Ignite Creation Date:
2024-05-06 @ 10:10 AM
Last Modification Date:
2024-10-26 @ 12:26 PM
Study NCT ID:
NCT03188315
Status:
UNKNOWN
Last Update Posted:
2017-06-15
First Post:
2017-06-13
Brief Title:
Studies of Small DNA Virus Encoded Oncogenes in Viral Carcinogenesis Using Laboratory Model Systems
Sponsor:
Heba Momen kamel
Organization:
Assiut University
Study Overview
Official Title:
Studies of Small DNA Virus Encoded Oncogenes in Viral Carcinogenesis Using Laboratory Model Systems
Status:
UNKNOWN
Status Verified Date:
2017-06
Last Known Status:
NOT_YET_RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Cancer is a devastating disease presenting an immense disease burden to affected individuals and their families as well as health care systems with 109 million new cases and 67 million deaths per year Approximately 12 of human cancers worldwide are caused by oncoviruses infection with more than 80 of cases occurring in the developing world
Tumor viruses can be classified into two groups based on their genetic material
1 DNA tumor viruses
1 Small DNA tumor viruses Papilloma viruses Polyoma viruses and adenoviruses
2 Complex DNA tumor viruses Herpes viruses and Hepatitis B viruses
2 RNA tumor viruses Hepatitis C viruses and human T-cell leukemia virus HTLV
There are around 100 types of HPV with different variations in their genetic and oncogenic potential 5 Thus HPV genotypes are divided into 2 groups based on their vulnerability High risk HPV HR-HPV and low risk HPV LR-HPV
The HPV genome encodes several oncoproteins 5 E6 and E7 are the main genes responsible for cell transformation mediated by HR-HPV and they modulate the activities of cellular proteins that regulate the cell cycle Thus the presence of E6E7 can be a specific marker for diagnosing precancerous lesions by HPV
Knowledge of the etiology of virus-mediated carcinogenesis the networking of pathways involved in the transition from infection to cancer and the risk factors associated with each type of cancer all suggest prophylactic and therapeutic strategies that may reduce the risk of virus-mediated cancer
Tumor viruses can be classified into two groups based on their genetic material
1 DNA tumor viruses
1 Small DNA tumor viruses Papilloma viruses Polyoma viruses and adenoviruses
2 Complex DNA tumor viruses Herpes viruses and Hepatitis B viruses
2 RNA tumor viruses Hepatitis C viruses and human T-cell leukemia virus HTLV
There are around 100 types of HPV with different variations in their genetic and oncogenic potential 5 Thus HPV genotypes are divided into 2 groups based on their vulnerability High risk HPV HR-HPV and low risk HPV LR-HPV
The HPV genome encodes several oncoproteins 5 E6 and E7 are the main genes responsible for cell transformation mediated by HR-HPV and they modulate the activities of cellular proteins that regulate the cell cycle Thus the presence of E6E7 can be a specific marker for diagnosing precancerous lesions by HPV
Knowledge of the etiology of virus-mediated carcinogenesis the networking of pathways involved in the transition from infection to cancer and the risk factors associated with each type of cancer all suggest prophylactic and therapeutic strategies that may reduce the risk of virus-mediated cancer
Detailed Description:
Study subjects
1 Inclusion criteria
Age 18 - 65 years old
Women who are positive for HPV diagnosed by routine screening Women willing to participate in the study and sign an informed consent
2 Exclusion criteria
Age extremes less than 18 years old or more than 65 years old
Immuno-comprised patients patients under steroid therapy or chemotherapy or patients with serious medical illness that could affect their immune system
Unknown medical history
Study Groups
Group 1 Cases Patients known to have Cancer cervix with any degree of malignancy diagnosed by routine screening or any other diagnostic tests
Group 2 Controls Women sharing the same inclusion and exclusion criteria but not known to have Cancer cervix
Aim of The Study
1 Studying the role of HPV as an example of small DNA viruses in cell transformation and carcinogenesis
2 Determining the most HPV genotypes associated with high risks of cancer cervix occurrence
3 Detection of the HPV oncogenes playing role cell transformation and malignancy
4 Studying the role of viral DNA integration in cellular transformation and carcinogenesis
Study methods
Samples collection and storing
Samples will be obtained from the cervix with the brush or swab by following the instructions corresponding to the type of collecting device
Collection tubes will be stored at room temperature 15-30 C
Samples will be sent to the laboratory in less than 14 days following collection
The tubes can be preserved for 2-3 weeks at room temperature
HPV detection
HPV cannot be propagated in tissue culture and therefore in most cases its accurate identification relies on molecular biology techniques such as polymerase chain reaction PCR
HPV Genotyping
PCR-RFLP shows good discriminatory power by differentiating between HR and LR HPV genotypes and it is possible to identify single or multiple infections
In this technique the amplified DNA is digested by restriction enzymes resulting in DNA fragments of various lengths Each fragment length is characteristic of a certain HPV genotype
The commonest restriction enzymes are BamHI Dd6eI HaeIII HinfI PstI and RsaI
HPV Oncogenes and oncoproteins
The main techniques used to detect mRNA for E6E7 oncogenes are two commercial assays PreTectW Proofer and APTIMAW HPV Assay These techniques are based on transcription-mediated amplification of full-length E6E7 transcripts using PCR
Statistical analysis
Data will be analyzed by one-way analysis of variance using SPSS software version 240 Values will be expressed as mean SD For comparison between 2 groups Students t test will be used to determine whether the cases was significantly different from the control Differences will be considered statistically significant at P005 while P001 will represent more significant change
1 Inclusion criteria
Age 18 - 65 years old
Women who are positive for HPV diagnosed by routine screening Women willing to participate in the study and sign an informed consent
2 Exclusion criteria
Age extremes less than 18 years old or more than 65 years old
Immuno-comprised patients patients under steroid therapy or chemotherapy or patients with serious medical illness that could affect their immune system
Unknown medical history
Study Groups
Group 1 Cases Patients known to have Cancer cervix with any degree of malignancy diagnosed by routine screening or any other diagnostic tests
Group 2 Controls Women sharing the same inclusion and exclusion criteria but not known to have Cancer cervix
Aim of The Study
1 Studying the role of HPV as an example of small DNA viruses in cell transformation and carcinogenesis
2 Determining the most HPV genotypes associated with high risks of cancer cervix occurrence
3 Detection of the HPV oncogenes playing role cell transformation and malignancy
4 Studying the role of viral DNA integration in cellular transformation and carcinogenesis
Study methods
Samples collection and storing
Samples will be obtained from the cervix with the brush or swab by following the instructions corresponding to the type of collecting device
Collection tubes will be stored at room temperature 15-30 C
Samples will be sent to the laboratory in less than 14 days following collection
The tubes can be preserved for 2-3 weeks at room temperature
HPV detection
HPV cannot be propagated in tissue culture and therefore in most cases its accurate identification relies on molecular biology techniques such as polymerase chain reaction PCR
HPV Genotyping
PCR-RFLP shows good discriminatory power by differentiating between HR and LR HPV genotypes and it is possible to identify single or multiple infections
In this technique the amplified DNA is digested by restriction enzymes resulting in DNA fragments of various lengths Each fragment length is characteristic of a certain HPV genotype
The commonest restriction enzymes are BamHI Dd6eI HaeIII HinfI PstI and RsaI
HPV Oncogenes and oncoproteins
The main techniques used to detect mRNA for E6E7 oncogenes are two commercial assays PreTectW Proofer and APTIMAW HPV Assay These techniques are based on transcription-mediated amplification of full-length E6E7 transcripts using PCR
Statistical analysis
Data will be analyzed by one-way analysis of variance using SPSS software version 240 Values will be expressed as mean SD For comparison between 2 groups Students t test will be used to determine whether the cases was significantly different from the control Differences will be considered statistically significant at P005 while P001 will represent more significant change
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None