summarized in a table at the end of the Results section. RESULTS In our four NF1 cases, there were one osteosarcoma, one leiomyosarcoma, one somatostatinoma and GIST and one GIST. NF1 was diagnosed at an adult age when these patients were admitted to our oncology department. The results generated by the literature search yielded 75 articles about NF and GIST. We summarized the clinical characteristics of 43 patients with NF1 and somatostatinoma. Forty-five articles involving NF and osteosarcoma were found, and of these, 26 involved NF1; from these articles, we identified the clinical features of 8 patients. Twenty-five articles were found concerning NF1 and leiomyosarcoma, and of those, we summarized the clinical features of 15 patients. CONCLUSIONS Here we reviewed somatostatinomas, GISTs, osteosarcomas and leiomyosarcomas occurring in NF1 patients. Patients with NF1 who present with gastrointestinal symptoms, should be carefully evaluated carefully with a high index of suspicion of potential GISTs, periampullary and duodenal tumors. Patients with pathological fractures or bone pain along with NF1 should be carefully screened for malignant bone tumors. Patients with NF1 can develop leiomyosarcoma less frequently than other malignancies, but the association of uterine leiomyoma and NF1 may not be fortuitous. Somatic mutations were defined for frequent tumors, including neurogenic tumors and GISTs but not for sarcomas due to the complexity of underlying mechanisms of the disease and tumorigenesis. Based on the findings; all NF patients can develop malignant tumors, including the less frequently observed ones. Therefore, we recommend that new genetic studies should be performed for rare malignancies in cases of NF1.