Journal of the American College of Nutrition, 2020
Objective: A significant portion of colorectal cancer patients lose weight preoperatively. Here w... more Objective: A significant portion of colorectal cancer patients lose weight preoperatively. Here we examine the influence of pre-operative significant weight loss on venous thromboembolism (VTE) risk and determine whether pre-operative BMI and albumin could influence VTE outcomes in patients who have lost significant weight prior to surgery. Methods: We conducted a retrospective cohort study using the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) and identified 103,455 colorectal cancer patients undergoing major surgery from 2008 to 2012. Patients were assigned to one of two groups based on whether they lost significant weight preoperatively or not. Simple and stepwise multiple logistic regressions were used to evaluate the association between pre-operative unintended weight loss and 30-days postoperative outcomes. The association between weight loss and postoperative thrombosis was further assessed across several strata. Results: The overall ...
Advances in experimental medicine and biology, 2019
Breast cancer and specifically metastatic breast cancer (mBC) constitutes a major health burden w... more Breast cancer and specifically metastatic breast cancer (mBC) constitutes a major health burden worldwide with the highest number of cancer-related mortality among women across the globe. Despite having similar subtypes, breast cancer patients present with a spectrum of aggressiveness and responsiveness to therapy due to cancer heterogeneity. Drug resistance and metastasis contribute to therapy failure and cancer recurrence. Research in the past two decades has focused on microRNAs (miRNAs), small endogenous non-coding RNAs, as active players in tumorigenesis, therapy resistance and metastasis and as novel non-invasive cancer biomarkers. This is due to their unique dysregulated signatures throughout tumor progression and their tumor suppressive/oncogenic roles. Identifying miRNAs signatures capable of predicting therapy response and metastatic onset in breast cancer patients might improve prognosis and offer prolonged median and relapse-free survival rate. Despite the growing report...
Disruptions in the human gut microbiome have been associated with a cycle of hepatocyte injury an... more Disruptions in the human gut microbiome have been associated with a cycle of hepatocyte injury and regeneration characteristic of chronic liver disease. Evidence suggests that the gut microbiota can promote the development of hepatocellular carcinoma through the persistence of this inflammation by inducing genetic and epigenetic changes leading to cancer. As the gut microbiome is known for its effect on host metabolism and immune response, it comes as no surprise that the gut microbiome may have a role in the response to therapeutic strategies such as immunotherapy and chemotherapy for liver cancer. Gut microbiota may influence the efficacy of immunotherapy by regulating the responses to immune checkpoint inhibitors in patients with hepatocellular carcinoma. Here, we review the mechanisms by which gut microbiota influences hepatic carcinogenesis, the immune checkpoint inhibitors currently being used to treat hepatocellular carcinoma, as well as summarize the current findings to supp...
Worldwide, colorectal cancer (CRC) is a deadly disease whose death rate ranks second among cancer... more Worldwide, colorectal cancer (CRC) is a deadly disease whose death rate ranks second among cancers though its incidence ranks third. Early CRC detection is key and is associated with improved survival outcomes. However, existing tests for CRC diagnosis have several weaknesses thus rendering them inefficient. Moreover, reliable prognostic tests that can predict the overall cancer outcome and recurrence of the disease as well as predictive markers that can assess effectiveness of therapy are still lacking. Thus, shifting to noninvasive liquid biopsy or blood-based biomarkers is vital to improving CRC diagnosis, prognosis, and prediction. Methylated circulating tumor DNA (ctDNA) has gained increased attention as a type of liquid biopsy that is tumor-derived fragmented DNA with epigenetic alterations. Methylated ctDNA are more consistently present in blood of cancer patients as compared to mutated ctDNA. Hence, methylated ctDNA serves as a potential biomarker for CRC that is worth inves...
mRNA-circRNA-miRNAs axes have been characterized in breast cancer, but not as risk-assessment axe... more mRNA-circRNA-miRNAs axes have been characterized in breast cancer, but not as risk-assessment axes for tumor initiation in early-onset breast cancer that is increasing drastically worldwide. To address this gap, we performed circular RNA (circRNA) microarrays and microRNA (miRNA) sequencing on acini of HMT-3522 S1 (S1) breast epithelial risk-progression culture model in 3D and chose an early-stage population miRNome for a validation cohort. Nontumorigenic S1 cells form fully polarized epithelium while pretumorigenic counterparts silenced for gap junction Cx43 (Cx43-KO-S1) lose epithelial polarity, multilayer and mimic premalignant in vivo mammary epithelial morphology. Here, 121 circRNAs and 65 miRNAs were significantly dysregulated in response to Cx43 silencing in cultured epithelia and 15 miRNAs from the patient cohort were involved in epithelial polarity disruption. Focusing on the possible sponging activity of the validated circRNAs to their target miRNAs, we found all miRNAs to...
Colorectal cancer (CRC) is the second leading cause of cancer deaths worldwide. Stage IV CRC pati... more Colorectal cancer (CRC) is the second leading cause of cancer deaths worldwide. Stage IV CRC patients have poor prognosis with a five-year survival rate of 14%. Liver metastasis is the main cause of mortality in CRC patients. Since current screening tests have several drawbacks, effective stable non-invasive biomarkers such as microRNA (miRNA) are needed. We aim to investigate the expression of miRNA (miR-21, miR-19a, miR-23a, miR-29a, miR-145, miR-203, miR-155, miR-210, miR-31, and miR-345) in the plasma of 62 Lebanese Stage IV CRC patients and 44 healthy subjects using RT-qPCR, as well as to evaluate their potential for diagnosis of advanced CRC and its liver metastasis using the Receiver Operating Characteristics (ROC) curve. miR-21, miR-145, miR-203, miR-155, miR-210, miR-31, and miR-345 were significantly upregulated in the plasma of surgery naïve CRC patients when compared to healthy individuals. We identified two panels of miRNA that could be used for diagnosis of Stage IV CR...
Breast cancer (BC) is the most predominant type of cancer among women. The aim of this study is t... more Breast cancer (BC) is the most predominant type of cancer among women. The aim of this study is to find new biomarkers that can help in early detection of BC, especially for those who are too young to be screened using mammography as per guidelines. Using microRNA microarray, we previously showed dysregulation of 74 microRNAs in tumors from early BC patients as compared with normal adjacent tissues, which we were interested in studying in blood circulation. In this study, we investigated the expression of 12 microRNA (miR-21/miR-155/miR-23a/miR-130a/miR-145/miR-425-5p/miR-139-5p/miR-451/miR-195/miR-125b/miR-100, and miR-182) in the plasma of 41 newly diagnosed Lebanese BC patients with early invasive ductal carcinoma as compared with 32 healthy controls. Total RNA was extracted from plasma, and expression levels of miRNA of interest were measured using RT-qPCR followed by statistical analysis; miR-21, miR-155, miR-23a, miR-130a, miR-145, miR-425-5p, and miR-139-5p were significantly...
Gastric cancer is the end result of a complex interplay between host genetics, environmental fact... more Gastric cancer is the end result of a complex interplay between host genetics, environmental factors, and microbial factors. The link between gut microbiome and gastric cancer has been attributed to persistent activation of the host’s immune system by gut microbiota. The end result of this dysregulated interaction between host epithelium and microbes is a state of chronic inflammation. Gut bacteria can promote anti-tumor immune responses through several mechanisms. These include triggering T-cell responses to bacterial antigens that can cross-react with tumor antigens or cause tumor-specific antigen recognition; engagement of pattern recognition receptors that mediate pro-immune or anti-inflammatory effects or via small metabolites that mediate systemic effects on the host. Here we review the role of the gut microbiome including H. pylori and non-H. pylori gastric bacteria, the immune response, and immunotherapy using checkpoint inhibitors. We also review the evidence for cross talk...
PURPOSE To assess the knowledge and intention for colorectal cancer (CRC) screening within the Le... more PURPOSE To assess the knowledge and intention for colorectal cancer (CRC) screening within the Lebanese community before and after a guided tour through an inflatable colon model. METHODS The Cancer Prevention and Control Program, Naef K. Basile Cancer Institute at the American University of Beirut Medical Center in collaboration with AMALOUNA educational nongovernmental organization launched awareness campaigns during which a walk-through inflatable colon was displayed. Pre- and post-surveys related to the age of screening, risk factors, symptoms, and CRC prevention were collected anonymously before and after touring the inflatable colon to assess the effectiveness of this educational tool. RESULTS Compiled data collected from 782 participants revealed that older age and higher education were predictors of favorable CRC screening knowledge and behaviors before entering the inflatable colon. Interestingly, touring the inflatable colon model significantly improved participants’ aware...
Colorectal cancer (CRC) is one of the most common cancers worldwide, with a high mortality rate, ... more Colorectal cancer (CRC) is one of the most common cancers worldwide, with a high mortality rate, especially in those that are diagnosed in late stages of the disease. The current screening blood-based markers, such as carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9), have low sensitivity and specificity. Meanwhile, other modalities are either expensive or invasive. Therefore, recent research has shifted towards a minimally invasive test, namely, liquid biopsy. Exosomes are favorable molecules sought in blood samples, since they are abundant, stable in circulation, and harbor genetic information and other biomolecules that could serve as biomarkers or even therapeutic targets. Furthermore, exosomal noncoding RNAs, such as miRNAs, lncRNAs, and circRNAs, have demonstrated the diagnostic potential to detect CRC at an early stage with a higher sensitivity and specificity than CEA and CA19-9 alone. Moreover, they have prognostic potential that is TNM stage specific an...
PURPOSE Breast cancer is the most prevalent female cancer and has a higher incidence in young Leb... more PURPOSE Breast cancer is the most prevalent female cancer and has a higher incidence in young Lebanese patients as compared with the West. Interestingly, this particularity of breast cancer in the Lebanese population was not found to be associated with higher BRCA1/2 gene mutations. Hence, our research focuses on investigating molecular mechanisms and associated epigenetic signatures that underlie breast cancer in young patients. We are specifically interested in microRNA (miRNA), small noncoding RNAs that act as master players at all stages of breast cancer development and that are increasingly recognized as potential diagnostic and prognostic biomarkers. We have previously shown that differential expression of certain miRNAs in Lebanese breast cancer tissues could be different than what is reported in the West. METHODS We recently assessed the miRNA microarray profile expression in Lebanese breast cancer tissues, performed a comparative miRNA profile analysis with matched American...
Research has been driven towards finding therapy predictive biomarkers for colorectal cancer (CRC... more Research has been driven towards finding therapy predictive biomarkers for colorectal cancer (CRC) with a special interest in studying the gut microbiome. Gut microbiome acts not only as a barrier to prevent bacterial invasion and infection, but it also affects the efficacy of hematopoietic-cell transplantation, chemotherapy, and immunotherapy. Recently, immunotherapy, which potentiates the host immune system, has revolutionized cancer therapy in general and CRC treatment specifically by increasing the quality of life and the survival of a subset of patients with this disease. In immunotherapy, the gut microbiome plays an important role in cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) blockade, programmed cell death protein 1 (PD-L1) mediation, and T cell stimulation. As such, this review will cover the role of gut microbiome in CRC, summarize approved immunotherapy treatments for CRC, and focus on the potential use of gut microbiome as a biomarker for immunotherapy.
Given the safety and potential benefits of intravenous ascorbic acid (AA) administration in cance... more Given the safety and potential benefits of intravenous ascorbic acid (AA) administration in cancer patients, there is merit in further exploring this therapeutic concept. In this review, we discuss the potential benefits of intravenous AA administration on colorectal cancer and we specifically focus on its effect on glycolysis in mutant and wild type RAS. We perform a PubMed and Ovid MEDLINE search using ascorbic acid, intravenous vitamin C, KRAS mutation, BRAF mutation and colorectal cancer (CRC) as keywords. At the cellular level, colorectal cancer cells undergo a metabolic shift called the Warburg effect to allow for more glucose absorption and utilization of glycolysis. This shift also allows AA to enter which leads to a disruption in the Warburg effect and a shutdown of the downstream KRAS pathway in mutated KRAS colon cancer cells. At the clinical level, AA is associated with tumour regression in advanced disease and improved tolerability and side effects of standard therapy. ...
Breast cancer is a major health problem that affects one in eight women worldwide. As such, detec... more Breast cancer is a major health problem that affects one in eight women worldwide. As such, detecting breast cancer at an early stage anticipates better disease outcome and prolonged patient survival. Extensive research has shown that microRNA (miRNA) are dysregulated at all stages of breast cancer. miRNA are a class of small noncoding RNA molecules that can modulate gene expression and are easily accessible and quantifiable. This review highlights miRNA as diagnostic, prognostic and therapy predictive biomarkers for early breast cancer with an emphasis on the latter. It also examines the challenges that lie ahead in their use as biomarkers. Noteworthy, this review addresses miRNAs reported in patients with early breast cancer prior to chemotherapy, radiotherapy, surgical procedures or distant metastasis (unless indicated otherwise). In this context, miRNA that are mentioned in this review were significantly modulated using more than one statistical test and/or validated by at least two studies. A standardized protocol for miRNA assessment is proposed starting from sample collection to data analysis that ensures comparative analysis of data and reproducibility of results.
Journal of the American College of Nutrition, 2020
Objective: A significant portion of colorectal cancer patients lose weight preoperatively. Here w... more Objective: A significant portion of colorectal cancer patients lose weight preoperatively. Here we examine the influence of pre-operative significant weight loss on venous thromboembolism (VTE) risk and determine whether pre-operative BMI and albumin could influence VTE outcomes in patients who have lost significant weight prior to surgery. Methods: We conducted a retrospective cohort study using the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) and identified 103,455 colorectal cancer patients undergoing major surgery from 2008 to 2012. Patients were assigned to one of two groups based on whether they lost significant weight preoperatively or not. Simple and stepwise multiple logistic regressions were used to evaluate the association between pre-operative unintended weight loss and 30-days postoperative outcomes. The association between weight loss and postoperative thrombosis was further assessed across several strata. Results: The overall ...
Advances in experimental medicine and biology, 2019
Breast cancer and specifically metastatic breast cancer (mBC) constitutes a major health burden w... more Breast cancer and specifically metastatic breast cancer (mBC) constitutes a major health burden worldwide with the highest number of cancer-related mortality among women across the globe. Despite having similar subtypes, breast cancer patients present with a spectrum of aggressiveness and responsiveness to therapy due to cancer heterogeneity. Drug resistance and metastasis contribute to therapy failure and cancer recurrence. Research in the past two decades has focused on microRNAs (miRNAs), small endogenous non-coding RNAs, as active players in tumorigenesis, therapy resistance and metastasis and as novel non-invasive cancer biomarkers. This is due to their unique dysregulated signatures throughout tumor progression and their tumor suppressive/oncogenic roles. Identifying miRNAs signatures capable of predicting therapy response and metastatic onset in breast cancer patients might improve prognosis and offer prolonged median and relapse-free survival rate. Despite the growing report...
Disruptions in the human gut microbiome have been associated with a cycle of hepatocyte injury an... more Disruptions in the human gut microbiome have been associated with a cycle of hepatocyte injury and regeneration characteristic of chronic liver disease. Evidence suggests that the gut microbiota can promote the development of hepatocellular carcinoma through the persistence of this inflammation by inducing genetic and epigenetic changes leading to cancer. As the gut microbiome is known for its effect on host metabolism and immune response, it comes as no surprise that the gut microbiome may have a role in the response to therapeutic strategies such as immunotherapy and chemotherapy for liver cancer. Gut microbiota may influence the efficacy of immunotherapy by regulating the responses to immune checkpoint inhibitors in patients with hepatocellular carcinoma. Here, we review the mechanisms by which gut microbiota influences hepatic carcinogenesis, the immune checkpoint inhibitors currently being used to treat hepatocellular carcinoma, as well as summarize the current findings to supp...
Worldwide, colorectal cancer (CRC) is a deadly disease whose death rate ranks second among cancer... more Worldwide, colorectal cancer (CRC) is a deadly disease whose death rate ranks second among cancers though its incidence ranks third. Early CRC detection is key and is associated with improved survival outcomes. However, existing tests for CRC diagnosis have several weaknesses thus rendering them inefficient. Moreover, reliable prognostic tests that can predict the overall cancer outcome and recurrence of the disease as well as predictive markers that can assess effectiveness of therapy are still lacking. Thus, shifting to noninvasive liquid biopsy or blood-based biomarkers is vital to improving CRC diagnosis, prognosis, and prediction. Methylated circulating tumor DNA (ctDNA) has gained increased attention as a type of liquid biopsy that is tumor-derived fragmented DNA with epigenetic alterations. Methylated ctDNA are more consistently present in blood of cancer patients as compared to mutated ctDNA. Hence, methylated ctDNA serves as a potential biomarker for CRC that is worth inves...
mRNA-circRNA-miRNAs axes have been characterized in breast cancer, but not as risk-assessment axe... more mRNA-circRNA-miRNAs axes have been characterized in breast cancer, but not as risk-assessment axes for tumor initiation in early-onset breast cancer that is increasing drastically worldwide. To address this gap, we performed circular RNA (circRNA) microarrays and microRNA (miRNA) sequencing on acini of HMT-3522 S1 (S1) breast epithelial risk-progression culture model in 3D and chose an early-stage population miRNome for a validation cohort. Nontumorigenic S1 cells form fully polarized epithelium while pretumorigenic counterparts silenced for gap junction Cx43 (Cx43-KO-S1) lose epithelial polarity, multilayer and mimic premalignant in vivo mammary epithelial morphology. Here, 121 circRNAs and 65 miRNAs were significantly dysregulated in response to Cx43 silencing in cultured epithelia and 15 miRNAs from the patient cohort were involved in epithelial polarity disruption. Focusing on the possible sponging activity of the validated circRNAs to their target miRNAs, we found all miRNAs to...
Colorectal cancer (CRC) is the second leading cause of cancer deaths worldwide. Stage IV CRC pati... more Colorectal cancer (CRC) is the second leading cause of cancer deaths worldwide. Stage IV CRC patients have poor prognosis with a five-year survival rate of 14%. Liver metastasis is the main cause of mortality in CRC patients. Since current screening tests have several drawbacks, effective stable non-invasive biomarkers such as microRNA (miRNA) are needed. We aim to investigate the expression of miRNA (miR-21, miR-19a, miR-23a, miR-29a, miR-145, miR-203, miR-155, miR-210, miR-31, and miR-345) in the plasma of 62 Lebanese Stage IV CRC patients and 44 healthy subjects using RT-qPCR, as well as to evaluate their potential for diagnosis of advanced CRC and its liver metastasis using the Receiver Operating Characteristics (ROC) curve. miR-21, miR-145, miR-203, miR-155, miR-210, miR-31, and miR-345 were significantly upregulated in the plasma of surgery naïve CRC patients when compared to healthy individuals. We identified two panels of miRNA that could be used for diagnosis of Stage IV CR...
Breast cancer (BC) is the most predominant type of cancer among women. The aim of this study is t... more Breast cancer (BC) is the most predominant type of cancer among women. The aim of this study is to find new biomarkers that can help in early detection of BC, especially for those who are too young to be screened using mammography as per guidelines. Using microRNA microarray, we previously showed dysregulation of 74 microRNAs in tumors from early BC patients as compared with normal adjacent tissues, which we were interested in studying in blood circulation. In this study, we investigated the expression of 12 microRNA (miR-21/miR-155/miR-23a/miR-130a/miR-145/miR-425-5p/miR-139-5p/miR-451/miR-195/miR-125b/miR-100, and miR-182) in the plasma of 41 newly diagnosed Lebanese BC patients with early invasive ductal carcinoma as compared with 32 healthy controls. Total RNA was extracted from plasma, and expression levels of miRNA of interest were measured using RT-qPCR followed by statistical analysis; miR-21, miR-155, miR-23a, miR-130a, miR-145, miR-425-5p, and miR-139-5p were significantly...
Gastric cancer is the end result of a complex interplay between host genetics, environmental fact... more Gastric cancer is the end result of a complex interplay between host genetics, environmental factors, and microbial factors. The link between gut microbiome and gastric cancer has been attributed to persistent activation of the host’s immune system by gut microbiota. The end result of this dysregulated interaction between host epithelium and microbes is a state of chronic inflammation. Gut bacteria can promote anti-tumor immune responses through several mechanisms. These include triggering T-cell responses to bacterial antigens that can cross-react with tumor antigens or cause tumor-specific antigen recognition; engagement of pattern recognition receptors that mediate pro-immune or anti-inflammatory effects or via small metabolites that mediate systemic effects on the host. Here we review the role of the gut microbiome including H. pylori and non-H. pylori gastric bacteria, the immune response, and immunotherapy using checkpoint inhibitors. We also review the evidence for cross talk...
PURPOSE To assess the knowledge and intention for colorectal cancer (CRC) screening within the Le... more PURPOSE To assess the knowledge and intention for colorectal cancer (CRC) screening within the Lebanese community before and after a guided tour through an inflatable colon model. METHODS The Cancer Prevention and Control Program, Naef K. Basile Cancer Institute at the American University of Beirut Medical Center in collaboration with AMALOUNA educational nongovernmental organization launched awareness campaigns during which a walk-through inflatable colon was displayed. Pre- and post-surveys related to the age of screening, risk factors, symptoms, and CRC prevention were collected anonymously before and after touring the inflatable colon to assess the effectiveness of this educational tool. RESULTS Compiled data collected from 782 participants revealed that older age and higher education were predictors of favorable CRC screening knowledge and behaviors before entering the inflatable colon. Interestingly, touring the inflatable colon model significantly improved participants’ aware...
Colorectal cancer (CRC) is one of the most common cancers worldwide, with a high mortality rate, ... more Colorectal cancer (CRC) is one of the most common cancers worldwide, with a high mortality rate, especially in those that are diagnosed in late stages of the disease. The current screening blood-based markers, such as carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9), have low sensitivity and specificity. Meanwhile, other modalities are either expensive or invasive. Therefore, recent research has shifted towards a minimally invasive test, namely, liquid biopsy. Exosomes are favorable molecules sought in blood samples, since they are abundant, stable in circulation, and harbor genetic information and other biomolecules that could serve as biomarkers or even therapeutic targets. Furthermore, exosomal noncoding RNAs, such as miRNAs, lncRNAs, and circRNAs, have demonstrated the diagnostic potential to detect CRC at an early stage with a higher sensitivity and specificity than CEA and CA19-9 alone. Moreover, they have prognostic potential that is TNM stage specific an...
PURPOSE Breast cancer is the most prevalent female cancer and has a higher incidence in young Leb... more PURPOSE Breast cancer is the most prevalent female cancer and has a higher incidence in young Lebanese patients as compared with the West. Interestingly, this particularity of breast cancer in the Lebanese population was not found to be associated with higher BRCA1/2 gene mutations. Hence, our research focuses on investigating molecular mechanisms and associated epigenetic signatures that underlie breast cancer in young patients. We are specifically interested in microRNA (miRNA), small noncoding RNAs that act as master players at all stages of breast cancer development and that are increasingly recognized as potential diagnostic and prognostic biomarkers. We have previously shown that differential expression of certain miRNAs in Lebanese breast cancer tissues could be different than what is reported in the West. METHODS We recently assessed the miRNA microarray profile expression in Lebanese breast cancer tissues, performed a comparative miRNA profile analysis with matched American...
Research has been driven towards finding therapy predictive biomarkers for colorectal cancer (CRC... more Research has been driven towards finding therapy predictive biomarkers for colorectal cancer (CRC) with a special interest in studying the gut microbiome. Gut microbiome acts not only as a barrier to prevent bacterial invasion and infection, but it also affects the efficacy of hematopoietic-cell transplantation, chemotherapy, and immunotherapy. Recently, immunotherapy, which potentiates the host immune system, has revolutionized cancer therapy in general and CRC treatment specifically by increasing the quality of life and the survival of a subset of patients with this disease. In immunotherapy, the gut microbiome plays an important role in cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) blockade, programmed cell death protein 1 (PD-L1) mediation, and T cell stimulation. As such, this review will cover the role of gut microbiome in CRC, summarize approved immunotherapy treatments for CRC, and focus on the potential use of gut microbiome as a biomarker for immunotherapy.
Given the safety and potential benefits of intravenous ascorbic acid (AA) administration in cance... more Given the safety and potential benefits of intravenous ascorbic acid (AA) administration in cancer patients, there is merit in further exploring this therapeutic concept. In this review, we discuss the potential benefits of intravenous AA administration on colorectal cancer and we specifically focus on its effect on glycolysis in mutant and wild type RAS. We perform a PubMed and Ovid MEDLINE search using ascorbic acid, intravenous vitamin C, KRAS mutation, BRAF mutation and colorectal cancer (CRC) as keywords. At the cellular level, colorectal cancer cells undergo a metabolic shift called the Warburg effect to allow for more glucose absorption and utilization of glycolysis. This shift also allows AA to enter which leads to a disruption in the Warburg effect and a shutdown of the downstream KRAS pathway in mutated KRAS colon cancer cells. At the clinical level, AA is associated with tumour regression in advanced disease and improved tolerability and side effects of standard therapy. ...
Breast cancer is a major health problem that affects one in eight women worldwide. As such, detec... more Breast cancer is a major health problem that affects one in eight women worldwide. As such, detecting breast cancer at an early stage anticipates better disease outcome and prolonged patient survival. Extensive research has shown that microRNA (miRNA) are dysregulated at all stages of breast cancer. miRNA are a class of small noncoding RNA molecules that can modulate gene expression and are easily accessible and quantifiable. This review highlights miRNA as diagnostic, prognostic and therapy predictive biomarkers for early breast cancer with an emphasis on the latter. It also examines the challenges that lie ahead in their use as biomarkers. Noteworthy, this review addresses miRNAs reported in patients with early breast cancer prior to chemotherapy, radiotherapy, surgical procedures or distant metastasis (unless indicated otherwise). In this context, miRNA that are mentioned in this review were significantly modulated using more than one statistical test and/or validated by at least two studies. A standardized protocol for miRNA assessment is proposed starting from sample collection to data analysis that ensures comparative analysis of data and reproducibility of results.
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Papers by Farah Nassar