Correlation of IDH1 gene expression error in breast tumor biopsy in patients with invasive ductal carcinoma.

One of the most important cancers in terms of worldwide prevalence is breast tumors, which have been less investigated in correlation with the enzyme Isocitrate Dehydrogenase 1 (IDH1) gene. The aim of this study was that expression of this gene could have significant effects on the progression of metastasis and invasive disease in breast cancer patients. We used the molecular method of RT-PCR with SYBR-Green to analyze breast tumor tissue from patients with metastasis and non-metastasis, the latter confirmed by the pathology department of Shohada-e Tajrish Hospital (serving as a control group). Also, patients population and its relationship with the degree of tumor in the IDH1 gene was investigated. The IDH1 gene has shown high expression in patients with metastatic breast cancer rather than in patients with non-metastatic breast cancer. The metastatic samples were compared with non-metastatic samples for IDH1 mRNA expression. In this research work, 72.5% (29 samples) were up-regulated in comparison to 27.5% of samples (11 samples) that did not exhibit high expression (P=0.000).  This study examined the IDH1 gene expression, suggesting that changes in this gene's expression could impact the prognosis of breast cancer. However, further research is needed to draw definitive conclusions.

Hub genes, key miRNAs and interaction analyses in type 2 diabetes mellitus: an integrative in silico approach.

Diabetes is a rising global metabolic disorder and leads to long-term consequences. As a multifactorial disease, the gene-associated mechanisms are important to know. This study applied a bioinformatics approach to explore the molecular underpinning of type 2 diabetes mellitus through differential gene expression analysis. We used microarray datasets GSE16415 and GSE29226 to identify differentially expressed genes between type 2 diabetes and normal samples using R software. Following that, using the STRING database, the protein-protein interaction network was constructed and further analyzed by Cytoscape software. The EnrichR database was used for Gene Ontology and pathway enrichment analysis to explore key pathways and functional annotations of hub genes. We also used miRTarBase and TargetScan databases to predict miRNAs targeting hub genes. We identified 21 hub genes in type 2 diabetes, some showing more significant changes in the PPI network. Our results revealed that GLUL, SLC32A1, PC, MAPK10, MAPT, and POSTN genes are more important in the PPI network and can be experimentally investigated as therapeutic targets. Hsa-miR-492 and hsa-miR-16-5p are suggested for diagnosis and prognosis by targeting GLUL, SLC32A1, PC, MAPK10, and MAPT genes involved in the insulin signaling pathway. Insight: Type 2 diabetes, as a rising global and multifactorial disorder, is important to know the gene-associated mechanisms. In an integrative bioinformatics analysis, we integrated different finding datasets to put together and find valuable diagnostic and prognostic hub genes and miRNAs. In contrast, genes, RNAs, and enzymes interact systematically in pathways. Using multiple databases and software, we identified differential expression between hub genes of diabetes and normal samples. We explored different protein-protein interaction networks, gene ontology, key pathway analysis, and predicted miRNAs that target hub genes. This study reported 21 significant hub genes and some miRNAs in the insulin signaling pathway for innovative and potential diagnostic and therapeutic purposes.

Molecular Characteristics of TYK2 Gene Expressions in Patients with Colorectal Cancer.

Background: TYK2 is a member of the JAK family and is known to mediate signals of multiple cytokines that play a crucial role in immune and inflammatory signaling. Activation of TYK2 in tumor cells has been linked to promote cell survival, growth, and invasion. This study aimed to investigate the expression of tyrosine kinase 2 (TYK2) in colorectal cancer (CRC) and adjacent control tissues. Materials and Methods: Quantitative Real-Time PCR (qRT-PCR) method was elaborated to examine the expression levels of TYK2 in 100 colorectal tumor tissues and adjacent tissues as a control. Furthermore, we analyzed the diagnostic power of the mentioned TYK2 by plotting the receiver operating characteristic (ROC) curve. Results: Our results revealed that the expression level of TYK2 was significantly up-regulated in CRC patients sample compared to the adjacent sample of the control group. Analysis of patient's clinic pathological features shows that expressions TYK2 were differently associated with lymph vascular invasion and TMN stage (P < 0.0001, P < 0.0006). Conclusion: These results indicated that TYK2 levels potential biomarkers for diagnosing colorectal cancer may be identified.

Diagnostic of Cytokeratin-19 Gene Expression in Iranian Breast Cancer Patients.

Sentinel lymph node (SLN) biopsy is currently the recommended procedure for axillary staging in clinically node-negative early breast cancer at diagnosis. The present study aimed to identify Cytokeratin-19 (CK19) gene profiles that accurately predicted the outcome of breast cancer patients. Fifty tumor samples from breast cancer patients were analyzed for the expression of the CK19 gene using quantitative PCR. Also, normal breast tissues (N = 50) were taken from the same patients that had undergone partial or total mastectomy. This gene signature was confirmed based on tumor's stage, grade, and estrogen receptor (ER) status, using conditional logistic regression. Based on these findings, the negative reported lymph nodes for metastasis had micrometastasis in significant values. There was a significant difference between normal and cancer samples in  CK19 expression. In this sentinel node evaluation, the relationship of this gene with tumor characteristics needs to be established and discussed finding a clear role for this gene in tumor outcome.

The hopeful anticancer role of oleuropein in breast cancer through histone deacetylase modulation.

Breast cancer (BC) is one of the most common cancers among women worldwide. Genetic, epigenetic, and environmental factors play a crucial role in BC development. Because epigenetic imbalance occurs earlier than expression in carcinogenesis and is reversible, epigenetic reprogramming strategies could be more useful for cancer prevention and therapy. There is evidence indicating that the use of herbal compounds with low toxicity can offer a real benefit in the prevention or treatment of cancer. Oleuropein (OLE), as a natural polyphenol, has shown the anticancer property in cancers. In this study, we investigated for the first time the link between histone deacetylase (HDAC) and OLE to have an anticancer effect in BC. The potential apoptotic and anti-invasive effects of OLE were tested using MCF-7 cells. Transcript expression of HDAC1 and HDAC4 genes after treatment was determined using quantitative reverse transcription polymerase chain reaction. OLE obviously reduced invasiveness and cell viability and simultaneously induced cell apoptosis in MCF-7 cancer cells. Dose-dependent reduction of HDAC4 was observed, whereas apparent changes could not be observed in HDAC1 expression. The current research indicated that OLE can inhibit proliferation and invasion of cells by inducing apoptosis likely through modulation of an important epigenetic factor, HDAC4, in MCF-7 cells. OLE has the potential to be a therapeutic drug for BC prevention and treatment.

Prevention of Cognitive Dysfunction after Cataract Surgery with Intravenous Administration of Midazolam and Dexmedetomidine in Elderly Patients Undergoing Cataract Surgery.

BACKGROUND: This study aimed to compare the effects of preoperative administration of midazolam and dexmedetomidine on cognitive dysfunction prevention after cataract surgery. MATERIALS AND METHODS: This research was a double-blind controlled clinical trial. In this study, 150 candidates for cataract surgery under general anesthesia, over 65 years, and similar to American Society of Anesthesiologists I and II characteristics were selected as the sample and randomly assigned to three groups. Participants of these three groups were treated with 0.1 mg/kg of midazolam, 1 µg/kg of dexmedetomidine, and the same volume of normal saline (control), respectively. Hemodynamic parameters and cognitive dysfunction score of the participants were measured using the Mini-Mental State Examination (MMSE) before the surgery, 24 h and 1 week after the surgery. RESULTS: An evaluation of hemodynamic parameters before anesthesia up to 24 h after the surgery showed no significant difference between the midazolam, dexmedetomidine, and control groups in terms of systolic and diastolic blood pressure, heart rate, and blood oxygen saturation (P > 0.05). In addition, there was no statistically significant difference between the midazolam and dexmedetomidine groups in the MMSE score before the surgery and 24 h and 1 week after that (P > 0.05). However, there was a significant difference between these two groups and control (P < 0.05). CONCLUSION: There was no significant difference between midazolam and dexmedetomidine in reducing postoperative cognitive dysfunction (POCD). However, there is a significant difference between these two groups and control. Hence, either midazolam or dexmedetomidine can be prescribed to reduce POCD in cataract surgeries.

Detection of gene expression in sentinel lymph node of primary breast cancer patients.

Sentinel lymph node (SLN) micrometstasis detection improves outcome for breast cancer follow up procedure. The aim of the present study was to identify gene profiles that accurately predicted the outcome of breast cancer patients. Fifty tumor sample from breast cancer patients were analyzed for the expression of 3 genes using quantitative-PCR. Also clinical verification for recurrence to distant organs was performed. Three gene signature were confirmed based on tumor's stage, grade, ER status, using conditional logistic regression. Based on this findings, the negative reported lymph nodes for metastasis, had micro metastasis in significant values. There was a significant difference between normal and cancer samples in 3 gene expression marker and also there was meaningful relationship between three gene expression with tumor's grade, stage according to progression of tumor. A novel gene expression signature predictive of micro metastatic patients was evaluated. In this assessment, relationship between this gene with tumor's features   that finding clear role for these genes with tumor's outcome, needs to be established.

Stimulation Effect of Low Level Laser Therapy on Sciatic Nerve Regeneration in Rat.

Introduction: Recent studies showed that low-level laser therapy (LLLT) accelerates the regeneration process of injured peripheral nerve tissue. The objective of this study was investigate the effect of LLLT (780 nm) on regeneration of injured right sciatic nerve of male Wistar rat. Methods: In this research work, the effect of LLLT (780 nm) on the regeneration process and reconstruction of injured peripheral right side sciatic nerve was investigated. Twelve adult male Wistar rats underwent surgery in aseptic conditions under general anesthesia to induce a lesion to their right side sciatic nerve according to standard protocol. Before suturing the location, only the experimental group was treated by laser. The damaged nerve was directly irradiated with (2 J, 100 mW, 40 seconds). The irradiation procedure was terminated in 21 days with little improvement (4 J, 200 mW, 40 seconds) across the skin surface of experimental group. Rats were selected randomly from each group to be sacrificed on different periods and histopathological examination was carried out on the extracted nerves. Results: Significant acceleration of revascularization and angiogenesis of the injury site was observed in the experimental group. Furthermore, a reduction of hemorrhages and increase in blood supply was observed. Also, Wallerian degeneration decreased while higher axonal density compared to the control rats was observed. Moreover, the cross-section analysis of the injured area on the 14th and 21st days as post-surgery showed that the nerve sheath diameter in the lesion area of the experimental group was reduced. While the ratio between thicknesses increased in the control group. Conclusion: The results of the current study suggest that laser phototherapy at 780 nm exactly could accelerate the regeneration process of injured peripheral nerves tissue.

Genomic Profiling of Chronic Myelogenous Leukemia: Basic and Clinical Approach.

Chronic myeloid leukemia (CML) is a hematological stem cell cancer driven by BCR-ABL1 fusion protein. We review the previous and recent evidence on the significance of CML in diagnostic and clinic management. The technical monitoring of BCR-ABL1 with quantitative real time-PCR has been used in assessing patient outcome. The cytogenetic mark of CML is Philadelphia chromosome, that is formed by reciprocal chromosomal translocations between human chromosome 9 and 22, t(9:22) (q34:q11). It makes a BCR-ABL1 fusion protein with an anomaly tyrosine kinase activity that promotes the characteristic proliferation of progenitor cells in CML and acute lymphoblastic lymphoma. The targeting of BCR-ABL1 fusion kinase is the first novel paradigm of molecularly targeted curing.

Spiritual Therapy in Coping with Cancer as a Complementary Medical Preventive Practice.

There are many of methods of treating cancer. However, the concept of curing the cancer is beyond our current knowledge. Some patients who have the cancer may seek an alternative manner of curing their disease. Alternative medicines, such as spiritual and complementary therapy, are able to cure the cancer and, at the least, are safe. Research on the importance of spirituality in cancer care has mainly been performed in geographically heterogeneous populations. The results are limited to these specific religious-cultural contexts and enlightened by contributions from ethnicity and religion. This article focused on the religiousness and spiritual support of cancer patients from diverse and heterogeneous groups around the globe. An electronic search of peer-reviewed articles was systematically performed to obtain the relevant literature with the CINAHL, PsycINFO, and PubMed databases. The keywords included religion, cancer, illness, psychotherapy, and spiritual and alternative treatment/therapies. The inclusion criteria for the reviews were that the documents were original quantitative research and published in English. Articles that were not directly relevant to the present objective were excluded. The present outcome of these review resources suggest that it may be helpful for clinicians to address spirituality, particularly with regard to prevention, healing, and survival of cancer patients. This article indicates that it may be useful for clinical oncologists to be informed of the prevalence of the use of spiritual medicine in their specialized field. In addition, patients should routinely be asked about the use of spiritual medicine as part of every cancer patient's evaluation.

Detection of Superior Markers for Polymerase Chain Reaction Diagnosis of Breast Cancer Micrometastasis in Sentinel Lymph Nodes.

Breast cancer is the most prevalent type of cancer among women around the world, and mortality is primarily caused by micro-metastatic disease. The complex mechanisms of breast cancer invasion and metastasis are intrinsically related to the malignant cell type so that early detection of micro-metastases can help prolongation of survival for patient. The aim of the present research work was evaluation of the expression status of mammoglobin protein as a candidate molecular marker in the negative sentinel lymph node (SLN). Fifty tumor specimens, and 50 normal adjacent breast tissue samples from the same patients were selected on the basis of having more than 10% tumor content for RNA extraction from SLNs. Tumor samples and normal adjacent breast tissue were archived in the form of frozen fresh tissue in liquid nitrogen. Real-time PCR was performed on a Bioner life express gradient thermal cycler system. Mammoglobin gene overexpression in breast cancer metastasis was investigated. Single marker results were mammaglobin 66.7% and CK19 50.0%, with 58.3% for the two in combination. Due to improved outcome with at least 3 genes (83.3%), it seems, triple marker evaluation will be most likely useful for detecting micro-metastases instead of studying separate genes.

Overexpression of the MUC1 Gene in Iranian Women with Breast Cancer Micrometastasis.

The membrane epithelial mucin MUC1 is expressed at the luminal surface of most simple epithelial cells, but expression is greatly increased in most breast cancers. The aims of present study were to investigate expression of the MUC1 gene and interactive affects in metastases. Whole cell RNA isolation from 50 sentinel lymph nodes (SNLs) of breast cancer patients was performed using reverse transcription and real-time PCR. All patients were diagnosed with breast cancer and without metastasis, confirmed by IHC staining. The evaluation of tumor and normal samples for expression of MUC1 gene, the results were 49.1% non-expressive and 45.3% expression (Student t, p = 0.03). Also in comparison of normal breast tissue and breast cancer SLN for MUC1 gene, MUC1 negative SLNs were 75.0% (18 samples) and MUC1 positive samples were 25.0% (6 samples). Over-expression of MUC1 gene may offer a target for therapy related to progression and metastasis in women with breast cancer.

Evaluation of Methylobacterium radiotolerance and Sphyngomonas yanoikoaie in Sentinel Lymph Nodes of Breast Cancer Cases.

It has been established that different kinds of bacteria agents are involved in various cancers. Although the mechanism of tumorigenesis is not clearly understood, there is evidence for the presence of bacteria within tumors, with at least a progression effect for some bacteria that prepare suitable microenvironments for tumor cell growth. The aim of current study was to evaluate bacterial dysbiosis in sentinel lymph nodes of breast cancer patients. One hundred and twenty three fresh-frozen sentinel lymph nodes and a corresponding number of normal adjacent breast tissue specimens and five normal mastectomy samples were investigated employing RT-PCR. In addition using genus-specific primers were applied. There was a significant differences as presence of Methylobacterium radiotolerance DNA recorded between patients and normal control group (p= 0.0). Based on our research work, further studies into the role of microbes in breast cancer would be of great interest.

Targeting of BUB1b Gene Expression in Sentinel Lymph Node Biopsies of Invasive Breast Cancer in Iranian Female Patients.

Detection of micrometastasis in sentinel lymph nodes (SLNs) is a very useful tool for appropriate assessment of the clinical stage of disease in breast cancer patients. Early identification of clinically relevant disease could lead to early treatment or staging approaches for breast cancer patient. Micrometastases in SLNs of women with invasive breast cancer are of great significance in this context. In this study we examined SLN biopsies considered to have small numbers of cancerous cells by real time RT-PCR. All of the samples underwent immunohistochemical staining for cytokeratin for confirmation of the presence or absence of micrometastases. BUB1b expression assay of selected patients with and without metastasis showed overexpression in the former, but not in normal breast and lymph node tissue. Our results may be taken into account in the discussion about the merits of routine use of molecular assessment in pathogenetic studies of SLNs.

Lack of Altered BECN1 Gene Expression in Iranian Patients with Acute Myeloid Leukemia

Acute myeloid leukemia (AML), one of the most prevalent leukemia types in adults, demonstrates great heterogeneity in molecular and clinical terms. Hence, there is a necessity to the mechanisms involved in AML generation in order to determine optimal treatment. This cross sectional study aimed to assess changes in BECN1 gene expression in with blood samples from 30 AML patients, compared with samples from 15 healthy persons. RNA was extracted and cDNA was synthesized and Real Time PCR applied to determine BECN1 gene expression. The results showed no significant differences in BECN1 gene expression between patients with AML and normal controls (P > 0.05). It appears that expression of BECN1 does not play a significant role in genesis of AML leukemia.

Downregulation of E-cadherin expression in breast cancer by promoter hypermethylation and its relation with progression and prognosis of tumor.

Breast cancer is the most common cancer in women around the world, and novel prognosis strategies is needed to control more accurate and effective of this malignant disease. Among the latest prognostic markers is E-cadherin, which mediates cell-cell adhesion by associating with catenins. Loss of E-cadherin gene (CDH1) function by genetic or epigenetic alteration leads to tumorigenesis. The aim of our study was to investigate E-cadherin gene promoter methylation in breast cancer, and its correlation with E-cadherin protein expression. Fifty primary breast cancers tissue with ductal type and 50 normal breast sample from the same patients that was located adjacent to tumor region as controls were provided by Imam Reza-based referral and teaching hospital affiliated to Tabriz University of Medical Sciences, Tabriz, Iran. CDH1 promoter region CpG sites methylation and E-cadherin protein expression were determined by bisulfite-specific polymerase chain reaction and Western blot analysis, and the resulting products were sequenced on an ABI automated sequencer for firm conclusion. CDH1 hypermethylation in breast tumor specimen (ductal type) was observed in 94 % (47 of 50) comparing with normal samples methylation, and the significant difference was (p = 0.000). Protein expression in tumor samples tends to diminish with the CDH1 promoter region methylation. In the group of 50 ductal carcinomas cases, most of the cases showing CDH1 hypermethylation correlated inversely with the reduced levels of expression of E-cadherin proteins (95 % of full-methylated tumor samples had no protein expression, and 4.5 % of them had weak expression levels). Possible association was observed between CDH1 methylation and its protein expression (p = 0.000). The results of methylation analysis in promoter region in ten CpG sites (863, 865, 873, 879, 887, 892, 901, 918, 920, and 940) suggested that abnormal CDH1 methylation occurs in high frequencies in ductal breast tumors probably sounds the process of carcinogenesis progression.