scholarly journals CTCF association with episomal HPV16 genomes regulates viral oncogene transcription and splicing

2021 ◽  
Author(s):  
Ian J Groves ◽  
George Tang ◽  
Nicholas Coleman
Keyword(s):  
High Risk ◽  
Binding Site ◽  
Virus Genome ◽  
Ctcf Binding ◽  
Human Papillomavirus 16 ◽  
Viral Oncogenes ◽  
Hpv16 Genome ◽  
Episomal Hpv16 ◽  
Genome Copy Number ◽  
Risk Of Cancer

AbstractHuman papillomavirus 16 (HPV16) is a high-risk alphapapillomavirus that is associated with cancers of mucosal epithelia. The virus genome exists in cells as an episome but can integrate and overexpress the E6 and E7 viral oncogenes. In related high-risk family members HPV18 and HPV31, host proteins including CTCF, an insulator, and SMC1A, a component of the cohesion complex, are known to interact with the viral genome and alter transcriptional activity, splicing patterns and episome amplification. However, the roles of these two proteins during HPV16 infection has not yet been fully examined. Here, we show during differentiation of the episomal HPV16-containing W12 cell line that CTCF association increases with the virus genome at the known E2 binding site, whilst additional CTCF binding now occurs at the putative L2 binding site, with SMC1A association occurring unchanged here. While expression of virus late transcripts (E4^L1, L2, L1) is stimulated, early transcript levels decrease by 48 hours, with the exception of the E6*IV spliced transcript. Conversely, in undifferentiated, monolayer W12 cells, CTCF knockdown increases the level of all early transcripts, whereas E6*IV level increases. Additionally, CTCF ablation as well as SMC1A knockdown results in decreases to HPV16 genome copy number. Taken together, this supports the model that while CTCF and SMC1A have a role in HPV16 genome maintenance, CTCF plays a greater part in regulating HPV16 oncogene splicing and expression during the natural lifecycle of the virus, and may be involved in a reduced risk of cancer development during episomal HPV16 infections.

Colorectal cancer knowledge and screening rates are lower than for breast cancer even in individuals at high risk of cancer

2001 ◽  
Vol 120 (5) ◽  
pp. A741-A741
Author(s):  
P ANG ◽  
D SCHRAG ◽  
K SCHNEIDER ◽  
K SHANNON ◽  
J JOHNSON ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Colorectal Cancer ◽  
High Risk ◽  
Cancer Knowledge ◽  
Risk Of Cancer

scholarly journals CanAssist Breast Impacting Clinical Treatment Decisions in Early-Stage HR+ Breast Cancer Patients: Indian Scenario

2019 ◽  
Author(s):  
Satish Sankaran ◽  
Jyoti Bajpai Dikshit ◽  
Chandra Prakash SV ◽  
SE Mallikarjuna ◽  
SP Somashekhar ◽  
...  
Keyword(s):  
High Risk ◽  
Early Stage ◽  
Risk Groups ◽  
Treatment Decisions ◽  
Low Risk ◽  
Not Given ◽  
Breast Cancer Patients ◽  
Number Of Patients ◽  
Risk Of Cancer ◽  
The Impact

AbstractCanAssist Breast (CAB) has thus far been validated on a retrospective cohort of 1123 patients who are mostly Indians. Distant metastasis–free survival (DMFS) of more than 95% was observed with significant separation (P < 0.0001) between low-risk and high-risk groups. In this study, we demonstrate the usefulness of CAB in guiding physicians to assess risk of cancer recurrence and to make informed treatment decisions for patients. Of more than 500 patients who have undergone CAB test, detailed analysis of 455 patients who were treated based on CAB-based risk predictions by more than 140 doctors across India is presented here. Majority of patients tested had node negative, T2, and grade 2 disease. Age and luminal subtypes did not affect the performance of CAB. On comparison with Adjuvant! Online (AOL), CAB categorized twice the number of patients into low risk indicating potential of overtreatment by AOL-based risk categorization. We assessed the impact of CAB testing on treatment decisions for 254 patients and observed that 92% low-risk patients were not given chemotherapy. Overall, we observed that 88% patients were either given or not given chemotherapy based on whether they were stratified as high risk or low risk for distant recurrence respectively. Based on these results, we conclude that CAB has been accepted by physicians to make treatment planning and provides a cost-effective alternative to other similar multigene prognostic tests currently available.

What Should Be Done in Inflammatory Bowel Disease Patients with Prior Malignancy?

2017 ◽  
Vol 35 (1-2) ◽  
pp. 50-55 ◽  
Author(s):  
Jacques Cosnes
Keyword(s):  
Inflammatory Bowel Disease ◽  
Urinary Tract ◽  
High Risk ◽  
Bowel Disease ◽  
Immunosuppressive Treatment ◽  
Intestinal Resection ◽  
Immunosuppressive Drugs ◽  
Inflammatory Bowel ◽  
Risk Of Cancer ◽  
Prior Malignancy

Background: Treatment of inflammatory bowel disease (IBD) in patients with prior malignancy is challenging because therapeutic immunosuppression required for controlling IBD activity may increase the risk of cancer recurrence. Key Messages: Contrary to the observations in the post-transplant population, retrospective observational studies of IBD patients with prior malignancy have not demonstrated that immunosuppressive drugs increased significantly the risk of new or recurrent cancer. However, these studies are highly biased and do not permit the use of these drugs. Factors like the time since treatment completion, severity, and subtype of prior cancer should be weighed along with the current IBD activity before choosing the best therapeutic strategy. In practice, most cases of prior cancer require a delay of at least 2 years before starting or resuming immunosuppressants, including anti-TNF agents. This delay should be extended to 5 years in cancer with a high risk of recurrence including cancer of the urinary tract, gastrointestinal cancer, leukemias, and multiple myeloma. A special attention should be paid to cancers with a high risk of late metastasis (breast, melanoma, renal cell carcinoma). Enteral nutrition, Budesonide, mesalamine, and limited intestinal resection should be considered following the completion of cancer treatment and prior to the safe initiation of immunosuppressive treatment for IBD. Thiopurines should be avoided in case of prior Epstein-Barr virus-related lymphoma, HPV-related carcinomas, and cancer of the urinary tract. Methotrexate and anti-TNF agents seem to be safe except for the risk of recurrent melanoma for the latter. Conclusion: IBD patients with prior malignancy should benefit from individual decisions made on a case-by-case basis.

scholarly journals Seminoma in Undescended Intra Abdominal Testis: A Case Report

1970 ◽  
Vol 18 (2) ◽  
pp. 131-133 ◽  
Author(s):  
MM Haque ◽  
AB Siddique ◽  
ABMG Rabbani ◽  
MA Quasem ◽  
AKMG Rahman ◽  
...  
Keyword(s):  
Case Report ◽  
High Risk ◽  
Testicular Tumor ◽  
Early Age ◽  
Sexually Active ◽  
Lower Abdomen ◽  
Undescended Testes ◽  
Cryptorchid Testis ◽  
Risk Of Cancer ◽  
Abdominal Testis

A mass in the lower abdomen in a sexually active man with a cryptorchid testis strongly points towards the diagnosis of malignancy in the abdominal testis.1 The incidence of testicular tumor is 11 times more in inguinal testes and 50 times more in intra abdominal testes. 2 Normally, the testes, which are inside the abdomen during gestation, migrate into the scrotum by the time of birth. Occasionally, boys are born with testes that are still in the abdomen or in the groin, not having completed their journey to the scrotum. These undescended testes are at high risk of cancer and should be moved into the scrotum at an early age or removed entirely.   doi: 10.3329/taj.v18i2.3194 TAJ 2005; 18(2): 131-133

scholarly journals 3'HS1 CTCF binding site in human β-globin locus regulates fetal hemoglobin expression

2021 ◽  
Author(s):  
Pamela Himadewi ◽  
Xue Qing David Wang ◽  
Fan Feng ◽  
Haley Gore ◽  
Yushuai Liu ◽  
...  
Keyword(s):  
Binding Site ◽  
Progenitor Cells ◽  
Globin Gene ◽  
Fetal Hemoglobin ◽  
Ctcf Binding ◽  
Ctcf Binding Site ◽  
Distal Enhancer ◽  
Erythroid Progenitor ◽  
Hematopoietic Stem ◽  
Ctcf Site

Mutations in the adult β-globin gene can lead to a variety of hemoglobinopathies, including sickle cell disease and β-thalassemia. An increase in fetal hemoglobin expression throughout adulthood, a condition named Hereditary Persistence of Fetal Hemoglobin (HPFH), has been found to ameliorate hemoglobinopathies. Deletional HPFH occurs through the excision of a significant portion of the 3 prime end of the β-globin locus, including a CTCF binding site termed 3'HS1. Here, we show that the deletion of this CTCF site alone induces fetal hemoglobin expression in both adult CD34+ hematopoietic stem and progenitor cells and HUDEP-2 erythroid progenitor cells. This induction is driven by the ectopic access of a previously postulated distal enhancer located in the OR52A1 gene downstream of the locus, which can also be insulated by the inversion of the 3'HS1 CTCF site. This suggests that genetic editing of this binding site can have therapeutic implications to treat hemoglobinopathies.

HPV: from infection to cancer

2007 ◽  
Vol 35 (6) ◽  
pp. 1456-1460 ◽  
Author(s):  
M.A. Stanley ◽  
M.R. Pett ◽  
N. Coleman
Keyword(s):  
Immune Response ◽  
Cancer Progression ◽  
Therapeutic Effects ◽  
Type I ◽  
Immune Recognition ◽  
Human Papillomavirus 16 ◽  
E6 And E7 ◽  
High Doses ◽  
Risk Of Cancer ◽  
Selection Of

Infection with HPV (human papillomavirus) 16 is the cause of 50% or more of cervical cancers in women. HPV16 infection, however, is very common in young sexually active women, but the majority mount an effective immune response and clear infection. Approx. 10% of individuals develop a persistent infection, and it is this cohort who are at risk of cancer progression, with the development of high-grade precursor lesions and eventually invasive carcinoma. Effective evasion of innate immune recognition seems to be the hallmark of HPV infections, since the infectious cycle is one in which viral replication and release is not associated with inflammation. Furthermore, HPV infections disrupt cytokine expression and signalling with the E6 and E7 oncoproteins particularly targeting the type I IFN (interferon) pathway. High doses of IFN can overcome the HPV-mediated abrogation of signalling, and this may be the basis for the therapeutic effects on HPV infections of immune-response modulators such as the imidazoquinolones that induce high levels of type I IFNs by activation of TLR (Toll-like receptor) 7. Using the unique W12 model of cervical carcinogenesis, some of these IFN-related interactions and their relevance in the selection of cells with integrated viral DNA in cancer progression have been investigated. Our data show that episome loss associated with induction of antiviral response genes is a key event in the spontaneous selection of cervical keratinocytes containing integrated HPV16. Exogenous IFN-β treatment of W12 keratinocytes in which the majority of the population contain episomes results only in the rapid emergence of IFN-resistant cells, loss of episome-containing cells and a selection of cells containing integrated HPV16 in which the expression of the transcriptional repressor E2 is down-regulated, but in which E6 and E7 are up-regulated.

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