AutoMap is a high performance homozygosity mapping tool using next-generation sequencing data.

Homozygosity mapping is a powerful method for identifying mutations in patients with recessive conditions, especially in consanguineous families or isolated populations. Historically, it has been used in conjunction with genotypes from highly polymorphic markers, such as DNA microsatellites or common SNPs. Traditional software performs rather poorly with data from Whole Exome Sequencing (WES) and Whole Genome Sequencing (WGS), which are now extensively used in medical genetics. We develop AutoMap, a tool that is both web-based or downloadable, to allow performing homozygosity mapping directly on VCF (Variant Call Format) calls from WES or WGS projects. Following a training step on WES data from 26 consanguineous families and a validation procedure on a matched cohort, our method shows higher overall performances when compared with eight existing tools. Most importantly, when tested on real cases with negative molecular diagnosis from an internal set, AutoMap detects three gene-disease and multiple variant-disease associations that were previously unrecognized, projecting clear benefits for both molecular diagnosis and research activities in medical genetics

Organ-specific metastasis of breast cancer: molecular and cellular mechanisms underlying lung metastasis

Background: Breast cancer (BC) is the most common type of cancer in women and the second cause of cancer-related mortality world-wide. The majority of BC-related deaths is due to metastasis. Bone, lung, brain and liver are the primary target sites of BC metastasis. The clinical implications and mechanisms underlying bone metastasis have been reviewed before. Given the fact that BC lung metastasis (BCLM) usually produces symptoms only after the lungs have been vastly occupied with metastatic tumor masses, it is of paramount importance for diagnostic and prognostic, as well as therapeutic purposes to comprehend the molecular and cellular mechanisms underlying BCLM. Here, we review current insights into the organ-specificity of BC metastasis, including the role of cancer stem cells in triggering BC spread, the traveling of tumor cells in the blood stream and their migration across endothelial barriers, their adaptation to the lung microenvironment and the initiation of metastatic colonization within the lung. Conclusions: Detailed understanding of the mechanisms underlying BCLM will shed a new light on the identification of novel molecular targets to impede daunting pulmonary metastases in patients with breast cancer. © 2018, International Society for Cellular Oncology

Association of MTHFR C677T Polymorphism with Preeclampsia in North East of Iran (Khorasan Province)

Background: Preeclampsia (PE) is one of the main causes of fetal and maternal mortality. The analysis of candidate gene polymorphisms can improve our understanding of the mechanisms underlying pathogenesis of PE. Present study is aimed at investigating the association between MTRR c.66A > G, MTHFR c.677C > T, MTHFR c.1298A > C, and MTR c.2756A > G polymorphisms and PE in Iranian women. Methods: About 117 women with history of PE and 103 healthy women with a pregnancy not complicated by PE were selected. The genomic DNA was extracted from peripheral blood. Single-nucleotide polymorphisms were genotyped using Real-Time PCR. Results: There was a significant difference between MTHFR c.677C > T polymorphism with PE (p = 0.045). The frequency of C/T heterozygous genotypes were (58 vs. 36) in the case and control groups, respectively. There were no statistically significant differences between other genetic polymorphisms. Conclusions: The results indicated that the MTHFR c.677C > T polymorphism may be associated with development of PE in Iranian women. © 2019, © 2019 Taylor & Francis Group, LLC

Crosstalk between breast cancer stem cells and metastatic niche: Emerging molecular metastasis pathway?

Metastatic colonization represents the final step of metastasis, and is the major cause of cancer mortality. Metastasis as an "inefficient" process requires the right population of tumor cells in a suitable microenvironment to form secondary tumors. Cancer stem cells are the only capable population of tumor cells to progress to overt metastasis. On the other hand, the occurrence of appropriate microenvironmental conditions within the target tissue would be critical for metastasis formation. Metastatic niche seems to be the specialized microenvironment to support tumor initiating cells at the distant organ. Master regulators not only determine cancer stem cell state, but also may have regulatory roles in metastatic niche elements. Meanwhile, both cancer stem cell and metastatic niche may function like two sides of the metastatic coin. Hypoxia inducible factors have multiple roles in regulation of both sides of this coin. TGF-β superfamily, also, have been considered as master regulators of epithelial to mesenchymal transition and metastasis and may play crucial roles in regulation of metastatic niche as well. In this regard, we hypothesize the presence of a possible emerging molecular pathway in the biological process of breast cancer metastasis. In this process, non-Smad TGF-β-induced metastasis connects cancer stem cell and metastatic niche formation through a central path, "Metastasis Pathway". © 2013 International Society of Oncology and BioMarkers (ISOBM)

MicroRNA and exosome: Key players in rheumatoid arthritis

Rheumatoid arthritis (RA) is known as one of important autoimmune disorders which can lead to joint pain and damage throughout body. Given that internal (ie, genetic and epigenetic alterations) and external factors (ie, lifestyle changes, age, hormones, smoking, stress, and obesity) involved in RA pathogenesis. Increasing evidence indicated that cellular and molecular alterations play critical roles in the initiation and progression of RA. Among various targets and molecular signaling pathways, microRNAs (miRNAs) and their regulatory networks have key roles in the RA pathogenesis. It has been showed that deregulation of many miRNAs involved in different stages of RA. Hence, identification of miRNAs and their signaling pathways in RA, could contribute to new knowledge which help to better treatment of patients with RA. Besides miRNAs, exosomes have been emerged as key messengers in RA pathogenesis. Exsosomes are nanocarriers which could be released from various cells and lead to changing of behaviors recipient cells via targeting their cargos (eg, proteins, messenger RNAs, miRNAs, long noncoding RNAs, DNAs). Here, we summarized several miRNAs involved in RA pathogenesis. Moreover, we highlighted the roles of exosomes in RA pathogenesis. © 2019 Wiley Periodicals, Inc

Tumor-associated macrophages and epithelial�mesenchymal transition in cancer: Nanotechnology comes into view

Tumor-associated macrophages (TAMs) are an important component of the leukocytic infiltrate of the tumor microenvironment. There is persuasive preclinical and clinical evidence that TAMs induce cancer inanition and malignant progression of primary tumors toward a metastatic state through a highly conserved and fundamental process known as epithelial�mesenchymal transition (EMT). Tumor cells undergoing EMT are distinguished by increased motility and invasiveness, which enable them to spread to distant sites and form metastases. In addition, besides becoming resistant to apoptosis and antitumor drugs, they also contribute to immunosuppression and get a cancer stem-cell like phenotype. Here, we will focus on selected molecular pathways underlying EMT�in particular, the role of TAMs in the induction and maintenance of EMT�and further discuss how the targeting of TAMs through the application of nanotechnology tools allows the development of a whole new range of therapeutics. © 2018 Wiley Periodicals, Inc

Breast cancer diagnosis: Imaging techniques and biochemical markers

Breast cancer is a complex disease which is found as the second cause of cancer-associated death among women. Accumulating of evidence indicated that various factors (i.e., gentical and envirmental factors) could be associated with initiation and progression of breast cancer. Diagnosis of breast cancer patients in early stages is one of important aspects of breast cancer treatment. Among of various diagnosis platforms, imaging techniques are main diagnosis approaches which could provide valuable data on patients with breast cancer. It has been showed that various imaging techniques such as mammography, magnetic resonance imaging (MRI), positron-emission tomography (PET), Computed tomography (CT), and single-photon emission computed tomography (SPECT) could be used for diagnosis and monitoring patients with breast cancer in various stages. Beside, imaging techniques, utilization of biochemical biomarkers such as proteins, DNAs, mRNAs, and microRNAs could be employed as new diagnosis and therapeutic tools for patients with breast cancer. Here, we summarized various imaging techniques and biochemical biomarkers could be utilized as diagnosis of patients with breast cancer. Moreover, we highlighted microRNAs and exosomes as new diagnosis and therapeutic biomarkers for monitoring patients with breast cancer. © 2017 Wiley Periodicals, Inc

Exosomal microRNAs: Novel players in cervical cancer

Cervical cancer ranks fourth for both mortality and morbidity in women globally. Exosomes are considered as extracellular vesicles, secreted continuously by many cells with a size range from 30 to 150 nm. Exosomes can encapsulate microRNAs (miRNAs) and release them for cellular communications. This exosome-induced miRNA transfer is a novel strategy for genetic exchange among cells. This trafficking modality affects many pathological as well as physiological conditions. Moreover, exosomes can protect the miRNAs against harsh environments and keep them very stable. Given that a variety of exosomal miRNAs derived from cervical cancer cells can be targeted to recipient cells and contribute to tumorgenesis, it has been documented that exosomal miRNAs could be applied as diagnostic and therapeutic biomarkers in the treatment of cervical cancer. Herein, we summarize the pathologic and diagnostic roles of exosomal miRNAs in the cervical cancer. Moreover, we highlight the roles of exosomal miRNAs in other cancers. © 2020 Future Medicine Ltd

Breast cancer diagnosis: Imaging techniques and biochemical markers

Breast cancer is a complex disease which is found as the second cause of cancer-associated death among women. Accumulating of evidence indicated that various factors (i.e., gentical and envirmental factors) could be associated with initiation and progression of breast cancer. Diagnosis of breast cancer patients in early stages is one of important aspects of breast cancer treatment. Among of various diagnosis platforms, imaging techniques are main diagnosis approaches which could provide valuable data on patients with breast cancer. It has been showed that various imaging techniques such as mammography, magnetic resonance imaging (MRI), positron-emission tomography (PET), Computed tomography (CT), and single-photon emission computed tomography (SPECT) could be used for diagnosis and monitoring patients with breast cancer in various stages. Beside, imaging techniques, utilization of biochemical biomarkers such as proteins, DNAs, mRNAs, and microRNAs could be employed as new diagnosis and therapeutic tools for patients with breast cancer. Here, we summarized various imaging techniques and biochemical biomarkers could be utilized as diagnosis of patients with breast cancer. Moreover, we highlighted microRNAs and exosomes as new diagnosis and therapeutic biomarkers for monitoring patients with breast cancer. © 2017 Wiley Periodicals, Inc

microRNAs: Key players in virus-associated hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is known as one of the major health problems worldwide. Pathological analysis indicated that a variety of risk factors including genetical (i.e., alteration of tumor suppressors and oncogenes) and environmental factors (i.e., viruses) are involved in beginning and development of HCC. The understanding of these risk factors could guide scientists and clinicians to design effective therapeutic options in HCC treatment. Various viruses such as hepatitis B virus (HBV) and hepatitis C virus (HCV) via targeting several cellular and molecular pathways involved in HCC pathogenesis. Among various cellular and molecular targets, microRNAs (miRNAs) have appeared as key players in HCC progression. miRNAs are short noncoding RNAs which could play important roles as oncogenes or tumor suppressors in several malignancies such as HCC. Deregulation of many miRNAs (i.e., miR-222, miR-25, miR-92a, miR-1, let-7f, and miR-21) could be associated with different stages of HCC. Besides miRNAs, exosomes are other particles which are involved in HCC pathogenesis via targeting different cargos, such as DNAs, RNAs, miRNAs, and proteins. In this review, we summarize the current knowledge of the role of miRNAs and exosomes as important players in HCC pathogenesis. Moreover, we highlighted HCV- and HBV-related miRNAs which led to HCC progression. © 2018 Wiley Periodicals, Inc