Telomerase activity in human brain tumors: astrocytoma and meningioma.

Somatic cells do not have telomerase activity but immortalized cell lines and more than 85 % of the cancer cells show telomerase activation to prevent the telomere from progressive shortening. The activation of this enzyme has been found in a variety of human tumors and tumor-derived cell lines, but only few studies on telomerase activity in human brain tumors have been reported. Here, we evaluated telomerase activity in different grades of human astrocytoma and meningioma brain tumors. In this study, assay for telomerase activity performed on 50 eligible cases consisted of 26 meningioma, 24 astrocytoma according to the standard protocols. In the brain tissues, telomerase activity was positive in 39 (65 %) of 50 patients. One sample t test showed that the telomerase activity in meningioma and astrocytoma tumors was significantly positive entirely (P < 0.001). Also, grade I of meningioma and low grades of astrocytoma (grades I and II) significantly showed telomerase activity. According to our results, we suggest that activation of telomerase is an event that starts mostly at low grades of brain including meningioma and astrocytoma tumors.

Evolutionary hypothesis of telomere length in primary breast cancer and brain tumour patients: a tracer for genomic-tumour heterogeneity and instability.

It was previously reported that tumour samples had shorter telomeres than the surrounding normal tissue. Hereby, the initial sign of correlation between malignant tissue and telomere behaviour could be noticed. Bridging knowledge between germ and somatic cells could facilitate understanding cellular evolution. The aim of our investigation was to provide evidence for the evolutionary hypothesis of TL (telomere length) in primary BC (breast cancer) and BTs (brain tumours), which might be applied as a prognostic and/or predictive marker. DNA extraction from the frozen tissues was performed using high pure PCR template preparation kit. Standard protocol of Telo TTAGGG Telomere Length Assay kit, a non-radioactive chemiluminescent assay, was used. The protein expression in extracted cells was analysed by immunofluorescence. We also detected telomerase activity. The G/T (genomic/tumour ratio) for TL in two groups of patients affected with primary BC and primary BT revealed significant differences in both BC patients (P = 0.025) and in BTs (P = 0.001). The pattern of telomere signals by Q-FISH (quantitative fluorescent in situ hybridization) show that in all samples, except one, SI (signal intensity) has been significantly decreased in tissue related to blood, either in BC patients or in patients with BTs (0.041≥P≥0.001). However, the data achieved by Q-FISH support the results of Southern blot. These data reflect a significant diversity either in BC or in BT patients, providing evidence for the evolutionary hypothesis of TL in cancer development and progression.

The effects of simvastatin on ischemia-reperfusion injury of sciatic nerve in adult rats.

Severe ischemia to nerve results in fiber degeneration and reperfusion results in oxidative injury to endothelial cells and augments fiber degeneration. Statins, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, the most widely used lipid-lowering drugs, have been demonstrated to play a neuroprotective role. So we evaluated the effectiveness of simvastatin in protecting sciatic nerve from ischemia-reperfusion injury using the model of experimental nerve ischemia. Sixty adult male Sprague-Dawley rats weighing 250-300 g were used. They were divided into ten groups (N=6 per group). We used ischemia model in these groups by occluding the femoral artery and vein with a silk suture 6-0 using slipknot technique. All ischemia groups were rendered in ischemic for 3 h reperfused for various times of zero (0 h), 3 h (3 hour reperfusion), 7 days (7 day reperfusion), 14 days (14 day reperfusion). Half of the groups had experimental simvastatin (1 mg/kg) i.v. injection treatment via tail vein 1 h before ischemia. The other half experienced only ischemia-reperfusion as control groups. After euthanasia, histological samples were taken from distal part of the sciatic nerve. Sections were cut at 5 microm and then were stained with H and E and modified trichrome. We used H and E stain for edema and trichrome gomori for ischemic fiber degeneration. Samples were observed to assess their fiber degeneration and edema changes. By observation the level of fiber degeneration and endoneurial edema were also decreased in these recent groups (in both ischemia and reperfusion duration). In conclusion, pre-ischemic administration of simvastatin exhibits neuroprotective properties in ischemia-reperfusion nerve injury.

Differentiating and Categorizing of Liposarcoma and Synovial Sarcoma Neoplasms by Fluorescence in Situ Hybridization.

BACKGROUND & OBJECTIVE: Soft tissue sarcomas (STS) constitute an uncommon and heterogeneous group of tumors of mesenchymal origin and various cytogenetic abnormalities ranging from distinct genomic rearrangements, such as chromosomal translocations and amplifications, to more intricate rearrangements involving multiple chromosomes. Fluorescence in situ hybridization (FISH) can be used to identify these chromosomal translocations and amplifications, and sub classify STS precisely. The current study aimed at investigating the usefulness of FISH, as a diagnostic ancillary aid, to detect cytogenetic abnormalities such as MDM2 (murine double minute 2) amplification and CHOP(C/EBP homologous protein) rearrangement in liposarcoma, as well as SYT (synaptotagmin) rearrangement in synovial sarcoma. METHODS: The FISH technique was used to analyze 17 specimens of liposarcoma for MDM2 amplification and CHOP rearrangement, and 10 specimens of synovial sarcoma for SYT rearrangement. The subtypes of liposarcoma and synovial sarcomas were reclassified according to the FISH results and compared with those of the respective histological findings. RESULTS: According to the FISH results in 17 liposarcoma cases, well-differentiated liposarcoma(WDLPS), dedifferentiated liposarcoma (DDLPS), and myxoidliposarcoma (MLPS)subtypes were 41%, 53%, and 6%, respectively. In different subtypes of liposarcoma, a total of 30% mismatches were observed between pathologic and cytogenetic results. According to the histological findings from FISH analysis, SYT rearrangement was found only in three out of 10 (30%) synovial sarcomas. CONCLUSION: The detection of cytogenetic abnormalities in patients with liposarcoma and synovial sarcoma by FISH technique provides an important objective tool to confirm sarcoma diagnosis and sub classification of specific sarcoma subtypes in such patients.

Sirenomelia with agenesis of corpus callosum.

Sirenomelia is a very rare anomaly presented with fusion of the lower limbs. Genitourinary, neural tube, and vertebral anomalies are found in most cases. We report a case of sirenomelia with agenesis of corpus callosum, which has not been reported previously.

Meningioangiomatosis in an otherwise healthy 13 year-old boy: A case report with emphasis on histopathological findings.

Meningioangiomatosis is regarded as a rare benign hamartomatous condition mostly involving the cerebral cortex and overlying leptomeninges. A strong association of MA with neurofibromatosis type 2 has been documented in published articles. Herein we report a case of an otherwise healthy 13-year-old boy with no family history or stigmata of neurofibromatosis who presented with intractable seizures. MRI revealed a 2x2 cm mass lesion in the frontal lobe. The patient underwent complete surgical resection of the lesion. Although the primary radiologic impression of the lesion was glioma, pathological evaluation of the resected specimen showed mainly proliferation of meningothelial cells and fibroblast-like cells with many thickened blood vessels, which are typical for diagnosis of meningioangiomatosis. After surgical removal of the lesion, the patient is free of seizures.

Kikuchi-Fujimoto Disease: a Case Report.

Kikuchi-Fujimoto disease or histiocytic necrotizing lymphadenitis is an idiopathic, self-limiting disorder and predominantly affects young women. We report a 35-year-old female who presented with soft to firm cervical lymphadenopathy and neck pain. She had multiple enlarged cervical nodes. Examination of other systems was normal. Lymph node biopsy was performed, and the histological features, and immunohistochemistry confirmed the diagnosis. The Patient was treated with non-steroidal anti-inflammatory drugs and low-dose prednisolone. A significant decrease in the size of lymph node and relief of neck pain occurred. During four years of follow-up, the patient developed no malignant disease or systemic and autoimmune diseases such as systemic lupus erythematosus. Kikuchi-Fujimoto disease is rare, clinicians should be aware of this condition as early diagnosis of the disease will lessen concerns of the patient's family.

Myeloid Sarcoma of the peritoneum at older ages: A case report and review of literature.

Myeloid sarcoma or granulocytic sarcoma (GS) is a rare disease with poor prognosis. It is characterized by the occurrence of tumor masses at an extra-medullary tissue. It is composed of myeloblastic cells and usually occurs in association with acute myeloid leukemia. Because of its nonspecific clinical and radiologic findings, its diagnosis might be challenging. It might be more commonly found in patients with specific cytogenetic abnormalities, particularly with the t (8; 21) translocation and less frequently the inv (16) type. We report a case of GS in a 62 years old man without particular previous pathologies, which brutally presented as an ascites and generalized edema. The laparoscopy showed involvement of greater omentum and peritoneum. The histologic examination of greater omentum showed granulocytic sarcoma. The bone marrow aspiration was normal. We started treatment of patient by standard acute myeloid leukemia's chemotherapy.

Hepatic iron overload and fibrosis in patients with beta thalassemia major after hematopoietic stem cell transplantation: A pilot study.

Currently, hematopoietic stem cell transplantation (HSCT) is the only curative option for patients with beta-thalassemia major, but liver iron overload in these patients will not decrease and hepatic fibrosis may still progress despite successful HSCT. Liver biopsy samples were taken from 14 patients (Out of 25 patients) who underwent HSCT. All patients met three criteria: negative HCV antibody, liver fibrosis in samples before HSCT and lack of regular treatment for iron overload after HSCT (Because patients did not consent to phlebotomy or they had not regular follow-up). We evaluated liver fibrosis and liver iron overload by a semi quantitative method, Perls' Prussian blue staining, before and after HSCT. HSCT was successful in all the patients. Liver iron overload did not change after transplant (P=0.61), but hepatic fibrosis progressed after transplant (P=0.01). In patients with beta thalassemia major who previously had some degree of liver fibrosis, HSCT alone cannot reduce liver iron overload and liver fibrosis will increase. We recommend that regardless of the amount of iron overload in patients with beta thalassemia major that have shown some degree of fibrosis in their liver biopsy before transplantation, appropriate steps should be taken to reduce iron overload as soon as possible after successful transplantation.

Bilateral Lymphoblastic Lymphoma of Breast Mimicking Inflammatory Breast Cancer: A Case Report and Review of Literature.

We report a 45 year-old woman who had bilateral breast masses with extradural involvement. Pathologic report revealed malignant high-grade lymphoblastic lymphoma. Systemic chemotherapy was performed but 3 months later, lesions indicating relapse in bone and breast re-appeared. She received salvage chemotherapy, but 4 months after that she was expired.

Prognostic and predictive value of copy number alterations in invasive breast cancer as determined by multiplex ligation-dependent probe amplification.

BACKGROUND: Breast cancer is a leading cause of morbidity and mortality in women worldwide. About 70 % of breast cancers are estrogen receptor (ER) positive. Blocking estrogen action by tamoxifen has been the treatment of choice in ER positive breast cancers for more than 30 years. In the past, several studies have revealed associations between gene copy number alterations and responsiveness to tamoxifen therapy, but so far no single gene copy number alteration could completely explain the response variation observed between individual breast cancer patients. Here, we set out to perform a simultaneous analysis of copy number alterations of several genes involved in the prognosis and response to therapy by multiplex ligation-dependent probe amplification (MLPA). METHODS: A case-control study was designed encompassing 170 non-metastatic ER positive breast cancer patients (case group = 85, control group = 85). All patients in the control group had received standard adjuvant tamoxifen treatment for 5 years without any evidence of recurrence. Patients in the case group had experienced early recurrences while receiving tamoxifen treatment. 76 % of the patients of the case group and 73 % of the patients of the control group had received anthracycline-based adjuvant chemotherapy. Gene copy number alterations detected by MLPA in both groups were compared. RESULTS: Amplification of CCND1 (OR = 3.13; 95 % CI = 1.35 to 7.26; p = 0.006) and TOP2A (OR = 3.05; 95 % CI = 1.13 to 8.24; p = 0.022) were significantly more prevalent in the case group, compared to the control group. In a multivariate analysis CCND1 (p = 0.01) and TOP2A (p = 0.041) amplifications remained significant predictors of recurrence. CONCLUSIONS: Our results indicate that CCND1 amplification may serve as a useful biomarker for hormone responsiveness, and that TOP2A amplification may serve as a useful prognostic biomarker.

Temporary paraplegia resulting from Gorham's disease involving the third lumbar vertebra and proximal femur: a five-year follow-up and review of the literature.

Gorham's disease is a rare musculoskeletal disease of unknown etiology characterized by progressive osteolysis and massive bone destruction. Here, we report an extremely rare case of Gorham's disease involving two far sites in the lumbar spine and trochanteric region, gradually resulting in paraplegia. The patient underwent cord decompression and chemotherapy, and resumed her normal life; she was followed up for nearly five years.

Alterations of telomere length in human brain tumors.

Telomeres at the ends of human chromosomes consist of tandem hexametric (TTAGGG)n repeats, which protect them from degradation. At each cycle of cell division, most normal somatic cells lose approximately 50-100 bp of the terminal telomeric repeat DNA. Precise prediction of growth and estimation of the malignant potential of brain tumors require additional markers. DNA extraction was performed from the 51 frozen tissues, and a non-radioactive chemiluminescent assay was used for Southern blotting. One sample t-test shows highly significant difference in telomere length in meningioma and astrocytoma with normal range. According to our results, higher grades of meningioma and astrocytoma tumors show more heterogeneity in telomere length, and also it seems shortening process of telomeres is an early event in brain tumors.

Expression of cyclin D2, P53, Rb and ATM cell cycle genes in brain tumors.

Cyclin D2, P53, Rb and ATM as cell cycle genes regulate cell growth and proliferation. Considering their roles, we assumed that they have different level of mRNA expression in different grades of brain tumors. To determine this point, we investigated the mRNA expression in two types of brain tumors, including astrocytoma and meningioma. The mRNA of 52 brain tumor samples were extracted; cyclin D2, P53, Rb and ATM mRNA expression was quantified using the real-time quantitative reverse-transcription polymerase chain reaction. We compared mRNA expression of these genes between astrocytoma and meningioma tumors and also between different grades of them. Cyclin D2, P53, Rb and ATM had higher expression in astrocytoma than meningioma tumors. Higher grade (III and IV) of astrocytoma tumors had up-regulation for cyclin D2 and ATM genes, but higher grades of these tumors showed down-regulation of P53 and Rb genes. Analysis of relative expression between two grades of meningioma tumors showed a high down-regulation in grade II related to grade I. Also, cyclin D2, P53, Rb and ATM mRNA expression in each group of tumors (meningioma and astrocytoma) showed a highly positive correlation in lower grades. Considering this fact and also different templates of up- and down-regulation for these genes' interaction in different types of brain tumors, it seems that these genes do not have a unique model of interaction.

Three-hit hypothesis in astrocytoma: tracing the polymorphism D1853N in ATM gene through a pedigree of the proband affected with primary brain tumor.

Ataxia telangictasia mutated (ATM) is involved in DNA repair pathway and cell-cycle checkpoints. ATM alterations were found in medulloblastomas, gliomas, but not in astrocytoma. The polymorphism D1853N was reported in healthy individuals and medulloblastomas. We could observe this polymorphism, heterozygously, in a proband affected with astrocytoma and traced it through her pedigree. We propose the three-hit hypothesis as a triangle initiators includes D1853N as a first predisposing hit, IVS 38- 63T --> A as a second hit deriving from the first somatic evolution before differentiation and IVS 38- 30 A --> G as a third hit through the development of an astrocytoma. In addition, the D1853N polymorphism was occurred in different allele from IVS 38- 63T --> A and IVS 38- 30 A --> G.