Al-Faisal University, Saudi Arabia
Circulating micro RNAs: Novel biomarkers in breast cancer-Breakthroughs in cancer research
Amal Qattan is currently working in the Department of Molecular Oncology at the King Faisal Specialist Hospital and Research Center (KFSHRC) Hospital, Riyadh-SA, and she is also a member in the scientific committee of the Zahra Breast Cancer Association and Assistant Professor in the College of Medicine at Al-Faisal University. She did graduation from the Medical School at UCL-UK and has been working since 2000 in the Oncology Department at King Faisal Specialist Hospital and Research Center at KFSHRC Hospital. Her primary interest is in personalized medicine using the state-of-the-art molecular, cellular, and bioinformatic technologies in support of a systems-biology based research approach to understanding the events that affect the sensitivity, or lack of it, among cancers to chemotherapy and hormonal therapies. She uses gene expression, microarrays, proteomics, and metabolite profiling to combat breast cancer. The goal of her work is to better determine an individual patient's response to specific cancer therapies. She focuses on understanding and controlling tumor dormancy; resistance in cancers; and microRNA as a master regulator of the expression of several genes in different phases of breast cancer. In the developing countries, breast cancer is still the most common cancer and its most daunting aspect is that 58% of all breast cancers present and are detected at an advanced stage. This makes it urgent to find and develop a panel of sensitive biomarkers for early detection before the disease becomes invasive and metastasis begins. The treatment of advanced breast cancers also presents a challenge. Therefore she is trying, with her group, to develop different therapeutic targets, which can be used to counter drug resistance, for metastasic breast cancer in particular. The hope is to open up a way to fight and cure the disease which would be more specific than traditional cancer medicines.
Several genetic, epigenetic and proteinaceous biomarkers have so far been found to be associated with breast cancer, but their robustness as indicators of disease remains uncertain. More significantly, most women in the developing countries present with this cancer only when it has reached an advanced stage. The treatment of advanced stage cancer presents several challenges but most important among them is the frequent development of resistance to chemotherapy and hormonal therapy, which leads to a high mortality rate. This resistance creates a need to identify sensitive biomarkers that could be useful in early detection and in following the progression of the disease; these might help to identify new therapeutic targets.
MicroRNAs (miRs) form a class of non-coding RNA that regulates post-transcriptional gene expression and thereby cellular processes. In breast cancers, dysregulation of the miRs’ expression can result in the progression of cancers. In addition, miRs have been shown to play a role in the development of resistance to drug therapy by regulating signaling cascades. From a cohort of 100 disease-free individuals and 127 breast cancer patients, the levels of these circulating miRNAs are being verified by qRT-PCR. The results of this part have shown over-expression of some types of miRs in the breast tumor patients, while the level of expression among others remains lower than those in normal individuals. Another interesting pattern has emerged when the relative levels of these circulating miRNAs were compared with their expression levels in breast tissue. In addition to intergroup comparisons, plasma miRNA expression levels of all groups were analyzed against cancerous breast tissue (RNA-Seq data from The Cancer Genome Atlas-TCGA). A differential set of miRNAs were identified in the plasma of breast cancer patients and 10 miRNAs were uniquely identified on the basis of ROC analysis. The most striking findings revealed that some of the tumor suppressor miRs in the plasma of luminal breast cancer patients was elevated, irrespective of subtype, and was elevated also in the plasma of TNBC breast cancer patients. We found also that, while most miRNAs in plasma reflected cellular levels some of them had an inverse pattern, suggesting that they were being selectively secreted into plasma. The circulated miRNA patterns indicate signatures which could serve as biomarkers for detection, and might be used in screening and distinguishing the type of tumor; they could also be used as targets for therapies.
Athar A. Khalil
American University of Beirut, Lebanon
The TbX2 subfamily of transcription factors: An emerging role in lung carcinogenesis
Will be added shortly
TBX’s are evolutionary conserved genes encoding T-box transcription factors that enhance or repress transcription. In mammals 18 members were described functionally and structurally, of which the TBX2-5 genes were shown to be expressed early on, in the lung bud and tracheae. Little is known however on the role of these genes in lung pathology in humans especially in lung cancer, a smoking-associated disease that is the leading cause of cancer-deaths worldwide. To fill this void our group surveyed the expression of TBX2-5 in various publicly available datasets and found that all four members were preferentially and highly expressed in normal lung, but markedly and consistently suppressed in lung adenocarcinoma (ADC) the most common histological subtype of lung cancer. Using immuno-staining with specific antibodies we confirmed a high expression of TBX2 members in normal adult lungs tissues. Moreover, TBX2-5 transcript and protein expression were assessed by real-time PCR, western blot, and immuno-staining which showed suppression of all the members in different ADC cell lines as compared to the normal immortalized bronchial cells. Transient over-expression of TBX2 members in human ADC cell lines (H1299 and H1944) was found to significantly inhibit lung cancer cell growth and proliferation. RNA-seq and pathways analysis revealed that over expressing TBX2 members in H1299 cells affect different pathways that are important in cell cycle progression and regulation. Our findings point to 1- a tumor suppressor role for TBX2 members in human ADC pathogenesis through regulating various cell cycle genes, and thus possible use of these proteins as potential drugs, and 2- a potential usage of these genes as biomarkers for diagnosis and prognosis in smokers with high risk of developing lung cancer.
Manikonda Prakash Rao
International and Constitutional Laws, India
Video presentation Title: Lung is Life – Chronic inflammation and mucus hyper secretion are fuses that ignite cancer – Prevention and management through exercise interventions
Manikonda Prakash Rao presented papers at various International conferences including ALL INDIA INSTITUTE OF MEDICALL SCIENCES New Delhi 2009 and 2012 for their conferences on Gerontology and Geriatric Medicine and WORLD ALLERGY ORGANIZATION OF US for their conferences on Allergy, Asthma and Immunology 2010 and 2012, National conferences on pulmonary diseases at Bhubaneswar and Chennai, Indo Global Health Care summit and Expo , International conference in 2014 at Hyderabad. He has been given award for Excellent Health Care by the Organizers of the International conference. He has also presented paper at AIIMS New Delhi, for their International conference on Multidisciplinary Health Care 2014 and 2016 and many others. Further, he has presented papers at international cancer conferences 1. Indo global cancer therapy conference at Hyderabad and Global cancer conference at Bengalore November 2015, International conference on Radiation Oncology and Anti-Cancer Therapy , at Dubai in the year 2016 November 21st and 22nd and many others. Excess mucus is a pathological feature of airway diseases and is a prominent feature of inflammation. There is dearth of therapies. He has devised exercises by which the excess mucus can be drained out within minutes from upper airway passages mouth, nose and pharynx, the primary sites of colonization of pathogens , the sinuses, the weigh stations to the brain and the trace of bronchial tree resulting in normal breathing.
The objective of the paper is to create awareness among people about alternative and complimentary methods to protect themselves from various diseases including throat and lung cancers. 1) Inflammation: is a physiological process and plays the role of immunological defense against infection, injury or allergy. Acute inflammation is defense process whereas Chronic inflammation is a disease process. 2) Hyper secretion of mucus: Is the result of goblet cell hyperplasia in respiratory mucosa and is a prominent feature of inflammation. It is an obstruction to the Lung function. They are correlated.. Chronic mucus hyper secretion is a potential risk factor for an accelerated loss of lung function. The thick viscous mucus in the Lungs will be conducive to pathogens.. Continued inflammation and mucus hyper Secretion may significantly contribute to transformation of normal cells into cancer cells i.e., the gene damaging effect gets increased.. 3) Bronchospasm: is an additional factor in Asthma patients.Chronic mucus hyper secretion is a potential risk factor for an accelerated loss of lung function. It increases risk of hospital admission as a result of lower respiratory tract infections.
Exercise is a potent medication in history. It can be used as a tool to prevent and manage various respiratory diseases including throat and lung cancers. Management of Hyper Secretion of mucus is very important for airway integrity. They are a) Upper airway passages cleansing Exercises: They help in cleansing mouth, nose and pharynx, the primary sites of colonization of pathogens and the sinuses, the way stations to the brain. These exercises should be practiced with hypertonic solution i.e., a solution having greater osmotic pressure than that of cells or body fluids and draws water out of cells thus inducing plasmolysis b) Physical, aerobic and yogic exercises: help in strengthening The Inspiratory and expiratory muscles.
Any mucus related respiratory health problem commences from upper airway passages and spread to tracheo bronchial tree as they constitute only one path way. The mucociliary clearance mechanism becomes defunct when excess and sticky mucus forms. Once the upper airway passages are cleaned of it, the defunct cilia become active and ciliate mucus towards mouth and it can be pushed out easily. The diseases originating from its pathway come under control. The exercises are based on the concept “ Once the offending factor, the excess mucus is removed, the origin of it, Inflammation gets resolved “ As a result of management of the above factors, , the gene damaging effect gets reduced i.e., ( The scope for repeated pressures of mutations on genes get reduced )