Vol 5, No 3 (2011)

Articles

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    Introduction:
    Accumulating evidences indicated that during increasing of the animals' age, the number and the functional properties of hematopoietic stem cells (HSCs) become altered because of a gradual decrease in replication potential.  The efficient factors in this process are DNA damaging, reduced telomerase activity, shortening of telomeres and oxidative stresses. For overcoming these factors, using of the anti-oxidants and activating of telomerase would be effective. The aim of this research was to study the effect of Nitric Oxide (NO) as an anti-oxidant on the cell proliferation, cell viability and telomerase activity of HSCs in vitro.
    Methods: HSCs were isolated from human cord bloods.  Cells were treated by L-Arginine and Sodium Nitro-Pruscide (as NO donors) in a dose dependent manner. The cell viability and proliferation were assayed by trypan blue, MTT and BrdU methods. The profile of aging was assayed by senescence sensitive β-Galactosidase staining and telomerase activity was assayed by TRAP-PCR E ISA method. Finally, Nitric Oxide Synthatase mRNA expression level was analyzed by RT-PCR.
    Result: HSCs those treated with SNP exhibited an increase 3-7 fold (400-1000 µmol) in NO production in comparison to untreated control cells (140µmol).Treatment of cells by L-Arg resulted lower release of NO (Up to 200 µmol) in comparison to SNP. Increasing NO production resulted to the inducing of cells growth potential and proliferation parameters up to 40% which accompanied  by the increasing of telomerase activity up to 25% in the presence of 100 µM of SNP or  1.0 mM of L-Arg in comparison to untreated control cells.
    Discussion: The present work demonstrates that NO affect telomerase activity and cellular replicative capacity in human hematopoietic stem cells. A significant behavior was observed on the telomerase activity and cell proliferation after treatment of cells. Induction of cell proliferation  was accompanied by a slight inhibition of HSCs senescence. Finally the telomerase induction and reduction in cell enescence were accompanied by increasing  of the cell proliferation parameters.

  • XML | PDF | downloads: 318 | views: 386 | pages: 11-15

    Introduction: Management of early relapsed or refractory lymphoma [Hodgkin & non- Hodgkin Lymphoma (HL & NHL)] is a matter of problem, especially when hematopietic stem cell support is not available. The aim of this study was to evaluate effectiveness of IEV Regimen (Ifosfamide, Epirubicin, VP16), in lymphoma patients who are not candidate for stem cell transplantation. Because the majority of our patients are nonadequate for stem cell transplantation (refuse of this modality and economic problem). This reason leads to use of more effective treatment. This trial approved with ethic committee of medical university.
    Patients and Methods: Twenty four patients (16 male and 8 female) with early relapsed i.e. before 6 months of primary therapy (N= 21) or refractory lymphoma (N= 3) were entered. Of 24 patients 18 were diagnosed as NHL and 6 as HL. 10 cases were in stage II, 12 cases in stage III and 2 cases in stage IV. In an inpatient setting all of the patients received 3- 4 consecutive cycles of IEV (Ifosfamide, Epirubicin, VP16) and MESNA equal to Ifosfamide for uroprotection. Cycles were repeated every 21 days, for a total of three courses.
    Results: The overall response rate was 92% (50% complete response and 42% partial response). Complete response were observed in 8 with NHL and 4 with HL and partial response in 9 with NHL and 1 with HL respectively. There was no response in 8% (1 patient with NHL and another with HL). Toxicities were: grade 1 neutropenia (10%) and 4 (40%), grade 1 thrombocytopenia (20%), grade 2 anemia (40%) nausea (100%), fever in 80%, neutropenic fever in 30%, pneumonia in 20%, of patients, but the majority of patients improved over treatment. One case died from progressive disease and co infection with no response to antibiotic therapy. The major cause of drug toxicity was Ifosfamide (high dose usage and 3 days continuous IV infusion). Tolerance to the regimen was good.
    Conclusions: Our results revealed the efficacy of the IEV regimen as salvage therapy in primary refractory and early relapsed NHL & HL without stem cell support.

  • XML | PDF | downloads: 129 | views: 195 | pages: 16-20

    Introduction: The myeloproliferative neoplasms (MPNs) are a heterogeneous group of diseases characterized by excessive production of blood cells by  hematopoietic precursors. Typically, they include polycythemia vera (PV), essential thrombocythemia (ET), idiopathic myelofibrosis(IMF), and chronic myeloid leukemia (CML). Philadelphia chromosome is the final diagnostic test for CML. Recently, JAK2 mutation introduced as a diagnostic marker for other MPNs. The aim of this study is evaluation of Philadelphia chromosome in CML patients and JAK2 mutation in MPNs patients that had been referred to a hematology/oncology clinic in Kermanshah between 2010-2011.
    Material and methods: In this study we evaluated common genetic disorders in 124 MPNs patients. Expression of B2A2 BCR-ABL mRNA in peripheral blood leucocytes was detected by a reverse transcriptase polymerase chain reaction (RT-PCR) for CML patients. Also, we used AS-RT-PCR method for the detection of the JAK2 mutation for all of 124 patients.
    Results: We found 93.7% CML patients (60/64) with positive Philadelphia chromosome. Also, 85% PV patients (17/20), 46.6% ET patients (14/30) and 40% IMF patients (4/10) had JAK2 mutation. Notably, we found a CML patient with positive Philadelphia chromosome and JAK2 mutation.
    Conclusion: Diagnosis of MPNs is often complex and expensive but, JAK2 mutation is a sensitive test, relatively cost-effective for proving clonality in MPNs. Also, more studies are required to determine the exact frequency and prognostic role of the JAK2 mutation in Philadelphia positive CML patients.

  • XML | PDF | downloads: 155 | views: 216 | pages: 21-23

    Introduction: Prostate cancer is one of the most common cancers among males and the second factor resulting to death due to cancer among them.(1) The median age of its diagnosis is 65 years. The initial treatment includes androgen ablation or orchiectomy.(2, 3) In case of patient’s hormone refractory, chemotherapy would be substituted. The objective of this study is the consideration of intermittent chemotherapy’s role in patients’ survival and their quality of life.
    Materials & Methods: Since (1384,07,07), 25 patients with Hormone Refractory Prostate Cancer that referred to Taleghani & Imam Reza hospital were enrolled in this study, and Taxotere, Mitoxantrone and Navalbine were prescribed along with Estramustin 140 mg/m2 and Prednisolone 10 mg/BD for 4 days respectively(4, 5, 6) and the quality of life (QoL), toxicity and overall survival were evaluated. The most toxicity included grade 2 and 3 neuropathy and neutropenia that was compliant for patients. The overall survival was 22months.
    Conclusion: Intermittent chemotherapy in elderly patients with hormone refractory prostate cancer provides compliant toxicity and improvement of QoL and overall survival.

  • XML | PDF | downloads: 133 | views: 198 | pages: 24-31

    Introduction: Allogeneic hematopoietic stem cell transplantation (HSCT) has been reported to be a successful curative treatment in AML patients. Myeloablative conditioning (MAC) is used more frequent as a preparing regimen. This study attempts to compare the outcome of patients who has received MAC and reduced- intensity conditioning (RIC).
    Methods: Totally, 618 patients with AML underwent HSCT at our center between 1991 and 2011. Of these, 564 received MAC (Busulfan plus Cyclophosphamide) and 54 patients received RIC consisting of Fludarabine and Busulfan. Patients with suitable performance were assigned in the MAC study group while patients who did not meet these criteria were assigned to the RIC group.
    Results: The median age at transplantation was 27 years for MAC and 30 years for RIC group (P value= 0.12). The median follow-up of survivors was 1.75 years for MAC and 4.5 years for RIC. The 3-year OS for MAC and RIC groups was 74.2% and 80.7% (P value= 0.75), respectively. The 3-year DFS was 67.2% for MAC and 69.7% for RIC, (P value= 0.73). The 3-year incidence of relapse for MAC and RIC groups was 16.80% and 26.40%, respectively (P value= 0.05).
    Conclusion: the results of the study showed borderline significance (P value=0.05) for incidence of relapse between MAC and RIC groups. However, to make accurate results longer follow up is required. No significant difference in OS and DFS was found between two groups. Further long- term follow- up of more cases is necessary to confirm this difference statistically. Our results indicated that the introduction of RIC allogeneic HSCT for AML patients, especially in elderly, was safe and feasible.

  • XML | PDF | downloads: 178 | views: 261 | pages: 32-35


    Angiogenesis which is the recruitment of new blood vessels is a critical Process in several chronic diseases and is an essential component of tumor or cancer progression. Development of therapies aimed at inhibiting the angiogenesis, in combination with classical anti-cancer therapies, is among the most intensively studied approaches to treat the cancer. In this study the effect of chlordiazepoxide (which is a proper anxiolytic drug) on angiogenesis in microcarrier-based collagen gel was assayed. Chlordiazepoxide beside its anxiolytic effect in patients showed strong inhibitory effect on human umbilical vein endothelial cells (HUVECs) tubulogenesis (angiogenesis) in collagen matrix, without toxic effects in the studied doses.

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    Inflammatory myopathy is a paraneoplastic syndrome. Inflammatory myopathy may be the first manifestation of underlying malignancy. It was reported in patients with colon cancer, breast cancer, ovarian cancer, lung cancer and non-Hodgkin lymphoma. There are few reports regarding inflammatory myopathy in patients with gastric cancer. We want to present inflammatory myopathy as early manifestation of gastric cancer in a 65 y/o Asian male.

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    Ganglioneuromas presented as a retroperitoneal tumor around the vital organs is a rare entity. A case with unusual presentation is reported. Young woman of 44 years old presented without any complaint ,that known during incidental abdominopelvic ultrasonography. It was treated with partial resection for debulking surgery. Debulking surgery with preservation of organ functions is feasible in these slow growing tumors for better quality of life.