Clinical Evaluation of a New Molecular Method for Detection of Micrometastases in Head and Neck Squamous Cell Carcinoma

8/1/2004 Carol G. Shores, MD, PhD; Xiaoying Yin, MD; William Funkhouser, MD; Wendell Yarbrough, MD Otolaryngology & Head Neck Surg. Objective To better detect occult cervical metastases. Design RNA from 153 cervical lymph nodes was analyzed for the presence of squamous cell carcinoma using quantitative cytokeratin (CK) 14 real-time reverse transcription polymerase chain reaction (RT-PCR). Detection of CK RNA in pathologically negative nodes was further analyzed by semi-step sectioning and CK immunohistochemistry. Subjects Thirteen consecutive patients with head and neck squamons cell carcinoma (HNSCC) presenting to the Department of Otolaryngology/Head and Neck Surgery of the University of North Carolina at Chapel Hill for neck dissection. Results Cytokeratin detection was deemed nonspecific if expressed at fewer than 50 molecules of CK 14 RNA per nanogram total RNA. Of 35 HNSCCs, 33 expressed CK 14 RNA, and 15 lymph nodes with routine pathologically positive metastasis were also positive for CK 14 RNA. Four lymph nodes that were pathologically negative nodes were positive for CK 14 RT-PCR, with 2 containing metastases detected by semi-step sectioning. Conclusions Cytokeratin 14 RT-PCR is very sensitive for detecting micrometastasis in lymph nodes that are negative by routine pathological examination, with a relatively high false-positive rate. Quantitative CK 14 RT-PCR could be used to identify nodes negative for tumor by standard pathological analysis that should be examined by step sectioning and CK immunohistochemistry. Identification of micrometastases in patients with HNSCC will allow for appropriate and aggressive treatment of patients with metastatic disease. Source: Arch Otolaryngol Head Neck Surg. [...]

2009-03-22T23:40:07-07:00August, 2004|Archive|

Genetic Patterns in Head and Neck Cancers That Contain or Lack Transcriptionally Active Human Papillomavirus

8/1/2004 See end of article for authors Journal of the National Cancer Institute Background: Transcriptionally active high-risk human papilloma viruses (HPVs), particularly HPV type 16 (HPV16), are found in a subset of head and neck squamous-cell carcinomas (HNSCCs). HPV16-associated carcinogenesis is mediated by expression of the viral E6 and E7 oncoproteins, which cause deregulation of the cell cycle by inactivating p53 and pRb, respectively. We tested the hypothesis that HPV-associated HNSCCs display a pattern of genetic alterations different from those of HNSCCs without HPV DNA. Methods: Polymerase chain reaction-based assays were used to examine 143 consecutive HNSCCs (106 of the oral cavity and 37 of the oropharynx) for the presence of HPV DNA and for viral E6 and/or E7 messenger RNA (mRNA) expression. The HPV DNA-and E6 and E7 mRNA-positive HNSCCs and an equal number of HPV DNA-negative HNSCCs were further analyzed for mutations in TP53, the gene encoding p53, and for allelic loss of 28 microsatellite markers at chromosome arms 3p, 6q, 8p, 9p, 13q, 17p, and 18q, including markers located in regions of chromosome arms 9p and 17p that harbor genes involved the p53 and pRb pathways. All statistical tests were two-sided. Results: Twenty-four (16.7%) of the 143 HNSCCs were positive for HPV16 DNA, and 12 of these HNSCCs (8.4% of total number) expressed E6 and E7 mRNAs. None of the HPV DNA-and E6/E7 mRNA-positive tumors had TP53 gene mutations, whereas nine (75%) of the 12 HPV DNA-negative tumors had such mutations (P<.001). Compared with the HPV DNA-negative [...]

2009-03-22T23:39:35-07:00August, 2004|Archive|

Susan T. Buffett, 72, Dies; Wife of Billionaire Investor

7/30/2004 Cody, WY By Matt Schudel Washington Post Susan Thompson Buffett, 72, the wife of billionaire investor Warren Buffett and, in her own right, the 17th richest woman in the world, died July 29 of a stroke while visiting friends in Cody, Wyo. She and Buffett, whose net worth of about $41 billion makes him the second richest man in the world after Bill Gates, were married in 1952 but had lived apart since 1977. Her primary residence was in San Francisco, while he stayed in the house they had bought together in Omaha in 1958. They remained on friendly terms and often traveled together. Warren Buffett was with his wife at a Cody hospital at the time of her death. Mrs. Buffett was a director of Berkshire Hathaway, her husband's holding company, and was president of the Buffett Foundation, which has contributed millions of dollars for education, medical research, population control and other charities. The foundation was criticized by abortion protesters in the 1990s for funding the RU-486 "abortion pill" and groups supporting abortion rights. She was known for her progressive views, had worked for civil rights and volunteered to help people in low-income housing. In evaluating organizations for possible contributions, Mrs. Buffett told the Omaha World-Herald last year in a rare interview, she sought people "who have heart and soul, the ability to organize and also to inspire -- a rare combination." Her shares in her husband's company have a current value of about $3 billion, which made [...]

2009-03-22T23:38:29-07:00July, 2004|Archive|

Patients who received three-drug combination show improved results

7/30/2004 CHICAGO, IL Journal Abstract Journal of Hemotoogy Adding paclitaxel to a cisplatin and 5-fluorouracil (5-FU) regimen led to significantly longer survival in patients with locally advanced head and neck cancer, according to a phase-3 study presented here at the Annual Meeting of ASCO. “This new chemotherapy combination may soon become the standard treatment option for some patients with head and neck cancer,” said lead researcher Ricardo Hitt, MD, from the Hospital '12 de Octubre' in Madrid. The expanded combination also halted tumor progression more effectively than the standard regimen, and patients who received the three-drug combination were more likely to retain the ability to speak and swallow, as well as exhibit less mucocitis. The study involved 384 patients who had various types of head and neck cancer, particularly tumors of the oropharynx, larynx and oral cavity. All patients were treatment naive. In the standard arm, patients received 100 mg/m2 of cisplatin daily, and 1 gm/m2 of 5-FU on days 1 through 5 of a 21-day cycle. In the expanded regimen, patients received 100 mg/m2 of cisplatin daily, 500 mg/m2 of 5-FU on days 1 through 5, and 175 mg/m2 of paclitaxel on the first day of a 21-day cycle. The trial “appeared to demonstrate a superior outcome and far better tolerability by adding paclitaxel to 5-FU and cisplatin for head and neck cancer in a dose schedule associated with less toxicity,” said Robert Mayer, MD, the director of the Center for Gastrointestinal Oncology at Dana-Farber Cancer Institute in Boston.

2009-03-22T23:38:00-07:00July, 2004|Archive|

TOBACCO CARCINOGENS, THEIR BIOMARKERS AND TOBACCO-INDUCED CANCER

7/30/2004 By Stephen S. Hecht Nature Reviews Cancer, Volume 3, #10 Preface The devastating link between tobacco products and human cancers results from a powerful alliance of two factors — nicotine and carcinogens. Without either one of these, tobacco would be just another commodity, instead of being the single greatest cause of death due to preventable cancer. Nicotine is addictive and toxic, but it is not carcinogenic. This addiction, however, causes people to use tobacco products continually, and these products contain many carcinogens. What are the mechanisms by which this deadly combination leads to 30% of cancer-related deaths in developed countries, and how can carcinogen biomarkers help to reveal these mechanisms? Summary * Tobacco products cause a variety of cancers, including those of the lung, oral cavity, nasal cavity, larynx, oropharynx, hypopharynx, oesophagus, stomach, liver, pancreas, bladder, ureter, kidney and cervix, and myeloid leukaemia. The carcinogens contained in tobacco products are responsible for these cancers. * There are more than 60 carcinogens in cigarette smoke and at least 16 in unburned tobacco. Among these, tobacco-specific nitrosamines (such as 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N'-nitrosonornicotine (NNN)), polycyclic aromatic hydrocarbons (such as benzo[a]pyrene) and aromatic amines (such as 4-aminobiphenyl) seem to have an important role as causes of cancer. * Carcinogen biomarkers — DNA adducts, protein adducts and urinary metabolites — provide objective measures of carcinogen uptake and metabolic activation and detoxification in people who use, or are otherwise exposed to, tobacco products. * DNA adducts are central to the carcinogenic process as induced by tobacco [...]

2009-03-22T23:37:31-07:00July, 2004|Archive|

Sore throat was first sign of oral cancer

7/29/2004 Oakland, MI By CASEY CURTIS The Daily Oakland Press Dave Nilson's sore throat lasted almost six months. Assuming it would go away without treatment was his biggest mistake. The pain - which began to spread to his neck and caused a small lump in his mouth - stayed. Eventually, the 44-year-old Troy resident went to his doctor for an examination and was sent home with antibiotics for strep throat. When the lump grew larger over a two week period, Nilson's doctor referred him to an oral cancer specialist who performed a biopsy. On Christmas Eve of 2002, Nilson received the devastating news that the lump was in fact stage three - almost the last stage - of squamous cell carcinoma. Never having smoked, chewed tobacco or drank alcohol, Nilson was utterly overwhelmed. Just a couple of years earlier, Nilson had lost his sister to melanoma and feared the worst. "I was thinking, 'Oh my God, you're going to die, too,' " he says. In February 2003, Nilson underwent a 15-hour procedure to have tissue, several lymph nodes and 60 percent of his tongue removed. His jaw was cracked in half to remove the affected areas and muscle from his chest was stretched upward to replace the tissue lost on the right side of his neck. Everything seemed to be going well, but Nilson developed "deadbone" in his jaw. That meant blood was not flowing to the bone. It restricted him from talking, eating and sometimes breathing. Nilson was given [...]

2009-03-22T23:36:57-07:00July, 2004|Archive|

The Ultimate Cancer Survivor

7/24/2004 The Washington Post Lance Armstrong has seen what W.B. Yeats called "The Cold Heaven". So even on the day that he is expected to cross the finish line in Paris, having beaten all the Spaniards, Italians and French, and after climbing peaks in the face of spitting Germans, sceptics, accusers and naysayers, what Armstrong will prefer that people remember him for was not his sixth Tour de France victory, but his near-death experience. It remains his most significant accomplishment: he lived. Six Tour de France titles is an epic achievement. In 100 years, no one has ever done such a thing; in fact, there's probably no other feat in sport to which it can be compared for sheer effort, pain, will and character. Armstrong rode more than 3200 kilometres over mountains, skirting oceans, in heat and hail, enduring physical and mental agonies. But the size of the record makes it all the more important to see Armstrong in small ways. That phrase "best ever" threatens to detach him from his central humanity; the trouble with becoming a sports immortal is that it puts him at a remove. That's the last thing Armstrong wants, because to him, his most essential quality is his most ordinary one. What's important about Armstrong is what binds him to the rest of us: he has suffered. He has been sick, wounded and tired with cancer. "Listen, I was there," he says. "I haven't forgot it. And I still use it. It's not always easy [...]

2009-03-22T23:36:15-07:00July, 2004|Archive|

Optical Wand used to detect cervical cancer

7/24/2004 Austin, TX By Linda Marsa LA TIMES An experimental imaging tool could lead to faster diagnosis, fewer false positive results and better follow-up than the current colposcopy. For many women, suspicious results from a cervical cancer screening may be just the beginning of a lengthy, and anxiety-filled, diagnostic process. They often must undergo a couple of follow-up tests and wait several weeks before receiving a definite answer. Not only could an experimental fiber optic device help doctors make a diagnosis much more efficiently than current methods, it also may eventually enable them to do on-the-spot treatment. “This tool could be a real advance over what we have,” says Dr. Daniel C. Sullivan, head of the cancer imaging program for the National Cancer Institute in Bethesda, Md. “It has the potential to be cheaper, quicker, and more accurate.” Every year, about 13,000 American women are diagnosed with cervical cancer, which has a 92% survival rate if treated in its early stages. The conventional screening for cervical cancer is a Pap smear, in which a swab of cervical tissue is examined under a microscope by a trained technician. When abnormal cells are detected, gynecologists visually inspect the cervix using a colposcope, a large electric microscope attached to a bright light. If they see abnormal cells, they'll perform a biopsy, in which a tissue sample is snipped from the cervix and shipped to a lab for further evaluation. However, colposcopy results are prone to human error: Cancers can be missed, or, in [...]

2009-03-22T23:35:06-07:00July, 2004|Archive|

Smoke signals

7/30/2004 By Oliver Childs Nature Biology, Voulume 4, Number 8 Smokers die an average 10 years earlier than non-smokers; so concludes a landmark study published in the British Medical Journal (26 June 2004). This and other findings of the now-famous prospective study of the long-term smoking habits of over 34,000 British male doctors are the culmination of 50-years research into the effects of cigarette smoking in this cohort. "Since the study began in 1951, tobacco has killed around 100 million people globally", commented Alex Markham of Cancer Research UK (http://news.bbc.co.uk, 25 June 2004). But quantification of the risk of smoking has been limited. The results of this study provide some sobering facts and figures for smokers: "It is clear that consistent cigarette smoking doubles mortality throughout adult life" (Reuters, 22 June 2004), remarked Richard Doll, the Oxford University professor who initiated the study and first discovered the link between smoking and lung cancer. However, the news is not all bad: "... we also know that stopping smoking will significantly limit the harm" (San Francisco Chronicle, 23 June 2004), said Richard Peto, Doll's 30-year colleague on the study. In fact, the study found that stopping smoking at age 50 added 6 years to life expectancy. Furthermore, stopping before the age of 30 avoids almost all hazard associated with smoking. The study conclusions are stark for those who continue to smoke, but also signal to those who are keen on quitting that it is not too late to do so. As Peto remarked, [...]

2009-03-22T23:39:01-07:00July, 2004|Archive|

Buffetts’ donation aids cancer research

7/20/2004 Onaha, NB BY STEVE JORDON Omaha World-Herald Omaha investor Warren Buffett and his wife, Susan, have donated $6 million for research in appreciation of the treatment for mouth cancer that Susan Buffett received last fall, resulting in her "remarkable recovery." "Mrs. Buffett is doing extremely well, and we're all very pleased that she has been able to resume her normal life activities," said Dr. David Eisele, professor at the University of California-San Francisco. Last October, Dr. Deborah Greenspan, a professor of clinical oral medicine at the university's medical center, found a "disturbing growth" at the base of Susan Buffett's mouth, the medical center said in a public notice. Greenspan referred Buffett to Dr. Brian Schmidt, an assistant professor of oral and maxillofacial surgery, who diagnosed her condition as potentially life-threatening cancer. Buffett met with Eisele, chairman of otolaryngology and head and neck surgery, who set up a treatment plan involving surgery and post-operative therapy through the medical center's cancer center. "Because of the seriousness of her diagnosis, Buffett spoke with specialists at a number of renowned cancer centers across the country," the medical center said. "She was relieved to learn that Eisele's plan would provide her with top-quality care close to her home in San Francisco." Eisele led the tumor-removal surgery, followed by surgery by Dr. Pablo Leon, an assistant professor of plastic and reconstructive surgery. Six weeks of radiation therapy conducted by Dr. Jeanne Quivey followed. The medical center credited the treatment team and "Buffett's own courage and [...]

2009-03-22T23:34:25-07:00July, 2004|Archive|
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