Clinical significance of serum protease activated receptor1 levels in patients with lung cancer.

OBJECTIVE: Protease-activated receptors (PAR) are G protein coupled receptors and they regulate many biological processes, including coagulation and cell survival and they might be good markers in some types of malignant tumors, providing useful information in diagnosis and prognosis. The objective of this study was to determine the clinical significance of the serum levels of PAR1 in lung cancer patients. PATIENTS AND METHODS: Eighty patients with lung cancer were enrolled into this study. Serum PAR1 levels were determined by the solid-phase sandwich ELISA method. Median age was 58.5-years old, range 36 to 80 years. RESULTS: The majority of the patients had NSCLC (85%) and stage IV disease (56%). The baseline serum PAR1 concentrations of the lung cancer patients were significantly higher than control group (median values 26.45 ng/mL v 0.07 ng/mL, p < 0.001). However, clinical variables including age, gender, histology, stage of disease, and response to chemotherapy were not found to be correlated with serum PAR1 levels (p > 0.05). Moreover, it failed to show any prognostic value on the survival of the lung cancer patients. CONCLUSIONS: The serum levels of PAR1 might have a diagnostic value in lung cancer patients. However, its predictive and prognostic values were not determined.

The diagnostic, predictive, and prognostic role of serum epithelial cell adhesion molecule (EpCAM) and vascular cell adhesion molecule-1 (VCAM-1) levels in breast cancer.

The purpose of this study was to determine the clinical significance of vascular cell adhesion molecule-1 (VCAM-1) and epithelial cell adhesion molecule (EpCAM) in breast cancer (BC) patients. Ninety-six BC patients and 30 age- and sex-matched healthy controls were enrolled into this study. Pretreatment serum markers were determined by the solid-phase sandwich (enzyme-linked immunosorbent assay (ELISA)). The median age at diagnosis was 48 years (range 29-80 years). Majority of the patients (71 %) had luminal subtype, and 38.5 % had metastatic disease. Twenty-nine (30 %) patients showed tumor progression, and 20 (21 %) patients died during follow-up. Median progression-free survival (PFS) and overall survival (OS) were 8.6 ± 1.7 and 35.5 ± 1.5 months, respectively. The baseline serum EpCAM levels of the patients were significantly higher than those of the controls (p < 0.001). There was no significant difference in the serum levels of VCAM-1 between the patients and controls (p = 0.47). No significant correlation was detected between the levels of the serum markers and other clinical parameters (p > 0.05). Patients with HER-2-positive and triple-negative tumors had significantly poorer PFS (p = 0.04 and p = 0.001, respectively), while metastatic disease and chemotherapy unresponsiveness had significantly adverse effect on OS analysis (p < 0.001 and p < 0.001, respectively). Neither serum VCAM-1 levels nor serum EpCAM levels were identified to have a prognostic role on either PFS or OS (VCAM-1 p = 0.76 and p = 0.32; EpCAM p = 0.16 and p = 0.69, respectively). Even though any predictive or prognostic role could not be determined for both markers, serum levels of EpCAM were found to have diagnostic value in BC patients.

Is there any diagnostic value of serum protease-activated receptor-1 (PAR1) levels on determination of epithelial ovarian carcinoma?

The role of molecular markers in ovarian cancer is still a matter of debate. Protease-activated receptor-1 (PAR1) might be a good marker in some types of malignant tumors and might provide useful information in diagnosis and prognosis. The objective of this study was to evaluate the serum levels of PAR1 in regard to diagnostic, predictive, and prognostic value in epithelial ovarian cancer (EOC) patients. Forty-four EOC patients were enrolled in this study. Serum PAR1 levels were determined by enzyme-linked immunosorbent assay (ELISA) method. Twenty-five age- and sex-matched healthy controls were included in the analysis. The median age of patients was 58 years old, ranging from 22 to 83 years, where most of them had advanced disease (stage III-IV) (n = 40, 91%). The median serum PAR1 values were significantly elevated in patients compared to healthy controls (1.52 ng/ml vs. 1.13 ng/ml) (p = 0.03), whereas any clinical variables including response to chemotherapy did not associate with serum assay (p > 0.05). Progression-free survival (PFS) and overall survival (OS) of patients who did not respond to chemotherapy nor had platinum resistance in relapsed disease were poorer in the analyses. On the other hand, serum PAR1 levels showed no significant adverse effect on either PFS or OS (p = 0.43 and p = 0.49, respectively). These results proved that baseline serum PAR1 levels of patients with EOC were significantly higher than those of healthy people. However, these assays suggested no predictive or prognostic value in this group of patients.

Modified DCF (mDCF) regimen seems to be as effective as original DCF in advanced gastric cancer (AGC)

PURPOSE: The aim of this retrospective study (from January 2007 to December 2011) was to investigate the efficacy and tolerability of mDCF schedule for chemotherapy-naïve AGC patients. PATIENTS: Patients (n = 54) with locally inoperable or distant metastasis and performance status of 0-2 were eligible. The triplet combination chemotherapy consisting of docetaxel 60 mg/m(2) on day 1, cisplatin 60 mg/m(2) on day 1, and 5-fluorouracil 600 mg/m(2) for 5 days of continuous infusion were administered every 21 days, up to nine cycles. Prophylactic G-CSF was not allowed. RESULTS: In all, 36 (67 %) patients were male and 18 (33 %) were female; median age was 59 years. The majority of patients (n = 46, 85 %) had metastatic disease and 8 (15 %) of them had locally advanced disease. Liver metastasis and peritonitis carcinomatosa were found in 20 (43 %) and 18 (39 %) of the 46 cases, respectively. The median cycle of chemotherapy was 6. In assessing 50 patients for response evaluation, one had complete response. Partial response was achieved in 27 (54 %) patients. Seventeen patients (34 %) had stable disease and 5 (10 %) had progressive disease, while 4 % (n = 2) and 11 % (n = 6) of the patients developed severe (grade 3-4) neutropenia and anemia, respectively. During the median follow-up time (6.9 months, range 0.4-24), 28 (52 %) patients died. The overall and progression-free survival were 10.7 [95 % CI 8.9-12.4] and 6.8 [95 % CI 5.8-7.8] months, respectively. CONCLUSIONS: Although this was not a prospective comparative study, the mDCF regimen seems to be as effective as the original DCF in AGC with acceptable and manageable side effects (AU)

Modified DCF (mDCF) regimen seems to be as effective as original DCF in advanced gastric cancer (AGC).

PURPOSE: The aim of this retrospective study (from January 2007 to December 2011) was to investigate the efficacy and tolerability of mDCF schedule for chemotherapy-naïve AGC patients. PATIENTS: Patients (n = 54) with locally inoperable or distant metastasis and performance status of 0-2 were eligible. The triplet combination chemotherapy consisting of docetaxel 60 mg/m(2) on day 1, cisplatin 60 mg/m(2) on day 1, and 5-fluorouracil 600 mg/m(2) for 5 days of continuous infusion were administered every 21 days, up to nine cycles. Prophylactic G-CSF was not allowed. RESULTS: In all, 36 (67 %) patients were male and 18 (33 %) were female; median age was 59 years. The majority of patients (n = 46, 85 %) had metastatic disease and 8 (15 %) of them had locally advanced disease. Liver metastasis and peritonitis carcinomatosa were found in 20 (43 %) and 18 (39 %) of the 46 cases, respectively. The median cycle of chemotherapy was 6. In assessing 50 patients for response evaluation, one had complete response. Partial response was achieved in 27 (54 %) patients. Seventeen patients (34 %) had stable disease and 5 (10 %) had progressive disease, while 4 % (n = 2) and 11 % (n = 6) of the patients developed severe (grade 3-4) neutropenia and anemia, respectively. During the median follow-up time (6.9 months, range 0.4-24), 28 (52 %) patients died. The overall and progression-free survival were 10.7 [95 % CI 8.9-12.4] and 6.8 [95 % CI 5.8-7.8] months, respectively. CONCLUSIONS: Although this was not a prospective comparative study, the mDCF regimen seems to be as effective as the original DCF in AGC with acceptable and manageable side effects.

Assessment of adrenal functions in patients with autosomal dominant polycystic kidney disease.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease and extrarenal manifestations may be observed in many organ systems. Hypothalamus-pituitary-adrenal axis was not evaluated extensively in patients with ADPKD. We aimed to evaluate this axis in these patients. METHODS: Twenty two patients with ADPKD and 27 healthy subjects were enrolled. Basal dehydroepiandrosterone sulfate (DHEAS) levels and cortisol and DHEA responses to low dose short adrenocorticotropin stimulation test were assessed. Correlation analyses of these parameters with glomerular filtration rates (GFR), renal volumes and pain characteristics in patients with ADPKD were performed. RESULTS: Patients with ADPKD had higher basal cortisol levels (12.1 ± 3.4 vs. 9.6 ± 4.3 µg/dL, p=0.033), and higher basal cortisol/DHEAS ratios (0.073 ± 0.05 vs. 0.045 ± 0.02, p=0.015) compared to controls. None of the subjects had inadequate response to adrenocorticotropin stimulation. Patients with ADPKD had lower delta cortisol (absolute increase between peak and basal) levels (10.3 ± 2.8 vs. 12.6 ± 4.2 µg/dL, p=0.026) compared to controls. Subgroup analysis showed that significant differences existed only between female patients and female controls. There was no significant correlation between cortisol levels and renal volumes or GFR. A significant correlation was found only between delta cortisol and pain frequency in female patients. CONCLUSIONS: Patients with ADPKD had higher basal cortisol levels, higher basal cortisol/DHEAS ratios and lower delta cortisol levels compared to controls, indicating promptly stimulated zona fasciculata function. Further studies are needed to confirm these results and to investigate possible underlying mechanisms.

Effect of oral administration of kefir on serum proinflammatory cytokines on 5-FU induced oral mucositis in patients with colorectal cancer.

In order to investigate the effect of kefir consumption on mucositis induced by 5-FU based chemotherapy (CT), we monitored the systemic immune response by measurement of the serum proinflammatory cytokine levels and we evaluated the anti-microbial effect of kefir with an agar diffusion method. Forty patients with colorectal cancer were included in this randomized prospective study. On the first 5 days of each CT cycle, the study group received oral lavage with kefir and then swallowed 250 ml of kefir while control group received oral lavage with 0.09% NaCl twice a day. Before and after every cycle of CT, the oral mucosa was assessed. Serum proinflammatory cytokine levels were evaluated before the initiation and after the third and the sixth cycle. Kefir was administered in 99 out of 205 courses. Mucositis developed in 27.3% of the courses given with kefir administration and in 21.7% of the courses given with 0.9% NaCl oral rinses. The difference between the two groups was not statistically significant (p > 0.05). When we compared the serum proinflammatory cytokine levels of the two groups at the baseline and following the third and the sixth cycles, we again found no statistically significant difference (p > 0.05). Kefir consumption at the mentioned doses made no statistically significant effect on serum proinflammatory cytokine levels and on the incidence of mucositis development in cancer patients. Under in vitro conditions, kefir inhibits only Staphylococcus epidermidis.

The effect of venlafaxine on ongoing and experimentally induced pain in neuropathic pain patients: a double blind, placebo controlled study.

BACKGROUND AND AIM: The aim of this randomized double blind placebo controlled study was to investigate the effectiveness and the safety of venlafaxine XR 75 and 150 mg on ongoing pain and on quantitative sensory tests in 60 patients with neuropathic pain for 8 weeks. METHODS: Evaluation parameters consisted of ongoing pain intensity (VAS), patient satisfaction, side effects, global efficacy and tolerance. Quantitative sensory measurements taken from the affected area before and after the drug treatment included pin-prick hyperalgesia, allodynia, detection and pain thresholds to electrical and heat stimuli, temporal summation of repetitive electrical and heat stimuli. RESULTS: A total of 55 patients completed the study. VAS scores decreased significantly compared to the baseline measurements in all groups. There was no significant difference between the groups regarding pain intensity and escape medication. The areas of allodynia and pin-prick hyperalgesia decreased significantly in venlafaxine groups compared to the placebo. There was no significant difference between the groups regarding the detection thresholds (electrical and heat). The pain threshold and the summation threshold to electrical stimuli and the summation threshold to heat stimuli increased significantly following treatment in both venlafaxine groups. In addition, the degree of the temporal summation to electrical and heat stimuli decreased significantly following treatment in both venlafaxine groups compared to the placebo. CONCLUSION: The study showed significant effect of venlafaxine in the manifestations of hyperalgesia and temporal summation, but not on the ongoing pain intensity. Furthermore, the quantitative sensory tests provided complementing information to the clinical measures.

Effectiveness of brachytherapy in the treatment of lip cancer: a retrospective study at the istanbul university oncology institute.

Stage T1 through T3 lip cancers can be treated primarily by brachytherapy (BRTX), with or without external radiotherapy (ERT), with adequate safety margins and good results. In this study, the outcomes of BRTX were reviewed for patients treated at the Brachytherapy Department of the Istanbul University Oncology Institute (IUOE). The medical records of 41 patients registered at IUOE with a diagnosis of lip cancer between 1988 and 2003 were reviewed. The median follow-up time was 88 months (24-160 mo). Among these patients, 21 patients with a primary tumor, 14 with tumors arising postoperatively, and 6 with postoperative recurrence of tumor were treated using BRTX. A total of 33 patients (80%) received BRTX alone and 8 (20%) received BRTX and ERT. The 10-year local control rate was 100%, 93%, and 67% for patients treated with BRTX alone, BRTX and surgery, and those treated for postoperative recurrence, respectively (P<.02). For patients treated with BRTX only and BRTX plus surgery, specific disease-free survival was 95% and 94%, respectively, and overall survival was 93% and 100%, respectively; these differences were not statistically significant. One patient with a postoperative recurrence who had been treated with BRTX died as a result of lip cancer. No patients developed any ulcerations, intra-oral complications, or mandibular necrosis. In the BRTX only group, 83% had excellent or good cosmetic results. In the surgery group, 62% had a contour deformity. In lip cancer management, BRTX results were comparable for local control, survival, and minimal late effects in normal tissue. This is in accordance with current reports in the medical literature. Satisfactory results were observed in patients with stage T1 and T2 lesions who had been treated with BRTX only and in patients with stage T3 lesions who had been treated with BRTX plus ERT, without a need for additional treatment modalities.

Multiple primary neoplasms at a single institution: differences between synchronous and metachronous neoplasms.

During the 10-year period (1987-1996) of our study, 26,255 patients with cancer were admitted to our clinic and, of these, 271 (1%) patients had multiple primary malignant tumors. Ninety-two (34%) patients had synchronous tumors (synchronous group), and 179 (66%) patients had metachronous tumors (metachronous group). The mean age at first diagnosis was higher in the former group. The ratio of men to women was 1.36 in the synchronous group and 0.74 in the metachronous group (p = 0.018). Smokers and drinkers were more common in the synchronous group. Breast cancer and lung cancer were most prevalent, and associations between head/neck and lung cancer and between breast and breast cancer were the most frequent associations in both the synchronous and the metachronous group. The frequency of aerodigestive tumors was higher and that of mesenchymal tumors was lower in the synchronous group than in the metachronous group. Localization in the medial region and in the head/neck was more frequent in the synchronous group than in the case of metachronous secondary tumors.

Crossover clinical study comparing the pharmacokinetics of etoposide (75 mg) administered as 25-mg capsules three times a day versus once a day.

Some investigators have postulated that a constant low blood level might be the ideal mode of treatment, while others have seen no reason to divide up the daily dose. To our knowledge, this study is the first to include crossover of subjects to eradicate individual differences. Our aim was to compare the pharmacokinetic effects of administering etoposide three times a day vs. once a day as 25 mg capsules. Two groups of four patients each received 75 mg/day oral etoposide for 2 days either as 75 mg once daily, or as 25 mg three times daily for 2 days. On days 8 and 9, the treatments were switched between groups. On the one-dose schedule, Cpeek (peak plasma concentration) was greater than 2 micrograms/ml in five patients and greater than 3 micrograms/ml in three patients, while in none of the patients on the three-dose schedule did the peak exceed 2 micrograms/ml. No significant difference was found in terms of Cmean (calculated by dividing the area under the curve by the observed time) between the two treatments. Variability of blood concentrations of etoposide over a 24 h period was high on the one-dose schedule (median 95%, range 54-148%) but it was lower on the three-dose schedule (median 39%, range 28%-55%). No significant differences were found between the two different dosing schedules in terms of the median duration of etoposide blood levels above 0.5 microgram/ml and above 1.0 microgram/ml. These results suggest that detailed clinical toxicity and efficacy data are needed to clarify the possible benefits of the fractionated administration of oral etoposide.

Angiogenesis and p53 protein expression in breast cancer: prognostic roles and interrelationships.

The authors have analyzed, on the one hand, the prognostic impact of microvessel density (MVD) and p53 protein expression in patients with breast cancer, and on the other hand, the correlation between the microvascular pattern and the p53 protein expression. Tumors from 120 patients whose paraffin-embedded tissue blocks were available were analyzed using the immunohistochemical method. MVD and p53 protein expression were correlated with histologic grade and tumor size, respectively. The patients with highly vascularized tumor (high MVD) had decreased overall survival (p = 0.04), whereas overexpressed p53 patients did not. In multivariate analysis, axillary lymph node status (p = 0.007), tumor size (p = 0.01), and MVD (p = 0.02) showed important prognostic influence on overall survival. When the simultaneous influence of MVD and p53 protein expression on survival were analyzed, no interrelationship was detected. The results demonstrate the prognostic impact of MVD on overall survival in breast cancer and no association between MVD and p53 protein expression.

Prevalence of childhood asthma in Istanbul, Turkey.

In order to determine the asthma prevalence in 6-12-year-old schoolchildren in Istanbul, we issued 2350 questionnaires, according to ISAAC criteria, in six randomly selected city primary schools to be completed at home by parents. A total of 2232 of the questionnaires were completed, an overall response rate of 94.9%, and 2216 questionnaires were taken into consideration. The prevalence of asthma was found to be 9.8% and wheezing 15.1%. To investigate the effect of socioeconomic status on the prevalence of asthma, we evaluated the heating system at home, the place of residence, the educational levels of the mother and father, the number of people living in the house, the sharing of bedrooms, and the annual family income. In conclusion, the prevalence of childhood asthma was not affected by any of these factors. Atopic family history, food allergy, eczema, and frequent otitis media and sinusitis attacks were evaluated and found to be significant in asthma prevalence.

Combined effects of epirubicin and tamoxifen on the cell-cycle phases in estrogen-receptor-negative Ehrlich ascites tumor cells.

Laboratory and clinical data suggest some interactions between cytotoxic agents and tamoxifen. The mechanisms of these interactions differ in estrogen-receptor-negative cell lines. The ability of tamoxifen to modify the effects of epirubicin on the cell-cycle phases of estrogen-receptor-negative Ehrlich's carcinoma ascitic cells (EATC) was studied in mice. The results showed that combination of tamoxifen with epirubicin decreased the thymidine labelling index more effectively than did either drug alone. Adding tamoxifen to epirubicin treatment induced both an early S-phase and G2-M-phase arrest and a later G0-G1-phase arrest in EATC. An increase of S0 cells in the quiescent fraction could play a role in these changes, and some of these quiescent cells may not be viable, causing them to die later. In conclusion, the data suggest that continuous exposure to tamoxifen might modify the effects of epirubicin via cell-cycle perturbations.

Immunohistochemical detection of p53 protein in rhabdomyosarcoma: association with clinicopathological features and outcome.

PURPOSE: Alteration in the p53 tumor suppressor gene is the most common tumor specific genetic change identified in most major cancer types including rhabdomyosarcomas. To investigate the overexpression of p53 and its relation to clinical features and outcome in patients with rhabdomyosarcoma (RMS), an immunocytochemical study was performed. METHODS: Formalin-fixed paraffin embedded tissue sections obtained from 42 cases of RMS were immunostained with a mouse monoclonal antibody p53-D07. Staining was assessed by evaluating the percentage of p53 immunopositive cancer cell nuclei. RESULTS: Nuclear accumulation of p53 protein was detected in 8 of 42 (19%) samples. Clinical analyses of patients demonstrated no correlation between positive staining and age, sex, histological subtype, stage and overall survival. This analysis, however, was limited by the small number of patients who demonstrated p53 immunostaining. Nonetheless, a statistically significant association was observed between p53 expression and adverse outcome. Nuclear p53 expression was associated with disease progression or recurrence (p <0.001) and with a worse event free survival (p = 0.0015). CONCLUSION: The nuclear p53 immunoreaction rate is low in RMS, but p53 expression appears to correlate with poor prognosis.

Intraperitoneal cisplatin--mitoxantrone in ovarian cancer patients with minimal residual disease.

A phase II trial was conducted to further explore the potential of salvage intraperitoneal (IP) cisplatin-based therapy in patients with residual ovarian cancer. Twenty-five patients were treated with a regimen of cisplatin (75 mg/m2) and mitoxantrone (15 mg/m2) delivered IP every three weeks for a maximum of six cycles. Ten patients achieved a pathologically complete response (pCR) and six were clinically stable without evidence of disease. After a median follow-up of 18 months, the median progression-free survival (PFS) was 16 months (95% confidence interval-CI-3-29%). The actuarial PFS at 24 months was 36% (95% CI 13-59). Overall eight out of 25 patients (32%) had an IP relapse and thus were considered as local treatment failures. The major toxic side effects were nausea, vomiting, abdominal pain and renal toxicity. Future trials exploring IP delivery of these drugs should attempt to optimize drug dose and schedule and subset analysis of clinical studies should help in identifying patients who are particularly sensitive to this therapeutic approach.

Juvenile Behçet's disease among 1784 Turkish Behçet's patients.

BACKGROUND: Behçet's disease is a chronic, relapsing disease, about which information on its clinical course in juveniles is only available from small groups of patients. MATERIALS AND METHODS: Patients suffering from Behçet's disease who had their first lesion at or before the age of 16 were evaluated in terms of: age at onset, mucocutaneous signs, and findings related to systemic involvement. Ninety-five patients, evaluated as having juvenile Behçet's disease (JBD), were detected among 1784 Turkish Behçet's patients. The mean age of these 95 patients (51 boys or men, 44 girls or women) who had JBD was 26.8 +/- 7.1 years. RESULTS: The difference between sexes in terms of age at onset, development period of second lesions, and systemic involvement was not found to be significant in JBD. Patients were divided into two groups, one showing severe disease (N = 27) and the other mild disease (N = 68). There was no significant difference between the two groups with respect to age, age at onset, and sex distribution. The interval between the development of the first and second lesions was shorter in the patient group with severe disease (P < 0.001) and the development of second lesion was most frequently seen in the first 5 years (P < 0.05). Systemic involvement developed also in a shorter time in the group with the severe disease (P < 0.01) and was most frequently encountered during the first 5 years (P < 0.05). Conversely, patients with the mild disease developed systemic involvement more frequently after 6 years or later. CONCLUSIONS: Severe Behçet's disease in children and juveniles shows no age or sex predilection, but leads to an earlier recurrence and more severe systemic signs than the mild form.

Serum tumor markers for detection of bone metastasis in breast cancer patients.

For the diagnosis of bone metastasis in breast cancer patients during systemic treatment serum tumor markers, including carbohydrate antigens 15-3 (CA 15-3) and 19-9 (CA 19-9), cancer antigen 125 (CA 125), alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), beta-2 microglobulin (BMG), ferritin, and tissue polypeptide antigen (determined by the M3 monoclonal antibody, TPS) were measured in 22 patients with known bone metastases and in 30 patients without documented metastases. The most useful single marker was CA 15-3. By stepwise discriminant analysis, it was found that 90% of the patients could be diagnosed truly by using the markers CA 15-3, BMG and ferritin. It is concluded that monitoring with combinations of tumor markers at regular intervals increases the diagnostic efficiency.