PHILADELPHIA – Studying thousands of patients, Japanese researchers have found a strong link between tooth loss and increased risk of three cancers – esophageal, head and neck, and lung. They suggest that preservation of teeth may decrease risk of developing these diseases.

In the May issue of Cancer Epidemiology, Biomarkers and Prevention, a journal of the American Association for Cancer Research, scientists from Aichi Cancer Center in Nagoya and Nagoya University Graduate School of Medicine speculate that bacterial infection and inflammation resulting from poor oral care that leads to tooth loss could also be driving development of these cancers. Periodontal disease is known to increase risk for stroke and heart disease.

SAN DIEGO - Cells lining the mouth reflect the molecular damage that smoking does to the lining of the lungs, researchers at The University of Texas M. D. Anderson Cancer Center report today at the annual meeting of the American Association for Cancer Research.

Examining oral tissue lining the mouth to gauge cancer-inducing molecular alterations in the lungs could spare patients and those at risk of lung cancer from more invasive, uncomfortable procedures used now, said senior researcher Li Mao, M.D., professor in M. D. Anderson's Department of Thoracic/Head and Neck Medical Oncology.

"We are talking about just a brushing inside of the cheek to get the same information we would from lung brushings obtained through bronchoscopy," said study presenter and first author Manisha Bhutani, M.D., a post-doctoral fellow in Thoracic/Head and Neck Medical Oncology.

Nereus Pharmaceuticals, Inc., a pioneer in drug discovery from marine microbial sources, today announced that enrollment has begun in a Phase 1b study evaluating the vascular disrupting agent (VDA) NPI-2358 in combination with standard chemotherapyterm in patients with non-small cell lung cancer (NSCLC). This study follows on positive outcomes in a Phase 1 single-agent clinical trial assessing the safety, pharmacokinetics, pharmacodynamics (PK/PD) and efficacy of NPI-2358 in various tumor types.

The open-label Phase 1b study will assess escalating doses of NPI-2358 in combination with docetaxel in patients with NSCLC who previously failed at least one chemotherapy regimen. The existing preclinical and clinical data suggests that VDAs may be complementary or synergistic with chemotherapeutics and anti-angiogenesis agents due to the different targets and mechanisms of action. NPI-2358 has a dual effect on tumors: It selectively attacks existing tumor blood vessels leading to hemorrhagic tumor necrosis without affecting normal vasculature, and it has a direct apoptotic effect on tumors cells. NPI-2358 in combination with chemotherapeutic agents in human xenograft models of NSCLC and other cancers was markedly more effective than either treatment alone.

A University of Rochester scientist discovered that the toxins in cigarette smoke wipe out a gene that plays a vital role in protecting the body from the effects of premature aging. Without this gene we not only lose a bit of youthfulness – but the lungs are left open to destructive inflammation and diseases such as chronic obstructive pulmonary disease (COPD) and lung cancer.

By identifying the Sirtuin (SIRT1) gene’s role in pulmonary disease, scientists also hope to find ways to restore it and jump-start lung healing. They’ve begun testing the powerful antioxidant resveratrol, which is extracted from red grape skins, to develop a treatment to target SIRT1 and reverse lung damage, or at least enhance the way standard COPD therapies work.

Pulmonary function tests are often performed before hematopoietic stem cell transplantation to screen for underlying respiratory problems. Recent research has suggested that pretransplant pulmonary function tests—particularly a measurement combining FEV₁ and the diffusing capacity of carbon dioxide (DLCO)—can predict posttransplant respiratory failure and mortality.¹

Jason Chien, MD, and colleagues retrospectively studied the pretransplant pulmonary function and arterial blood gasses of 2,852 cancer patients who received allogeneic stem cell transplants during a 12-year period. FEV₁, FVC, total lung capacity, DLCO, and alveolar-arterial oxygen tension difference (PaO₂) were measured. Patients in the nonmyeloablative group received 2Gy total body irradiation. Those in the myeloablative group received either total-body-irradiation-based or non-total-body-irradiation-based regimens. According to Dr. Chien, an Assistant Professor of Pulmonary and Critical Care Medicine at the Fred Hutchinson Cancer Center, “Assessment of pretransplant pulmonary function tests is very important, given their relationship with mortality risk. We would like to see every transplant center in the world screen their patients with pretransplant pulmonary function tests.”

The results of the study, conducted by researchers at the University of Virginia School of Medicine in Charlottesville and The Children’s Hospital of Philadelphia in Pennsylvania, were presented today at the annual meeting of the Radiological Society of North America (RSNA).

“It’s long been hypothesized that prolonged exposure to secondhand smoke may cause physical damage to the lungs, but previous methods of analyzing lung changes were not sensitive enough to detect it,” said Chengbo Wang, Ph.D., magnetic resonance physicist in the Department of Radiology at The Children’s Hospital of Philadelphia.

TORONTO, June 15 – Current cancer therapies often succeed at initially eliminating the bulk of the disease, including all rapidly proliferating cells, but are eventually thwarted because they cannot eliminate a small reservoir of multiple-drug-resistant tumor cells, called cancer stem cells, which ultimately become the source of disease recurrence and eventual metastasistermterm. Now, research by scientists at the University of Pittsburgh School of Medicine suggests that for chemotherapyterm to be truly effective in treating lung cancers, for example, it must be able to target a small subset of cancer stem cells, which they have shown share the same protective mechanisms as normal lung stem cells. They are presenting this ground-breaking research at the Tissue Engineering and Regenerative Medicine International Society (TERMIS) North American Chapter meeting being held June 13 to 16 at the Westin Harbor Castle conference center in Toronto.

GAINESVILLE, Fla. — Talcum powder has been used for generations to soothe babies’ diaper rash and freshen women’s faces. But University of Florida researchers report the household product has an additional healing power: The ability to stunt cancer growth by cutting the flow of blood to metastaticterm lung tumors.

The study, published in the European Respiratory Journal in April, reveals that talc stimulates healthy cells to produce endostatin, a hormone considered the magic bullet for treating metastatic lung cancer. The UF researchers say talc is an exciting new therapeutic agent for a cancer largely considered incurable.

An earlier indication of whether chemotherapyterm benefits non–small cell lung cancer patients—provided by positron emission tomography (PET) imaging—can guide doctors in offering them better care, according to researchers in the May Journal of Nuclear Medicine.

“Our study demonstrates that patients who respond to chemotherapy can be identified early in the course of their treatment, and these patients will generally exhibit prolonged overall survival,” explained Claude Nahmias, professor of radiology and medicine at the University of Tennessee Medical Center in Knoxville. “Although we studied a relatively small number of patients—and our results should be interpreted with caution—it is clear that a repeat PET study with the radiotracer fluorodeoxyglucose (FDG) at the end of the first cycle of chemotherapy would allow the identification of those patients for whom the therapy was futile,” he said. “The ability to provide an early indication of therapeutic response has the potential to improve patient care by identifying those patients who do not benefit from their current treatment,” explained Nahmias. “Patients would benefit from either having chemotherapy and its associated toxic side effectsterm stopped or going on to a different, and hopefully more adequate, therapeutic approach,” added the co-author of “Time Course of Early Response to Chemotherapy in Non–Small Cell Lung Cancer Patients With 18F-FDG PET/CT.”

- Clinicians may be one step closer to having a critical tool in identifying which smokers are at higher risk for developing lung cancer, the deadliest of all cancers, thanks to an assessment model generated by researchers at The University of Texas M. D. Anderson Cancer Center.

The prediction tool detailed in the May 2 issue of the Journal of the National Cancer Institute is the first designed to assign a score assessing a person's risk for the disease. It is also the first to use standard clinical and epidemiological data easily gathered by healthcare professionals, including: smoking habit; exposure to environmental tobacco smoke; family history of cancer; hay fever; emphysema; and exposure to dust, or asbestos.

A new study sheds light on how some small-molecule tyrosine kinase inhibitors, including two that are currently being used clinically to treat cancer, interact with wild-type and mutated forms of the epidermal growth factor receptor (EGFRtermtermterm). The research, published in the March issue of the journal Cancer Cell, published by Cell Press, may help to guide rational use of currently available EGFR inhibitors and provides new direction for the design and development of even more potent inhibitors that are tailored to specific EGFR mutants.

Many human malignancies exhibit mutated forms of the EGFR, a tyrosine kinase that plays a critical role in signaling pathways controlling cell proliferation and survival. Although the specific mechanisms are unclear, studies have shown that some EGFR mutations are associated with increased sensitivity to small-molecule tyrosine kinase inhibitors. To better understand how distinct mutant EGFRs interact with inhibitors on a structural level, Dr. Michael J. Eck from Harvard Medical School and the Dana-Farber Cancer Institute and colleagues studied the enzyme activity of two lung cancer-derived EGFR mutants and determined their crystal structures when bound to several different commonly used inhibitors.

By mapping the interlocking structures of small molecules and mutated protein "receptors" in non-small cell lung cancer (NSCLC) cells, scientists at Dana-Farber Cancer Institute and their colleagues have energized efforts to design molecules that mesh with these receptors, potentially interfering with cancer cell growth and survival.

In a study published in the March issue of Cancer Cell, researchers led by Michael Eck, MD, PhD, of Dana-Farber used X-ray crystallography to determine the structure of two mutated forms of the epidermal growth factor receptor (EGFRtermtermterm) in lung cancer cells. EGFR, a protein known as a tyrosine kinase, plays a key role in relaying growth signals within cells. When mutated, it can become overactive, leading to excessive cell division and cancer.

Long-term, high-level exposure to bacterial endotoxin-- a contaminant found in raw cotton fiber and cotton dust -- is associated with a 40 percent decrease in lung cancer risk among female Chinese textile workers, according to a new study in the March 7 Journal of the National Cancer Institute.

Since the 1970s, studies in the U.S. and abroad have reported a lower than average risk of lung cancer for textile workers. Additionally, studies have shown that workers in other occupations with high endotoxin exposure, such as dairy farmers, have reduced lung cancer risks as well. Although many researchers thought endotoxin might be associated with reduced risk of lung cancer, no previous studies had quantified the relationship between endotoxin exposure and lung cancer risk.

Sunesis Pharmaceuticals, Inc. today announced that the company will advance the small-cell lung cancer trial in treatment-sensitive patients to Stage 2. The company reported initial results from the first stages of two Phase 2 clinical trials of SNS-595, a novel cell-cycle inhibitor, in first- line relapsed/refractory small cell and non-small cell lung cancers. Anti- tumor activity was observed, including evidence of stable disease, minor responses and partial responses reported in one arm of the small cell lung cancer study, and minor and mixed responses and stable disease in the non- small cell lung cancer trial. Sunesis initiated the Phase 2 studies of SNS-595 in small cell lung cancer and non-small cell lung cancer in 2006 to evaluate the compound's activity as a single agent in the second-line treatment setting. Both clinical trials utilized a two-stage design, enabling an interim assessment of clinical activity in order to determine next steps for the compound's evaluation in each tumor indication. All patients received doses of 48 mg/m2 every three weeks, the maximum-tolerated dose identified in Phase 1 clinical trials. Consistent with prior findings, SNS-595 was generally well-tolerated. Sunesis' Phase 2 small cell lung cancer clinical trial included two arms of relapsed or refractory patients -- treatment sensitive and treatment refractory. With nine of eleven evaluable patients in the treatment-sensitive arm of the trial having stable disease or objective responses by the end of two cycles of treatment, the clinical results have exceeded the pre-specified requirement of at least two partial or complete responses in the first 20 evaluable patients for advancing to Stage 2. Based on the interim data analysis reported today, Sunesis plans to continue Phase 2 clinical evaluation of SNS-595 in treatment-sensitive small cell lung cancer patients who had previously responded to first-line therapy, but subsequently relapsed after more than three months.

Antibodies that selectively bind and destroy cancer cells represent some of the most promising cancer therapy approaches being developed today. Several of these antibodies have reached the market, including cetuximabtermterm (Erbituxterm, ImClone Systems), which targets the epidermal growth factor receptor (EGFRtermtermterm) protein. However, a study conducted at the Dana-Farber Cancer Institute and the Ludwig Center at Dana-Farber/Harvard Medical School now suggests that antibodies binding a particular protein conformation, caused by hyperactivation, might have distinct therapeutic advantages over antibodies, like cetuximab, that bind to wild-type (normal) target proteins.