Resveratrol Selectively Induces DNA Damage, Independent of Smad4 Expression, in Its Efficacy against Human Head & Neck Squamous Cell Carcinoma

Source: Clinical Cancer Research Author: Robert A. Sclafani, University of Colorado School of Medicine, Campus Box 8101, Room 9100, Aurora, CO 80045. Phone: 303-724-3271; Fax: 303-724-3215; E-mail:[email protected]   Abstract Purpose: Alterations in Smad4 signaling and its loss cause genomic instability and head and neck squamous cell carcinoma (HNSCC), suggesting that agents that target both Smad4-dependent and -independent pathways could control HNSCC. Experimental Design: Resveratrol efficacy was evaluated against the HNSCC cells FaDu, Cal27, Det562, and Cal27-Smad4 for viability, DNA damage, cell-cycle progression, and apoptosis, as well as γ-H2AX expression, and focus formation (γ-H2AX and Brca1). Resveratrol efficacy was also examined in nude mice for FaDu xenograft growth. Xenografts were analyzed for γ-H2AX and cleaved caspase-3. Results: Resveratrol (5–50 μmol/L) suppressed viability and induced DNA damage in FaDu and Cal27 cells but not in normal human epidermal keratinocytes and human foreskin fibroblasts, showing its selectivity toward HNSCC cells; however, Det562 cells were resistant to resveratrol even at 100 μmol/L. Cal27 cells stably transfected withSmad4 showed similar resveratrol effects as parental Cal27, indicating that a lack of resveratrol effect in Det562 cells was independent of Smad4 status in these cells. Furthermore, resveratrol caused S-phase arrest and apoptotic death of FaDu and Cal27 cells together with induction of Brca1 and γ-H2AX foci. Resveratrol (50 mg/kg body weight) treatment also inhibited FaDu tumor growth in nude mice, and γ-H2AX and cleaved caspase-3 were strongly increased in xenografts from resveratrol-treated mice compared with controls. Conclusion: Our findings for the first time showed antiproliferative, DNA damaging, and apoptotic effects of resveratrol in [...]

2011-08-15T10:20:48-07:00August, 2011|Oral Cancer News|

Laser Surgery On Tongue Cancer Successful for Aerosmith Musician

Source: KSAT Author: Brian Mylar Aerosmith Musician Shows Progress Fighting Cancer SAN ANTONIO -- Aerosmith will be performing in Mexico and South America this fall and one of the band members will be along for the tour thanks to a radical medical procedure. In one Aerosmith song, bassist Tom Hamilton sends a message to his throat and tongue cancer with the lyrics "you've got no business with me." Five years ago, Hamilton underwent chemotherapy and radiation for tongue-base cancer, but it came back and extended into his voice box. That is when he turned to Dr. Steven Zeitels. "This is not your classic way, or even traditional way, to try and remove a cancer from the tongue base," Zeitels said. Radical surgery was now Hamilton's only option. But that could leave his voice and breathing passage permanently damaged. "I was just terrified," Hamilton said. "I really though, 'Oh, I am looking at not being able to talk.'" Zeitels has treated vocal cord cancer with the green-light KTP laser, so Hamilton agreed to be the first person treated that way for tongue base cancer. The laser emits a green light, which is concentrated in the extra blood running through the cancer. "Where there is a lot of cancer, there will be a lot of blood," Zeitels said. "Where there is a lot of blood, there will be a lot of combustion so that you are actually watching the tissues burn completely different" But not everyone is a candidate for this surgery. [...]

2011-08-08T16:41:44-07:00August, 2011|Oral Cancer News|

Ischemic Stroke, Transient Ischemic Attack after Head & Neck Radiotherapy

Source: AHA Journals Author: Chris Plummer, PhD; Robert D. Henderson, PhD; John D. O'Sullivan, MD; Stephen J. Read, PhD Abstract Background and Purpose—Cerebrovascular disease can complicate head and neck radiotherapy and result in transient ischemic attack and ischemic stroke. Although the incidence of radiation vasculopathy is predicted to rise with improvements in median cancer survival, the pathogenesis, natural history, and management of the disease are ill defined. Methods—We examined studies on the epidemiology, imaging, pathogenesis, and management of medium- and large-artery intra- and extra-cranial disease after head and neck radiotherapy. Controlled prospective trials and larger retrospective trials from the last 30 years were prioritized. Results—The relative risk of transient ischemic attack or ischemic stroke is at least doubled by head and neck radiotherapy. Chronic radiation vasculopathy affecting medium and large intra- and extra-cranial arteries is characterized by increasing rates of hemodynamically significant stenosis with time from radiotherapy. Disease expression is the likely consequence of the combined radiation insult to the intima-media (accelerating atherosclerosis) and to the adventitia (injuring the vasa vasorum). Optimal medical treatment is not established. Carotid endarterectomy is confounded by the need to operate across scarred tissue planes, whereas carotid stenting procedures have resulted in high restenosis rates. Conclusions—Head and neck radiotherapy significantly increases the risk of transient ischemic attack and ischemic stroke. Evidence-based guidelines for the management of asymptomatic and symptomatic (medium- and large-artery) radiation vasculopathy are lacking. Long-term prospective studies remain a priority, as the incidence of the problem is anticipated to rise with improvements in [...]

2011-08-08T12:12:22-07:00August, 2011|Oral Cancer News|

Convergence in Head and Neck Cancer

Source: Eurekalert.org Powerful new technologies that zoom in on the connections between human genes and diseases have illuminated the landscape of cancer, singling out changes in tumor DNA that drive the development of certain types of malignancies such as melanoma or ovarian cancer. Now several major biomedical centers have collaborated to shine a light on head and neck squamous cell cancer. Their large-scale analysis has revealed a surprising new set of mutations involved in this understudied disease. In back-to-back papers published online July 28 in Science, researchers from the Broad Institute, Dana-Farber Cancer Institute, Johns Hopkins Kimmel Cancer Center, the University of Pittsburgh, and the University of Texas MD Anderson Cancer Center have confirmed genetic abnormalities previously suspected in head and neck cancer, including defects in the tumor suppressor gene known as p53. But the two teams also found mutations in the NOTCH family of genes, suggesting their role as regulators of an important stage in cell development may be impaired. "This adds a new dimension to head and neck cancer biology that was not on anyone's radar screen before," said Levi A. Garraway, a senior associate member of the Broad Institute, an assistant professor at Dana-Farber Cancer Institute and Harvard Medical School, and a senior author of one of the Science papers. "Head and neck cancer is complex and there are many mutations, but we can infer there is a convergence on a cellular process for which we previously did not have genetic evidence. It shows that if you [...]

Head and Neck Cancer Study

Source: American Journal of Neuroradiology BACKGROUND AND PURPOSE: Radiographic determination of viable disease in cervical adenopathy following RT for head and neck cancer can be challenging. The purpose of this study was to evaluate the utility of US, with or without FNA, in regard to the postradiotherapy effects on documented metastatic adenopathy in patients with oropharyngeal cancer. MATERIALS AND METHODS: This study included 133 patients with node-positive oropharyngeal cancer who were irradiated from 1998 to 2004. Sonographic evaluation was performed within 6 months of completion of radiation. Posttreatment US results were compared with pretreatment CT images and were recorded as the following: progression, suspicious, indeterminate, posttreatment change, or regression (positive) versus nonsuspicious or benign (negative). FNAC was classified as nondiagnostic, negative, indeterminate, or positive. Results of US and US-guided FNAC were correlated with findings at neck dissection and disease outcome. RESULTS: Of 203 sonographic examinations, 90% were technically feasible and yielded a nonequivocal imaging diagnosis. Of 87 US-guided FNAs, 71% yielded a nonequivocal tissue diagnosis. The PPV and NPV of initial posttreatment US were 11% and 97%. Sensitivity and specificity were 92% and 28%. The PPV and NPV of US-guided FNA were 33% and 95%, and the sensitivity and specificity were 75% and 74%. On serial sonographic surveillance, of 33 patients with nonsuspicious findings, only 1 (3%) had neck recurrence. Of 22 patients with questionable findings on CT and negative findings on US, none had a neck recurrence. CONCLUSIONS: In experienced hands, serial US is an inexpensive noninvasive reassuring follow-up [...]

$1 Million Donated for Head and Neck Cancer Research at Ohio State University Comprehensive Cancer Center

Source: Ohio State University- James Cancer Center COLUMBUS, Ohio – Two siblings are honoring their deceased parents by pledging $1 million to create an endowed chair in head and neck cancer research at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC– James). Ron Alford of Westerville, Ohio, along with his sister Barb Cantlin and her husband Mike of Newark, Ohio, have pledged the additional funding over the next four years. Their $1 million pledge adds to the original $500,000 donation made by John Alford to create the first research endowment at The James shortly after the free-standing cancer hospital opened in July 1990. After his wife died of stomach cancer in 1987, John Alford chose to honor her memory by creating the Mary E. Alford Cancer Research Endowment Fund for cancer research at The James. When John Alford died of esophageal cancer in 1996, his children donated an additional $500,000 to create the Mary E. and John W. Alford Cancer Research Endowment Fund at The James. With the latest gift pledge, once the fund reaches $2 million it will be renamed the Mary E. and John W. Alford Research Chair in Head and Neck Cancer. “The level of support shown by the Alford family through the years to The James is a testament to their lifelong mission of trying to improve and enhance the lives of others,” says Dr. Michael Caligiuri, director of Ohio State’s Comprehensive Cancer Center [...]

Can HPV Vaccine Prevent Oral Cancer?

Source: WebMD.com June 23, 2011 -- Can HPV vaccines stop the explosive rise of HPV-related head and neck cancer? HPV (human papillomavirus) vaccines protect against the sexually transmitted strains of HPV that cause cervical cancer. The same HPV strains -- spread by kissing and by oral sex -- cause oropharyngeal (OP) cancer, the form of head and neck cancer that affects the back and sides of the throat, the base of the tongue, and the tonsils. There's strong evidence that HPV vaccines prevent cervical cancer. There's no direct proof that these vaccines prevent throat cancer, but the rapid rise in cases among young people has some experts wanting to vaccinate first and get proof later. "We don't need to wait until all these molecular events are understood," Dong Moon Shin, MD, of Emory University's Winship Cancer Center, tells WebMD. "The time is now. For the HPV vaccine, cost is the only issue as side effects are minimal. Routine HPV vaccination has to be implemented very soon, for both boys and girls." In the U.S., that recommendation is made by the Advisory Committee on Immunization Practices (ACIP). The ACIP now recommends routine HPV vaccination only for girls and young women in order to prevent cervical cancer. It permits vaccination of boys who want protection against HPV-caused genital warts. For two years, the ACIP has been mulling whether to recommend the HPV vaccine for boys. This would help prevent cervical cancer in unvaccinated women. It also would prevent HPV-related anal cancer and [...]

Oral, Head and Neck Cancers Continue to Increase While Most U.S. Cancer Death Rates are on the Decline

Source: SHOTS (NPR's Health Blog) The rate at which Americans die from cancer continues to fall, according to the latest estimates from the American Cancer Society. As a result, nearly 900,000 cancer deaths were avoided between 1990 and 2007, the group figures. Survival gains have come as mortality rates have declined for some of the most common malignancies, including colorectal cancer, breast cancer in women and prostate cancer. Still, the ACS estimates there will nearly 1.6 million new cancers diagnosed this year, and about 572,000 deaths from the disease. The incidence of cancers hasn't budged much for men in recent years, after falling quite a bit during the first half of the last decade. Cancer incidence for women has been falling since 1998. The report was just published online by CA: A Cancer Journal for Clinicians. Lung cancer remains the biggest killer for both men and women. All told, about 160,000 people in the U.S. are expected to die from it this year. Starting in 1987, more women have died from lung cancer each year than breast cancer. One section of the report focuses on a persistent and, in some cases, widening gap in cancer death rates between people with the least education and those with the most. Educational attainment is often used in research as a proxy for socioeconomic status. American Cancer Society epidemiologist Elizabeth Ward, one of the report's authors, tells Shots, "People of a lower socioeconomic status are more likely to smoke and less likely to get [...]

Glowing Cornell Dots Target Cancer

SOURCE: Journal of Clinical Investigation, June 13, 2011 (Ivanhoe Newswire)-- New medical technology is showing that Cornell dots may be a potential cancer diagnostic tool. The U.S Food and Drug Administration (FDA) has recently approved the first clinical trial in humans using Cornell Dots- brightly glowing nanoparticles that can light up cancer cells in PET-optical imaging. Cornell Dots are silica spheres less than eight nanometers in diameter that enclose several dye molecules. To make the dots stick to tumor cells, organic molecules that bind to tumor surfaces, or even specific locations within the tumors, can be attached to a polyethylene glycol shell. This shell, also referred to as PEG, prevents the body from recognizing the dots as foreign substances. When exposed to near-infrared light, the dots fluoresce much brighter than dye to serve as a beacon identifying the target cells. Researchers say this technology enables visualization during surgical treatment. Cornell Dots were first developed in 2005 by Hooisweng Ow, a coauthor of the paper on this study and once a graduate student working with Ulrich Wiesner, Cornell Professor of Materials Science and Engineering. Ow and other researchers of this technology are currently in the process of forming a new commercial entity in New York City that will help transition this research into commercial products that will benefit cancer patients. Michelle S. Bradbury, M.D, of the Memorial Sloan-Kettering Cancer Center and an assistant professor of radiology at Weill Cornell Medical College, was quoted as saying, "This is the first FDA IND approved [...]

2011-06-15T11:14:48-07:00June, 2011|Oral Cancer News|

Palifermin Decreases Severe Oral Mucositis of Patients Undergoing Postoperative Radiochemotherapy for Head and Neck Cancer: A Randomized, Placebo-Controlled Trial

Source: Journal of Clinical Oncology Purpose: Radiochemotherapy of head and neck cancer causes severe mucositis in most patients. We investigated whether palifermin reduces this debilitating sequela. Methods: We conducted a multicenter, double-blind, randomized, placebo-controlled trial in 186 patients with stages II to IVB carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx. Patients received 60 or 66 Gy after complete (R0) or incomplete resection (R1), respectively, at 2 Gy/fraction and five fractions per week. Cisplatin 100 mg/m2 was administered on days 1 and 22 (and on day 43 with R1). Patients were randomly assigned to receive weekly palifermin 120 μg/kg or placebo from 3 days before and continuing throughout radiochemotherapy. Trained evaluators performed oral assessments twice weekly. The primary end point was the incidence of severe oral mucositis (WHO grades 3 to 4). Overall survival and time to locoregional progression were also assessed. Analysis was by intention to treat. Results: Severe oral mucositis was seen in 47 (51%) of 92 patients administered palifermin and 63 (67%) of 94 administered placebo (P = .027). Palifermin decreased the duration (median, 4.5 v 22.0 days) and prolonged the time to develop (median, 45 v 32 days) severe mucositis. Neither patient-reported mouth and throat soreness scores nor treatment breaks differed between treatment arms. After median follow-up of 32.8 months, 23 deaths (25%) had occurred in both treatment arms, and disease had recurred in 25 (27%) and 22 (24%) of palifermin- and placebo-treated patients, respectively. Conclusion: Palifermin reduced the occurrence of severe oral mucositis in [...]

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