Prognostic Significance of Tumor Tissue NeuGcGM3 Ganglioside Expression in Patients Receiving Racotumomab Immunotherapy.

Expression of N-glycolyl GM3 (NeuGcGM3) ganglioside was detected in the tumor specimens of patients who were on Racotumomab anti-idiotype vaccine maintenance treatment, and prognostic significance as a biomarker was investigated. No statistically significant association was observed in the multivariate analysis between overall survival and tissue NeuGcGM3 IHC levels. Although numerically there was a difference favoring less intense IHC for better prognosis, this did not reach statistical power. However, there was a strong correlation between Racotumomab doses and overall survival (OS). Mean OS of the patient with more than 10 Racotumomab application was significantly longer than the patient who had less than 10 injections (70.7 months vs. 31.1 months, p < 0.001). We propose that, regardless of staining intensity, the presence of NeuGcGM3 in patient tissues might be an indicator of benefit in Racotumomab treatment.

Muir-Torre syndrome: a case report and review of the literature.

Muir-Torre syndrome is a rare autosomal dominant genodermatosis characterized by the occurrence of sebaceous gland neoplasm associated with visceral malignancies. Most patients present with sebaceous adenomas, but cystic sebaceous neoplasms have been reported as specific markers of the syndrome. Gastrointestinal and genitourinary cancers are the most common internal malignancies. Colorectal cancer is the commonest visceral neoplasm in Muir-Torre syndrome patients. In this case report, we describe a rare case of Muir-Torre syndrome associated with colon cancer, and we demonstrate the important role of the dermatopathologist in alerting the clinician to the possibility of Muir-Torre syndrome when the diagnosis of sebaceous neoplasm is made.

Matrix metalloproteinase-9 decreased after chemotherapy in patients with non-small cell lung cancer.

AIMS AND BACKGROUND: The aim of the study was to investigate the alteration in serum matrix metalloproteinase-9 (MMP-9) levels after chemotherapy and the association between the changes in serum levels of MMP-9 and response to chemotherapy in patients with advanced stage non-small cell lung cancer. METHODS AND STUDY DESIGN: Twenty-eight consecutive patients with advanced non-small cell lung cancer and 24 healthy controls were enrolled in the study. The patients were treated with cisplatin-based combination chemotherapy. After two cycles, the response was evaluated. Before and after two cycles of chemotherapy, serum samples were collected from the patients. RESULTS: Prechemotherapy MMP-9 (ng/ml) levels were significantly higher in patients with advanced stage non-small cell lung cancer than in controls (7.2 ± 2.8 vs 4.5 ± 2.1, P <0.001). Prechemotherapy MMP-9 levels were elevated compared to postchemotherapy levels as well (7.2 ± 2.8 vs 5.2 ± 3.3, P = 0.005). Prechemotherapy MMP-9 levels were significantly higher than postchemotherapy MMP-9 levels in patients with partial response (7 patients) (8.2 ± 1.8 and 3.2 ± 2.3, respectively; P = 0.018), but the pre- and postchemotherapy MMP-9 levels were no different in patients with stable disease or progressive disease (21 patients) (7 ± 3.1 and 5.9 ± 3.3, respectively; P = 0.08). CONCLUSIONS: The difference between pre- and postchemotherapy MMP-9 levels in responders was more prominent than that in nonresponders. Whether the decline in serum MMP-9 levels might be used as a marker of response to chemotherapy should be investigated in larger studies.

Prognostic and predictive value of vascular endothelial growth factor and its soluble receptors, VEGFR-1 and VEGFR-2 levels in the sera of small cell lung cancer patients.

OBJECTIVES: Small cell lung cancer (SCLC) has a rapid growth rate and is characterized by early metastases. Tumor growth is dependent on angiogenesis. Vascular endothelial growth factor (VEGF) is an important regulator of angiogenesis. Whether surveillance of pre- and post-treatment serum VEGF and especially its receptors VEGF-1 and VEGF-2 levels in SCLC patients have impact on clinical outcome is unknown. METHODS: From February 2001 to January 2003, 39 consecutive patients with histological proven SCLC were enrolled into the study. Pre-treatment (n: 39) and post-treatment (n: 25) samples of the same patients were collected at the time of their response evaluation. The levels of VEGF and its receptors VEGFR-1 and VEGFR-2 were measured in the serum by quantitative sandwich enzyme immunoassay technique. RESULTS: The median pre-treatment serum VEGF, VEGFR-1, and VEGFR-2 levels which were significantly higher than the normal controls were 1,200 pg/ml (range, 1,414.3 +/- 956.2 pg/ml), 85 pg/ml (range, 97.8 +/- 70.7 pg/ml), and 11,550 pg/ml (range, 14,481 +/- 6,267 pg/ml), respectively. We detected a poor but positive correlation between VEGF and VEGFR-2 (r: 0.46, p: 0.003). Pre-treatment low serum VEGF (<728.5 pg/ml) value (p: 0.02) and good response to treatment (p: 0.008) were found as good prognostic factors by multivariate analysis. CONCLUSIONS: Low serum VEGF concentration is a significant and independent prognostic factor in SCLC patients. Surveillance of VEGF and its receptors to predict chemotherapy response is not useful. Whether the levels of serum VEGF and its receptors VEGFR-1 and VEGFR-2 have value in detecting treatment modalities of SCLC need further studies.

Gemcitabine and cisplatin as neo-adjuvant chemotherapy for non-small cell lung cancer: a phase II study.

The combination of gemcitabine and cisplatin is one of the most active chemotherapy regimens against non-small cell lung cancer (NSCLC). This study was designed to evaluate the efficacy and safety of gemcitabine combined with cisplatin in a 3-week cycle regimen for patients with operable, early stage NSCLC. Gemcitabine at a dose of 1000 mg/m(2) on days 1 and 8 of each 21-day cycle for 3 cycles, followed by cisplatin at a dose of 75 mg/m(2) on day 1 was administered to patients with previously untreated, operable, early stage (IB-IIIA) NSCLC. A total of 47 patients (46 male, mean age 56.0+/-8.0 years) who met the eligibility criteria were enrolled. The pathological complete response rate was 5.3% of operated patients and 4.3% of total patients. At visit 4, 57.1% of the patients had partial response, 38.1%, stable disease and 4.8%, progressive disease. The main toxicities - leukopenia, neutropenia and thrombocytopenia - were usually clinically asymptomatic and did not require hospitalization. Non-hematological toxicities were minimal and manageable. Disease free and 12-month overall survival rates were over 70% and 80%, respectively. This study demonstrates that the administration of gemcitabine and cisplatin combination for 3 cycles is effective and tolerable for patients with operable, early stage NSCLC. Low toxicity profile and promising survival outcome suggest that this regimen has an encouraging activity in this subset of patients.

Is lower socio-economic status a risk factor for Helicobacter pylori infection in pregnant women with hyperemesis gravidarum?

BACKGROUND/AIMS: Lower socio-economic status was demonstrated to be a major risk factor for infection with H. pylori infection in the general population. The aim of the present study was to investigate any possible association between infection with H. pylori and hyperemesis gravidarum and between socio-economic status and H. pylori infection in pregnant women with hyperemesis gravidarum. METHODS: Fifty-six pregnant women with hyperemesis gravidarum and 90 control pregnant women were enrolled in the study. Forty-five (80.4%) subjects in the hyperemesis gravidarum group and 72 (80%) subjects in the control group were assessed as lower socio-economic status by questionnaire. Specific serum immunglobulin G for H. pylori was assayed by fluorescent enzyme immunoassay method for both groups. RESULTS: Serologically positive H. pylori infection was detected in 46 (82.1%) subjects of the hyperemesis gravidarum group and in 58 (64.4%) of the controls (p=0.024). With respect to the patients with lower socio-economic status, 40 (88.9%) of the 45 patients with hyperemesis gravidarum and 49 (68.1%) of the 72 controls were positive for H. pylori (p=0.013). CONCLUSIONS: This study supports the studies suggesting an association between H. pylori and hyperemesis gravidarum. In addition, the lower socio-economic status may also be an important risk factor for infection with H. pylori in pregnant women with hyperemesis gravidarum.

Serum levels of intercellular adhesion molecule-1 and nitric oxide in patients with chronic hepatitis related to hepatitis C virus: connection fibrosis.

BACKGROUND/AIMS: Chronicity of inflammation or fibrosis of liver parenchyma in patients with hepatitis C virus infection can be related to features of immunological responses in the liver. Adhesive interactions and free radicals are two important aspects of this inflammatory response. The aim of this study was to investigate serum sICAM-1 and nitric oxide levels in the sera of patients with post-hepatitis C chronic hepatitis. METHODOLOGY: Twenty chronic hepatitis patients diagnosed histopathologically and positive for antihepatitis C virus antibody and 20 healthy carriers of hepatitis C virus were included as study and control groups, respectively. Serum hepatitis C virus-RNA, sICAM-I, nitric oxide, blb, albumin and ALT determinations were made in the specimens of each subject in the study and control group. RESULTS: The mean serum sICAM-I levels of study and control subjects were 463.85 +/- 20.42 ng/mL and 241.85 +/- 13.71 ng/mL, respectively (p < 0.01). The same values for nitric oxide levels were 53.57 +/- 3.63 mumol/L and 32.17 +/- 2.19 mumol/L in the same order and also significantly different from each other (p < 0.01). There was a close correlation between fibrosis scores and serum sICAM-I levels (r = 0.77, p < 0.001), serum albumin (r = -0.54, p = 0.014) and ALT (r = 0.49, p = 0.02). Nitric oxide levels, on the other hand, negatively correlated with fibrosis scores (r = -0.59, p = 0.006), sICAM-1 (r = -0.57, p = 0.009) and ALT (r = -0.54, p = 0.013). CONCLUSIONS: Increased serum levels of sICAM are associated with increased fibrotic changes of patients with hepatitis C virus infection, whereas, nitric oxide which may be a suppressor molecule for fibrosing levels are inversely related to fibrotic process.

Systolic pulmonary artery pressure and serum uric acid levels in patients with hyperthyroidism.

BACKGROUND: The aim of this study was to investigate systolic pulmonary artery pressure (SPAP) and serum uric acid (SUA) levels in patients with hyperthyroidism and after euthyroid state was reached. METHODS: Twenty five (10 male, 15 female, mean age 49.8 +/- 11.6 years) consecutive patients with hyperthyroidism (18 due to toxic nodular goiter, seven to Graves' disease) and 25 (eight male, 17 female, mean age 48.7 +/- 8.7 years) healthy controls were included in the study. Thyroid hormones, SUA, glucose, urea, creatinine, and transthoracic echocardiography were performed in all patients. All tests were repeated after treatment of hyperthyroidism. RESULTS: Mean SPAP and SUA levels in patients with hyperthyroidism were significantly higher than in controls (30.4 +/- 8.5 vs. 22 +/- 3.7 mmHg, p <0.0001, and 5.1 +/- 1.1 vs. 4.3 +/- 0.5 mg/dL, p = 0.004, respectively). Elevated SPAP and SUA levels in patients with hyperthyroidism decreased significantly after treatment to levels comparable with controls (24.4 +/- 5.4 mmHg, p = 0.001 and 4.6 +/- 0.9 mg/dL, p = 0.002, respectively). Correlation between SPAP and SUA levels, however, was not significant in hyperthyroid population and after euthyroid stage was reached (r = 0.34, p = 0.097, and r = 0.256, p = 0.216, respectively), possibly due to relatively low number of patients (overall correlation of SPAPs and SUAs was r = 0.4, p <0.0001). CONCLUSIONS: Hyperthyroidism should be included in differential diagnosis of pulmonary arterial hypertension. However, further investigations are needed to determine the exact mechanism between hyperthyroidism and pulmonary hypertension.

Serotonin transporter gene polymorphism in irritable bowel syndrome.

OBJECTIVES: Serotonin is a key mediator of intestinal peristalsis, and after it is secreted, it is effectively cleansed from the neuronal gap by means of a high affinity substance called serotonin transporter (SERT), which depends on the Na+ and Cl- ions localized in the presynaptic neuronal membranes. The aim of this study was to investigate SERT polymorphism in patients with irritable bowel syndrome (IBS). METHODS: SERT gene polymorphism was assessed by polymerase chain reaction on DNA chains obtained from leukocytes in serum samples from 54 patients diagnosed with IBS and 91 healthy subjects. The polymorphism of two regions (variable number tandem repeats and the SERT gene-linked polymorphic region [5-HTTLPR]) of SERT was assessed. RESULTS: SERT polymorphisms were found to be similar in healthy subjects and IBS patients (p > 0.05). IBS patients were divided into three groups: diarrhea predominant (n = 18), constipation predominant (n = 26), and alternating diarrhea and constipation (n = 10). These groups were compared with respect to gene polymorphism, and it was found that the 5-HTTLPR allele S/S genotype occurred with greater frequency in the constipation predominant group than in the other two subgroups (p < 0.05), and L/S genotype frequency in the diarrhea predominant group was higher than those in the constipation and control groups. CONCLUSIONS: No relationship was found between IBS and SERT gene polymorphism. It is conceivable that the presence of the S/S genotype in IBS patients carries an increased risk of the constipation predominant type of IBS, whereas the presence of the 5-HTTLPR allele L/S genotype carries an increased risk of the diarrhea predominant type.

Effects of glibenclamide, metformin and insulin on the incidence and latency of death by oubain-induced arrhythmias in mice.

This study was performed to investigate possible effects of glibenclamide, insulin and metformin on the death latency and incidence caused by a cardiac glycoside, oubain. Mice of both sexes were injected with oubain (i.p. 20 mg x kg (-1), glibenclamide (s.c. 0.1-10 mg x kg (-1), insulin (s.c. 0.3-3 U kg (-)) and metformin (i.p. 200 mg x kg (-1)) and combinations of the last three drugs with oubain. Death latency was measured and lethality incidence was calculated. Death was assessed by visual observation. Plasma glucose level was evaluated from the tail blood. Glibenclamide (0.1 mg x kg (-)) prolonged the latency from 11.3 plus minus 1.2 to 15.8 plus minus 1.8 min but failed to decrease the incidence of death. At higher doses (1--10 mg x kg (-1)) it had no effects on the latency or the incidence. 0.3 U kg (-1)insulin decreased the incidence from 73.7 to 33.3% ( P< 0.05) without affecting the latency. However the higher dose (3 U kg (-1)) did not have any effects on the incidence or the latency. Oubain increased blood glucose level from 114.1 plus minus 3.8 (control) to 152.1 plus minus 5.3 mg x dl (-1). Metformin (200 mg x kg (-1)) did not affect either the latency or the incidence of death. While metformin did not decrease plasma glucose, insulin and higher doses of glibenclamide (1--10 mg x kg (-1)) markedly lowered glucose in blood. However, at the dose of 0.1 mg x kg (-1)glibenclamide did not alter the glucose level in the blood but prevented oubain from increasing it. Insulin (0.3 U kg (-1)) and, to some extent, glibenclamide (0.1 mg x kg (-)) but not metformin could be effective antiarrhythmic agents against oubain-induced arrhythmias.

The effect of recombinant hepatitis B vaccine therapy in chronic hepatitis B infection.

BACKGROUND/AIMS: Immune-modulator and antiviral treatments for carriers of hepatitis B virus are known to have poor efficacy with a high cost and frequent side effects, which has led to investigation of new treatment modalities. The aim of this study was to determine the efficacy of recombinant hepatitis B vaccine in the treatment of patients with chronic hepatitis B (HBV DNA >5 pg/ml, ALT>60) infection diagnosed histopathologically and asymptomatic carriers (HBV DNA<5 pg/ml, ALT <40, Anti Hbe positive) of the virus. METHODS: The vaccine (Gen Hevac B Pasteur) was administered at baseline and at months one and six to patients with chronic hepatitis and asymptomatic carriers. Ten cases with chronic hepatitis B infection were assigned to a control group to whom no treatment was given. Biochemical and microbiological investigations were performed at baseline and at months three, six and twelve in all cases. Seroconversion of Hbe Ag, loss of HBV DNA and normalization of ALT were considered as a positive response. RESULTS: Patients with chronic hepatitis B who were given the vaccine were found to have significantly low levels of HBV DNA at 12 months (63.2+/-20pg/ml) compared to baseline values (174.4+/-36.9pg/ml), while controls were found to have high levels of HBV DNA at 12 months (223.1+/-33pg/ml) compared to baseline values (165.2+/-33.2pg/ml) (p<0.05). At 12 months, HBV DNA had become negative in seven of 19 patients given the vaccine (36.8%) Four patients with chronic hepatitis (36.35%) were observed to have HBeAg seroconversion and one patient (5.2%) HBsAg seroconversion at the end of 12 months and there were four (21.05%) patients who responded positively to vaccine therapy in this group. Asymptomatic carriers and controls did not have seroconversion of HBs Ag. Also, HBV DNA did not become negative in controls. CONCLUSION: It may be concluded that recombinant hepatitis B vaccine is effective in the treatment of chronic hepatitis B.