Vol 11, No 3 (2017)

Published: 2017-07-02

Original Article(s)

  • XML | PDF | downloads: 172 | views: 365 | pages: 172-177

    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.
    Subjects 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.

  • XML | PDF | downloads: 135 | views: 280 | pages: 185-191

    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.
    Subjects 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.

  • XML | PDF | downloads: 155 | views: 352 | pages: 192-198

    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.
    Subjects 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 werefunctionally 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.

     

  • XML | PDF | downloads: 145 | views: 396 | pages: 199-208

    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.
    Subjects 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.

  • XML | PDF | downloads: 207 | views: 392 | pages: 209-216

    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.
    Subjects 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.

  • XML | PDF | downloads: 146 | views: 259 | pages: 217-224

     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.
    Subjects 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% had del 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.

  • XML | PDF | downloads: 171 | views: 511 | pages: 225-231

    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.
    Subjects 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.

  • XML | PDF | downloads: 112 | views: 365 | pages: 241-246

    Background: Familial colorectal cancer type X (FCCX) is a subtype of mismatchrepair (MMR)-proficient colorectal cancerin whichthe patients are clinicallyat risk for Lynch syndrome (LS), a common hereditary cancer predisposing syndrome.In this study, we describeda new clinicopathological feature of the condition in central Iran.
    Subjects and Methods: We designed a descriptive, retrospective study to screenat-riskcolorectal cancer (CRC) patients,usingAmsterdam 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 FCCXand 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.

     

Review Article(s)

  • XML | PDF | downloads: 163 | views: 392 | pages: 178-184

    Background: Patientsgenerallyhave 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.

  • XML | PDF | downloads: 154 | views: 338 | pages: 232-240

    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.

  • XML | PDF | downloads: 188 | views: 260 | pages: 251-262

    Colorectal cancer (CRC) is one of the most common cancers worldwide and considered to be one of the hassle 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.

Case Report(s)

  • XML | PDF | downloads: 161 | views: 493 | pages: 247-250

    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.