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Tumor educated platelets ITGA2b and SELP mRNA by reverse transcription-quantitative polymerase chain reaction (RT-qPCR).

mRNA expression

Amany H Radwan, doctor

Aml A Rayan, doctor

Ola A Afifi, doctor

Fatma M Helbawi, doctor

1. To study the expression pattern of Integrin alpha 2b (ITGA2b) and Selectin P (SELP) genes of Tumor educated platelets in pancreatic and biliary tree cancer and its diagnostic value.
2. To investigate correlation between expression levels of ITGA2b and SELP genes and stages of pancreatic and biliary tree cancer.
3. To investigate correlation between expression levels of ITGA2b, SELP genes, CA 19-9 and CEA in pancreatic and biliary tree cancer patients.

Malignant tumors arising in the biliary tract and pancreas are aggressive malignancies characterized by a poor prognosis and most of cases are diagnosed at advanced stages and have poor outcome . The most common pancreatic cancer is ductal adenocarcinoma, which accounts for about 80% of all pancreatic cancers. Pancreatic cancer is a highly lethal gastrointestinal cancer with a low 5-year survival rate and difficulty in early detection . Biliary tract cancers can be divided into intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer. CEA and CA 19-9 are the most common used serum biomarker for cancer screening and the diagnosis of pancreatic and biliary cancer.

Platelets are an essential component of the tumor microenvironment and serve as local and systemic respondents during tumor initiation and tumor metastasis. After interaction with tumor cells or tumor associated biomolecules, platelets can alter their RNA profile, and this process give rise to the so-called tumor educated platelets (TEPs). Tumor cells can directly and indirectly produce changes on platelet RNA and protein content, emerging a new term called liquid biopsy which reflect the presence of cancer and thus give hope to many that they might precede protein markers as a cancer-specific biomarker. Alterations in the TEPs RNA profile have been described as a novel source of potential biomarkers and can be used for early detection of cancer and treatment monitoring. Platelet biomarker transcripts can be transferred from tumor cells to platelets, although in some studies, the putative origin of the biomarker is the megakaryocyte (endogenous).

Integrin Alpha 2b (ITGA2b) gene encodes a member of the integrin alfa chain family of proteins which is proteolytically processed to form subunit of the alpha-IIb/beta-3 integrin cell adhesion receptor which is play crucial role in the blood coagulation system, by mediating platelets aggregation . Selectin P (SELP) gene encodes a protein that is stored in the alpha granules of platelets and Weibel-Palade bodies of endothelial cells. This protein redistributes to the plasma membrane during platelet activation and degranulation and mediates the interaction of activated endothelial cells or platelets with leukocytes. ITGA2b and SELP are cancer related genes and of the mRNA TEPs putative endogenous biomarkers which have a high value for detection of cancer, so, tumor educated platelets (TEPs) broadened the spectrum of liquid biopsy applications, and may enable blood-based cancer diagnostics.

ITGA2b and SELP Expression in Cancer Pancreas and Biliary Tract Cancer

Diagnostic Value of Tumor-Educated Platelets Integrin Alpha 2b (ITGA2B) and Selectin P (SELP) mRNA Expression in Pancreatic and Biliary Tract Cancer

To study the expression pattern of ITGA2b and SELP genes of Tumor educated platelets in pancreatic and biliary tree cancer and its diagnostic value.

3- To investigate correlation between expression levels of ITGA2b, SELP genes, CA 19-9 and CEA in pancreatic and biliary tree cancer patients.

Assiut University

Doctor

Skin and Connective Tissue Diseases

Breast Neoplasms

Breast Diseases

Skin Diseases

Anticoagulants

Vasodilator Agents

Respiratory System Agents

Anticonvulsants

Antineoplastic Agents

Estrogens

Warfarin

Theophylline

3,3'-diindolylmethane

Protective Agents

This group will have up to 100 women who are carriers of a BRCA1 deleterious mutation. To ensure safety, women in this group will not be able to participate in the study if they are under medications with warfarin, theophylline, or anticonvulsants; or if they are pregnant, breast-feeding or planning to become pregnant within 6 months of the research project. Women in this group will receive 300 mg per day of Rx Balance BioResponse DIM for six weeks. Supplements will be given free of charge. A blood sample (20cc) and a urine sample (20cc) will be collected from these women during two clinic visits; the second visit will be during the six weeks of DIM supplementation (4-6 weeks after the first clinic visit).

This group will have up to a 100 women who are carriers of a BRCA1 deleterious mutation. This group will not receive DIM. Women that choose not to take DIM will be in this group. A blood sample (20cc) and a urine sample (20cc) will be collected from these women during two clinic visits; the second visit will be 4-6 weeks after the first clinic visit.

This group will have up to 100 women who do not carry a BRCA1 mutation but who come from BRCA1 carrier family (a family with at least one individual that has tested positive for a BRCA1 mutation). A control subject is considered negative for a BRCA1 mutation if she has been confirmed by direct DNA sequencing to not be a carrier of this gene. A blood sample (20cc) and a urine sample (20cc) will be collected from these women at a single clinic visit.

Diindolylmethane (DIM)

Joanne Kotsopoulos, PhD

Marcia Llacuachaqui, HonBSc

Steven A Narod, MD

Women with a BRCA1 mutation face a lifetime risk of breast cancer of approximately 70% and a lifetime risk of ovarian cancer of approximately 40%. A number of potential anti-cancer nutrients have been proposed, however, it is important that diet supplements be evaluated prior to general recommendation.

The risk of breast and ovarian cancer in carriers of a BRCA1 mutation might be lowered by some nutritional supplements. For example, green tea, broccoli and vitamin D are of potential interest. One dietary supplement that is thought to have potential for BRCA1 carriers is diindolylmethane (DIM), which is an active ingredient in broccoli and other green vegetables. DIM - is found in vegetables like broccoli and is available as a supplement in health food stores. The investigators think that DIM may increase the production of the normal copy of BRCA1 and offset the effect of the mutation.

The purpose of this study is to determine that there is a potential for oral DIM supplementation to result in the increased production of the BRCA1 protein in BRCA1 mutation carriers. The results of the study will also serve as an evaluation of the current use and success of preventive strategies for BRCA1 mutation carriers.

The Potential for Oral Diindolylmethane (DIM) Supplementation to Increase the Production of the BRCA1 Protein in BRCA1 Mutation Carriers

The Potential for Oral DIM Supplementation to Increase the Production of the BRCA1 Protein in BRCA1 Mutation Carriers

BioResponse

Women's College Hospital

Dr. Steven A. Narod, MD

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
ITGA2b and SELP Expression in Cancer Pancreas and Biliary Tract Cancer	NCT05493878	Pancreas Cancer	mRNA expression	-	Assiut University
The Potential for Oral Diindolylmethane (DIM) Supplementation to Increase the Production of the BRCA1 Protein in BRCA1 Mutation Carriers	NCT01022333	Breast Cancer	Diindolylmethan...	25 Years - 45 Years	Women's College Hospital

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