2020 CiteScore: 2.6
Ardeshir Ghavamzadeh, MD.
Vol 11, No 1 (2017)
Background: Acute promyelocytic leukemia (APL) is a unique subtype of acute leukemia. APL is a curable disease; however, drug resistance, early mortality, disease relapse and treatment-related complications remain challenges in APL patient management. One issue underlying these challenges is that the molecular mechanisms of the disease are not sufficiently understood.
Materials and Methods: In this study, we performed a meta-analysis of gene expression profiles derived from microarray experiments and explored the background of disease by functional and pathway analysis.
Results: Our analysis revealed a gene signature with 406 genes that are up or down-regulated in APL. The pathway analysis determined that MAPK pathway and its involved elements such as JUN gene and AP-1 play important roles in APL pathogenesis along with insulin-like growth factor–binding protein-7.
Conclusions: The results of this meta-analysis could be useful for developing more effective therapy strategies and new targets for diagnosis and drugs.
Background: Hemorrhagic cystitis (HC) is one of the most challenging complications in hematopoietic stem cell transplantation (HSCT). Estrogen is one of the suggested treatments for controlling this problem.
Subjects and Methods: We performed a randomized case-control study to evaluate the efficacy of oral conjugated estrogen on HC management in 56 HSCT patients. Patients were randomly assigned to the drug group (received 6.25 mg conjugated estrogen oral tablets in a daily single dose during hematuria period) or control group.
Result: The median time to complete response was 36 and 24 days in the drug and control group, respectively. The median time of down stage was 24 days in the drug group and 12 days in control group. Adjusted for HC grades, the relative risk of complete response for patients in control group was 1.613 times more than that of patients in drug group; nevertheless, not significant (p=0.122).
Conclusion: Our study did not show any benefit in use of oral conjugated estrogen in the management of HC.
Background: To determine the frequency of the single nucleotide polymorphism M287T in exon 9 of the AS3MT gene in Iranian population and to assess the difference in allele frequencies with other ethnicities.
Subjects and Methods: Genotyping analysis was performed on 150 healthy subjects using the PCR-RFLP assay. We used chi-square analysis to check the deviation from Hardy–Weinberg equilibrium and compare of the observed genotype frequencies in various ethnic. The level of statistical significance was considered as p<0.05.
Results: The homozygous CC, homozygous TT and heterozygous CT genotypes were observed in 2%, 80% and 18% of participated individuals. The SNP rs11191439 passed the Hardy-Weinberg equilibrium chi-squared test with p-value>0.05 and had a minor allele frequency (MAF)>5%.
Conclusion: Iranians are genetically very similar to Caucasian and African individuals and they are considerably different from other East Asians including Koreans, Chinese and Japanese individuals. Due to genetic polymorphisms can contribute to the variability in AS3MT activity; they may contribute to interindividual as well as intra-ethnic differences in response to the detoxification of arsenic.
Background: The study attempts to assess the relationship between chimerism analysis using polymerase chain reaction of short tandem repeat (STR) and the incidence of chronic graft versus host disease (GvHD) as well as survival.
Methods: The retrospective cohort included all patients who received allo-HSCT between 2005 to 2013. Data collected by day +100 were reviewed in terms of the incidence of chronic GvHD and survival. Chimerism was evaluated for whole blood, T-cell and PMN cells on days 15, 30 and 60, respectively using polymerase chain reaction of short tandem repeat (STR).
Results: Forty (69%) patients developed chronic GvHD, 11 (19%) relapsed and 22 (39.7%) died during the study. There was a significant relationship between chronic GvHD and chimerism analysis including whole blood on day 60 (P=0.001), PMN on day 60 (p= 0.05) and T-cell on days 15 (p=0.028), 30(p=0.01) and 60 (p=0.004). Patients with chronic GvHD showed a long-term survival as compared with those without chronic GvHD (P=0.0013).
Conclusion: Conducting continuous analysis of chimerism provides an opportunity to initiate immediate measures to prevent complications.
Background: Tyrosine kinase inhibitors (TKIs) were the first drugs to use an intracellular signaling molecule as a therapeutic target. Unresponsiveness to TKIs limits therapeutic options, making allogeneic hematopoietic stem cell transplantation (HSCT) the only option leading to molecular remission. The aim of this study is to characterize CML patients unresponsive to first- and/or second-generation TKI therapy who underwent HSCT and to describe the main factors associated with treatment failure.
Subjects and Methods: Twenty one CML patients who underwent allogeneic HSCT and had previously used first- and/or second-generation TKIs from January 2005 to May 2014.
Results: Of the 21 patients, 52.4% were male, with a median age of 49 years (23-65 years) and 85.7% had chronic phase CML at the time of diagnosis; 28.6% showed inadequate treatment adherence to TKI therapy. Thirteen patients were resistant and eight were intolerant to TKIs; additionally, nine did not have T315I mutation. Ten transplantations involved related donors, and more than a half of patients (11) died, three of which due to graft failure. Most patients who survived transplantation were in the chronic phase of disease at the time of HSCT.
Conclusion: The population was composed mainly of young age patients at diagnosis, male, white, and coming from areas in the state of Rio Grande do Sul other than Porto Alegre and metropolitan region. Low adherence to TKI therapy may be related to unresponsiveness to treatment, especially in patients with acquired resistance, or this low adherence, together with the presence of molecular changes, may have led to the need for HSCT.
Background: Triple-negative breast cancers (TNBC) have a more aggressive course and are associated with poorer prognosis in comparison with other subtypes of breast cancer. One of the most common subtypes of TNBC is basal-like. The aim of this study was to investigate clinicopathological characteristics and clinical course of TNBC in Iranian women and compare them with other studies.
Subjects and Methods: Between March 2009 and February 2011, patients with breast cancer in Cancer Institute of Iran were selected and then followed-up for 2 years. Paraffin-embedded tumor block of all TNBC patients were evaluated for CK5/6 and EGFR using IHC method.
Results: Among 267 breast cancer patients, 60 cases with TNBC were identified (22.5%), 31 patients (51.7%) had basal-like and 29 patients (48.3%) had non-basal-like tumors. The median age of participants with TNBC was 49.6 years. Among our patients, 70% had positive lymph nodes.93.4% of all patients at the time of diagnosis were stage II or III and tumor size was at least 3 centimeters. No grade 1 TNBC was found in this study. During the follow-up period, there were 26 recurrences and 7 deaths.
Conclusion: The percentage of basal-like subtype among Iranian women with TNBC was lower compared to other studies, while bone metastases, clinical stage, lymph node involvement and tumor size were higher. Clinicopathological findings in basal and non-basal-like subgroups were not different, but the probability of lymph node involvement was more common in patients who were EGFR positive.
Background: In developed or developing countries, the most common cancer in women is breast cancer with a pick in 40–50 years in Asia. Herein, we compared the association between IHC with FISH in HER2-positive breast cancer patients and affection of trastuzumab on disease free survival and overall survival (OS).
Subjects and Methods: Immunohistochemical (IHC) analysis of hormone receptors and HER2 was performed in 133 patients with breast cancer between 2003 and 2014. Patients were selected for Herceptin adjuvant treatment, according to IHC 3+ or FISH+. The specimens for pathology reports were fixed at 10% neutral-buffered formalin (pH=7.4) for 24 hours, then sliced into 4 μm sections.
Results: The mean age of patients at diagnosis was 46.39 years (range, 24-78 years), 100% female. Concordance rates between IHC and FISH were 31.1% for IHC 2+ and 84.1% for IHC 3+ (p<0.001). The 87 patients had age ≤50 years and 46 patients had >50 years. Of the 133 patients, 30 patients (22.6%) had metastasis and 72 (54.1%) had right involvement. Ninety three (69.9%) patients had lymph node invasion. 48 patients (36.1%) were treated with trastuzumab and 85 (63.9%) were treated without trsastuzumab. The 10-year survival rate was 70% and the mean survival was 49 months.
Conclusions: We recommend clinicians that FISH analysis is as a predictor in breast cancer patients with IHC score 2+. In contrast, FISH analysis of IHC 3+ samples was no useful. Trastuzumab therapy is effective and tolerated for breast cancer with IHC 3+ and probably IHC 2+/FISH+.
Background: Legionella pneumophila (L. pneumophila) is a gram-negative bacterium which causes Legionnaires’ disease as well as Pontiac fever. The Legionella infections in patients suffering from neutropenia- as a common complication of cancer chemotherapy- can distribute rapidly. We aimed to detect of L. pneumophila in haematological malignancy suffering patients with neutropenic fever by targeting the (macrophage infectivity potentiator) mip gene.
Subjects and Methods: Serum and urine specimens were obtained from 80 patients and presence of mip gene of L. pneumophila in specimens was investigated by PCR.
Results: The L. pneumophila infection was detected in 21 (26.2%) and 38 (47.5%) of urine and serum specimens, respectively.
Conclusion: Our findings indicated that the relative high prevalence of L. pneumophila in the studied patients group which show the necessity of considering this microorganism in future studies from detection and treatment point of view in cancer patients.
Background: Emotional Intelligence (EQ) is positively associated with mental health and it can have a crucial role in mental disorder therapy by suitable coping mechanisms. The present study aimed to evaluate the relationship of EQ with anxiety and depression among the women with breast cancer.
Subjects and Methods: During 2013 and in a cross-sectional study, 98 breast cancer patients (14 to 21 years old) entered into the study. For data collection, the following instruments were the Bar-On EQ inventory, Beck Depression Inventory and Cattle Anxiety Inventory.
Results: There was an inverse relationship between anxiety with intrapersonal (p<0.01, r=0.39) and stress management (p<0.01, r=0.37) components and also between anxiety and total scores of EQ (p<0.05, r=0.22). There was an inverse significant association between depression and intrapersonal components (p<0.05, r=0.23), general mood (p<0.01, r=0.46) and adaptation (p<0.01, r=0.38) and also between depression and a total score of EQ (p<0.01, r=0.42).
Conclusion: The results of this present study confirmed the important role of EQ. Also, the results can be an inspiration for the future studies regarding the training of EQ skills in the treatment of mental disorder (anxiety and depression) among patients with breast cancer.
Background: For adult ALL patients, the indications and appropriate timing of allogeneic hematopoietic stem cell transplantation (AHSCT) continue to be debated. The primary aim of this single-institution study was to compare the results of our adult ALL patients that had been allografted with those reported in the current literature.
Subjects and Methods: This study included 53 consecutive adults with acute lymphoblastic leukemia (ALL) who underwent allogeneic hematopoietic stem cell transplantation (AHSCT) with myeloablative (92%) and reduced-intensity (8%) conditioning between 1993 and 2011.
Results: Mean patient age was 27 years (SD:8.62) and donor age was 33.7 years (SD:9.47). Fourteen patients were in first remission; 21 in ≥2nd remission, 15 in relapse and 3 had primary refractory leukemia. Thirty-four, 15 and 4 patients received busulfan plus cyclophosphamide, cyclophosphamide/total body irradiation and fludarabine-based regimens, respectively. For graft-versus-host disease (GVHD) prophylaxis, cyclosporine plus methotrexate were used. Forty-six donors were related and 7 were unrelated. Thirty patients received granulocyte-colony stimulating factor (G-CSF) mobilized peripheral blood and 23 received bone marrow as stem cell source. Twenty-six patients relapsed at a mean duration of 11.3 months (SD:19.1). Forty-four patients succumbed to their disease after a mean follow-up of 13.6 months (SD:19.5). The cause of mortality was relapse (n=24; 54.5%) and transplant-related etiologies (n=20; 45.5%). The estimated five year probabilities of overall survival (OS) and progression-free survival (PFS) were 37% and 12%, respectively.
Conclusion: By multivariate analyses, transplantation in first remission was the most important predictor of transplant success.
Mesenchymal stem cells (MSCs), as major stem cells for cell therapy, have been studied from different aspects in preclinical and clinical settings for more than a decade. These cells modulate the immune system (humoral and cellular immune responses) in vitro by producing soluble factors (anti-inflammatory molecules) and/or making cell-cell contacts. Hence, they could be used in regenerative medicine, tissue engineering and immune therapy. MSCs-based therapy have been recently used for treatment of cancer regarding the migratory potential of these cells towards tumor cells which makes them considerable candidates, also for cell therapy in both allogeneic and autologous settings. So, this review attempts to focus on the factors secreted by MSCs such as cytokines, their functional role in mounting and controlling immune responses mediated by different immune cell subpopulations and their significance in regenerative medicine in clinical trials. Although, further studies remain to be done to increase our knowledge of regulating development mechanisms, homeostasis and tissue repair in order to provide new tools to implement the efficacy of cell therapy trials. Although MSCs have been proved safe and effective for cell therapy, there are still challenges to overcome before widely applying MSCs in clinic.
Peripheral blood stem cell transplantation (PBSCT) is an effective treatment for hematological malignancies. Mobilization of peripheral blood progenitor cells performs in different ways among transplantation centers. Forceful mobilization schedules are comprised of growth factor alone, chemotherapy along with growth factor and also, a newly combination of novel agent such as plerixafor with any approach. With the appearance of numerous modifications in stem cell mobilization field over the past decade and advent of novel stem cell mobilization techniques, it seems to be necessary to review recent publications about stem cell mobilization strategies to respond above cited issues. Relevant literature was identified by a PubMed search (1996–2016) of English-language literature using the terms mobilization, Allogeneic Stem Cells Transplantation, Autologous Stem Cells Transplantation and technical aspects of apheresis. Although many institutions have established their own procedures to improve stem cell mobilization success rates accompanying cost-effectiveness considerations, an optimal stem cell mobilization regimen and methods have not been well-defined, yet. Practical guidelines are required to address critical clinical issues including proper growth factor, the most Impressive chemotherapy and its dosage and appropriate time for leukapheresis initiation. Hence, based on literature, we prepared practical guidelines in this review.
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