Low intracellular zinc induces oxidative DNA damage, disrupts p53, NFκB, and AP1 DNA binding, and affects DNA repair in a rat glioma cell line

Source: Proceedings of the National Academy of Sciences of the United States of AmericaAuthors: Emily Ho and  Bruce N. Ames* Abstract Approximately 10% of the U.S. population ingests <50% of the current recommended daily allowance for zinc. We investigate the effect of zinc deficiency on DNA damage, expression of DNA-repair enzymes, and downstream signaling events in a cell-culture model. Low zinc inhibited cell growth of rat glioma C6 cells and increased oxidative stress. Low intracellular zinc increased DNA single-strand breaks (comet assay). Zinc-deficient C6 cells also exhibited an increase in the expression of the zinc-containing DNA-repair proteins p53 and apurinic endonuclease (APE). Repletion with zinc restored cell growth and reversed DNA damage. APE is a multifunctional protein that not only repairs DNA but also controls DNA-binding activity of many transcription factors that may be involved in cancer progression. The ability of the transcription factors p53, nuclear factor κB, and activator protein 1 (AP1) to bind to consensus DNA sequences was decreased markedly with zinc deficiency, as assayed by electrophoretic mobility-shift assays. Thus, low intracellular zinc status causes oxidative DNA damage and induces DNA-repair protein expression, but binding of p53 and important downstream signals leading to proper DNA repair are lost without zinc.   The following news story is scientifically tied together with the study above; one explains the other. Please follow this link to read the study titled: Nutritional and Zinc Status of Head and Neck Cancer Patients: An Interpretive Review http://oralcancernews.org/wp/?p=14841   This news story was resourced by the Oral Cancer Foundation, and vetted [...]

2013-07-03T17:11:25-07:00July, 2013|Oral Cancer News|

Nutritional and Zinc Status of Head and Neck Cancer Patients: An Interpretive Review

Source: Journal of the American College of NutritionAuthors: Ananda S. Prasad, MD, PhD, MACN, Frances W.J. Beck, PhD, Timothy D. Doerr, MD, Falah H. Shamsa, PhD, Hayward S. Penny, MS, RD, Steven C. Marks, MD, Joseph Kaplan, MD, Omer Kucuk, MD and Robert H. Mathog, MD  Abstract In this review, we provide evidence based on our studies, for zinc deficiency and cell mediated immune disorders, and the effects of protein and zinc status on clinical morbidities in patients with head and neck cancer. We investigated subjects with newly diagnosed squamous cell carcinoma of the oral cavity, oropharynx, larynx, and hypopharynx. Patients with metastatic disease and with severe co-morbidity were excluded. Nutritional assessment included dietary history, body composition, and prognostic nutritional index (PNI) determination. Zinc status was determined by zinc assay in plasma, lymphocytes, and granulocytes. Pretreatment zinc status and nutritional status were correlated with clinical outcomes in 47 patients. Assessment of immune functions included production of TH1 and TH2 cytokines, T cell subpopulations and cutaneous delayed hypersensitivity reaction to common antigens. At baseline approximately 50% of our subjects were zinc-deficient based on cellular zinc criteria and had decreased production of TH1 cytokines but not TH2 cytokines, decreased NK cell lytic activity and decreased proportion of CD4+ CD45RA+ cells in the peripheral blood. The tumor size and overall stage of the disease correlated with baseline zinc status but not with PNI, alcohol intake, or smoking. Zinc deficiency was associated with increased unplanned hospitalizations. The disease-free interval was highest for the group which had both zinc sufficient and nutrition sufficient [...]

2013-07-03T17:11:10-07:00July, 2013|Oral Cancer News|

Radiation Treatment Breaks and Ulcerative Mucositis in Head and Neck Cancer

Source: The OncologistAuthors: Gregory Russo, Robert Haddad, Marshall Posnerb and Mitchell MachtayaReceived January 31, 2008.Accepted May 14, 2008.First published online in THE ONCOLOGIST Express on August 13, 2008. • Disclosure: The content of this article has been reviewed by independent peer reviewers to ensure that it is balanced, objective, and free from commercial bias. No financial relationships relevant to the content of this article have been disclosed by the authors, planners, independent peer reviewers, or staff managers of the article.   Abstract Unplanned radiation treatment breaks and prolongation of the radiation treatment time are associated with lower survival and locoregional control rates when radiotherapy or concurrent chemoradiotherapy is used in the curative treatment of head and neck cancer. Treatment of head and neck cancer is intense, involving high-dose, continuous radiotherapy, and often adding chemotherapy to radiotherapy. As the intensity of treatment regimens has escalated in recent years, clinical outcomes generally have improved. However, more intensive therapy also increases the incidence of treatment-related toxicities, particularly those impacting the mucosal lining of the oral cavity, pharynx, and cervical esophagus, and results in varying degrees of ulcerative mucositis. Ulcerative mucositis is a root cause of unscheduled radiation treatment breaks, which prolongs the total radiation treatment time. Alterations in radiotherapy and chemotherapy, including the use of continuous (i.e., 7 days/week) radiotherapy to ensure constant negative proliferative pressure, may improve efficacy outcomes. However, these approaches also increase the incidence of ulcerative mucositis, thereby increasing the incidence of unplanned radiation treatment breaks. Conversely, the reduction of ulcerative [...]

2013-07-03T16:36:04-07:00July, 2013|Oral Cancer News|

Cessation of alcohol drinking, tobacco smoking and the reversal of head and neck cancer risk

Source: International Journal of EpidemiologyAccepted September 28, 2008  Abstract Background Quitting tobacco or alcohol use has been reported to reduce the head and neck cancer risk in previous studies. However, it is unclear how many years must pass following cessation of these habits before the risk is reduced, and whether the risk ultimately declines to the level of never smokers or never drinkers. Methods We pooled individual-level data from case–control studies in the International Head and Neck Cancer Epidemiology Consortium. Data were available from 13 studies on drinking cessation (9167 cases and 12 593 controls), and from 17 studies on smoking cessation (12 040 cases and 16 884 controls). We estimated the effect of quitting smoking and drinking on the risk of head and neck cancer and its subsites, by calculating odds ratios (ORs) using logistic regression models. Results Quitting tobacco smoking for 1–4 years resulted in a head and neck cancer risk reduction [OR 0.70, confidence interval (CI) 0.61–0.81 compared with current smoking], with the risk reduction due to smoking cessation after ≥20 years (OR 0.23, CI 0.18–0.31), reaching the level of never smokers. For alcohol use, a beneficial effect on the risk of head and neck cancer was only observed after ≥20 years of quitting (OR 0.60, CI 0.40–0.89 compared with current drinking), reaching the level of never drinkers. Conclusions Our results support that cessation of tobacco smoking and cessation of alcohol drinking protect against the development of head and neck cancer. This news story was resourced by the [...]

2013-07-03T16:25:24-07:00July, 2013|Oral Cancer News|

SSRI Prevents Depression in Head, Neck Cancer

Source: MedPage TodayBy Salynn Boyles, Contributing WriterPublished: June 21, 2013  Prophylactic escitalopram cut the incidence of depression in head and neck cancer patients by more than 50% and improved quality of life, a clinical trial showed. Significantly fewer patients taking the antidepressant developed depression, when compared with those on placebo (10% vs 24.6%; stratified log-rank test, P=.04), according to a study in the June 20 issue of JAMA Otolaryngology Head and Neck Surgery. "Depression is very common among patients with this disease, but it is not easy to predict who will become depressed at the beginning of treatment," University of Nebraska Medical Center professor of head and neck oncology William Lydiatt, MD, told MedPage Today. "That's why the prevention paradigm may offer considerable benefit at an acceptable risk." As many as half of head and neck cancer patients develop clinical depression within months of their diagnosis and suicide rates are among the highest in patients with a medical illness, Lydiatt noted. "The burden of treatment is extensive and frequently includes dysphagia, disfigurement, voice alterations, mucositis, need for tracheostomy and feeding tubes, fatigue and depression," the researchers wrote. They chose the generic version of the popular SSRI Lexapro for the trial to give patients an affordable treatment option that's well tolerated in the elderly. The randomized, double-blind trial included 148 newly diagnosed head and neck cancer patients entering treatment who did not yet have a diagnosis of depression. The patients were stratified by sex, site of disease, stage, and primary modality of [...]

2013-06-21T14:10:07-07:00June, 2013|Oral Cancer News|

Teen HPV Rates Were Cut In Half After The Vaccine Went Public

Source ThinkProgress.orgBy Annie-Rose Strasser Published Jun 19, 2013 at 2:35 pm   Following the 2006 introduction of a vaccine against cancer-causing human papillomavirus, rates of HPV in teen girls have plummeted to nearly half, a new study found on Wednesday. The Journal of Infectious Diseases reports that HPV infection in girls ages 14 to 19 dropped from 11.5 percent for the years 2003-2006 to 5.1 percent for 2007-2010. Since HPV can lead to cervical cancer, the results also could herald a drop in cancer rates for girls in this age range, too. The study illustrates a great advancement in public health, but it also underlines the consequences for those huge numbers of women and girls who are still not getting their vaccinations; in 2011, only 35 percent of girls ages 13-17 received all three shots in the vaccination series, and only 30 percent of women ages 19-26 had received the vaccine. Fear-mongering and conspiracy theories over the side effects of the HPV vaccine are a major reason that inoculation rates are so low. While the Centers for Disease control have deemed the shots safe, and especially effective for young girls, 16 percent of parents report not letting their children get the shots for fear of side effects. In fact, incidents of cancer from HPV are rising in the U.S., and the CDC says rates of inoculation are “unacceptably low.” These dangerous theories are fueled by conservatives like Rep. Michele Bachmann (R-MN), who campaigned on her insistence that HPV vaccines cause “mental [...]

2013-06-20T11:53:25-07:00June, 2013|Oral Cancer News|

Vaccine is credited with steep fall of HPV in teenagers.

Source The New York TimesBy SABRINA TAVERNISEPublished: June 19, 2013 342 Comments  The prevalence of dangerous strains of the human papillomavirus — the most common sexually transmitted infection in the United States and a principal cause of cervical cancer — has dropped by half among teenage girls in recent years, a striking measure of success for a vaccine against the virus that was introduced only in 2006, federal health officials said on Wednesday.   Dr. Judith L. Schaechter gives an HPVvaccination to a 13-year-old girl in heroffice at the University of Miami LeonardM. Miller School of Medicine.    The sharp decline in the infection rate comes at a time of deepening worry among doctors and public health officials about the limited use of the HPV vaccine in the United States. Health departments across the country are scrambling for ways to increase vaccination rates, while nonprofit groups are using postcard reminders and social media campaigns and pediatricians are being encouraged to convince families of the vaccine’s benefits. There are some signs that resistance to the vaccine may be growing. A study published in the journal Pediatrics in March found that 44 percent of parents in 2010 said they did not intend to vaccinate their daughters, up from 40 percent in 2008. Because it prevents a sexually transmitted infection, the vaccine comes with a stigma. Some parents worry it promotes promiscuity. And it has been controversial. During the Republican primary in 2011, Representative Michele Bachmann, Republican of Minnesota, said the vaccine could have [...]

2013-06-20T11:31:05-07:00June, 2013|Oral Cancer News|

Reasons for Not Vaccinating Adolescents: National Immunization Survey of Teens, 2008–2010

Source: PediatricsAuthors: Paul M. Darden, MD, David M. Thompson, PhD, James R. Roberts, MD, MPH, Jessica J. Hale, MSa, Charlene Pope, PhD, MPH, RN, Monique Naifeh, MD, MPHa, and Robert M. Jacobson, MDPublished Online: March 18, 2013    Abstract OBJECTIVE: To determine the reasons adolescents are not vaccinated for specific vaccines and how these reasons have changed over time. METHODS: We analyzed the 2008–2010 National Immunization Survey of Teens examining reasons parents do not have their teens immunized. Parents whose teens were not up to date (Not-UTD) for Tdap/Td and MCV4 were asked the main reason they were not vaccinated. Parents of female teens Not-UTD for human papillomavirus vaccine (HPV) were asked their intent to give HPV, and those unlikely to get HPV were asked the main reason why not. RESULTS: The most frequent reasons for not vaccinating were the same for Tdap/Td and MCV4, including “Not recommended” and “Not needed or not necessary.” For HPV, the most frequent reasons included those for the other vaccines as well as 4 others, including “Not sexually active” and “Safety concerns/Side effects.” “Safety concerns/Side effects” increased from 4.5% in 2008 to 7.7% in 2009 to 16.4% in 2010 and, in 2010, approaching the most common reason “Not Needed or Not Necessary” at 17.4% (95% CI: 15.7–19.1). Although parents report that health care professionals increasingly recommend all vaccines, including HPV, the intent to not vaccinate for HPV increased from 39.8% in 2008 to 43.9% in 2010 (OR for trend 1.08, 95% CI: 1.04–1.13). CONCLUSIONS: Despite doctors increasingly recommending adolescent vaccines, parents [...]

2013-06-20T10:42:12-07:00June, 2013|Oral Cancer News|

NIH scientists find promising biomarker for predicting HPV-related oropharynx cancer

Source: National Cancer InstitutePublished: 6-17-13  Researchers have found that antibodies against the human papillomavirus (HPV) may help identify individuals who are at greatly increased risk of HPV-related cancer of the oropharynx, which is a portion of the throat that contains the tonsils. In their study, at least 1 in 3 individuals with oropharyngeal cancer had antibodies to HPV, compared to fewer than 1 in 100 individuals without cancer.  When present, these antibodies were detectable many years before the onset of disease. These findings raise the possibility that a blood test might one day be used to identify patients with this type of cancer.               Genomic structure of HPV      The results of this study, carried out by scientists at the National Cancer Institute (NCI), part of the National Institutes of Health, in collaboration with the International Agency for Research on Cancer (IARC), were published online June 17,  2013, in the Journal of Clinical Oncology. Historically, the majority of oropharyngeal cancers could be explained by tobacco use and alcohol consumption rather than HPV infection. However, incidence of this malignancy is increasing in many parts of the world, especially in the United States and Europe, because of increased infection with HPV type 16 (HPV16). In the United States it is estimated that more than 60 percent of current cases of oropharyngeal cancer are due to HPV16.  Persistent infection with HPV16 induces cellular changes that lead to cancer. HPV E6 is one of the viral genes that contribute to tumor formation. Previous [...]

2013-06-18T12:16:01-07:00June, 2013|Oral Cancer News|

Sexual Activity–Related Outcomes After Human Papillomavirus Vaccination of 11- to 12-Year-Olds

Source: PediatricsPublished Online: October 15, 2012By: Robert A. Bednarczyk, PhD, Robert Davis, MD, MPH, Kevin Ault, MD, Walter Orenstein, MD, and Saad B. Omer, MBBS, PhD, MPH   ABSTRACT: OBJECTIVE: Previous surveys on hypothesized sexual activity changes after human papillomavirus (HPV) vaccination may be subject to self-response biases. To date, no studies measured clinical markers of sexual activity after HPV vaccination. This study evaluated sexual activity–related clinical outcomes after adolescent vaccination. METHODS: We conducted a retrospective cohort study utilizing longitudinal electronic data from a large managed care organization. Girls enrolled in the managed care organization, aged 11 through 12 years between July 2006 and December 2007, were classified by adolescent vaccine (HPV; tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis, adsorbed; quadrivalent meningococcal conjugate) receipt. Outcomes (pregnancy/sexually transmitted infection testing or diagnosis; contraceptive counseling) were assessed through December 31, 2010, providing up to 3 years of follow-up. Incidence rate ratios comparing vaccination categories were estimated with multivariate Poisson regression, adjusting for health care–seeking behavior and demographic characteristics. RESULTS: The cohort included 1398 girls (493 HPV vaccine–exposed; 905 HPV vaccine–unexposed). Risk of the composite outcome (any pregnancy/sexually transmitted infection testing or diagnosis or contraceptive counseling) was not significantly elevated in HPV vaccine–exposed girls relative to HPV vaccine–unexposed girls (adjusted incidence rate ratio: 1.29, 95% confidence interval [CI]: 0.92 to1.80; incidence rate difference: 1.6/100 person-years; 95% CI: −0.03 to 3.24). Incidence rate difference for Chlamydia infection (0.06/100 person-years [95% CI: −0.30 to 0.18]) and pregnancy diagnoses (0.07/100 person-years [95% CI: −0.20 to 0.35]), indicating little [...]

2013-06-17T11:03:53-07:00June, 2013|Oral Cancer News|
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