ABSTRACT
Background: Aberrant activation of phosphatidylinositol-3 kinases [PI3K]/AKT/mTOR [mammalian target of rapamycin] pathway is a critical event during gastric cancer progression. Selective function of AKT inhibitor AZD5363 in PI3KCA mutant gastric cancer necessitates the assessment of PI3KCA mutations in these patients
Methods: The study included 100 patients with gastric cancer who underwent surgical resection at Imam Reza Hospital, Tehran, Iran, between January 2009 and December 2016. Mutations in codon 1047 of PIK3CA were evaluated by tetra-primer ARMS-PCR and direct sequencing methods
Results: We detected p.H1047R and p.H1047L in eight and three samples, respectively. Also, a significant association was found between PIK3CA mutations and lymphatic invasion. Kaplan-Meier analysis demonstrated no significant differences in overall survival between patients with and without mutations
Conclusion: Our study detected gain-of-function mutations in exon 20 of PI3KCA gene in 11% of gastric cancer patients. Future studies are needed to assess the mutation rate in other regions of this gene to find eligible patients for targeted therapies
ABSTRACT
Background: Familial hypercholesterolemia [FH] is a frequent autosomal dominant disorder of lipoprotein metabolism. This disorder is generally caused by mutations in low-density lipoprotein receptor [LDLR], apolipoprotein B 100 [APOB], and proprotein convertase subtilisin/kexin type 9 [PCSK9] genes. In the present study, we aimed at identifying the common LDLR and APOB gene mutations in an Iranian population
Methods: Eighty unrelated Iranian patients with FH entered the study, based on Simon Broome diagnostic criteria. All samples were screened for two common APOB gene mutations, including R3500Q and R3500W, by the means of ARMS-PCR and PCR- RFLP assays, respectively. In addition, exons 3, 4, 9, and 10 of LDLR gene were sequenced in all patients
Results: A novel mutation in exon 3 [C95W] and a previously described mutation in exon 4 [D139H] of LDLR gene were found. Three previously reported polymorphisms in LDLR gene as well as three novel polymorphisms were detected in the patients. However, in the studied population, no common mutations were observed in APOB gene
Conclusion: The results of our study imply that the genetic basis of FH in Iranian patients is different from other populations
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Apolipoprotein B-100 , Receptors, LDL , GeneticsABSTRACT
Background: Telomeres are evolutionary, specialized terminal structures at the ends of eukaryotic chromosomes containing TTAGGG repeats in human. Several human diseases have been known to be associated with dramatic changes in telomere length. The aim of the present study was to assess the correlation between the relative leukocyte telomere length [LTL] and infertility in a group of Iranian azoospermic males
Methods: In this casecontrol pilot study, relative telomere length [RTL] of peripheral blood leukocytes from a total of 30 idiopathic nonobstructive azoospermic males and 30 healthy fertile males was evaluated using real-time PCR. RTL was calculated as T [telomere]/S [single copy gene] ratio and compared between infertile and fertile groups
Results: Patients with azoospermia showed significantly shorter RTL than fertile males [0.54 vs. 0.84, p < 0.05]. The area under the receiver operating characteristic [ROC] curve was estimated to be 99.8%, suggesting LTL as a potential marker for the diagnosis of azoospermia
Conclusion: Our findings demonstrated a probable association between telomere shortening and azoospermia in a population of Iranian infertile men affected by idiopathic azoospermia
ABSTRACT
Objective: The genetic variants of the long non-coding RNA ANRIL [an antisense non-coding RNA in the INK4 locus] as well as its expression have been shown to be associated with several human diseases including cancers. The aim of this study was to examine the association of ANRIL variants with breast cancer susceptibility in Iranian patients
Materials and Methods: In this case-control study, we genotyped rs1333045, rs4977574, rs1333048 and rs10757278 single nucleotide polymorphisms [SNPs] in 122 breast cancer patients as well as in 200 normal age-matched subjects by tetra-primer amplification refractory mutation system polymerase chain reaction [T-ARMS-PCR]
Results: The TT genotype at rs1333045 was significantly over-represented among patients [P=0.038] but did not remain significant after multiple-testing correction. In addition, among all observed haplotypes [with SNP order of rs1333045, rs1333048 rs4977574 and rs10757278], four haplotypes were shown to be associated with breast cancer risk. However, after multiple testing corrections, TCGA was the only haplotype which remained significant
Conclusion: These results suggest that breast cancer risk is significantly associated with ANRIL variants. Future work analyzing the expression of different associated ANRIL haplotypes would further shed light on the role of ANRIL in this disease
Subject(s)
Humans , Female , Adult , Breast Neoplasms/genetics , Case-Control Studies , Genotype , Polymorphism, Single Nucleotide , Polymerase Chain Reaction , HaplotypesABSTRACT
Background: Ovarian cancer is the most fatal tumor of female's reproductive system, and several genetics and environmental factors are involved in its development. Various studies have already identified suitable biomarkers to facilitate the early detection, prognosis evaluation, and the assessment of treatment response. However, the aim of this review was to investigate the role of long non-coding RNAs [lncRNAs] in tumorigenesis process of ovarian cancer and their potential applications as ovarian cancer biomarkers
Methods: We performed an online literature search of the MEDLINE/PubMed databases using the key words ovarian cancer, lncRNA, and biomarker
Results: We found that several lncRNAs have been shown to be deregulated in ovarian cancer and the specific mechanism of their enrollment in ovarian cancer has been defined for a few of them. In addition, expression profiling has revealed an association between lncRNAs and patients' survival, metastasis potential as well as treatment response
Conclusions: Expression profiling as well as methylation analysis of lncRNAs in ovarian cancer may lead to the identification of novel biomarkers that can help in the classification of patients based on prognosis and treatment response
Subject(s)
Humans , Women , RNA, Long Noncoding , Carcinogenesis , Biomarkers, TumorABSTRACT
Objective: The aim of this study was to clarify the mechanism by which lactobacilli exert their cytotoxic effects on cervical cancer cells. In addition, we aimed to evaluate the effect of lactobacilli on the expression of human papilloma virus [HPV] onco-genes
Materials and Methods: In this experimental study, using quantitative real-time polymerase chain reaction [PCR], we analyzed the expression of CASP3 and three autophagy genes [ATG14, BECN1 and alpha 2 catalytic subunit of AMPK [PRKAA2]] along with HPV18 E6 and E7 genes in HeLa cells before and after treatment with Lactobacillus crispatus and Lactobacillus rhamnosus culture supernatants
Results: The expression of CASP3 and autophagy genes in HeLa cells was decreased after treatment with lactobacilli culture supernatants. However, this de-crease was not significant for PRKAA2 when compared with controls. In addition, expression of HPV E6 was significantly decreased after treatment with lactobacilli culture supernatants
Conclusion: Lactobacilli culture supernatants can decrease expression of ATG14 and BECN1 as well as the HPV E6 oncogene. It has been demonstrated that the main changes occurring during cervical carcinogenesis in cell machinery can be reversed by suppression of HPV oncogenes. Therefore, downregulation of HPV E6 by lactobacilli may have therapeutic potential for cervical cancer. As the role of autophagy in cancer is complicated, further work is required to clarify the link between downregulation of autophagy genes and antiproliferative effects exerted by lactobacilli
ABSTRACT
Objective: Hypoxia-Inducible Factor [HIF]-1 plays an essential role in the body's response to low oxygen concentrations and regulates expression of several genes implicated in homeostasis, vascularization, anaerobic metabolism as well as immunological responses. Increased levels of HIF-1alpha are associated with increased proliferation and more aggressive breast tumor development. Lactobacilli have been shown to exert anti-cancer effects on several malignancies including breast cancer. However, the exact mechanism of such effect is not clear yet. The aim of this study was to analyze the expression of selected genes from HIF pathway in a triple negative breast cancer cell line [expressing no estrogen and progesterone receptors as well as HER-2/Neu], MDA-MB-231, following treatment with two lactobacilli culture supernatants
Materials and Methods: In this experimental study, we analyzed the expression of HIF-1alpha, SLC2A1, VHL, HSP90, XBP1 and SHARP1 genes from HIF pathway in MDA-MB-231 cells, before and after treatment with Lactobacillus crispatus and Lactobacillus rhamnosus culture supernatants [LCS and LRS, respectively] by means of quantitative reverse-transcription polymerase chain reaction [qRT-PCR]
Results: Both LRS and LCS had cytotoxic effects on MDA-MB-231 cells, while the former type was more cytotoxic. LRS dramatically down-regulated expression levels of the HIF-1alpha, HSP90 and SLC2A1 in the MDA-MB-231 cells. LCS had similar effect on the expression of HSP90, to what was observed in the LRS treatment. The expression level of tumor suppressor genes VHL and SHARP1 were also decreased in LCS treated cells
Conclusion: Although both LCS and LRS had cytotoxic effects on the MDA-MB-231 cells, it is proposed that LRS could be more appropriate for pathway directed treatment modalities, as it did not decrease expression of tumor suppressor genes involved in HIF pathway. Down-regulation of HIF pathway mediated oncogenes by LRS suggests that the cytotoxic effects of this Lactobacillus may at least be partly caused by this mechanism. As previous studies have shown that inhibition of HIF-1alpha and HSP90 expressions have therapeutic impact on cancer treatment, the inhibitory effect of LRS on expression of these genes implies that this Lactobacillus can be used in treatment strategies
ABSTRACT
Trisomy 9 is a rare chromosome disorder with high neonatal mortality. It is often seen in mosaic form. Most patients who survive are severely mentally retarded. The main features of this syndrome are "bulbous" nose, microphthalmia, dislocated limbs, and other anomalies of skeletal, cardiac, genitourinary, and central nervous system. Most patients have developmental and cognitive impairment. Patients with mosaicism survive longer than non-mosaics, but it was believed that the degree of mosaicism in lymphocytes or fibroblasts does not associate with survival or degree of impairment. In this report, we present a 2,5-year-old male case of mosaic trisomy 9, to show the wide range of clinical findings in this chromosome disorder. The patient had cardiac anomalies, inguinal hernia, and undescendent testes. He had low-set slightly malformed ears, deeply-set malformed eyes, small palpebral fissures, micrognathia, developmental delay and unilateral optic hypoplasia. The most prominent facial anomaly in this patient was eye anomalies. Cytogenetic analysis with G banding showed karyotype 47XY,+9 in 44% of peripheral lymphocytes examined [47XY,+9[22], 46XY[28]]. His parents' karyotypes were normal. Moderate developmental delay, which was detected in this patient shows that the range of motor and cognitive impairment in this chromosomal disorder is quite broad. This fact should be considered in genetic counseling as well as prenatal diagnosis of this chromosomal disorder
Subject(s)
Humans , Male , Child, Preschool , Trisomy , Mosaicism , Cytogenetic AnalysisABSTRACT
Background: Robertsonian translocations are structural chromosomal abnormalitiescaused by fusion of two acrocentric chromosomes. In carriers of such translocations,different modes of segregations would result in the formation of either balanced [alternatesegregation mode] or unbalanced [adjacent 1, adjacent 2, and 3:1 segregationmodes] gametes. In addition, there is an increased risk for imprinting disorders intheir offspring. Although it has been estimated that 1/1000 healthy persons carry aRobertsonian translocation, homozygosity for this type of structural chromosomalabnormality has been reported rarely. Most of reported cases are phenotypicallynormal but experience adverse pregnancy outcomes
Case Presentation: In this paper, a report was made on a normal female with a historyof 4 consecutive first trimester fetal losses and a normal son referred to Centerfor Comprehensive Genetics Services, Tehran, Iran, in summer 2015. Cytogeneticanalyses of proband and her infant showed 44,XX, der[13;14][q10;q10]x2 and 45,XY, der[13;14][q10;q10], respectively. Parents of proband have been shown to have45,XY,der[13q;14q] and 45,XX,der[13q;14q] karyotypes, respectively
Conclusion: The present report was in agreement with the few reports of homozygosityfor Robertsonian translocation which demonstrated normal phenotypes forsuch persons and possibility of giving birth to phenotypically normal heterozygotecarriers of Robertsonian translocations
ABSTRACT
Context: Multiple myeloma [MM] is a B-cell malignancy characterized by monoclonal expansion of abnormal plasma cells in the bone marrow. It accounts for 10% of hematological malignancies. Although patients respond to a wide range of anticancer modalities, relapse occurs in a significant number of the cases. Immunotherapeutic approaches have been evolved to tackle this problem. Cancer-testis antigens CTAs as a group of tumor-associated antigens are appropriate targets for cancer immunotherapy as they have restricted expression pattern in normal tissues except for testis which is an immune-privileged site. Expression of these antigens has been assessed in different malignancies including MM
Evidence Acquisition: We performed a computerized search of the MEDLINE/PubMed databases with key words: multiple myeloma, cancer-testis antigen, and cancer stem cell and immunotherapy
Results: Several CTAs including NY-ESO-1, MAGE and GAGE family have been shown to be expressed in MM patients. Cellular and humoral immune responses against these antigens have been detected in MM patients
Conclusions: The frequent and high expression level of CTAs in MM patients shows that these antigens can be applied as cancer biomarkers as well as targets for immunotherapy in these patients
Subject(s)
Humans , Immunotherapy , Antigens, Neoplasm , Neoplastic Stem Cells , Biomarkers, Tumor , Testicular NeoplasmsABSTRACT
Objective: During the past decade, the importance of biomarker discovery has been highlighted in many aspects of cancer research. Biomarkers may have a role in early detection of cancer, prognosis and survival evaluation as well as drug response. Cancer-testis antigens [CTAs] have gained attention as cancer biomarkers because of their expression in a wide variety of tumors and restricted expression in testis. The aim of this study was to find putative biomarkers for breast cancer
Materials and Methods: In this applied-descriptive study, the expression of 4 CTAs, namely acrosin binding protein [ACRBP], outer dense fiber 4 [ODF4], Rhox homeobox family member 2 [RHOXF2] and spermatogenesis associated 19 [SPATA19] were analyzed at the transcript level in two breast cancer lines [MCF-7 and MDA-MB-231], 40 invasive ductal carcinoma samples and their adjacent normal tissues as well as 10 fibroadenoma samples by means of quantitative real-time reverse transcription polymerase chain reaction [RT-PCR]
Results: All four genes were expressed in both cell lines. Expression of ODF4 and RHOXF2 was detected in 62.5% and 60% of breast cancer tissues but in 22.5 and 17.5% of normal tissues examined respectively. The expression of both RHOXF2 and ODF4 was upregulated in cancerous tissues compared with their normal adjacent tissues by 3.31- and 2.96-fold respectively. The expression of both genes was correlated with HER2/neu overexpression. RHOXF2 expression but not ODF4 was correlated with higher stages of tumors. However, no significant association was seen between expression patterns and estrogen and progesterone receptors status
Conclusion: ODF4 and RHOXF2 are proposed as putative breast cancer biomarkers at the transcript level. However, their expression at protein level should be evaluated in future studies
ABSTRACT
Cancer-testis [CT] antigens are a group of antigens with a restricted expression in normal tissues, except testis, and they have aberrant expression in different tumors. This pattern of expression has made them promising targets for immunotherapy and cancer detection. Our aim was to find new members of this group that might be useful as markers in the detection of cancer and immunotherapy. A descriptive study conducted in referral centers of Tehran University of Medical Science from january 2008 to January 2009. We analyzed the expression of two testis-specific genes named ODF4 [outer dense fiber of sperm tails 4] and TEX101 [testis expressed 101] in 20 chronic myeloid leukemia [CML] and 20 normal samples by reverse transcription-polymerase chain reaction and sequencing. Immunogenicity of TEX101 was evaluated by means of enzyme-linked immunosorbent assay. These two genes were expressed in 30% of CML patients but not in any of the healthy donors. Humoral response against TEX101 was not detected in any samples. TEX101 and ODF4 are CT genes useful for detection of CML. Unlike many CT genes, overexpression of TEX101 was not shown to induce immunologic responses in these samples. According to the previous studies, overexpression of TEX101 leads to suppression of cancer invasion and metastasis; thus, the induction of the expression of TEX101 in cancer by epigenetic mechanisms may be a treatment strategy