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 lung cancer compared with smokers who had the lowest levels after accounting for smoking history.

Researchers have discovered an important element for making night vision possible in nocturnal mammals: the DNA within the photoreceptor rod cells responsible for low light vision is packaged in a very unconventional way, according to a report in the April 17th issue of Cell, a Cell Press publication. That special DNA architecture turns the rod cell nuclei themselves into tiny light-collecting lenses, with millions of them in every nocturnal eye.

"The conventional architecture seen in almost all nuclei is invariably present in the rod cells of diurnal mammals, including primates, pigs and squirrels," said Boris Joffe of Ludwig-Maximilians University Munich. "On the other hand, the unique inverted architecture is universally present in nocturnal mammals," for instance, mice, cats and deer.

That architecture has important ramifications for the optical properties of those cells, added Jochen Guck of the University of Cambridge. "Diurnal nuclei are basically scattering obstacles," he said. "In nocturnal animals, they are little lenses. In one case, light is scattered in all directions and in the other it is focused in the forward direction," meaning that even at night, what little light there is can travel deeper into the eye where it can be perceived.

Coming to the realization that the structure of the nuclei of rod cells might have something to do with animals' behavior at night versus during the day took a great leap and an interdisciplinary team, Joffe added. That's because biologists typically think of DNA and its packaging into chromatin in terms of its effect on gene activity. "We tried every other possible explanation," Joffe added. "The idea that it had something to do with vision was a daring idea. People laughed at first."

In non-dividing cells, DNA is associated with proteins to form the so-called chromatin, with more condensed "heterochromatin" at the periphery and less condensed "euchromatin" in the interior. Although cell type-specific variants of nuclear architecture can differ notably in details, the researchers explained, the pattern described above is nearly universal and is conserved in both single-celled and multicellular organisms. The reason for the evolutionary stability of nuclear architecture is most probably the important role that the spatial arrangement of chromatin plays in regulating nuclear functions, they said.

Given that notion, the team took great interest in the fact that the nuclei of mouse rod cells shows essentially the opposite, inverted pattern. The central portion of their nuclei is occupied by a large mass of heterochromatin, while transcription factors that control the activity of genes are enriched at the nuclear periphery.

Mice aren't born with those unusual rod cells, they now report. Rather, the conventional nuclear architecture in their rod cells is completely transformed over the animals' first few weeks into the inverted pattern.

The inverted nuclear architecture found in mice is also present in other nocturnal animals, they found. "Our data revealed a wholly unexpected but very clear correlation between the rod nuclear architecture and lifestyle that was further supported by data on nearly forty animals," the researchers said. "Nocturnal mammals had the inverted pattern, while the diurnal ones showed the conventional one."

The correlation between the inverted nuclear architecture and night vision suggested that the inverted pattern might have an optical ramification, they said. After all, nocturnal mammals see at light intensities a million times lower than those available during the day, and their rod photoreceptors are known to possess a light sensitivity down to the level of a few photons. This high sensitivity demands a large number of rod cells, which increases the thickness of the retinas' outer nuclear layer (ONL). The optimization of light transmission through the ONL could therefore provide crucial advantages for nocturnal vision.

Indeed, measurements of how individual nuclei taken from the rod cells of nocturnal animals interact with light show that they act as collecting lenses. Computer simulations indicate that columns of such nuclei like those found in nocturnal animals' retinas would channel light efficiently toward the light-sensing rod outer segments.

The importance of this special nuclear arrangement comes only when you consider the columns, Guck said. "If each nuclei scattered light, it would all be over. The inversion in nocturnal animals makes sure that light is passed from one nucleus to the next. It is handed down so that it doesn't scatter."

The results show that despite the strong evolutionary conservation of the conventional pattern, nuclear architecture in rod cells was modified several times in the evolution of mammals, Joffe said.

"Taken together, paleontological, molecular, and morphological data strongly suggest (1) that the inverted pattern appeared very early in the evolution of mammals as an adaptation to nocturnal vision in this primarily nocturnal group of animals, (2) that, correspondingly, the conventional pattern was repeatedly reacquired in mammals that readopted a diurnal lifestyle, and (3) that restoration of the conventional architecture most likely demanded selective pressure for the conventional nuclear architecture," the researchers wrote. "Comparison of the inverted and conventional patterns can therefore highlight the advantageous features that predetermine the nearly universal prevalence of the conventional nuclear architecture."

Twice weekly acupuncture treatments relieve debilitating symptoms of xerostomia - severe dry mouth - among patients treated with radiation for head and neck cancer, researchers from The University of Texas M. D. Anderson Cancer Center report in the current online issue of Head & Neck.

Xerostomia develops after the salivary glands have been exposed to repeated doses of therapeutic radiation. People who have cancers of the head and neck typically receive large cumulative doses, rendering the salivary glands incapable of producing adequate saliva, said Mark S. Chambers, M.S., D.M.D., a professor in the Department of Dental Oncology. Saliva substitutes, lozenges and chewing gum bring only temporary relief, and the commonly prescribed medication, pilocarpine, has short-lived benefits and bothersome side effects of its own.

"The quality of life in patients with radiation-induced xerostomia is profoundly impaired," said Chambers, the study's senior author. "Symptoms can include altered taste acuity, dental decay, infections of the tissues of the mouth, and difficulty with speaking, eating and swallowing. Conventional treatments have been less than optimal, providing short-term response at best."

M. Kay Garcia, LAc, Dr.P.H., a clinical nurse specialist and acupuncturist in M. D. Anderson's Integrative Medicine Program and the study's first author, noted that patients with xerostomia may also develop nutritional deficits that can become irreversible.

Garcia, Chambers and their team of researchers conducted a pilot study to determine whether acupuncture could reverse xerostomia. Acupuncture therapy is based on the ancient Chinese practice of inserting and manipulating very thin needles at precise points on the body to relieve pain or otherwise restore health. In traditional Chinese medicine, stimulating these points is believed to improve the flow of vital energy through the body. Contemporary theories about acupuncture's benefits include the suggestion that needle manipulation stimulates natural substances that dilate blood vessels and increase blood flow to different areas of the body.

The M. D. Anderson study included 19 patients with xerostomia who had completed radiation therapy at least four weeks earlier. The patients were given two acupuncture treatments each week for four weeks. The acupuncture points used in the treatment were located on the ears, chin, index finger, forearm and lateral surface of the leg. All patients were tested for saliva flow and asked to complete self-assessments and questionnaires related to their symptoms and quality of life before the first treatment, after completion of four weeks of acupuncture, and again four weeks later.

The twice weekly acupuncture treatments produced highly statistically significant improvements in symptoms. Measurement tools included: the Xerostomia Inventory, asking patients to rate the dryness of their mouth and other related symptoms; and the Patient Benefit Questionnaire, inquiring about issues such as mouth and tongue discomfort; difficulties in speaking, eating and sleeping; and use of oral comfort aids. A quality-of-life assessment conducted at weeks five and eight showed significant improvements over quality-of-life scores recorded at the outset of the study.

"In this pilot study, patients with severe xerostomia who underwent acupuncture showed improvements in physical well-being and in subjective symptoms," Dr. Chambers said. "Although the patient population was small, the positive results are encouraging and warrant a larger trial to assess patients over a longer period of time."

Garcia said that a phase III, placebo-controlled trial is planned and is currently under review. She also noted that in other studies, the M. D. Anderson researchers are examining whether acupuncture can prevent xerostomia in patients treated for head and neck cancer, not just treat it.

Speaking on April 19 at the Experimental Biology 2009 meeting in New Orleans, Dr. Kristine Krajnak, a team leader in the Engineering and Control Technologies Branch of the Health Effects Laboratory Division of NIOSH in Morgantown, West Virginia, described results from the first study to directly link the different physical responses of tissue that occur with exposure to different vibration frequencies with biological mechanisms underlying the development of vascular dysfunction. Her presentation is part of the scientific program of The American Physiological Society.

The study, along with results of other studies conducted by NIOSH, supports the importance of reducing job-related exposure to vibration. Ongoing research is evaluating the effectiveness of anti-vibration devices, such as anti-vibration gloves and tools.

Higher frequency vibrations produced by an electric sander (greater than 100 Hz) are smoother than the slower vibrations of an electric hand drill (approximately 63 Hz) and therefore are less likely to cause users discomfort.

Don't let that fool you into not using protective devices that can reduce your exposure to vibration, she says. The new research study conducted at the National Institute for Occupational Safety and Health (NIOSH) suggests that exposure to high and low frequencies cause different physiological responses, but both may affect the risk of developing vibration-induced peripheral vascular dysfunction.

Of the 1.1 to 1.5 million U.S. workers exposed to hand transmitted vibration on a fairly regular basis, approximately half eventually develop some disorder such as Vibration White Finger, in which a single finger or sometimes the entire hand turns white and numb when exposed to the cold, due to restricted blood flow.

Workers also may experience reductions in tactile sensitivity, grip strength, and/or manual dexterity. Earlier studies have shown that risk goes up with frequency and duration of exposure, although NIOSH studies are underway to determine why certain people appear more susceptible to shorter exposure durations.

Dr. Krajnak's team looked at two aspects of vibration injury about which very little is known: the mechanisms of injury and the differences in response to frequency of vibration. The researchers used rats, since the tissues, nerves and arteries of rat-tails are similar to those in human fingers and the tails are known to respond to vibration in a way similar to that seen in fingers.

For four hours a day (the longest time a human can be exposed to workplace vibration according to U.S. and international standards) for 10 days, 15 rats (five in each group) were placed in a container where their tails were vibrated at either 63, 125 or 250 Hz. One control group of five rats accompanied them to the experimental area, to make sure any results seen were not related to noise or change of locale. A second control group stayed in their home cages, uninvolved in the activity.

After the last exposure, the scientists examined the tail arteries for changes. Neither control group had changes, suggesting the changes seen were directly related to the effects of vibration. The rats that experienced high frequency (125 and 250 Hz) vibration had higher levels of measures of oxidative stress, while rats that experienced the lower frequency (65 Hz) vibration showed higher levels of pro-inflammatory factors.

Gastric cancer (GC) is the fourth most common malignancy and the second most frequent cause of cancer-related death in the world. The carcinogenesis of GC involved numerous genetic and epigenetic alterations, as well as many environmental risk factors. Environmental pollutants such as polycyclic aromatic hydrocarbons (PAHs) and halogenated hydrocarbons (HAHs) are well-known carcinogens that play important roles in GC development. The toxic effects of PAHs and HAHs are mediated by a conserved signaling pathway that binds and activates the aryl hydrocarbon receptor (AhR). AhR is a ligand-activated transcription factor and can mediate the carcinogenic and other toxic effects of a variety of environmental pollutants. Many studies in recent years have demonstrated a close relationship between AhR and tumorigenesis. However, the role of AhR in gastric tumorigenesis is still unclear.

A research team led by Dr Min-Hu Chen from China addressed this problem. Their study was published on April 14, 2009 in the World Journal of Gastroenterology.

In this study, RT-PCR, real-time PCR, and Western blotting were performed to detect AhR expression in 39 GC tissues and five GC cell lines. AhR protein was detected by immunohistochemistry (IHC) in 190 samples: 30 chronic superficial gastritis (CSG), 30 chronic atrophic gastritis (CAG), 30 intestinal metaplasia (IM), 30 atypical hyperplasia (AH), and 70 GC. The AhR agonist tetrachlorodibenzo-para-dioxin (TCDD) was used to treat AGS cells. MTT assay and flow cytometric analysis were performed to measure the viability, cell cycle and apoptosis of AGS cells.

They found that AhR expression was significantly increased in GC tissues and GC cell lines. IHC results indicated that the levels of AhR expression gradually increased, with the lowest levels in CSG, followed by CAG, IM, AH and GC. AhR expression and nuclear translocation were significantly higher in GC than in precancerous tissues. TCDD inhibited proliferation of AGS cells via induction of growth arrest at the G1-S phase.