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1.  Effect of Short Hydration on Cisplatin-Induced Nephrotoxicity in Cancer Patients: A Retrospective Study 
Background: The aim of this study was to evaluate the protective role of short hydration against nephrotoxicity induced by cisplatin (CDDP).
Materials and Methods: Twenty-two patients (13 men and 9 women) under CDDP therapy were enrolled in this retrospective study between 2009 and 2014. The CDDP was given in 500 ml of isotonic solution, and before and after CDDP administration, the patients received 10mEq potassium chloride15% and 1gr magnesium sulfate in 1000 ml isotonic saline. Renal parameters were evaluated on the first day of each cycle of CDDP therapy.
Results: Median cumulative CDDP dose was 465 mg/m2. Based on renal parameters, the prevalence of CDDP-induced nephrotoxicity (CIN) was 22.7%, while no hypokalemia and hypomagnesemia were observed.
Conclusion: Short hydration accompanied with potassium chloride and magnesium sulfate may decrease the risk of CIN.
PMCID: PMC5767284
Cisplatin; Nephrotoxicity; Hydration; Magnesium; Potassium
2.  Complications of Transfusion-Dependent β-Thalassemia Patients in Sistan and Baluchistan, South-East of Iran 
Background: Thalassemia syndromes are among prevalent hereditary disorders imposing high expenses on health-care system worldwide and in Iran. Organ failure represents a life-threatening challenge in transfusion- dependent β-thalassemia (TDT) patients. The purpose of the present study was to determine the frequency of organ dysfunctions among TDT patients in Sistan and Baluchistan province in South-East of Iran.
Materials and Methods: Laboratory and clinical data were extracted from medical records as well as by interviews. Standard criteria were applied to recognize cardiac, gonadal, endocrine and renal dysfunctions. The collected data were analyzed using the SPSS statistics software (Ver.19).
Results: A total of 613 TDT patients (54.3% males and 45.7% females) were included in this study. The mean age of patients was 13.3 ±7.7 years old. Cardiac events comprised the most encountered complications (76.4%), following by hypogonadism (46.8%), parathyroid dysfunction (22%), thyroid abnormalities (8.3%), diabetes (7.8%) and renal disease (1.8%). Hypogonadism comprised the most identified complication in patient <15 years old, while the cardiac complications were the most frequent sequela in patients >15 years old (P<0.01).
Conclusion: As cardiac events are significantly more common among TDT patients, close monitoring of the heart function is recommended for identifying patients with cardiac problems.
PMCID: PMC5767285
β- thalassemia major; Iron overload; Organ dysfunction; Cardiac disease
3.  A Cross-Sectional Study of Glycemic Status and Zinc Level in Patients with Beta-Thalassemia Major 
Background: Endocrinopathies and diabetes mellitus are prevalent in patients with beta-thalassemia major
Recently some studies demonstrate a link between low levels of serum zinc level and higher prevalence of diabetes. The aim of this study was to evaluate the glucose tolerance in patients suffered from beta-thalassemia major and determine the association of Homeostasis Model Assessment (HOMA) parameters with zinc status among these patients.
Materials and Methods: In this cross sectional study, clinical data of patients who were suffered from thalassemia major, aged≥10 years were collected. Serum ferritin concentration, fasting blood sugar, fasting blood insulin and serum zinc level were assessed after overnight fasting. Moreover, oral glucose tolerance test was performed. Homeostasis Model Assessment (HOMA-2) was used for calculating beta-cell function, insulin resistance and sensitivity for normoglycemic and pre-diabetic subjects.
Results: of the 163 patients diagnosed with beta-thalassemia major, 10%, 53% and 37% were diabetic, pre-diabetic and normal, respectively. Mean serum zinc concentration was equal to 18.90±10.93µg/dl, and it was not significantly different across diabetic, pre-diabetic and normal groups. Pre-diabetic patients had significantly lower beta-cell function compared to normal subjects (P=0.0001). An inverse relation was documented between beta-cell function on one hand and total units of blood transfusion and ferritin level on the other hand (r=-0.29, P=0.004 and r=-0.27, P=0.03, respectively). The analysis adjusted for multiple possible confounders showed that there is no significant association between HOMA parameters and serum zinc level.
Conclusion: Impaired glucose metabolism and low serum zinc level were quite common among our study participants. The findings of the study also signifies the substantial role of follow-up in early detection and appropriate treatment.
PMCID: PMC5767286
Beta thalassemia; Diabetes mellitus; Zinc
4.  Multiple Extramedullary Plasmacytoma in a Setting of Complete Bone Marrow Remission: Food for Thought  
Extramedullary plasmacytoma as a mode of relapse in multiple myeloma (MM) is unusual. Current recommendations do not incorporate the routine use of 18-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET/CT) imaging prior to haematopoietic stem cell transplant (HSCT) in MM. We report a case of relapsed MM with complete remission as per IMWG criteria. In the interim period, before the HSCT, the patient had localizing neurological signs and symptoms attributed to multiple extramedullary plasmacytomas. The uniqueness of this case is that this patient after complete marrow remission with no obvious external masses had unexpected, symptomatic multiple extramedullary plasmacytomas. This case illustrates the need for integration of FDG PET/CT imaging into routine pre-HSCT investigations in relapsed MM to prevent missing any asymptomatic extramedullary plasmacytomas.
PMCID: PMC5767287
Haematopoietic stem cell transplantation; Multiple myeloma; Extramedullary plasmacytoma; Positron emission tomography
5.  The Use of Filgrastim in Patients with Hodgkin Lymphoma Receiving ABVD 
Background: There is conflicting data about the increased risk of pulmonary toxicity when granulocyte-stimulating factor (G-CSF) is given in combination with bleomycin. No clear consensus for management of patients with Hodgkin lymphoma (HL) who require G-CSF support exists. Our objective was to evaluate whether there is an increase in pulmonary toxicity in patients who receive bleomycin and G-CSF during treatment for HL.
Materials and Methods: We conducted a single-center retrospective analysis of patients with Hodgkin Lymphoma from January 2003 until July 2015. All patients who received at least 1 dose of bleomycin and followed at our institution were included. Patients were evaluated for pulmonary toxicity starting from the day of first dose of bleomycin until 1 year after initiation of bleomycin. Data on pre-identified risk factors for pulmonary toxicity were also collected.
Results: Fifty-four patients met inclusion criteria. Twenty-one patients received bleomycin alone, and 33 patients received bleomycin and G-CSF. There was no statistically significant (p = 0.50) difference in the development of pulmonary toxicity between the two groups. Crude hazard ratio for development of pulmonary toxicity in the bleomycin and G-CSF cohort was 1.58 (95% confidence interval, CI: 0.41-6.12). On multivariate analysis, the hazard ratio for development of pulmonary toxicity was 1.71 (95% CI: 0.43-6.81).
Conclusion: This study does not find evidence that the combination of bleomycin and G-CSF increases the risk for bleomycin- induced pulmonary toxicity. We recommend G-CSF use in HL patients receiving bleomycin when needed to maintain dose intensity.
PMCID: PMC5767288
Bleomycin; Granulocyte stimulating factor; Bleomycin induced-pulmonary injury; Hodgkin lymphoma; Treatment complications
6.  Rare Presentation of Refractory Thrombotic Thrombocytopenic Purpura: Jejunal Stricture 
Thrombotic thrombocytopenic purpura is a rare thrombotic disease characterized by episodes of thrombocytopenia and microangiopathic hemolytic anemia due to disseminated microvascular thrombosis. Thrombotic thrombocytopenic purpura was first described in 1924 by Moschowitz as a disease presenting with a pentad of signs and symptoms (anemia, thrombocytopenia, fever, hemiparesis and hematuria). Previous studies have described atypical manifestations of thrombotic thrombocytopenic purpura such as hemolysis, anemia and thrombosis.
PMCID: PMC5767289
TTP; Chron’s-disease
7.  Hepatosplenic Gamma Delta T-Cell Lymphoma (HSGDTCL): Two Rare Case Reports from Western India  
Peripheral T cell lymphomas are a heterogeneous group of post-thymic, mature lymphoid malignancies, accounting for approximately 10-15% of all non-Hodgkin's lymphomas. Hepatosplenic T-cell lymphoma (HSGDTCL) is a rare entity, which is characterized by primary extra nodal disease with typical sinusoidal or sinusal infiltration of the liver and the spleen, respectively by expression of the T-cell receptor γδ chain, and by a number of other frequent clinicopathologic features, including aggressive course of disease. Secondary involvement of liver by hematopoietic malignancies is much more common as compared to primary liver involvement. Primary involvement of liver by non- Hodgkin’s lymphoma (NHL) is documented and mostly DLBCL (diffuse large B cell lymphoma) type. But, T cell lymphoma primarily arising from liver is very rare. It occurred commonly in immunocompromised patients and prognosis is very poor. Here, we present two case reports of Hepatosplenic gamma-delta T-cell lymphoma (HSGDTCL) and both are immunocompetent patients. Liver biopsy from the mass and subsequent IHC (immunohistochemistry) were performed for the purpose of diagnosis, which were positive for LCA (leukocyte common antigen), CD2 and negative for CD5, CD20 and CD79a. First patient was a 63-year-old female with hepatitis C virus seropositivity presented with liver mass simulating hepatocellular carcinoma. Second patient was a 60-year- old male, chronic alcoholic patient, presented with liver mass and lytic bony lesion in pelvis. Both patients were managed with conventional CHOP (cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisolone) and showed complete response after 4 cycles of chemotherapy. After completion of 6 cycles of chemotherapy, both patients remained under 6-month surveillance period for any recurrence of the disease.
PMCID: PMC5767290
Hepatosplenic gamma delta T cell lymphoma (HSGDTCL); Immuno competent patients; CHOP
8.  Restarting Thalidomide-Dexamethasone Regimen in a Post-Abortive Female with Multiple Myeloma: Effective Clinical Response Possible 
Nowadays, the prevalence of Multiple Myeloma (MM) seems to have been increasing among young females. Here, we report that thalidomide is contraindicated in pregnant women diagnosed with MM and those desirous of subsequent pregnancy. In this case report, we compared the clinical response of Thalidomide-Dexamethasone therapy in a post-abortive woman with persistently elevated β-hCG levels due to retained products of conception, undergoing hysterectomy later. This case report underlines the clinical significance of age, the effect of Thalidomide-Dexamethasone therapy even after initial discontinuation and the response to high β-hCG levels.
PMCID: PMC5767291
Multiple myeloma; Post-aborted woman; Thalidomide-dexamethasone therapy; High β-hCG levels
9.  Hematological Reference Intervals for Healthy Iranian Blood Donors 
Background: Development of locally-derived hematological reference intervals is necessary for improving the quality of health care and clinical trials. However hematological reference intervals are affected by several variables including age, gender and environmental factors. Therefore this study was conducted to determine the gender and age-specific hematological reference intervals of healthy Iranian blood donors.
Materials and Methods: Selected hematological indices of 394 healthy blood donor volunteers, donating blood at Tehran Blood Transfusion Center were analyzed. Hematological reference intervals, stratified by age and gender were compared. The results of current study were also compared with those of US population.
Results: There were significant gender-related differences for mean values of hematological indices, with males having higher mean values of RBC, HCG, HCT and MCV than females. While the mean of PLT and MCH were higher in women. Age-related differences for mean values of RBC and MCH were also significant. The comparison of reference intervals, stratified by both gender and age showed that RBC, HGB and HCT values were higher in males than females in all age groups. But MCH values of females in all age groups and WBC and PLT counts in females older than 30 years were higher compared to the males in the same age group. The results of this study showed some similarity with US population, with narrower intervals.
Conclusion: This study suggests that gender and age-specific, locally derived hematological reference intervals should be referred to, before interpretation of any laboratory test result.
PMCID: PMC5767292
Reference values; Blood donors; Iran; Gender; Age
10.  Protective Isolation for Patients with Haematological Malignancies: A Pilot Study Investigating Patients’ Distress and Use of Time 
Background: Patients with haematological malignancies are often hospitalized in protective isolation until full neutrophil recovery in order to prevent infections. This descriptive pilot study evaluate the level of isolation-related distress and the use of free time in a sample of Italian onco-haematological patients who were hospitalized in protective isolation.
Materials and Methods: Participants were 18 patients hospitalized in hematologic ward to receive induction therapy (n=12) or autologous stem cell transplant (n=6). They completed a self-report questionnaire before discharge.
Results: Participants reported a moderate level of isolation-related distress, anxiety, and boredom: the more the anxiety and the boredom, the more the distress (r=.77; P<.001), (r=.79; P<.001), respectively. The activities performed during isolation were: watching TV (72.2%), reading (55.6%), thinking (33.3%), surfing in Internet or using PC (33.3%), and playing games or making cross-words (16.7%). Participants who reported pessimistic thinking had higher isolation-related distress (P=.004) as well as anxiety (P<.001) and boredom (P=.001).
Conclusion: Haematology Units should support isolated patients in spending their time in recreational activities, allowing more contacts with immediate relatives and friends, providing free TV and Wi-Fi connection inside the room. In addition, patients should have to keep themselves physically active. Isolation-related distress could also be reduced by providing psychological support.
PMCID: PMC5767293
Patient isolation; Social isolation; Hematopoietic stem cell transplantation; Time perception
11.  Mechanism Action of Platelets and Crucial Blood Coagulation Pathways in Hemostasis 
Blood is considered to be precious because it is the basic necessity for health; our body needs a steady provision of oxygen, supplied via blood, to reach billions of tissues and cells. Hematopoiesis is the process that generates blood cells of all lineages. However, platelets are the smallest blood component produced from the very large bone marrow cells called megakaryocytes and they play a fundamental role in thrombosis and hemostasis. Platelets contribute their hemostatic capacity via adhesion, activation and aggregation, which are triggered upon tissue injury, and these actions stimulate the coagulation factors and other mediators to achieve hemostasis. In addition, these coordinated series of events are the vital biological processes for wound healing phases. The aim of this review is to summarize and highlight the important pathways involved in achieving hemostasis that are ruled by platelets. In addition, this review also describes the mechanism action of platelets, including adhesion, activation, aggregation, and coagulation, as well as the factors that aid in hemostasis and wound healing.
PMCID: PMC5767294
Platelets; Hemostasis; Coagulation pathways; Coagulation factors; Wound healing
12.  Acute Myeloid Leukemia—Genetic Alterations and Their Clinical Prognosis  
Acute myeloid leukemia (AML) is a group of hematological diseases, phenotypic and genetically heterogeneous, characterized by abnormal accumulation of blast cells in the bone marrows and peripheral blood. Its incidence rate is approximately 1.5 per 100,000 in infants younger than 1 year of age and 25 per 100,000 persons in octogenarians. Traditionally, cytogenetic markers are used to stratify patients in three risk categories: favorable, intermediate and unfavorable. However, the forecast stratification and the treatment decision for patients with normal karyotype shows difficulties due to the high clinical heterogeneity. The identification of several genetic mutations additional to classical molecular markers has been useful in identifying new entities. Nowadays, many different mutations and epigenetic aberrations have been implicated in the diagnostic, prognostic and treatment of AML. This review is focused on describing the most important molecular markers with implications for clinical practice.
PMCID: PMC5767295
AML; Mutations; Molecular marker; Cytogenetic; Risk groups
13.  Familial Colorectal Cancer Type X in Central Iran: A New Clinicopathologic Description 
Background: Familial colorectal cancer type X (FCCX) is a subtype of mismatch repair (MMR)-proficient colorectal cancerin which the patients are clinically at risk for Lynch syndrome (LS), a common hereditary cancer predisposing syndrome. In this study, we described a new clinicopathological feature of the condition in central Iran.
Materials and Methods: We designed a descriptive, retrospective study to screenat-risk colorectal cancer (CRC) patients, using Amsterdam II criteria and Molecular analysis in Isfahan (central Iran) throughout 2000-2013 period.
Results: 219 early-onset (≤ 50 years) CRC patients of 1659 were selected for the evaluation. Amsterdam II criteria were positive in 45 families; of whom 31 were finally analyzed by molecular testing.
MMR deficiency was detected in 7/31 probands (22.6%) as affected to LS, so 24 families (77.4%) were identified as FCCX. The mean age of the probands at diagnosis among FCCX families was 45.3 years (range 24-69) versus 38.0 years (range 31-50) in LS families. The frequency of CRC among FCCX and LS families was calculated 27.9% and 67.5%, respectively. Also, the most frequent extracolonic cancer among both FCCX and LS families was stomach by 25.5% and 30.8%, respectively. Tumor site was proximal to the splenic flexure in 20.8% and 57.1% of index CRC patients in FCCX and LS families, respectively.
Conclusion: Given the relative high frequency of FCCX and its different phenotype among Iranian populations, we need to set up more advanced molecular studies for exploration of unknown molecular pathways leading to tumorigenesis in this class of CRC patients.
PMCID: PMC5625475
Familial colorectal cancer type X; Clinicopathologic; Lynch syndrome; Iran
14.  Patterns of DNMT1 Promoter Methylation in Patients with Acute Lymphoblastic Leukemia  
Background: Acute lymphoblastic leukemia (ALL) is a clonal malignant disorder characterized by an uncontrolled proliferation of immature T or B lymphocytes. Extensive studies have shown that the epigenetic changes, especially modified DNA methylation patterns in the regulatory regions through the DNA methyltransferase (DNMTs), play an important role in the development of genetic disorders and abnormal growth and maturation capacity of leukemic stem cells (LSCs).The aim of this study was to evaluate the changes in DNMT1 promoter methylation and its expression pattern in patients with ALL.
Materials and Methods: In this experimental study, methylation specific PCR (MSP) was used to assess the methylation status of DNMT1 promoter regions in samples collected from ALL patients (n=45) and healthy control subjects. According to this method, un-methylated cytosine nucleotides are converted to uracil by sodium bisulfite and the proliferation of methylated and un-methylated regions are performed using specific primers for target sequences.
Results: None of the patients with B and T-ALL showed methylated promoter regions of the DNMT1 gene, while the methylation pattern of both pre-B ALL patients and the control group showed a relative promoter methylation.
Conclusion: Analysis of promoter methylation patterns in various subgroups of ALL has revealed the importance of DNMT1 in the regulation of gene expression. Likewise, extensive data have also highlighted the methylation-based mechanisms exerted by DNAM1 as one of the main participants regulating gene expression in B-ALL and T-ALL patients. Investigation of the overall DNA methylation pattern offers significant improvements in the prediction of disease prognosis and treatment response.
PMCID: PMC5625466
Acute lymphocytic leukemia; Epigenetic; Methylation; DNA methyltransferase
15.  Attitudes toward Telling the Truth to Cancer Patients in Iran: A Review Article 
Background: Patients generally have the right to be informed of their condition, but the debate over the issue of truth disclosure is still present. The attempt of this study is to review the approaches toward truth- telling to cancer patients in Iran.
Materials and Methods: This study is a narrative review that included articles published in Iran on attitudes toward telling the truth to cancer patients. The present study extracted data from articles published in PubMed, Science Direct, Scientific Information Database (SID), Magiran, Iran Medex, Google Scholar, Iranian Research Institute for Information Science and Technology with key terms such as truth disclosure, breaking bad news, death awareness and disclosure of diagnosis without any time restriction.
Results: Totally, 21 articles including 14 in English and 7 in Persian were selected and reviewed. The results of the study have shown that although treatment team and caregivers are unwilling to disclose the truth to patients, they have a tendency to obtain more information about their disease.
Conclusion: As the incidence of cancer has increased worldwide, telling the truth to patients seeking more information about cancer disease would be inevitable, but more studies are required to provide scientific procedures based on evidence for truth disclosure, not the whole, to cancer patients.
PMCID: PMC5625467
Telling the truth; Cancer patient; Breaking bad news; Review article; Iran
16.  Expression Analysis of Long Non-Coding PCAT-1in Breast Cancer 
Background: The prostate cancer-associated non-coding RNA transcript 1 (PCAT-1) is a newly identified long non- coding RNA whose participation in tumorigenesis of a variety of cancers has been observed. In the present study, we aimed at analysis of its expression in breast cancer patients.
Materials and Methods: The expression of PCAT-1 was assessed using real-time reverse transcription polymerase chain reaction in tumor samples obtained from 47newly diagnosed breast cancer patients as well as their corresponding adjacent non-cancerous tissues (ANCTs).
Results: We detected significant over-expression of PCAT-1 in 12/47 (25.5%) of tumoral tissues compared with their corresponding ANCTs. However, no significant association has been found between the levels of PCAT-1 transcripts and patients’ clinical data such as tumor size, stage, grade, estrogen and progesterone receptors or Her2/neu status.
Conclusion: PCAT-1 is possibly involved in the pathogenesis of fraction of breast cancers. Future studies are needed to evaluate its precise function in breast cancer.
PMCID: PMC5625468
Breast cancer; lncRNA; PCAT1
17.  Absolute and Functional Iron Deficiency Anemia among Different Tumors in Cancer Patients in South Part of Iran, 2014 
Background: Anemia is a common problem in cancer patients. This study aimed to investigate the frequency rate of absolute and functional iron deficiency anemia among different tumors and its distribution in different stages of cancer in solid tumors.
Materials and Methods: This study was performed on 597 patients with cancer referred to Ali-Ebne-Abitaleb Hospital in Zahedan. Laboratory tests included serum iron, transferrin saturation, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and complete blood count (CBC). The malignancy type and stages were recorded. Data were analysed using SPSS statistics software (Ver.19).
Results: Four hundred and fifty-seven patients (76.5 %) diagnosed with solid tumors and 140 (23.5%) suffered from hematologic malignancies. Among patients with solid tumors, functional iron deficiency had the highest rate (300 patients had anemia and 243 (53.2%) of whom were functionally iron deficient), but in hematologic malignancies most of patients had not iron deficiency (66 patients had not iron deficiency against 12 patients had absolute iron deficiency and 62 patients had functional iron deficiency anemia) (P-value=0.021). No significant differences were observed among the various stages of cancers in terms of degrees of iron deficiency (P>0.05).
Conclusion: The results of the study showed that solid tumors had a higher rate of absolute and functional iron deficiency anemia, compared to hematologic malignancies. But there was no difference between the different stages of the disease.
PMCID: PMC5625469
Iron deficiency anemia; Cancer; Hematologic malignancies; Chemotherapy
18.  How Do Donor-Recipient CMV Serostatus and Post-Hematopoietic Stem Cell Transplantation CMV Reactivation Affect Outcomes in Acute Leukemia Patients? 
Background: This study evaluated CMV serostatus in donors and recipients of hematopoietic stem cell transplantation (HSCT) and its effects on CMV reactivation of patients and all aspects of CMV on HSCT outcomes.
Materials and Methods: Seven hundred and five adult acute leukemia patients (AML=408 and AML=297) who had undergone HSCT were included in this retrospective study. We categorized donor-recipient pairs in three risk groups: positive donors (D+) were studied as high-risk group, including either R+ or R-(n=485), R-D- as low-risk group (n=32) and R+D- as intermediate group (n=15).
Results: There was no statistically difference in CMV reactivation among these risk groups (P=0.14).CMV infection rate was lower in R+D+ than R+D-(p=0.050). Multivariate analysis showed that patients developing CMV infection had lower overall survival (p=0.04, HR: 1.43, CI=1.00- 2.05) and higher non- relapse mortality (P=0.01, HR: 1.62, CI=1.11-2.38). Relapse rate did not change in CMV reactivated patients (P=0.94).
Conclusion: The results of the study indicated that asCMV reactivation occurred more in R+D- patients compared to R+D+ ones, and was associated with inferior OS and higher NRM it could be suggested that in contrast to general belief, if the recipient is seropositive , seropositive donor is preferred to a seronegative one.
PMCID: PMC5625470
CMV serostatus; Hematopoietic stem cell transplantation; Outcome; CMV infection; Acute leukemia
19.  High Prevalence of Vitamin D Deficiency in Newly Diagnosed Acute Myeloid Leukemia Patients and Its Adverse Outcome 
Background: Although several studies have supported a preventive and therapeutic role of vitamin D (Vit D) for different types of cancers, we face insufficient documentation in acute myeloid leukemia (AML). So, we examined whether the serum calcidiol (25(OH)D) levels at the time of induction therapy have any impact on response and relapse in AML patients.
Materials and Methods: Blood samples were collected from 65 patients on days 0 and 28th of treatment to evaluate serum concentration of 25(OH)D and its effects on complete remission (CR) achievement, relapse rate and hospitalization length.
Results: Of the 65 patients who were included in the study, 38 were male (58.5%) and 27 were female (41.5%). Median age at the time of treatment was 37 years (range 15-68). 6% of the participants were older than 60 years. In regard to 25(OH)D levels, 81.5% of AML patients were deficient (levels <20 ng/ml). There was a significant difference in CR between patients with sufficient and deficient level of 25(OH)D. Deficient patients had longer length of hospitalization than those with sufficient levels. Also Vitamin D deficient patients had higher serum ALP levels. The mean level of 25(OH)D on treatment day 28th in our study was significantly lower than the baseline value.
Conclusion: The results of the study showed that serum 25(OH)D levels deficiency was highly prevalent among Iranian AML patients. Furthermore, higher Vit D levels in AML patients were associated with better outcome in these patients.
PMCID: PMC5625471
Acute myeloid leukemia (AML); Vitamin D; Remission; Relapse
20.  Cytogenetic Abnormalities with Interphase FISH Method and Clinical Manifestation in Chronic Lymphocytic Leukemia Patients in North-East of Iran 
Background: Chronic lymphocytic leukemia (CLL) is one of the most prevalent adult leukemias. This malignancy is known by lymphocytosis for a duration of more than 3 months. In fact, it is a heterogeneous clinical disease with changeable progression. Chromosomal aberrations are significant parameters to predict result and survival rate and find treatment strategies for each patient. Cytogenetic methods are known as sensitive and relatively new procedures to detect abnormalities in genome.
Materials and Methods: In order to identify CLL-related chromosomal abnormalities, 48 CLL patients included 38 Men and 10 Women with mean age of 58.25±36 were enrolled in this case series study.The survey was done at Cancer Molecular Pathology Research Center, Mashhad University of Medical Sciences. Interphase fluorescent in situ hybridization (I-FISH) was done on unstimulated peripheral blood or bone marrow samples, which were cultured in whole medium culture; it was used to detect chromosomal abnormalities such as 11q- , 13q14-, 17p- , 6q- and trisomy 12 in CLL patients.
Results: Analysis demonstrated that 45.5% of CLL cases had chromosomal abnormalities; 13.63% haddel 17p, 40.90% had del 13q14 and 9.09% had del 11q. Statistical analysis of data revealed a significant relevancy between age variable and splenomegaly occurrence (P value<0.05). The younger the patients were, the less the splenomegaly occurrence.
Conclusion: Laboratory findings were correlated with clinical data.
PMCID: PMC5625472
Chromosomal aberration; chronic lymphocytic leukemia (CLL); Interphase FISH (I-FISH); Polymerase chain reaction (PCR)
21.  Aberrant Methylation of APAF-1 Gene in Acute Myeloid Leukemia Patients 
Background: Acute myeloid leukemia (AML) is a heterogeneous clonal disorder characterized by immature myeloid cell proliferation and bone marrow failure. Various genetic and epigenetic factors have been found to be influential in such patients.
Methylation silencing of APAF-1, a putative tumor suppressor gene (TSG), has been found in several human malignancies. In this study, we explored the association of APAF-1 methylation status with AML patients.
Materials and Methods: We studied the methylation status of APAF-1 gene in 101 AML patients and 50 healthy subjects as controls. Genomic DNA was extracted from leukocytes in peripheral blood or bone marrow and the methylation status of APAF-1 gene promoter was detectedusing methylation-specific PCR (MSP) method with specific methylated and unmethylated primers. Gene expression was analyzed using real time RT-PCR.
Results: The prevalence of methylated (MM) and hemi-methylated (MU) CpG dinucleotides within the APAF-1 gene promoter of AML patients was 12 (11.9%) and 45 (44.6%), respectively, while no methylation was detected in the control samples (p < 0.001). Our results showed a higher frequency of methylated APAF1 in FLT3-ITD mutated cases (p=0.04). APAF1 mRNA expression was significantly lower in methylated cases compared with normal cases.
Conclusion: The present study indicated the increased frequency of hypermethylation of APAF-1 gene promoter in AML patients. APAF-1 aberrant CpG island methylation was associated with transcriptional downregulation in AML patients. Therefore, promoter methylation of APAF-1 gene could be considered as an epigenetic factor that contributes to the development of AML.
PMCID: PMC5625473
Acute myeloid leukemia; Epigenetics; Methylation; APAF-1; MSP
22.  Cytogenetic Abnormalities in Myelodysplastic Syndromes: An Overview 
Karyotype is one of the main constituents of the International Prognostic Scoring System (IPSS) and revised-IPSS that are the cornerstones for the prognostication of patients with myelodysplastic syndromes (MDS). Del(5q), –7/del(7q), +8 and –Y are among the most extensively studied cytogenetic abnormalities in MDS. The same applies for normal karyotype. There are hundreds of other rare cytogenetic abnormalities that have been reported in MDS, included but not limited to –X, 3q abnormalities, +13/del(13q), i(17q), +21/–21. However, due to a very low number of patients, their impact on the prognosis of MDS is limited. Knowledge of the molecular consequences of different cytogenetic abnormalities allows us to modify treatment regimens based on drugs most active against the specific karyotype present, allowing for the opportunity to individualize MDS treatment and improve patient care and prognosis.
PMCID: PMC5625474
Cytogenetics; Karyotype; Myelodysplastic syndromes; Myelodysplasia; Chromosomal abnormalities
23.  Pseudohypercalcemia in Multiple Myeloma: A Case Report  
Hypercalcemia is a common finding in patients with multiple myeloma. Clinical manifestations of hypercalcemia correlate with the level of serum calcium. Ionized serum calcium (Ca (I)) will be increased in true hypercalcemia. In pseudohypercalcemia the Ionized Ca is normal, although binding of calcium to abnormal immunoglobulin causes increased serum calcium level. In the asymptomatic multiple myeloma patients with moderate to severe hypercalcemia, measurement of ionized calcium is critical to exclude pseudohypercalcemia. Here, we describe an asymptomatic 44-year-old man with multiple myeloma who had severe hypercalcemia, but normal serum Ionized Ca level.
PMCID: PMC5625476
Multiple myeloma; Psudohypercalcemia
24.  Colorectal Cancer Screening: A Comprehensive Review to Recent Non-Invasive Methods 
Colorectal cancer (CRC) is one of the most common cancers worldwide and considered to be one of the hassles in medical communities. CRC develops from precancerous polyps in the colon or rectum and is preventable and curable by an early diagnosis and with the removal of premalignant polyps. In recent years, scientists have looked for inexpensive and safe ways to detect CRC in its earliest stages. Strong evidence shows that screening for CRC is a crucial way to reduce the incidence and mortality of this devastating disease. The main purpose for screening is to detect cancer or pre-cancer signs in all asymptomatic patients. In this review, we holistically introduce major pathways involved in the initiation and progression of colorectal tumorgenesis, which mainly includes chromosome instability (CIN), microsatellite instability (MSI), the CpG island methylator phenotype (CIMP), and we then will discuss different screening tests and especially the latest non-invasive fecal screening test kits for the detection of CRC.
PMCID: PMC5625477
Colorectal cancer (CRC); Chromosome instability (CIN); Microsatellite instability (MSI); The CpG- island methylator phenotype (CIMP); Fecal screening kit
25.  Anti-Apoptotic Effects of Osteopontin via the Up-Regulation of AKT/mTOR/β-Catenin Loop in Acute Myeloid Leukemia Cells 
Background: The conventional chemotherapeutic regimens which applied for treatment of acute myeloid leukemia (AML) mostly target tumor bulk but not leukemic stem cells (LSCs). Aberrant expression or activation of mediators such as osteopontin (OPN) or PI3K/PTEN/Akt/mTOR pathway plays a key role in making prone to develop leukemia. Preventing or treating cancer by curcumin (CUR) has been suggested recently. CUR induces apoptosis and growth inhibition through various mechanisms in leukemic cells. In present study, we tried to measure the toxic response in vitro to CUR for evaluation ofchangesin cell viability, survival and molecular-mediated resistance in primary AML cells.
Materials and Methods: Isolated primary CD34+/CD38− bone marrow derived AML cells were treated with CUR, Daunorubicin (DNR) and/or their combination by MTT assay, Annexin V/PI staining, and colony-formation. The mRNA expression of OPN/AKT/mTOR/PTEN/β-catenin genes was measured by Real-Time PCR. The siRNA against OPN was applied for CUR- treated cells.
Results: Growth inhibition effect of DNR increased in combination with CUR on primary CD34+/CD38- AML cells. Suppression of OPN with siRNA increased the cytotoxic effects of CUR. Likewise, OPN gene expression increased in response to CUR treatment in AML cells. AKT, mTOR, β-catenin or PTEN gene expression increased by CUR, but OPN siRNA decreased the level of mRNA expression of mentioned molecular pathway.
Conclusion : The chemo-resistance of AML cells against therapy might be relevant to increasing of OPN mRNA expression and activity of other mediators including AKT, mTOR, PTEN, and β-catenin. In this context, targeting of OPN might be more impact on CD34+ AML cells.
PMCID: PMC5574411
Curcumin; Acute myeloid leukemia; Osteopontin

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