Exhaled Breath Compounds Identify Early Lung Cancer

The diagnosis of lung cancer can involve a number of tests, but specific compounds in exhaled breath have been discovered that may be used to diagnose the disease in its early stages.

Of all cancers, lung cancer is the biggest killer in both men and women it causes more deaths than colon, breast and prostate cancer combined according to the American Lung Association (Chicago, IL, USA).

Scientists at the University of Louisville (KY, USA) used a silicone microprocessor and mass spectrometer to test exhaled breath of patients with suspected lung cancer for specific volatile organic compounds (VOCs) known as carbonyls. These included aldehydes and ketones, organic compounds with carbon double-bonded to oxygen, which are at very low concentrations and produced by the human body.

The team developed the silicone microprocessor, which was coated with an amino-oxy compound that binds to carbonyl compounds found in exhaled breath. Measuring the levels of carbonyls in exhaled breath has provided the investigators with a way to accurately identify early lung cancer. After removing malignant nodules in certain patients, the team found that these elevated carbonyl concentrations returned to normal. The scientists made the discovery when they were examining patients with "suspicious" lung lesions.

Michael Bousamra, MD, an associate professor at the University of Louisville, said when discussing the potential for use of this technique as a standard test. “Instead of sending patients for invasive biopsy procedures when a suspicious lung mass is identified, our study suggests that exhaled breath could identify which patients may be directed for an immediate intraoperative biopsy and resection. The novelty of this approach includes the simplicity of sample collection and ease for the patients.”

Professor Bousamra added, “Although the data are preliminary, we found that patients with an elevation of three or four cancer-specific carbonyl compounds was predictive of lung cancer in 95% of patients with a pulmonary nodule or mass. Conversely, the absence of elevated VOC levels was predictive of a benign mass in 80% of patients.” The study was presented at the 50th Annual Meeting of the Society of Thoracic Surgeons, held January 25–29, 2014, in Orlando (FL, USA).

source: www.labmedica.com

Dedicated Blood DNA Collection Tube

A new collection tube for routine clinical use that was designed to preserve DNA in blood samples was recently certified for use as a diagnostic product in Europe.

The PAXgene Blood DNA System standardizes blood collection and DNA purification from whole blood samples. The integration of sample collection and purification and a single processing tube streamlines workflow and shortens processing time, resulting in cost savings. The PAXgene Blood DNA System is the first step to consistent, reliable results. 

PRINCIPLE

The PAXgene Blood DNA System is an integrated and standardized system for collection and stabilization of whole blood specimens and isolation of their genomic DNA. The system requires the combined use of PAXgene Blood DNA Tubes for blood collection and stabilization, followed by DNA isolation using the PAXgene Blood DNA Kit. Blood is collected into PAXgene Blood DNA Tubes, which contain a proprietary blend of reagents that both prevents blood coagulation and stabilizes white blood cells. Blood samples can be stored in the tubes for up to 14 days at room temperature. DNA is isolated from the tubes using appropriate buffers supplied in the PAXgene Blood DNA Kit. Highly pure genomic DNA is obtained, suitable for use in a wide range of downstream applications. 

PROCEDURE

The PAXgene Blood DNA procedure is shown in the flowchart PAXgene Blood DNA procedure. Blood samples (8.5 ml) are collected in PAXgene Blood DNA Tubes, where they may be stored or transported. For DNA isolation, the blood is transferred to processing tubes (supplied already filled with cell lysis buffer), and the solution is mixed to lyse red and white blood cells. Cell nuclei and mitochondria are pelleted by centrifugation, washed, and resuspended in digestion buffer. Protein contaminants are removed by incubation with a protease. DNA is precipitated in isopropanol, washed in 70% ethanol, dried, and resuspended in resuspension buffer. 

Adekoga Adeniji

Hormonal 'POETry' Key to Valentine's Day Romance

The Science of Sex and Love

Valentine's Day means flowers, massage, and POETry. Referring to prolactin, oxytocin, estrogen, and testosterone, of course.

All 4 of those "love hormones" play key roles in romance and sexual function for both women and men, according to 2 experts with The Endocrine Society. 

Clinicians can play an important role in helping patients understand how these hormones influence our bodies and our psyches, suggested Nanette Santoro, MD, and Bradley D. Anawalt, MD, following a webinar sponsored by the society. In fact, clinicians can help patients who are experiencing difficulties that might prevent them from celebrating Valentine's Day the way they would like to, they offered. 

Taking a sexual history is important in evaluating menopausal women, because many have issues but may hesitate to raise them with their clinician on their own, noted Dr. Santoro, Professor and E. Stewart Taylor Chair of Obstetrics and Gynecology at the University of Colorado at Denver. Clinicians may be similarly reluctant to start the discussion. 

"Many physicians feel 'trapped' by these questions precisely because the patient is bashful about bringing it up, and thus it presents itself as a last-minute issue as the doctor literally has his or her hand on the office doorknob: 'Oh, by the way...'," she explained. 

Dr. Santoro suggests that clinicians either ask the simple question "Are you satisfied with your sex life?" or use the Female Sexual Function Index, an easy-to-administer questionnaire available online. ^[1]

 

For men, physicians increasingly are asking them about erectile dysfunction, and patients increasingly are willing to share that information, according to Dr. Anawalt. Loss of libido, however, is addressed less often. 

"Male sexuality is not just about erections," he said during the webinar, noting that high testosterone levels do not correlate with sexual function. However, he explained, small decreases in testosterone can affect sexual desire and satisfaction, as can visual cues and relationship issues. 

"Low testosterone levels are seldom the cause for erectile dysfunction," Dr. Anawalt said. "Total testosterone levels must be very low (< 150 ng/dL) before erectile function is affected, and even then, many men still have normal erections. They just lack sexual desire." 

In fact, estrogen is actually more important to normal male sexual function than previously realized, ^[2,3] Dr. Anawalt noted. This recent finding could have important implications for men being treated with hormonal suppression for prostate cancer. 

In the end, though, estrogen and testosterone "provide the fuel but not the fire," he said. In other words, no hormone alone can spark mutual attraction in a couple if it's not there to begin with.

The Chemistry of Women's Desire

Estrogen and testosterone are not the only hormones involved in female sexuality, Dr. Santoro noted. Prolactin, the "hormone of lactation," generally has no effect on libido in normally cycling women, but it can suppress sexual desire when levels are too high, such as in women who are breastfeeding, have prolactin-producing tumors, or are taking medications that affect dopamine pathways. 

"[Prolactin is] one hormone that I think is little known but may have a profound effect on desire," Dr. Santoro said. "I think it needs to be thought about in an endocrine setting." 

Oxytocin, the "cuddly hormone," induces uterine contractions and facilitates milk ejection after childbirth. Elevated levels appear during orgasm, but its role in female sexual desire isn't as clear as it is in men. Indeed, oxytocin has been linked with both enhanced and diminished sexual desire in women. ^[4,5]

 

Estrogen directly affects vaginal engorgement and lubrication, and it regulates female genital tissues' "receptivity" to sexual activity. Until recently, estrogen was the only treatment for vaginal dryness and painful intercourse, problems that reportedly affect 30%-40% of postmenopausal women. In February 2013, the US Food and Drug Administration (FDA) approved the novel selective estrogen receptor modulator ospemifene as the first nonestrogen therapy for moderate to severe dyspareunia in postmenopausal women.

"It's a very welcome thing, because there are many women out there who can't take estrogen. You want to give them an alternative, but we had nothing except for lubricants and moisturizers, and they don't always work," Dr. Santoro said. 

Some evidence suggests that testosterone also correlates with female sexual desire and satisfaction. ^[6,7] Nonetheless, the FDA has been reluctant to approve the testosterone patch for women because the long-term safety isn't known, Dr. Santoro noted. ^[8]

 

Moreover, no drug is likely to address all of the issues that affect female sexuality. "Context may mean a great deal, Dr. Santoro said. "In a lot of the models of female sexuality...relationship issues seem to have a bigger role. More than any of these hormones, in other studies of women and sexuality, the quality of their relationships dictates how sexual function plays out." 

In the clinical setting, she advised, a woman who responds affirmatively when asked about sexual problems should be questioned further about the specifics of the problem, as well as about relationship issues and whether she has experienced past sexual abuse. 

"Women who are survivors of sexual abuse can have sexual problems crop up at seemingly illogical times of life -- menopause being one of them -- and the problem can play out as pelvic pain and other issues that lead to sexual aversion," Dr. Santoro said. 

Referral to a sex therapist can be helpful for patients in whom hormonal abnormalities have been ruled out, she added.

POETry in Men

Hormones play different roles in male sexuality, Dr. Anawalt explained. Prolactin is the "stop" hormone, oxytocin the "soul mate" hormone, estrogen the "Adam's rib of male sexuality," and testosterone "the hormone of desire." 

When men engage in sex with a partner, blood concentrations of prolactin increase to a greater degree than in men who experience orgasm through masturbation, Dr. Anawalt said. Prolactin likely is responsible for the immediate decline in sexual desire and the onset of sleepiness following orgasm. "Prolactin may be an indicator of satiety," he said. 

Chronic elevations in prolactin can create a permanent "stop mode" by reducing blood testosterone and estrogen levels. This would explain the reduced sexual desire that often accompanies medications such as antidepressants or antipsychotics which suppress pituitary hormonal regulation, he noted. 

Oxytocin appears to have more "subtle, nuanced" effects on male behavior. Several recent studies document the hormone's effects on the emotional aspects of male sexuality. For example, administration of intranasal oxytocin increased the physical distance between men with monogamous partners and other women, but it did not have that effect on single men. ^[9] Men given oxytocin also rated their female partners as more attractive compared with unfamiliar women. ^[10]

 

Other recent studies suggest that oxytocin in men increases their empathy for and speed of response to facial expression cues ^[11]; increases activity in brain areas associated with arousal, reward, memory, and social bonding ^[12]; and increases their willingness to share emotions. ^[13]

 

Another study compared the effects of a 20-minute massage with those of 20 minutes of reading, finding that both increase oxytocin levels. ^[14]

 

"It's clear that physical touch is one of the important stimulants of oxytocin, and any kind of a setting where you're more relaxed is going to tend to be associated with higher oxytocin levels," Dr. Anawalt said. 

For Valentine's Day purposes, a 20-minute massage with scented oil to release oxytocin might be the perfect romance enhancer, he advised.

References

1. Rosen R, Brown C, Heiman J, et al. The Female Sexual Function Index (FSFI): a multi-dimensional self-report instrument for the assessment of female sexual function. J Sex Marital Ther. 2000;26:191-208. Abstract
   
2. Matsumoto AM. Reproductive endocrinology: estrogens -- not just female hormones. Nat Rev Endocrinol. 2013;9:693-694. Abstract
   
3. Finkelstein JS, Lee H, Burnett-Bowie SA, et al. Gonadal steroids and body composition, strength, and sexual function in men. N Engl J Med. 2013;369:1011-1022. Abstract
   
4. Magon N, Kalra S. The orgasmic history of oxytocin: Love, lust, and labor. Indian J Endocrinol Metab. 2011;15 Suppl 3:S156-S161.
   
5. Courtois F, Carrier S, Charvier K, Guertin PA, Journel NM. The control of male sexual responses. Curr Pharm Des. 2013;19:4341-4356. Abstract
   
6. Pluchino N, Carmignani A, Cubeddu A, et al. Androgen therapy in women: for whom and when. Arch Gynecol Obstet. 2013;288:731-837. Abstract
   
7. Hobbs K, Handler L. Clinical inquiry: which treatments help women with reduced libido? J Fam Pract. 2013;62:102-103.
   
8. Testosterone therapy: is it for women? Some try testosterone to boost a sagging libido, but this therapy is still unproven in women. Harv Womens Health Watch. 2013;20:6-7.
   
9. Scheele D, Striepens N, Güntürkün O, et al. Oxytocin modulates social distance between males and females. J Neurosci. 2012;32:16074-16079. Abstract
   
10. Scheele D, Wille A, Kendrick KM, et al. Oxytocin enhances brain reward system responses in men viewing the face of their female partner. Proc Natl Acad Sci U S A. 2013;110:20308-20313. Abstract
    
11. Tollenaar MS, Chatzimanoli M, van der Wee NJ, Putman P. Enhanced orienting of attention in response to emotional gaze cues after oxytocin administration in healthy young men. Psychoneuroendocrinology. 2013;38:1797-1802. Abstract
    
12. Burri A, Heinrichs M, Schedlowski M, Kruger TH. The acute effects of intranasal pxutpcom administration on endocrine and sexual function in males. Psychoneuroendocrinology. 2008;33:591-600. Abstract
    
13. Lane A, Luminet O, Rimé B, Gross JJ, de Timary P, Mikolajczak M. Oxytocin increases willingness to socially share one's emotions. Int J Psychol. 2013;48:676-681. Abstract
    
14. Morhenn V, Beavin LE, Zak PJ. Massage increases oxytocin and reduces adrenocorticotropin hormone in humans. Altern Ther Health Med. 2012;18:11-18. Abstract
    
    source: www.medscape.net
    
                                            

Prostate Tops List of Most Inheritable Cancers

One legacy that most men could do without is an inherited risk for prostate cancer, but a massive cohort study shows that for some men, genetic history hints at oncologic destiny.

Data on both identical (monozygotic) and fraternal (dizygotic) twins from the comprehensive birth-to-death registries in Denmark, Finland, Norway, and Sweden show that a man whose monozygotic twin has prostate cancer has a 32% risk for the disease himself, whereas a dizygotic twin whose brother has prostate cancer has only a 16% risk, said Jaakko Kaprio, MD, PhD, professor of genetic epidemiology at the University of Helsinki.

The estimated heritability of prostate cancer — the degree to which genes contribute to risk — was 58% (95% confidence interval, 52 - 63), which is the highest for any malignancy studied, Dr. Kaprio reported here at the American Society of Human Genetics 63rd Annual Meeting.

"These estimates for common cancers are greater than previously estimated. For rare cancers, such as testicular cancer, the concordance risk was substantial. We believe it provides an accurate estimate of familial risk prediction," Dr. Kaprio told Medscape Medical News.
 
Table. Cancers With Significant Heritability

Cancer Type	Heritability Estimate,     %	95% Confidence Interval
Prostate	58	52–63
Testicular	36	2–95
Breast	28	12–52
Kidney	23	11–42
Lung	25	12–44
Melanoma	39	8–81
Ovarian	28	15–47
Stomach	24	5–65
Uterine	24	14–87
Colon	16	2–63

The magnitude of the genetic contribution to prostate cancer found in this study is higher than the estimated 42% seen in a previous study of Nordic twins ( N Engl J Med. 2000;343:78-85). Dr. Kaprio explained that this difference can be attributed to the fact that his team expanded the original cohort to include data from Norway, had 10 additional years of follow-up data, and had an aging cohort, with a resultant increase in incident cancers.

Dr. Kaprio's team looked at data on 133,689 monozygotic and dizygotic pairs as part of the Nordic Twin Registry of Cancer. They used time-to-event analysis to estimate heritability and familial cancer risk.

What's Going On?
This study raises important questions about the interplay between genetics and environment in cancer, said Richard Stevens, PhD, professor of cancer epidemiology at the University of Connecticut Health Center in Farmington.

"It's a very strong study. The exciting thing about this study with prostate cancer is that it's certainly saying something about mechanism that we don't get," he explained.

The study supports the presence of genetic polymorphisms in prostate cancer, and to a lesser degree breast cancer, that can cumulatively contribute to risk, he said.

"The specific polymorphisms we're aware of — familial syndromes — account for very little breast cancer or prostate cancer. There are other genes where allelic variation and risk is moderate. There must be a lot of those genes with moderate risk; you put them together and it makes you more susceptible," Dr. Stevens said.
The study was supported by the Ellison Foundation and the Nordic Cancer Union. The study authors and Dr. Stevens have disclosed no relevant financial relationships. 
 
American Society of Human Genetics (ASHG) 63rd Annual Meeting: Abstract 43. Presented October 23, 2013.

source: www.medscape.net

CANCER: AN IMMINENT GLOBAL DISASTER

Cancer cases are expected to surge 57% worldwide in the next 20 years, an imminent "human disaster" that will require a renewed focus on prevention to combat, according to the World Health Organization.

The World Cancer Report, produced by the WHO's specialized cancer agency and released on World Cancer Day, predicts new cancer cases will rise from an estimated 14 million annually in 2012 to 22 million within two decades. Over the same period, cancer deaths are predicted to rise from 8.2 million a year to 13 million.

The rising incidence of cancer, brought about chiefly by growing, aging populations worldwide, will require a heavier focus on preventive public health policies, said Christopher Wild, director of the International Agency for Research on Cancer.

"We cannot treat our way out of the cancer problem," he said. "More commitment to prevention and early detection is desperately needed in order to complement improved treatments and address the alarming rise in cancer burden globally."

The report notes that the rocketing cost of responding to the "cancer burden" -- in 2010, the economic cost of the disease worldwide was estimated at $1.16 trillion -- is hurting the economies of rich countries and beyond the means of poor ones.

The report said about half of all cancers were preventable and could have been avoided if current medical knowledge was acted upon. The disease could be tackled by addressing lifestyle factors, such as smoking, alcohol consumption, diet and exercise; adopting screening programs; or, in the case of infection-triggered cancers such as cervical and liver cancers, through vaccines.

Cutting smoking rates would have a significant impact, as lung cancer remained the most commonly diagnosed cancer (1.8 million cases a year, or 13% of total cancer diagnoses) and the deadliest, accounting for about one-fifth (1.6 million) of all cancer deaths worldwide.

There is a silver lining to the report, some experts said: It may lend urgency to the fight against cancer. Countries such as the United States present examples of success stories stemming from legislation and financial resources devoted to cancer prevention.

Smoking rates remain high in Asia and Africa. China -- where one-third of the world's cigarettes are smoked, according to the World Health Organization -- only recently moved to ban indoor public smoking.

The report's authors suggested governments take similar legislative approaches to those they had taken against tobacco in attempting to reduce consumption of alcohol and sugary drinks, and in limiting exposure to occupational and environmental carcinogens, including air pollution.

According to the report, the next two most common diagnoses were for breast (1.7 million, 11.9%) and large bowel cancer (1.4 million, 9.7%). Liver (800,000 or 9.1%) and stomach cancer (700,000 or 8.8%) were responsible for the most deaths after lung cancer.

The report said the growing cancer burden would disproportionately hit developing countries -- which had the least resources to deal with the problem -- due to their populations growing, living longer and becoming increasingly susceptible to cancers associated with industrialized lifestyles.

More than 60% of the world's total cases occur in Africa, Asia and Central and South America.

And these regions account for about 70% of the world's cancer deaths - a situation that is made worse by the lack of early detection and access to treatment.

Annual figures include donations by private donors and governments for prevention and treatment. Spending by recipient countries not included. More than 90% of cancer funding is spent on anti-tobacco campaigns.

Experts say the good news is that we can all take straightforward steps to cut risk. About 30% of cancer deaths are due to the five risks: obesity, low fruit-and-vegetable intake, lack of physical activity, tobacco use, alcohol use.

Smoking is the single most important risk factor for cancer causing over 20% of global cancer deaths and about 70% of global lung cancer deaths. Cancer-causing viral infections such as HPV are responsible for up to a fifth of cancer deaths in low and middle-income countries.

Governments needed to appreciate that screening and early detection programs were "an investment rather than a cost," said Bernard Stewart, co-editor of the report -- and low-tech approaches had proven successful in some developing countries.

The World Cancer Report, which is published about once every five years, involved a collaboration of around 250 scientists from more than 40 countries. Tuesday is World Cancer Day.