lung canser

Long Term Ozone Exposure Raises The Risk Of Dying From Lung Disease

Fri, 24 Apr 2009 20:21:00 +0300

Long-term exposure to elevated levels of ground ozone a major constituent of smog significantly raises the risk of dying from lung disease, according to a new nationwide study of cities that evaluated the impact of ozone on respiratory health over an 18-year period.

The study found that the risk of dying from respiratory disease is more than 30 percent greater in metropolitan areas with the highest ozone concentrations than in those with the lowest ozone concentrations.

Over the last decade, several nationwide studies have shown that long-term exposure to tiny particles of dust and soot in air pollution is a risk factor for death from heart and lung disease. However, it was unclear whether long-term exposure to ozone, a widespread pollutant in summertime haze, was linked to a higher risk of dying from lung disease itself.

The new study, published in the March 12 issue of the New England Journal of Medicine, is the first nationwide population study on the long-term impact of ozone on human health, and the first to separate ozone's effects from those of fine particulate matter, the tiny particles of pollutants emitted by factories, cars, and power plants.

"Many studies have shown that a high-ozone day leads to an increase in risk of acute health effects the next day, for example, asthma attacks and heart attacks," says George D. Thurston, Sc.D. who directed the air pollution exposure assessment part of the study. "What this study says is that to protect the public's health, we can't just reduce the peaks, we must also reduce long-term, cumulative exposure." Dr. Thurston is a professor in the Department of Environmental Medicine at NYU School of Medicine, a part of NYU Langone Medical Center.

Ozone in the upper atmosphere protects against harmful ultraviolet (UV) radiation. At ground level, ozone, or O3, forms when nitrogen dioxide from tailpipes, coal-fired power plants and other industries collides wi.. ( devamı )

Preclinical Data Presented On ARIAD's Investigational MTOR Inhibitor, Deforolimus, In Lung Cancer And Other Solid Tumor Models

Thu, 23 Apr 2009 19:26:00 +0300

"The single-agent activity of deforolimus observed in preclinical models provides a compelling rationale for our recently initiated Phase 2 clinical trial of deforolimus in patients with non-small cell lung cancer whose tumors have a KRAS mutation. These results are particularly important considering the limitations of available treatments for such patients," said Timothy P. Clackson, Ph.D., senior vice president and chief scientific officer of ARIAD. "In addition, the data on deforolimus in combination with Merck's IGF-1R inhibitor, MK-0646, confirm the rationale for using these two investigational drugs together in diverse types of solid tumors. Our ongoing Phase 1 trial of this combination represents an important opportunity for our oncology partnership."

Deforolimus in Non-Small Cell Lung Cancer with KRAS Mutation

Deforolimus demonstrated potent single-agent, anti-tumor activity in preclinical models of non-small cell lung cancer with a KRAS mutation.

Approximately 20 percent of non-small cell lung tumors have KRAS mutations, and these tumors typically do not respond well to EGFR inhibitors, such as erlotinib. In a panel of more than one hundred lung-cancer cell lines, deforolimus showed greater inhibition of tumor growth than erlotinib in 79 percent of cell lines tested and 84 percent of KRAS mutant cell lines. Further, deforolimus potently inhibited the growth of erlotinib-resistant, KRAS-mutant tumors in three different mouse models.

These data lend support for the choice of patients with advanced non-small cell lung cancer whose tumors have a KRAS mutation as the target population for study in the ongoing randomized, double-blind, placebo-controlled Phase 2 clinical trial of oral deforolimus.

Deforolimus and MK-0646 Combination
.. ( devamı )

Genetic Source Of Rare Childhood Cancer Found; Gene Is Implicated In Other Cancers

Thu, 23 Apr 2009 19:25:00 +0300

The search for the cause of an inherited form of a rare, aggressive childhood lung cancer has uncovered important information about how the cancer develops and potentially sheds light on the development of other cancers.

The finding by researchers at Washington University School of Medicine in St. Louis, Children's National Medical Center in Washington, D.C., the International Pleuropulmonary Blastoma Registry at Children's Hospitals and Clinics of Minnesota, and other collaborating institutions adds the final link to the chain connecting the gene DICER1 to cancer development something that had been suspected but until now not definitively demonstrated.

The results were presented April 19, 2009, at the 100th Annual Meeting of the American Association of Cancer Research in Denver. The study shows that some children with the rare cancer pleuropulmonary blastoma (PPB) are born with a deleterious mutation in DICER1, a master controller gene that helps regulate the expression of other genes. The children studied came from families with a history of PPB or related disorders.

"PPB is the first malignancy found to be directly associated with inherited DICER1 mutations, making the cancer an important model for understanding how mutations and loss of DICER1 function lead to cancer," says lead author D. Ashley Hill, M.D., chief of pathology at Children's National Medical Center. "Additionally, we now believe that PPB tumors arise from an unusual mechanism in which cells carrying mutations induce nearby cells to become cancerous without becoming cancerous themselves."

Hill was principal investigator of the study, which began while she was on the Washington University faculty.

Only 50 to 60 cases of PPB are diagnosed each year around the world. Most children with PPB are under five years old. The cancer progresses from air-filled lung cysts in the early stage to solid lung tumors in later stages. If detected in the earl.. ( devamı )

Poniard Announces Publication Of Results Of Picoplatin Phase 2 Study In Journal Of Clinical Oncology

Thu, 23 Apr 2009 19:24:00 +0300

Poniard Pharmaceuticals, Inc. (Nasdaq: PARD), a biopharmaceutical company focused on oncology, announced that results of its Phase 2 clinical trial of picoplatin in patients with recurrent small cell lung cancer (SCLC) were published in the April 20, 2009, print issue of the Journal of Clinical Oncology(1). Picoplatin demonstrated a survival benefit in this open-label, multi-center Phase 2 trial of SCLC patients who failed prior platinum-containing first-line chemotherapy or who progressed within six months of first-line therapy. The median overall survival was 27 weeks and the median one-year survival rate was 17.6 percent in this patient population of mostly platinum-refractory and -resistant patients.

Poniard is currently evaluating the efficacy and safety of picoplatin in the pivotal Phase 3 SPEAR (Study of Picoplatin Efficacy After Relapse) SCLC trial, which is being conducted under a Special Protocol Assessment (SPA) agreement with the U.S. Food and Drug Administration (FDA). The Company reached its enrollment target in this international, multi-center, randomized, controlled trial in March 2009.

SCLC is the most aggressive lung cancer and tends to be widely disseminated by the time of diagnosis. The prognosis for patients with SCLC that has progressed despite chemotherapy is exceedingly poor regardless of stage. Effective second-line treatment for SCLC is a major unmet need. There is no standard chemotherapy for second-line platinum-refractory or -resistant SCLC.

"New treatments are desperately needed for patients with platinum-resistant and -refractory small cell lung cancer due to the rapid relapse of the disease and the slim chance that patients will experience long-term survival," said John Eckardt, M.D., lead author of the JCO publication, picoplatin clinical trial investigator, and chief medical officer of DAVA Oncology. "I am encouraged that picoplatin extended survival in this patient group and was gen.. ( devamı )

Encouraging Results Published On Use Of TomoTherapySM In Lung Cancer Treatment

Wed, 22 Apr 2009 15:27:00 +0300

TomoTherapy Incorporated (NASDAQ: TOMO) cited recently published encouraging preliminary results of an ongoing Phase I clinical trial on the use of intensity-modulated (IMRT) and image-guided radiation therapy (IGRT) focusing on the concept of accelerated hypofractionation to overcome tumor repopulation, one of the well-known mechanisms of radiation resistance, using TomoTherapySM for non-small cell lung cancer (NSCLC).

The paper, published in Technology in Cancer Research and Treatment (Technol Cancer Res Treat. 2008 Dec;7(6):441-8.) titled, "Dose Escalated, Hypofractionated Radiotherapy Using Helical Tomotherapy for Inoperable Non-Small Cell Lung Cancer: Preliminary Results of a Risk-Stratified Phase I Dose Escalation Study," evaluates a study devised to test the safety of escalating the biologically-effective tumor dose via hypofractionated treatment regimens using 25 fractions over five weeks. Traditionally, radiotherapy is delivered over six to seven weeks, or even longer (sometimes up to 10-11 weeks) if dose-escalation is the goal. A downside to dose escalation in this manner is that tumor repopulation occurs during the prolonged delivery time. Shorter dose-escalated schedules have historically been avoided because of the expectation of severe toxicities. The University of Wisconsin (UW) School of Medicine and Public Health investigators hypothesized that the conformal dose-delivery abilities of TomoTherapy, with helical IMRT and IGRT, would permit safe dose-escalation with shorter schedules, thereby limiting accelerated repopulation, and possibly improving tumor control.

According to its authors, the study demonstrates that the use of TomoTherapy technology may allow for higher doses of radiation therapy than are conventionally administered to be delivered over a shorter treatment course, with lower than expected toxicities. Helical TomoTherapy allows for delivery of image-guided, intensity-modulated radia.. ( devamı )

Specific Lung Cancer Susceptibility Gene Identified By Researchers

Wed, 22 Apr 2009 15:26:00 +0300

University of Cincinnati (UC) cancer cell biologists have identified a distinct gene linked to increased lung cancer susceptibility and development. They say this gene - known as RGS17 - could result in a genetic predisposition to develop lung cancer for people with a strong family history of the disease.

With further investigation, they believe the gene could be used to identify high-risk patients who may benefit from earlier, more aggressive lung cancer screening.

Marshall Anderson, PhD, and his colleagues report their findings in the April 15, 2009, issue of the journal Clinical Cancer Research.

"Understanding how the RGS17 gene impacts cancer development could change clinical diagnosis and treatment as radically as discovery of the breast cancer genes (BRCA1 and BRCA2) did," explains Anderson, who has led the multi-institutional Genetic Epidemiology of Lung Cancer Consortium (GELCC) studying the genetic basis of lung cancer since 1997. "A proven genetic test could help us identify people at risk before the disease progresses."

According to the American Cancer Society, lung cancer is the leading cause of cancer related disease and death. Although tobacco smoke is the primary environmental cause of the disease, science has shown there is also a strong genetic component to the disease.

"This study represents a significant contribution to our understanding of lung cancer susceptibility and is another step toward to the goal of preventive medicine," says David Christiani, MD, MPH, a professor of occupational medicine and environmental health at the Harvard School of Public Health, whose two-page commentary on the study is published in conjunction with the GELCC team's scientific findings. "The authors undertook a daunting challenge of performing a family-based study of lung cancer in an effort to identify specific causal genes."

Genes, which are located in fixed positions on the cell.. ( devamı )

Peregrine Pharmaceuticals Reports Positive Preliminary Data From Phase II Bavituximab Lung Cancer Trial

Wed, 22 Apr 2009 15:25:00 +0300

Peregrine Pharmaceuticals, Inc. (Nasdaq: PPHM), announced that updated preliminary data from the initial cohort of 21 patients in its Phase II trial evaluating bavituximab in combination with carboplatin and paclitaxel showed that 11 of 17 evaluable patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) achieved an objective tumor response according to RECIST criteria, after completing the maximum six treatment cycles. The company also reported that patient dosing is underway in the expansion stage of the trial, which will enroll an additional 28 patients for a total of 49 patients overall.

"We are very pleased to see these additional objective tumor responses in this difficult-to-treat cancer following the full regimen of six treatment cycles of bavituximab and chemotherapy," said Steven W. King, president and CEO of Peregrine. "These updated results build on the impressive data we reported after only four treatment cycles, which had already exceeded the pre-defined number of objective tumor responses needed to expand the trial to the larger cohort."

Mr. King added, "The tumor response data to date from this trial compares favorably to published studies with current standard-of-care lung cancer treatments, and we are looking forward to seeing results from the entire study. With dosing now underway in the expanded patient cohort, we expect to resume the brisk pace of enrollment achieved in the first cohort, with the goal of completing patient enrollment around mid-year. We intend to provide further updates as patient treatment and follow-up continue in the coming months."

The primary objective of the multi-center, open-label Phase II study is to assess the overall response rate to bavituximab with carboplatin and paclitaxel. In the trial's Simon two-stage design, 21 patients with previously untreated locally advanced or metastatic NSCLC were initially enrolled and 17 of these patients were deemed evaluable.. ( devamı )

Urine Test May Predict Lung Cancer Risk In Smokers

Tue, 21 Apr 2009 21:35:00 +0300

Scientists in the US may have uncovered why some smokers get lung cancer while others do not: they found that those with the highest urine levels of a known biomarker for the uptake of a cancer-causing chemical found in tobacco had a two-fold increased risk of developing lung cancer than those with the lowest levels.

The study was the work of Dr Jian-Min Yuan, associate professor of public health at the University of Minnesota, and colleagues, and is being presented at the 100th Annual Meeting of the American Association for Cancer Research, which is taking place from 18 to 22 April, at the Colorado Convention Center in Denver.

"A history of smoking has always been thought of as a predictor of lung cancer, but it is actually not very accurate," said Yuan, explaining in a press statement that the big question that has been challenging researchers is why it raises risk in some people and not others.

Studies have shown that the chemical NNAL, a metabolic byproduct of the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, induces lung cancer in laboratory animals, but we don't know what it does to humans.

Yuan and colleagues wanted to find out if the amount of NNAL in the urine of humans might predict their risk of lung cancer.

To do this they used data from two large cohort studies: the Shanghai Cohort Study which covers 18,244 men, and the Singapore Chinese Health Study, which coveres 63,257 men and women. These studies included personal interviews to assess diet, lifestyle, levels of cigarette smoking, and results of blood and urine analysis from over 50,000 people.

From these records Yuan and colleagues found 246 current smokers who later developed lung cancer and matched them with 245 smokers who did not develop lung cancer during the ten years that ensued after they enrolled in the studies and gave their interviews and samples.

They grouped the participants.. ( devamı )

Determining If A Smoker Is At Risk For Lung Cancer By Testing Urine

Tue, 21 Apr 2009 21:34:01 +0300

Researchers may have uncovered why lung cancer afflicts some smokers and not others, according to data presented at the American Association for Cancer Research 100th Annual Meeting 2009.

"A history of smoking has always been thought of as a predictor of lung cancer, but it is actually not very accurate," said Jian-Min Yuan, Ph.D., M.D., associate professor of public health at the University of Minnesota. "Smoking absolutely increases your risk, but why it does so in some people but not others is a big question."

Yuan and colleagues hypothesized that the presence of the metabolite NNAL in a patient's urine might predict risk of lung cancer. This metabolite has been shown to induce lung cancer in laboratory animals, but the effect in humans had not yet been studied.

Researchers collected data from 18,244 men enrolled in the Shanghai Cohort Study and 63,257 men and women from the Singapore Chinese Health Study. In addition to in-person interviews to assess levels of cigarette smoking, dietary and other lifestyle factors, researchers collected blood and urine samples from more than 50,000 patients.

To evaluate the impact of NNAL, researchers identified 246 current smokers who later developed lung cancer and 245 smokers who did not develop lung cancer during the 10-year period following initial interview and collection of urine samples.

Levels of NNAL in the urine were divided into three groups. Compared to those with the lowest levels, patients with a mid-range level of NNAL had a 43 percent increased risk of lung cancer, while those at the highest level had a more than two-fold increased risk of lung cancer after taking into account the effect of number of cigarettes per day, number of years of smoking, and urinary levels of cotinine on lung cancer risk.

Levels of nicotine in the urine were also calculated. Those with the highest levels of nicotine and NNAL had an 8.5-fold increase in the risk of .. ( devamı )

Human Lung Tumors Destroy Anti-Cancer Hormone Vitamin D, Pitt Researchers Find

Tue, 21 Apr 2009 21:34:00 +0300

Human lung tumors have the ability to eliminate Vitamin D, a hormone with anti-cancer activity, a new study from the University of Pittsburgh Cancer Institute (UPCI) suggests. Results of the study, Abstract Number 2402, are being presented at the 100th annual meeting of the American Association for Cancer Research (AACR), April 18 to 22, in Denver.

"High levels of Vitamin D help the body produce proteins with anti-tumor activity," explained principal investigator Pamela Hershberger, Ph.D., a research assistant professor in UPCI's Department of Pharmacology and Chemical Biology. "We've discovered that lung cancer cells make an enzyme called CYP24, which counteracts the positive effects of Vitamin D. To better study it, we developed the first radioactive-free assay that measures the amount of Vitamin D in tissues and blood."

According to Dr. Hershberger, this test is sensitive enough to have clinical potential. "We hope this new assay will help identify the best approaches to maintain therapeutic levels of Vitamin D in tissues," she said.

Lung cancer is the leading cause of cancer death in the United States in both men and women, killing 160,000 people annually, and remains one of the most difficult cancers to treat. The five-year survival rate remains low, and better treatments are much needed. According to Dr. Hershberger, it is possible that one day Vitamin D could be used as a chemopreventive agent to improve patient outcomes.

This study was supported by UPCI's Lung Cancer Specialized Program of Research Excellence.

Source

University of Pittsburgh Cancer Institute .. ( devamı )