Monthly Archives: May 2006

Revolution In The Fight Against Cancer & Viruses

  • 5/31/2006
  • Australia
  • press release
  • Biocompare.com

A recent scientific discovery could herald the introduction of fast, effective treatments for cancer and viruses.

In a paper published in the May edition of Nature Biotechnology, scientists describe how they have manipulated a process that occurs naturally throughout the human body, into a potential therapeutic tool.

“The process, called RNA interference, blocks the production of proteins that create cancer and viruses,” said research leader and Director of the Monash Institute of Medical Research (MIMR), Professor Bryan Williams.

“We’ve exploited this process by creating short interfering RNA, or siRNA, that are being developed into drugs to fight viruses and cancer,” he said. “We’ve now taken this a step further and worked out how we can create siRNA with different cellular properties to target different diseases.”

While previous studies had demonstrated siRNA had the potential to be a potent anti-cancer and anti-viral agent, Professor Williams had shown there was a danger siRNA-based drugs could cause a dangerous inflammatory response.

Professor Williams and his team have now discovered the physical structure of siRNA are key to creating effective anti-cancer and anti-viral drugs. This will allow both the development of siRNA-based drugs to react differently for different diseases.

“By ‘tweaking’ the structure of siRNA to target specific diseases, we can dictate whether we want a particular siRNA-based drug to block or promote an immune response, to increase the effectiveness of the treatment,” he said.

“While our research is at an early stage, human trials using siRNA are currently underway in the USA and Europe. We’re confident our have a significant impact on the way siRNA is being developed as a weapon in the fight against viruses and cancer,” said Professor Williams.

May, 2006|Archive|

Transfection of oral squamous cell carcinoma with human papillomavirus-16 induces proliferative and morphological changes in vitro

  • 5/29/2006
  • Palo Alto, CA
  • Karl Kingsley et al.
  • Cancer Cell Int, May 22, 2006; 6(1): 14

Background:
Human papillomavirus has been implicated in virtually all cervical cancers and is believed to be the primary etiological factor that transforms cervical epithelia. The presence of HPV in oral cancers suggests that HPV may play a similar role in transforming the oral epithelia.

The prevalence of HPV in oral cancers is highly variable, however, presenting problematic issues regarding the etiology of oral cancers, which must be investigated more thoroughly. Past analyses of HPV in cancers of the oral cavity have largely been confined to retrospective studies of cancer patients.

The purpose of this study was to examine the potential for HPV16 infection to alter the proliferative phenotype of oral squamous cell carcinoma in vitro.

Results:
This study found that the oral squamous cell carcinoma cell line, CAL27, transfected with HPV16, exhibited significantly increased proliferation, compared with non-transfected CAL27. The increased proliferation was observed under low density conditions, even in the absence of serum. Moreover, these effects were specific to proliferation, adhesion, and morphology, while cell viability was not affected.

Conclusion:
This study represents one of the first investigations of the effects of HPV16 infection on the proliferation, adhesion, and morphology of an oral squamous cell carcinoma cell line in vitro. The finding that HPV16 has the ability to measurably alter adhesion and proliferative potential is significant, indicating that HPV may have multiple influences on precancerous and cancerous lesions and should be explored as a risk factor and mediator of cancer phenotypes. These measurements and observations will be of benefit to researchers interested in elucidating the mechanisms of oral cancer transformation and the factors governing carcinogenesis and progression.

Authors:
Karl Kingsley, Devin Johnson, and Susan O’malley

May, 2006|Archive|

IMRT using simultaneously integrated boost (SIB) in head and neck cancer patients

  • 5/29/2006
  • Zurich, Switzerland
  • G Studer et al.
  • Radiat Oncol, January 1, 2006; 1(1): 7

Background:
Preliminary very encouraging clinical results of intensity modulated radiation therapy (IMRT) in Head Neck Cancer (HNC) are available from several large centers. Tumor control rates seem to be kept at least at the level of conventional three-dimensional radiation therapy; the benefit of normal tissue preservation with IMRT is proven for salivary function.

There is still only limited experience with IMRT using simultaneously integrated boost (SIB-IMRT) in the head and neck region in terms of normal tissue response.

The aim of this work was (1) to establish tumor response in HNC patients treated with SIB-IMRT, and (2) to assess tissue tolerance following different SIB-IMRT schedules.

Results:
Between 1/2002 and 12/2004, 115 HNC patients have been curatively treated with IMRT. 70% received definitive IMRT (dIMRT), 30% were postoperatively irradiated. In 78% concomitant chemotherapy was given.SIB radiation schedules with 5-6 x 2 Gy/week to 60-70 Gy, 5 x 2.2 Gy/week to 66-68.2 Gy (according to the RTOG protocol H-0022), or 5 x 2.11 Gy/week to 69.6 Gy were used.

After mean 18 months (10-44), 77% of patients were alive with no disease. Actuarial 2-year local, nodal, and distant disease free survival was 77%, 87%, and 78%, respectively. 10% were alive with disease, 10% died of disease. 20/21 locoregional failures occurred inside the high dose area. Mean tumor volume was significantly larger in locally failed (63 cc) vs controlled tumors (32 cc, p <0.01), and in definitive (43 cc) vs postoperative IMRT (25 cc, p <0.05); the locoregional failure rate was twofold higher in definitively irradiated patients.

Acute reactions were mild to moderate and limited to the boost area, the persisting grade 3/4 late toxicity rate was low with 6%. The two grade 4 reactions (dysphagia, laryngeal fibrosis) were observed following the SIB schedule with 2.2 Gy per session.

Conclusion:
SIB-IMRT in HNC using 2.0, 2.11 or 2.2 Gy per session is highly effective and safe with respect to tumor response and tolerance. SIB with 2.2 Gy is not recommended for large tumors involving laryngeal structures.

Authors:
G Studer, P Huguenin, J Davis, G Kunz, U Lutolf, and C Glanzmann

Authors’ affiliation:
Department of Radiation Oncology, University Hospital, Zurich, Switzerland

May, 2006|Archive|

Clinical significance of serum p53 antibodies in oral cancer

  • 5/29/2006
  • Ahmedabad, India
  • RN Sainger et al.
  • Tumori, March 1, 2006; 92(2): 134-9

Aim and Background:
The incidence and mortality due to oral cancer have increased worldwide. In India, the use of tobacco has been found to be the major etiological factor for the development of oral cancers. Various studies on serum p53 antibodies have suggested their clinical importance as prognostic markers in cancer. However, there is a dearth of data on serum p53 antibodies in oral cancer patients in India. The present study was carried to evaluate the clinical significance of serum p53 antibodies in oral cancer.

Materials and Methods:
The serum p53 antibody status was analyzed by means of ELISA in 55 healthy individuals, 60 patients with oral precancerous conditions, 75 untreated oral cancer patients, and 86 follow-up blood samples of the oral cancer patients.

Results:
We found serum p53 antibodies in 23% of cancer patients.The frequency of p53 antibody positivity was higher in patients with lymph node metastasis, advanced disease and well-differentiated tumors. Furthermore, p53 antibody positivity strongly correlated with poor treatment outcome in cancer patients. Kaplan-Meier survival analysis showed significantly poorer disease-free survival in patients with serum p53 antibodies.

Conclusion:
The results of this study suggest the usefulness of serum p53 antibodies in the prognostication of oral cancer patients.

May, 2006|Archive|

On the natural course of oral lichen lesions in a Swedish population-based sample

  • 5/29/2006
  • London, England
  • Roosaar A, Yin L et al.
  • British Dental Journal (2006); 200, 563

The natural course appeared benign in the great majority of lesions in this cohort.

Oral lichen planus (OLP) is classed as a precancerous condition, but there is conflicting evidence on this matter from different studies. In 1973-4, subjects were investigated for oral mucosal lesions in a Swedish county, and a cohort of 327 with oral lichen lesions (OLLs) was identified. (In 1973-4, no distinction was made between OLP and oral lichenoid reaction, so the two categories were combined as OLL in this study.)

In 1993-4, a sample of 80 subjects still living in the area was selected from the remaining 194, and 55 of them were re-examined. In this sample, 14 of 36 initial white lesions had resolved, while 4 had turned to red lesions. In 19 red lesions, 5 had resolved, and 4 had turned white. No malignancies were observed.

For the whole cohort, in 2002, incidence of specified cancers (SIRs) and mortality from all and specific causes (SMRs) was identified from the excellent Swedish registries, and none was significantly elevated. The authors consider that OLLs carry a low risk of harm.

Source:
J Oral Pathol Med 2006; 35: 257-261

May, 2006|Archive|

Pot’s low cancer risk a surprise finding

  • 5/26/2006
  • Los Angeles, CA
  • Heather Burke, Bloomberg News
  • Seattle Post-Intelligencer (seattlepi.newsource.com)

Marijuana smoke thought to be similar to tobacco

People who smoke marijuana may be at less risk of developing lung cancer than tobacco smokers, according to a new study.

The study of 2,200 people in Los Angeles found that even heavy marijuana smokers were no more likely to develop lung, head or neck cancer than non-users, in contrast with tobacco users, whose risk increases the more they smoke.

The findings are a surprise because marijuana smoke has some of the same cancer-causing substances as tobacco smoke, often in higher concentrations, said the senior researcher, Donald Tashkin, a professor at the David Geffen School of Medicine at the University of California-Los Angeles.

One possible explanation is that THC, a key ingredient in marijuana not present in tobacco, may inhibit tumor growth, he said in an interview.

“You can’t give marijuana a completely clean bill of health,” said Tashkin, who is to present the study to a conference of the American Thoracic Society. “I wouldn’t give any smoke substance a clean bill of health. All you can say is we haven’t been able to confirm our suspicions that marijuana might be a risk factor for lung and head and neck cancer.”

About 1,200 adults under age 60 with cancer of the lung, tongue, mouth, throat or esophagus, took part in the study, as well as about 1,000 without cancer, between 1999 and 2003.

Marijuana use was found to be no greater or less in any of the groups — 44 percent of those with lung cancer, 41 percent with head or neck cancers, and 42 percent of those without cancer, said Tashkin.

Other studies had suggested marijuana smoking was a risk factor for cancer, Tashkin said. Marijuana smokers inhale more deeply than tobacco smokers and often hold the smoke in their lungs more than four times longer, depositing more tar, he said.

The results of Tashkin’s study confirm some earlier research, said Paul Armentano, a senior policy analyst at the National Organization for the Reform of Marijuana Laws, which advocates legalizing marijuana use.

“It’ll be surprising results in light of the way marijuana has been presented for many years by the government and the media, as a cancer-causing agent,” Armentano said.

Dr. Bertha Madras, deputy director for demand reduction at the White House’s drug policy office, said she couldn’t directly comment on the study without seeing the details.

“There is strong evidence that chronic marijuana use can lead to adverse effect on lung function such as increased bronchitis and lung inflammation,” Madras said.

The study was funded by the National Institute on Drug Abuse, Tashkin said.

May, 2006|Archive|

Characterization of RNA in Saliva

  • 5/25/2006
  • Los Angeles, CA
  • Noh Jin Park et al.
  • Clinical Chemistry. 2006;52:988-994.)

Background:
We have previously shown that human mRNAs are present in saliva and can be used as biomarkers of oral cancer. In this study, we analyzed the integrity, sources, and stability of salivary RNA.

Methods:
We measured the integrity of salivary RNA with reverse transcription followed by PCR (RT-PCR) or RT-quantitative PCR (RT-qPCR). To study RNA entry sites into the oral cavity, we used RT-PCR analysis of salivary RNA from the 3 major salivary glands, gingival crevice fluid, and desquamated oral epithelial cells. We measured stability of the salivary ß-actin mRNA by RT-qPCR of salivary RNA incubated at room temperature for different periods of time. We measured RNA association with other macromolecules by filtering saliva through pores of different sizes before performing RT-qPCR. To assess RNA–macromolecule interaction, we incubated saliva with Triton X-100 for different periods of time before performing RT-qPCR.

Results:
In most cases, we detected partial- to full-length salivary mRNAs and smaller amounts of middle and 3′ gene amplicons compared with the 5′. RNA was present in all oral fluids examined. Endogenous salivary ß-actin mRNA degraded more slowly than exogenous ß-actin mRNA, with half-lives of 12.2 and 0.4 min, respectively (P <0.001). Salivary RNA could not pass through 0.22 or 0.45 µm pores. Incubation of saliva with Triton X-100 accelerated degradation of salivary RNA.

Conclusions:
Saliva harbors both full-length and partially degraded forms of mRNA. RNA enters the oral cavity from different sources, and association with macromolecules may protect salivary RNA from degradation.

Authors:
Noh Jin Park1, Yang Li1,3, Tianwei Yu1, Brigitta M.N. Brinkman1 and David T. Wong1,2,3,4,5,

Authors’ affiliations:
1 Dental Research Institute,
2 UCLA School of Dentistry,
3 Johnson Comprehensive Cancer Center,
4 Division of Head and Neck Surgery/Otolaryngology, and
5 Henry Samueli School of Engineering, UCLA, Los Angeles, CA

May, 2006|Archive|

Diagnostic work-up and outcome of cervical metastases from an unknown primary

  • 5/25/2006
  • Cologne, Germany
  • O Guntinas-Lichius et al.
  • Acta Otolaryngol, May 1, 2006; 126(5): 536-44

Conclusions.
An intensive diagnostic work-up including (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) detects many unknown primary tumours, leads to a low emergence rate of primary tumours, and selects carcinoma of unknown primary with much more favourable results after neck dissection and postoperative radiotherapy.

Objective.
To investigate the optimal diagnostic approach and best treatment modality for rare head and neck cancer of unknown primary.

Patients and methods.
In a retrospective study, 69 patients admitted from 1987 to 2002 with cervical lymph node metastases without apparent primary were reviewed. Test characteristics of all diagnostic procedures were calculated. Disease-free and overall survival rates were calculated. Major prognostic factors were analysed univariately.

Results.
At the primary site FDG-PET showed the best sensitivity with 69% and the highest negative predictive value with 87%. Computed tomography and magnetic resonance imaging had a better specificity with 87% and 95%, respectively. The primary tumour was detected in 23 cases (33%). Frequent primary tumour origin was the palatine tonsil (n=8, 35%), base of the tongue (n=6, 26%) and lung (n=4, 17%).
All patients with unknown primary were treated by neck dissection. Adjuvant radiotherapy was performed in 26 patients (57%), concurrent radiochemotherapy was performed in 12 patients (26%). The primary emergence rate was 7%. The 5-year overall survival rate was inferior in patients with detected primary in comparison with patients with unknown primary (22% versus 52%). Significant prognostic factors in case of unknown primary were M stage, smoking, alcohol consumption and tonsillectomy. Radiotherapy but not chemotherapy with carboplatin influenced the overall survival.

Authors:
O Guntinas-Lichius, J Peter Klussmann, S Dinh, M Dinh, M Schmidt, R Semrau, and RP Mueller

Authors’ affiliation:
Department of Otorhinolaryngology, Cologne, Germany

May, 2006|Archive|

RADPLAT: An Alternative to Surgery?

  • 5/25/2006
  • Durham, NC
  • Lee W.T. Alkureishi et al.
  • The Oncologist, Vol. 11, No. 5, 469-480, May 2006

Head and neck cancer frequently presents at a late stage, leading to a poor prognosis despite optimal treatment with surgery and/or radiotherapy. Chemotherapy for advanced disease has shown little benefit as a single-modality treatment, and the use of concurrent chemoradiation is limited by problems with severe toxicity at higher doses.

RADPLAT is the acronym used to describe a new technique, combining intra-arterial delivery of cisplatin with systemic neutralization by i.v. sodium thiosulphate, and concurrent radiotherapy. This allows very high cisplatin dose intensities to be used while potentially minimizing adverse systemic effects.

Initial results suggest that excellent locoregional control rates are achievable in patients with unresectable disease, with a favorable side-effect profile when compared with conventional chemoradiation protocols. In addition, RADPLAT may potentially be of benefit in selected patients with resectable disease, allowing for preservation of organ function and quality of life without compromising locoregional control or survival.

While current phase II data are encouraging, phase III randomized controlled trials are required in order to directly compare RADPLAT with i.v. chemoradiation therapy, the current standard of care. This article reviews the evolution of the RADPLAT concept, from initial clinical trials to its current application in the treatment of patients with advanced head and neck cancer.

Note: The full text of the article is available here

Authors:
Lee W.T. Alkureishi(a), Remco de Bree(b), Gary L. Ross(c)

Authors’ affiliations:
a Department of Plastic Surgery, Canniesburn Hospital, Glasgow Royal Infirmary, Glasgow, United Kingdom;
b Department of Otolaryngology/Head and Neck Surgery, VU University Medical Center, Amsterdam, The Netherlands;
c Department of Plastic Surgery, Christie Hospital, Manchester, United Kingdom

May, 2006|Archive|

Cysteine Containing Chewing Gum Developed In Finland Is Hoped To Become A New Way For The Prevention Of Upper Digestive Tract Cancers

  • 5/25/2006
  • Helsinki, Finland
  • staff
  • Medical News Today (www.medicalnewstoday)

It has been estimated that in developed countries up to 80 % of the cancers of mouth, pharynx and oesophagus are caused by smoking and alcohol drinking. According to Finnish researchers these epidemiological findings can at least in part be explained by the fact that alcohol drinking and smoking result in a strong local exposure of the upper digestive tract to acetaldehyde, and they have proved that acetaldehyde exposure can be markedly prevented by a tablet that releases amino acid, l-cysteine.

The research group of professor Mikko Salaspuro, University of Helsinki and Helsinki University Hospital, Finland, published already in 1990s a hypothesis, that microbes representing normal human digestive tract flora produce locally acetaldehyde from ethanol and that this may expose them for an increased risk of digestive tract cancers.

The hypothesis was strongly supported by Japanese studies showing that digestive tract cancer risk is markedly increased in Japanese drinkers, who have a decreased ability to remove acetaldehyde because of a gene mutation. The cause and effect relationship was subsequently strongly supported by a novel finding of the Finnish research group showing that after a small dose of alcohol Asians with the above mentioned gene mutation have 2-3 times higher concentrations of acetaldehyde in their saliva than those with the normal acetaldehyde removing enzyme. Most recently, a research group from NIH reported a mechanism that induces DNA-damage in those acetaldehyde concentrations that are found in the saliva after drinking of alcohol.

It has been known already for decades that a harmless aminoacid l-cysteine is able to bind effectively acetaldehyde and thereby eliminate its toxicity. On this basis professor Salaspuro and professor Martti Marvola, University of Helsinki, started to develop l-cysteine containing and acetaldehyde eliminating preparations that eventually could be used for the prevention of digestive tract cancers. The first two preparations were slowly l-cysteine releasing tablets that effectively eliminated acetaldehyde derived to the mouth and saliva either after a challenge of alcohol or during smoking.

The methods developed by the research groups of Salaspuro and Marvola have been patented world wide. The owner of the patents is nowadays Finnish company Biohit Oyj. The first commercial product based on this patented method is l-cysteine containing chewing gum that was launched on the market in the 11th International Congress of Oral Cancer on May 14-17, in Italy.

“We know that with this chewing gum it is possible to eliminate acetaldehyde totally from the saliva during smoking. We do hope that this will in the future turn out to be a novel method for the prevention of alcohol and tobacco smoking associated oral cancers. However, long term randomised controlled trials are naturally needed before the possible cancer preventive effects can be proved. We are currently planning that type of studies”, says Salaspuro.

With the saliva carcinogenic acetaldehyde is distributed after swallowing to the pharynx, oesophagus and stomach. Consequently, the effects of l-cysteine may extend to the whole upper digestive tract area. On the other hand, carcinogenic acetaldehyde can be produced also endogenously by the oral microbes from various foodstuffs with high sugar or carbohydrate content, especially in an achlorhydric stomach. Atrophic gastritis and achlorhydria are well known risk factors of gastric cancer. Therefore, in addition to the chewing gum, also other cysteine containing preparations are under development. The goal is to develop new products releasing slowly cysteine in different parts of the gastrointestinal tract by which acetaldehyde can be eliminated not only in the mouth but also in the stomach and may be also in the large intestine.

May, 2006|Archive|