Essay On P16ink4a Overexpression

HeLa cells have had a positive influence on medicine in many ways including with giving us knowledge about the human papillomavirus (HPV) DNA and HPV18-positive. HeLa cells have been linked to changes in microRNA expression. Since HPV18 has been associated with very aggressive adenocarcinomas, this finding may explain why Dr. Gey was surprised by the prolific growth of HeLa cells in culture. Routine Papanicolaou smear screening may not detect rapidly progressive cervical carcinomas; the new HPV vaccine holds the promise of preventing these tumors. (Hutchins).

The purpose of this research was to determine the mechanisms in naked mole-rats that restricts cell proliferation and tumor formation. Contact inhibition is a mechanism observed where cell proliferation stops when two cells come in contact with one another. This process is caused by elevated levels of p27 cyclin-dependent kinase inhibitor which stops cells in the G1 phase from dividing. The cylcin-dependent kinase inhibitor p16 is also thought to regulate contact inhibition but its levels do not change in mice or human samples. Tumor-suppressor genes Rb and p53 are present in high concentration during contact inhibition to help control cell proliferation and apoptosis respectively. It was hypothesized that the naked mole-rats' cancer resistivity

Did you know there is more of a link between cervical cancer and HPV than smoking and lung cancer? Cervical cancer is currently the fourth most common cancer in women and the second leading cause of death from cancer in women. Along with those statistics, human papillomavirus is the most common sexually transmitted viral disease amongst men and women worldwide. The prevalence of women having a strain of HPV that ultimately leads to or increases the chance of cervical cancer is highly relatable. What is pathophysiology, signs, symptoms, prevention, and treatments of this ailment? You might ask will be covered in the next few pages of this paper.

Human Papillomavirus (HPV) is a double -stranded deoxyribonucleic acid (DNA) virus that only infects humans with an attraction to both cutaneous and mucosal surfaces such as the cervix, anus, tonsil, and oropharynx (Clark, 2013). HPV is a type of oncogenic virus that goes into the cells and can cause several diseases. Over the years, research has surfaced connecting genital HPV to several types of cancer. There are over a hundred strains of HPV but the most high risk strains, 16 and 18, have been shown to cause vulvar, vaginal, anal, and the most concerning, cervical cancer (Chan, Ng, & Wong, 2012). Genital HPV

Human Papilloma Virus (HPV) is a double stranded DNA virus. There are many genotypes HPV and some of them are oncogenic. They have envelope proteins E6 and E7 on their cell wall which are associated to initiate cancer. Anogenital lesions associated to HPV are divided into ‘low-risk’ types (6, 11, 34, 40, 42, and 43) and ‘high risk’ types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 69, 73, and 82). Most of the low risk HPV infections are asymptomatic and are not fatal, however infection to high risk HPV such as type 16 and 18 may cause cervical, anal, vaginal, vulvar and penile cancer (Centre of Disease Control, 2012). Low risk HPV generally cause warts on the skin surface which rarely develop into malignancy. Type 16 and 18 both were originally isolated from cervical carcinomas of human body. More than 70% of human cervical is due to the infection of either HPV 16 or 18. According to CDC, in 2008 it was estimated 11,070 cases of cervical cancer in United States and about 3,870 deaths due to cervical cancer. Higher percentage of HPV persistent infection occurs by HPV-16 and the risk of getting cervical cancer due the progression of disease is higher for HPV 16 and 18 and 45 (Tino F. Schwarz, 2008).

HPV, human papillomavirus is a communal infection that is common among adults. It is one of the main sources of sexual transmitted infection. Over 75% of women that are sexually active are most likely to be infected at least once in their life. This virus is known to be a worldwide disease. According to the World Health Organization, the risk of acquiring HPV infection is highest soon after a sexual encounter. Most of these infections are self-limiting and harmless. The virus is harmless because a number of people don’t realize they are infected, because the virus is often subclinical. Persistent infections with oncongenic HPV types can cause cervical cancer in women. Even though, both male and female can be affected by the

In the United States, cervical cancer is known as one of the most common cancers amongst females and it is estimated that 1/3 of the females diagnosed will die (Parkin, Bray, Ferlay, & Pisani, 2005). HPV 16 is the most common detected virus in cervical cancer patients, but there are 14 HPV types that are considered high-risk (Parkin, Bray, Ferlay, & Pisani, 2005). HPV is related to cervical cancer as the virus changes the cells of the cervix and causes cervical dysplasia, which untreated, leads to cancer (Dizon & Krychman, 2010). Examining the problem from a global perspective, Biological Study on Cervical Cancer (IBSCC) study group, concluded that “HPV DNA was detected in 93% of the tumors and … HPV 16 was present in 50% of the specimens…” (Bosch, Manos, Muñoz, Sherman, Jansen, Peto & Shan, 1995). This group collected samples of 1000 patients whom were diagnosed with stage 3 cervical cancer from 32 hospitals in 22 countries (Bosch, Manos, Muñoz, Sherman, Jansen, Peto & Shan, 1995). As, represented earlier with current statistics, it’s evident that more people are diagnosed each year with cervical cancer that have HPV present

Among the 12, 200 new cases of cervical cancer ninety-percent of them are caused or attributed to HPV (ACS).

Human cervical cancer is one of the most popular cancers in women of reproductive age around the globe (Baken et al., 1995). The human papillomavirus (HPV) causes cervical cancer. The main factors responsible for the cervical cancers are viral infection, inordinate sexual behavior, multiple sexual partners, weak immune system, and smoking

Inactivation of Rb function provokes a compensatory rise in expression of p16INK4A, 22 which used as a marker for HPV in oropharyngeal cancers (Ang et al., 2010; Mellin et al., 2005; Weinberger et al., 2006). The present standard management of locally advanced oropharyngeal cancers is surgery followed by adjuvant radiotherapy with defenetive chemotherapy (Marur et al., 2010). However, these treatments show less-favourable outcome and dramatically improve patient’s survival. This data points to a clear need for biomarkers to resolve the risk of locoregional or distant disease failure in HPV patients, and innovative approaches of targeting viral oncogenes and the specific immune therapy also needed.

Methods: We analyzed primary cervical carcinomas, peri-tumor biopsies and lymph nodes in 20 women with invasive cancer (FIGO stage I-II) who underwent radical pelvic surgery and lymphonodectomy. HPV DNA was searched by broad spectrum PCR in 142 DNA samples extracted from paraffin embedded tissues. Viral genotypes were identified by direct sequencing analysis.

Silva et al. (Ref. 83) have performed a comprehensive analysis of the inactivation mechanisms (mutation, homozygous and hemizygous deletion, and promoter hypermethylation) in of 100 primary breast carcinomas. RT-PCR showed expression variable of the p14ARF transcript, with 17% overexpression and 26% decreased expression. No detectable alterations were observed in the majority of cases with overexpressed p14ARF mRNA, but 77% of tumors with decreased expression showed one or more of these genetic alterations (Ref. 83). A significant correlation was observed between decreased p14ARF expression and poor prognostic parameters. The same group later studied the inactivation mechanisms that alter the levels (Ref. 84). Furthermore, the interdependence of inactivation mechanisms was studied since it had been reported that p14ARF was altered in tumors in concordance with p16INK4a. They showed that promoter hypermethylation was the major mechanism of inactivation of these genes, which was present in 31% and 50% of the tumors that showed decreased p16INK4a and p14ARF expression, respectively. No detectable inactivation mechanisms were observed in tumors overexpressing p16INK4a or p14ARF. In conclusion, these tumor suppressor proteins were often co-altered in human breast

Evidently, in the 1990s the relationship between HPV and cervical neoplasia was confirmed.[7] According to Bosch et al., the 1990s produced the key results of case-control and cohort studies, and witnessed an increasing number of results on the clinical uses of HPV-DNA testing in screening and triage, [24] and, as Liaw et al. (1995) noted in their case control studies, it was also becoming apparent that those with multiple HPV infections have a higher risk of developing cancer of the cervix. [26]

We have also shown that MALAT1, SRSF1, and SRSF protein kinase 1 (SRPK1) form a complex. Interestingly, SRSF1 has been demonstrated to stabilize tumor suppressor p53 by preventing its ubiquitin-proteasome system-mediated degradation via complex formation with mouse double minute 2 homolog (Mdm2), a ubiquitin ligase, in the nucleus (20). The resulting phenomenon is oncogene-induced senescence (OIS) (21), a protective antiproliferative mechanism activated by oncogenic signaling upon stress-induced inactivation of a tumor suppressor. Based on our preliminary results, in conjunction with literature evidence, we hypothesize that MALAT1 overexpression disrupts RRM2 and RS domain interaction in SRSF1, subsequently impairing RS domain phosphorylation and SRSF1 nuclear translocation. This change in subcellular localization destabilizes p53, leading to loss of OIS in HPV-negative cervical cancer (HNCC). The goal of our lab is to examine the role of MALAT1 in SRSF1/p53-mediated OIS via HNCC in vitro (Aim 1) and in vivo (Aim 2) experimental models utilizing MALAT1-specific antisense oligonucleotide (ASO) therapy. Completion of this project will lead to a clearer understanding of whether MALAT1 is an underlying cause of HNCC development. The results generated from this proposal will improve scientific knowledge and clinical practices by providing a new MALAT1-mediated mechanism underlying HNCC tumorigenesis and

In recent a meta-analysis was shown that HPV malignant (high-risk HPV) in HNSCC was 2.8 times greater than benign HPV (low-risk HPV). In 2003 the International Agency for research of cancer has found that HPV plays an important role in many cancers of HNSCC. Ringstrom et al also investigated the type of HPV infection is present in HNSCC, and he supported the role of HPV in head and neck cancer.