Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Histopathologically confirmed primary female breast cancer patients with age group (20-70 years)

Healthy female volunteers not suffering from any disease

Nadia Hamdy, PhD

Long non-coding RNAs (lncRNAs) play an important role in different types of cancer, including breast cancer, through regulation of gene expression and epigenetic signatures. Genetic variations such as single nucleotide polymorphisms (SNPs) in lncRNAs have been found to be associated with cancer. Our aim was to provide information about the role of LINC00511 SNPs (rs11657109 or rs17780195 or rs9906859, rs4432291 and rs1558535) in breast cancer susceptibility in the Egyptian population.

1. Introduction 1.1. Background: Breast cancer (BC) is one of the most common types of cancer in women nowadays as it is estimated that 1.6 million BC cases occur around the world each year. There were approximately 500000 women die due to BC annually making it a leading cause of cancer mortality among females. It represents 23% of the total cancer cases and 14% of the cancer deaths in females. It represents 52% of BC cases and 62% of deaths in economically developing countries. In Egypt, BC is reported to be the most frequent cancer in females (38.8%) and the age adjusted rate of BC is 49.6 per 100.000 population. Breast cancer can be classified based on the hormones and HER2 status to Luminal A BC (Estrogen Receptor(ER) + , Progesterone Receptor(PR) +/- , Human epidermal growth factor receptor 2 (HER2) -) , Luminal B BC (ER+, PR+/-, HER2 +), HER2 BC (ER-, PR- and HER2+) and Triple negative BC (TNBC) (ER-, PR- and HER2-).TNBC is an aggressive cancer due to its recurrence and fewer targeted medicines. BC can become a metastatic cancer and transfer to distant organs such as bones, lung and brain, which is the cause of its incurability. Early diagnosis of the disease leads to good prognosis and increasing the survival rate. Traditional prognostic factors, such as tumor size, tumor grade, and lymph node metastasis status, are the most important prognostic factors for BC. However, including the genetic information is needed in prognosis. As a typical cancer, BC occurs because of the interaction of genetic and nongenetic factors.

   It has been reported that long non-coding RNAs (lncRNAs) play an important role in different types of cancer, including BC, through regulation of gene expression and epigenetic signatures. LncRNAs are greater than 200 nucleotides in length. LncRNAs undergo different biological actions, such as regulating RNA stability, transcriptional regulation, acting as a scaffold, RNA enhancer, miRNA sequestration and guiding protein-DNA interaction. LncRNAs are implicated in gene expression regulation at many levels, including alternative splicing, and changing of protein localization, chromatin modification, transcription, and post-transcriptional processing. Moreover, lncRNAs are involved in several hallmarks of cancer, including uncontrolled proliferation, angiogenesis, evading cell death and metastasis. It is noteworthy to mention that, abnormal expression of lncRNAs contribute significantly to cancer susceptibility and progression in BC cases.

   Long intergenic non-coding RNA 00511 (LINC00511) is a 2265 bp ncRNA and is located on chromosome 17q24. Previous studies found that it exerts an oncogenic function in many cancers, such as BC, non-small cell lung cancer, ovarian cancer and glioma. In BC cases, being oncogenic, LINC00511 promotes tumor growth by accelerating the G1/S transition and inhibiting apoptosis. It has been demonstrated that there is an association between LINC00511 and BC growth and invasion, where competitive binding between LINC00511 and the microRNA-185 (miR-185) affects BC prognosis and progression. LINC00511 sponges miR-185-3p preventing this miRNA from binding to its target mRNA, hence, free mRNA is there, with more expression of the transcription factor E2F1, which eventually, promotes BC proliferation and progression.

   Genetic variations such as single nucleotide polymorphisms (SNPs) in lncRNAs have been found to be associated with cancer. They affect the function of target genes, through the alteration of the process of splicing and stability of mRNA conformation, leading to the modification of their downstream interacting partners. Mutant variants can affect the expression and secondary structure of lncRNAs, which may affect the status of the binding site(s) for miRNAs, furthermore, altering the interaction between miRNAs and mRNAs. SNPs in lncRNAs may increase or reduce the risk of cancer, depending on the function of lncRNA, as it may act as oncogene or tumor suppressor gene, a hypothesis to be explored. Moreover, SNPs in lncRNAs may increase or reduce the risk of cancer, depending on the location of these SNPs, if in a noncoding area or not. Identifying such loci, if mutant or not, involved in BC progression or prevention, will be an important issue for understanding BC pathogenesis as well as for discovering new targets for cancer diagnosis, prevention, and/or treatment.

   1.2 Aim of the Work Providing information about the role of LINC00511 SNPs (rs11657109 or rs17780195 or rs9906859, rs4432291 and rs1558535) in BC susceptibility.

   1.3 Previous Studies Findings Chong et al. found that there was an association between LINC00511 SNPs and BC in the Chinese population. we studied the same associations but in our Egyptian population.
2. Subjects 2.1 Ethics Statement An ethical approval was obtained from Ain Shams University, Faculty of Pharmacy's review board Research Ethical Committee approval (REC ID 6, date: November 11, 2020). The study was conducted in accordance to the Declaration of Helsinki Guidelines. A written informed consent was taken from all participants.

   2.2 Power Analysis and Sample Size Calculations Sample size calculation was done using PS: Power and Sample Size Calculations software, version 3.0.11 for MS Windows (William D. Dupont and Walton D., Vanderbilt University, Nashville, Tennessee, USA). The α-error level was fixed at 0.05, the power was set at 80%. The minimum optimum sample size should be 85 participants for each SNP group.

   2.3 Study participants Will be Classified into two main groups
   * Cases group n= 267, BC female patients from National cancer institute (NCI), Cairo, Egypt.
   * Controls group n= 150, healthy female volunteers. Clinical data was obtained from medical records and the original pathology reports. The following data parameters were recorded and assessed: age of the patient, tumor size (defined by mammography or magnetic resonance techniques diameter (mm or cm) on diagnosis), initial tumor stage, BIRADs classification according to the American College of Radiology and nodal status according to the TNM classification of American Joint Committee on Cancer (AJCC).
3. Methods 3.1 Blood sampling Blood samples (5 ml) were collected from controls and BC patients, on EDTA anticoagulant vacutainers and stored at -20º C until biochemical assessment.

3.2 Biochemical Assessment was performed in the pharmacology and Biochemistry Department Lab at the Faculty of Pharmacy, The British University in Egypt and Advanced biochemistry research lab at the faculty of pharmacy, Ain Shams University.

3.3 DNA Extraction A DNA Extraction Kit (QIAamp DNA Blood Mini Kit) (Cat. No. 51104; Zymo Research, USA) was used to extract DNA from whole blood collected on EDTA anticoagulant vacutainers, according to the manufacturer's instructions.

3.4 DNA Quantification It was done using a Quawell UV-Vis spectrophotometer Q5000 (USA). 3.5 SNPs Genotyping TaqMan® SNP genotyping assay was used to perform genotyping for LINC00511 polymorphisms (rs11657109 or rs17780195 or rs9906859 or rs4432291 and rs1558535) through using the TaqMan Universal Master Mix No UNG (Thermo Fisher Scientific, USA) and StepOnePlus™ qPCR system (Applied Biosystems, USA).

3.6 Statistical analysis Statistical Package for the Social Sciences (SPSS) v.23.0 software and SHEsis software were used to perform all statistical analyses. Student's t-test and χ 2 test were used to compare quantitative and qualitative variables between cases and control groups, respectively. Logistic regression was applied to find out the association between LINC00511 SNPs and BC susceptibility. A stratified analysis was applied to further investigate the relationship between LINC00511 SNPs and BC susceptibility. To find out more about the relationship between BC susceptibility and LINC00511 SNPs, a stratified analysis was used. SHEsis software was used to do the haplotype analysis to test the combined effect of the studied SNPs.

Analyses with P value less than or equal to 0.05 were considered statistically significant.

Five milliliters of blood were collected from controls and BC patients into EDTA anticoagulant vacutainers and stored at -20º C until biochemical assessment.

Female cases and controls to find out the association of their data with female breast cancer.

Association of SNPs in Long Intergenic Noncoding RNA 00511 (LINC00511) With Breast Cancer Among the Egyptian Population

Studying the Association of Genetic Variations in Long Intergenic Noncoding RNA 00511 (LINC00511) With Breast Cancer Among the Egyptian Population

By collecting patients' data in an excel file and performing appropriate statistical analysis

British University In Egypt

Ain Shams University

Professor

Respiratory Tract (Lung and Bronchial) Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Substance Related Disorders

Behaviors and Mental Disorders

Rare Diseases

Lung Neoplasms

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Tobacco Use Disorder

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Substance-Related Disorders

Chemically-Induced Disorders

Mental Disorders

Psychotic Disorders

Ovarian Cancer

Ovarian Epithelial Cancer

Herbal and Botanical

All Drugs and Chemicals

Cola

Lung cancer cases diagnosed prior to 2007 among baseline smokers in the PLCO

Subjects without lung cancer among smokers at baseline in the PLCO study

Measured total NNAL and PheT as biomarkers of exposure

Non-intervention

Timothy Church, Ph.D.

Lung cancer is the leading cause of cancer death in the United States. Currently it remains impossible to predict which smokers will get cancer. Each puff of a cigarette delivers a mixture of over 60 known carcinogens. Biomarkers that quantify carcinogen levels and metabolism are a useful tool and available to use. The purpose of this study is to assess the link between tobacco smoke carcinogen biomarkers and the risk of developing lung cancer.

Lung cancer is the leading cause of cancer death in the United States. Approximately 90% of lung cancer is caused by cigarette smoking. While most lung cancer cases occur in smokers or ex-smokers, only 15-25% of smokers will get lung cancer. Currently it remains impossible to predict which smokers will get cancer.

Each puff of a cigarette delivers, along with nicotine, a mixture of over 60 known carcinogens. Most of these carcinogens require metabolic activation before they can negatively affect cell DNA and cause cancer. Biomarkers that quantify carcinogen levels and metabolic activity of carcinogens are a useful tool and available to use. The purpose of this study is to assess the link between tobacco smoke carcinogen biomarkers and the risk of developing lung cancer.

This observational case-control study will involve a random selection from a group of smokers who are participating in the Prostrate, Lung, Colon, and Ovarian Cancer (PLCO) Screen Trial. The chosen cases will include 300 incident lung cancer cases and 300 controls (participants who have had no diagnosis of lung cancer). Demographic and baseline data from the PLCO database will be obtained. Prior baseline blood samples from the PLCO trial will be obtained as well. Based on age, sex, and smoking history, participants will be grouped into triplets in order to pool their blood samples. These samples will then be analyzed to determine whether distributions of biomarker levels in lung cancer participants differ from those in non-lung cancer participants. This study will not involve recruitment of any participants, as data and samples from the PLCO trial will be used and no new blood samples will be obtained.

Assessing the Link Between Smoke Carcinogen Biomarkers and Lung Cancer Risk - 1

Prostate, Lung, Colon, and Ovarian Cancer (PLCO) Screen Trial

National Institute on Drug Abuse (NIDA)

University of Minnesota

Symptoms and General Pathology

Nervous System Diseases

Neoplasm Metastasis

Brain Neoplasms

Neoplastic Processes

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Anti-Infective Agents

Antirheumatic Agents

Anti-Inflammatory Agents

Analgesics

Chloroquine

Chloroquine diphosphate

Amebicides

Antiprotozoal Agents

Antiparasitic Agents

Antimalarials

Anti-Inflammatory Agents, Non-Steroidal

Analgesics, Non-Narcotic

Anthelmintics

250 mg chloroquine once a day by mouth beginning one week prior to beginning radiation therapy and continue for a total of five weeks.

250 mg chloroquine once a day by mouth beginning one week prior to beginning radiation therapy and continue for a total of five weeks

Albert DeNittis, MD

This research is being done to determine if a short course of Chloroquine (five weeks) before, during and after whole brain radiation therapy (WBRT) will improve the overall survival of subjects being treated for brain metastases.

Hypothesis one: A short course of chloroquine one week prior and four weeks after initiation of WBRT is tolerable and significantly increases the median survival time of patients suffering from brain metastasis as assessed one, three, six, nine, twelve and 24 months post radiotherapy, when compared to historic controls.

Hypothesis two: The presence of one or both single-nucleotide polymorphisms (SNP)s in the gene coding for the immunoregulatory enzyme indoleamine 2,3-dioxygenase 2 (IDO2) improves the clinical outcomes of WBRT or the response to CQ co-treatment.

3.2. Specific Aims:

The specific aims of this study are:

1. Determine patients physical profiles prior WBRT and at regular intervals afterwards up to 24 months after radiotherapy.
2. Record the status of patient metastases (i.e. number, location, size)
3. Determine patients' KPS values.
4. Record the incidence and causes of mortality of patients.
5. Determine the genotype of IDO2 for each patient.
6. Following data analysis, test the validity of the two hypotheses.

IDO2 Genetic Status Informs the Neoadjuvant Efficacy of Chloroquine (CQ) in Brain Metastasis Radiotherapy

IDO2 Genetic Status Informs the Neoadjuvant Efficacy of Chloroquine in Brain Metastasis Radiotherapy.

Record the status of patient metastases (i.e. number, location, size)

Determine patients physical profiles prior WBRT and at regular intervals afterwards up to 24 months after radiotherapy

Main Line Health

Principal Investigator

Digestive System Diseases

Carcinoma

Carcinoma, Hepatocellular

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Liver Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Antineoplastic Agents

Chlorotrianisene

Sorafenib

Protein Kinase Inhibitors

Enzyme Inhibitors

Patients will be treated by Transcatheter arterial chemoembolization every 12 ± 2 weeks dependent on CT evaluation. Before each TACE, dynamic CT will be performed for pre-treatment evaluation. When no viable tumor is seen on CT, TACE is to be discontinued.

Patients will be treated by Transcatheter arterial chemoembolization every 12 ± 2 weeks dependent on CT evaluation, plus sorafenib adjuvant therapy. Before each TACE, dynamic CT will be performed for pre-treatment evaluation. When no viable tumor is seen on CT, TACE is to be discontinued. patients will receive sorafenib 400 mg/d between each TACE. Patient will start receiving Sorafenib on Day 4 (up to Day 7) after 1st TACE (Day 1) and will interrupt after evening dose 4 days before each next TACE and re-start Sorafenib on Day 4 (up to Day 7) after each TACE cycle.Additional sorafenib treatment is optional and will be judged by investigator in the subject's best medical interest.

sorafenib is an oral, multikinase inhibitor approved for the treatment of advanced hepatocellular carcinoma

sorafenib

Transcatheter arterial chemoembolization was performed by the injection of small embolic particles coated with chemotherapeutic agents selectively into an artery directly supplying a tumor.

TACE

Chau-Ting Yeh, MD/PhD

Transcatheter arterial chemoembolization (TACE) + sorafenib therapy has been demonstrated to exert a beneficial effective on time-to-tumor-progression (TTP) in patients with unresectable hepatocellular carcinoma (HCC) in some studies. However, the beneficial effect varies among studies conducted in different areas of the world. The objectives of this study are (1) to understand whether GALNT14 TT genotype patients respond better than do GALNT14 non-TT genotype patients when treated by TACE; and (2) to understand whether GALNT14 non-TT genotype patients can benefit from TACE plus sorafenib (Nexavar) combination therapy. Patients enrolled will be stratified by GALNT14 genotyping. The GALNT14 "non-TT" patients were then randomized into two subgroups to evaluate the safety, tolerability and efficacy of TACE plus sorafenib therapy.

The primary endpoint of this study is the efficacy of TACE with or without sorafenib combination therapy evaluated by complete remission (CR).

The secondary endpoints are:

1. Time to partial or complete response (PR + CR).
2. Time-to-tumor-progression (TTP) and the progression free survival (PFS).
3. Overall survival (OS).
4. Safety and tolerability of TACE plus sorafenib therapy.

The strategy of TACE + sorafenib is now being intensively investigated. It is a safe approach with significant beneficial effect on TTP in some studies, but the beneficial effect on OS remains uncertain. In the present study, we hypothesized that the GALNT14 genotype might play a role in this issue. Our pilot study indicated that GALNT14 "TT" genotype was associated with a favorable complete response rate in patients treated by TACE alone. This genotype was present in \~ 25% of Chinese population coming from Taiwan, Colorado (US), or Beijing (China), and in \~ 7% of Italian population. But it was present in \~ 50% of Japanese population. The lower percentage of a TACE - favorable genotype in Chinese and Italian population could explain the different results between Japanese and Chinese/Italian clinical trials. It is possible that in a population with higher percentage of TACE - favorable genotype (GALNT14 "TT"), the beneficial effect of sorafenib adjuvant treatment might not be detected. In this study, we proposed to examine the TACE + sorafenib effect in patients with GALNT14 "non-TT" genotype, a TACE - unfavorable genotype.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Association of SNPs in Long Intergenic Noncoding RNA 00511 (LINC00511) With Breast Cancer Among the Egyptian Population	NCT06357689	Breast Cancer		20 Years - 70 Years	Ain Shams University
Assessing the Link Between Smoke Carcinogen Biomarkers and Lung Cancer Risk - 1	NCT00218179	Tobacco Use Dis... Lung Cancer	Non-interventio...	55 Years - 74 Years	University of Minnesota
IDO2 Genetic Status Informs the Neoadjuvant Efficacy of Chloroquine (CQ) in Brain Metastasis Radiotherapy	NCT01727531	Brain Metastasi...	Chloroquine dip...	18 Years -	Main Line Health
Clinical Trial for GALNT14 Genotype - Guided, Sorafenib in Combination With TACE in Hepatocellular Carcinoma	NCT02504983	Hepatocellular ...	sorafenib TACE	20 Years - 90 Years	Chang Gung Memorial Hospital
Association of SNPs in Long Intergenic Noncoding RNA 00511 (LINC00511) With Breast Cancer Among the Egyptian Population	NCT06357689	Breast Cancer		20 Years - 70 Years	Ain Shams University

Spots Global Cancer Trial Database for snps

Every month we try and update this database with for snps cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for snps

Every month we try and update this database with for snps cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for snps cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.