Retrospective analysis of patients with relapsed or refractory testicular nonseminous germ cell tumors treated with autologous stem cell transplantation.

BACKGROUND AND AIM: About 20-25% of the testicular germ cell tumors (TGCT) are relapsed or refractory after first line therapy and optimal treatment for this group is poorly defined. We aimed to analyze the efficacy and safety of autologous stem cell transplantation (ASCT) in this patient group.Material and. METHODS: 19 patients with 28 ASCT were retrospectively analyzed. All the patients were treated with BEP (Bleomycin, etoposide, cisplatin) as first line therapy and TIP(paclitexalifosfamide, cisplatin) was given as salvage chemotherapy. Stem cell collection was performed with TIP and granulocyte stimulating factor. ASCT was performed with carboplatin(700mg/m2) and etoposite(750mg /m 2). The results were provided as median(min-max). P<0.05 was accepted as statistical significant level. RESULTS: After ASCT, complete(CR) and partial remission (PR) rates were 47.3% and 31 .5% respectively. The median overall survival(OS) and progression free survival (PFS) were 18(0-37.4 months) and 7(0-15months) months respectively. Estimated 2-year OS was 47.4% and PFS was 35.3%. Grade 3/4 toxicities including diarrhea, mucositis, and toxic hepatitis were observed in 5 patients. Only one patient died due to complication of transplantation. CONCLUSION: Although the number of the patients in this study is limited, ASCT seems to be a safe and effective treatment modality in relapsed refractory non-seminomatousTGCT with an acceptable OS, PFS and mortality rates.

Radioisotope synovectomy with rhenium186 in haemophilic synovitis for elbows, ankles and shoulders.

We have performed 221 radioisotope synovectomy (RS) in more than 150 children and young adults with haemophilia, age ranging 3-30 years (mean 15) in Ege Hemophilia Center, Izmir, Turkey for last 7 years. We always preferred to use Yttrium 90 (Y(90)) for knees; however, since 2005, we started using rhenium 186 (Re(186)) for medium-sized joints with respect to safety. In this article, we have evaluated long-term experience ranging from 6 months to 3 years (mean 18 months) with Re(186) for elbows (n = 35), ankles (n = 26) and shoulders (n = 2) in total of 63 RS procedures for 49 patients. Their age range was 3-30 years and mean age was 15.5. Two mCi of Re(186) intra-articularly injected for treating target joints and chronical synovitis. After RS, joint bleedings were decreased for all patients. The best results were obtained for all joints in patients with grade-II synovitis as like earlier experience with Y(90). Excellent rates (no bleeding) were observed in grade-II synovitis in 81% and 46% for elbows vs. 86% and 57% for ankles after 6 months and after 1 year follow-up of patients, respectively. In grade-III synovitis, excellent rates were 53% and 25% for elbows and 44% and 29% for ankles, respectively. In five joints for five patients, repeated injections were needed for better outcome. No adverse events such as radioisotope leakage, local inflamatory reactions or malignancy development were observed during and after RS. For medium-sized joints, RS with Re(186) seems to be either effective or safe treatment method. Our results confirm those previously published by others on the value of Re(186) synoviorthesis in medium-sized joints in haemophilia patients. After this experience, we changed our protocol and we use Re(186) for all medium-sized joints for treating chronical synovitis.

Aplidin synergizes with cytosine arabinoside: functional relevance of mitochondria in Aplidin-induced cytotoxicity.

Aplidin (plitidepsin) is a novel marine-derived antitumor agent presently undergoing phase II clinical trials in hematological malignancies and solid tumors. Lack of bone marrow toxicity has encouraged further development of this drug for treatment of leukemia and lymphoma. Multiple signaling pathways have been shown to be involved in Aplidin-induced apoptosis and cell cycle arrest in G1 and G2 phase. However, the exact mechanism(s) of Aplidin action remains to be elucidated. Here we demonstrate that mitochondria-associated or -localized processes are the potential cellular targets of Aplidin. Whole genome gene-expression profiling (GEP) revealed that fatty acid metabolism, sterol biosynthesis and energy metabolism, including the tricarboxylic acid cycle and ATP synthesis are affected by Aplidin treatment. Moreover, mutant MOLT-4, human leukemia cells lacking functional mitochondria, were found to be resistant to Aplidin. Cytosine arabinoside (araC), which also generates oxidative stress but does not affect the ATP pool, showed synergism with Aplidin in our leukemia and lymphoma models in vitro and in vivo. These studies provide new insights into the mechanism of action of Aplidin. The efficacy of the combination of Aplidin and araC is currently being evaluated in clinical phase I/II program for the treatment of patients with relapsed leukemia and high-grade lymphoma.

Role of intercellular communications in breast cancer multicellular tumor spheroids after chemotherapy.

Tumor heterogeneity is an important feature that is especially involved in tumor aggressiveness. Multicellular tumor spheroids (MTS) may provide some benefits in different steps for investigation of the aggregation, organization, differentiation, and network formation of tumor cells in 3D space. This model offers a unique opportunity for improvements in the capability of a current strategy to detect the effect of an appropriate anticancer agent. The aim of this study was to investigate the cellular interactions and morphological changes following chemotherapy in a 3D breast cancer spheroid model. Distribution of the gap junction protein "connexin-43" and the tight junction protein "occludin" was investigated by immunohistochemistry. Cellular interactions were examined by using transmission and scanning electron microscopies as well as light microscopy with Giemsa staining after treating cells with doxorubicin, docetaxel, and doxorubicin/docetaxel combination. Statistical analyses showed significant changes and various alterations that were observed in all groups; however, the most prominent effect was detected in the doxorubicin/docetaxel combination group. Distinct composition as a vessel-like structure and a pseudoglandular pattern of control spheroids were detected in drug-administered groups. Immunohistochemical results were consistent with the ultrastructural changes. In conclusion, doxorubicin/docetaxel combination may be more effective than the single drug usage as shown in a 3D model. The MTS model has been found to be an appropriate and reliable method for the detection of the changes in the expression of cellular junction proteins as well as other cellular proteins occurring after chemotherapy. The MTS model can be used to validate the effects of various combinations or new chemotherapeutic agents as well as documentation of possible mechanisms of new drugs.

Intracranial venous thrombosis associated with severe antithrombin-III deficiency in pregnancy.

We report a patient with intracranial venous thrombosis in the third trimester of pregnancy associated with severe antithrombin-III deficiency. The evaluation of protein C, protein S and antithrombin-III levels in patients with thrombotic events during pregnancy may reveal the specific cause of the thrombotic event and thereby influence patient management

Up-regulation of serine/threonine protein phosphatase type 2A regulatory subunits during methylprednisolone-induced differentiation of leukaemic HL-60 cells.

Serine/threonine protein phosphatase 2A (PP2A) may play a role in leukaemic cell differentiation of the HL-60 myeloid leukaemic cell-line after methylprednisolone induction. We have investigated the specific enzyme activity and expression of catalytic and regulatory subunits of PP2A. The resulting specific enzyme activity and immunoblots showed an increase in enzyme activity and the expression of regulatory subunits after methylprednisolone treatment. There was no change in the expression of PP2A catalytic subunits. It is suggested that the effect of methylprednisolone on leukaemic differentiation may be the result of PP2A upregulation.

Asecretory POEMS Syndrome with Widespread Osteosclerotic Lesions.

POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes) is a rare disease and constitues 1-2% of plasma cell dyscrasia. Most of the patients have few sclerotic bone lesions and more than 90% of patients have serum and/or urinary M-protein. In this report, we present a patient with POEMS syndrome who had severe polyneuropathy and unusual widespread osteosclerotic lesions without M- rotein in serum and urine. According to our knowledge, this is the first case of asecretory POEMS syndrome with multipl sclerotic lesions and polyneuropathy. Our patient is still well and able to work actively 4 years after diagnosis with the treatment of 12 courses of VAD by reducing the vincristine dosage.

Augmentation of methylprednisolone-induced differentiation of myeloid leukemia cells by serine/threonine protein phosphatase inhibitors.

To elucidate the roles of serine/threonine protein phosphatases type 1 (PP1) and type 2A (PP2A) in methylprednisolone-induced differentiation of HL60 cells into granulocytes and K562 cells into monocytes, we examined the effect of serine/threonine protein phosphatase inhibitors, okadaic acid and Cal-A on the proliferation/differentiation of HL60 and K562 cells. Okadaic acid and Cal-A augmented methylprednisolone induced granulocytic differentiation and cell death of HL60 cells and monocytic differentiation and cell death of K562 cells in different dose ranges, respectively. These data suggest an important role of PP1 and PP2A in the mechanism leading to differentiation of leukemic cells.

Increased oxidative stress in dilated cardiomyopathic heart failure.

In the present study, we assessed oxidative stress in patients with dilated cardiomyopathy of ischemic or idiopathic etiology. For this reason we measured whole blood reduced glutathione, erythrocyte superoxide dismutase, susceptibility of erythrocyte membranes and erythrocytes to peroxidation, and SH content of erythrocyte membranes in 12 patients (8 men and 4 women, ages 31 to 66 years) with idiopathic dilated cardiomyopathy, in 11 patients (8 men and 3 women, ages 32 to 65 years) with ischemic dilated cardiomyopathy, and in 21 healthy volunteers (12 men and 9 women, ages 25 to 67 years). There was no statistically significant difference between the two patient groups for the indicators studied (P >0.05). Blood glutathione, erythrocyte superoxide dismutase, and membrane SH content of both groups of patients was decreased compared with controls (P <0.05), whereas erythrocyte and membrane susceptibility to peroxidation were increased (P <0.05). We conclude that patients with idiopathic or ischemic dilated cardiomyopathy exhibit abnormalities of a range of markers of increased oxidative stress. These abnormalities may contribute to contractile dysfunction, increased incidence of fatal arrhythmias, and sudden death.

The role of reactive oxygen metabolites in ulcerative colitis.

SUMMARY: : Reactive oxygen metabolites (ROMs) contribute to tissue injury in inflammatory bowel disease. The aim of this study is to examine the role of ROMs in the tissue injury in ulcerative colitis (UC). The study group consisted of 27 patients with UC (14 active, 13 quiescent) and a control group of 10 patients with various anal diseases. We measured the content of malondialdehyde (MDA), superoxide dismutase (SOD), and myeloperoxidase (MPO) in colorectal biopsies. MDA was measured by the thiobarbituric acid assay. SOD and MPO were measured using the nitro blue tetrazolium and odianisidine methods, respectively. The MDA, SOD, and MPO tissue levels were significantly different between the patients with active UC, the patients with quiescent UC, and the control subjects (p < 0.001). A positive correlation was found between the tissue concentrations of MDA and MPO and the activity of the disease (p < 0.001). The SOD tissue concentrations were negatively correlated with the disease activity (r = -0.507, p < 0.05).

Periodontal health status and treatment needs for index age groups in Turkey based on CPITN values.

A national oral health pathfinder survey has been conducted by our research team in Turkey, in collaboration with the WHO European Region. Some of the data obtained by this survey were for CPITN values for age groups above 10 years, and can be summarized as follows: formula: (see text) These findings demonstrate that preventive periodontal therapy and community-based prophylaxis methods, will undoubtedly be of prime importance in future nationwide dental health service planning in Turkey.

Changes in the serum levels of CK-MB, LDH, LDH1, SGOT and myoglobin due to cardiac surgery.

Elevation of serum levels of enzymes due to myocardial necrosis is considered to be a specific finding for myocardial infarction. This study was designed to determine the changes in the levels of LDH, SGOT enzymes, LDH1, CK-MB isoenzymes and myoglobin in patients who have had coronary bypass grafting and who have had atriotomy for surgical correction without any evidence of myocardial infarction diagnosed by clinical, hemodynamic and electrocardiographic findings. It was found that CK-MB, LDH, LDH1 and myoglobin showed significant elevations which mimicked a perioperative myocardial infarction. SGOT also increased, but remained within the normal range. CK-MB, LDH and LDH1 increased more in the coronary bypass grafted patients whereas myoglobin increased in the patients who had atriotomies. It was concluded that in order to demonstrate a perioperative myocardial infarction it is necessary to determine at least two of these enzymes for a long period and to correlate these results with the clinical, hemodynamic and electrocardiographic findings.

[A comparison of the frequency of hepatitis B surface antigen and antibody in hospital and nonhospital personnel]. / Hastane personeli ve hastane disindan kisilerde hepatit B Yüzey antijeni ve antikoru sikliginin karsilastirilmasi.

HBsAg and Anti-HBs positivity was determined in hospital personnel and volunteer blood donors (controls) by using Enzyme Immuno Assay (EIA) method. The combined prevalence of antigen-antibody positivity among hospital personnel was 40.52% (HBsAg 5.57%, Anti-HBs 34.94%) while it was present 37% (HBsAg 6% Anti-HBs 31%) in controls. The frequency of the antigen and antibody in hospital personnel and controls did not differ significantly.