All posts by Laura Damiano

Legumes are better than meat for our health

Cancer, Nutrition, , , , , , , , , , , , ,

March2A study published this month on Cell Metabolism1 reveals that a diet high in meat proteins increases the risk for health-related diseases, whereas a diet rich in plant proteins  does not show the same adverse effects.

The team guided by Dr. Longo at the University of Southern California analyzed a nationally representative study sample of 6,381 subjects from the National Health and Nutrition Examination Survey (NHANES) III program with an average age of 65 years. Considering the entire group, a high and moderate protein diet was positively correlated with diabetes-related mortality, but not cancer mortality. When the population was divided into two groups –  50-65 years and  65 and older- , the protein intake showed different effects on subjects’ health. Subjects in the midlife group, consuming a high protein diet had a 74% increase in the risk of all-cause mortality and four-times increase in the risk of cancer mortality compared to the low protein group. In contrast, a high protein diet did not have the same negative effects on elderly subjects. Elderly subjects consuming a high protein diet had a reduction in both all-cause (23%) and cancer mortality (60%), when compared to a low protein diet.  This may be due to the fact that elderly people have impaired digestive and nutrient absorption abilities that can cause malnutrition and frailty; therefore a higher protein intake is beneficial at older ages to prevent diseases.

The authors link the effect of protein consumption on mortality to the insulin-like growth factor 1 (IGF-1) , showing that in humans an increase in IGF-1 is correlated with an increased risk of cancer in subjects 50-65 years old with a high protein diet. Instead, IGF-1 levels decrease in elderly subjects. They also performed experiments in mouse models demonstrating that a low protein diet is responsible for smaller melanoma and breast cancer cell derived tumors with circulating levels of IGF-1 correlating with the protein content in the diet. However, the mechanism of IGF-1 involvement  in protein intake and mortality is not well elucidated.

Despite the lack of a well-defined mechanism, this study demonstrates that a low protein diet in middle age people is beneficial for preventing cancer mortality through “at least, in part, regulating circulating IGF-1″. These findings are important in a country, the United States, where adults consume 1.0–1.3 g grams of proteins/kg of body weight/day, instead of the 0.7 to 0.8 g of proteins/kg of body weight/day recommended by the Food and Nutrition Board of the Institute of Medicine. According to previous reports, this study also shows that plant proteins, such as legumes, do not have the same unfavorable effect of animal proteins; in contrast, their intake has beneficial effects at all ages!

Beans might be healthier than hamburgers!

1. Morgan E. Levine, Jorge A. Suarez, Sebastian Brandhorst, Priya Balasubramanian, Chia-Wei Cheng, Federica Madia, Luigi Fontana, Mario G. Mirisola, Jaime Guevara-Aguirre, Junxiang Wan, Giuseppe Passarino, Brian K. Kennedy, Min Wei, Pinchas Cohen, Eileen M. Crimmins, Valter D. Longo. Low Protein Intake Is Associated with a Major Reduction in IGF-1, Cancer, and Overall Mortality in the 65 and Younger but Not Older Population. Cell Metabolism, 2014; 19 (3): 407-417 DOI: 10.1016/j.cmet.2014.02.006

Breast cancer survival: run, don’t walk,

Cancer, , , , , , , , , , , , , , , , , ,

A recent Untitled-1 study from Dr. Paul T. Williams on International Journal of Cancer describes the benefits of intense physical exercises on breast cancer survival 1.

Physical activity improves our health conditions reducing the risk of many diseases, such as cardiovascular diseases, diabetes, and cancer. Previous studies linked regular physical exercises, even mild activity, with decreased breast cancer risk 2,3. Instead, the study reported here points out the importance of an intense physical activity over a mild activity.

Paul Williams from Lawrence Berkeley National Laboratory surveyed 986 breast cancer survivors, 272 runners and 714 walkers.  When the two groups where considered together, breast cancer mortality decreased proportionally to the hours of exercises (23.9% per metabolic equivalents-MET-hours/day). Instead, when the two groups were considered separately, breast cancer mortality was lower in runners than in walkers (66.5% difference), and in runners the mortality decreased proportionally to the hours of exercise (87.4% lower for 1.8 to 3.6 MET-hours/d). There was a correlation with age of death, suggesting that running was more effective in preventing mortality later than earlier in life. Although previous studies correlated BMI and adiposity with breast cancer mortality, in this report neither BMI, education, or diet influence the mortality. The incongruence might be due to the leaner cohort considered here, as pointed out by the same author. Physical activity alters metabolism, influencing blood concentration of different biomarkers used for breast cancer (estradiol, fasting insulin, and C-reactive protein), thus indicating a profound effect on its progression at the metabolic and molecular level.

As Williams discusses in the paper, this study presents some limitations, such as the small number of subjects. Moreover, although this study describes very accurately the information about women’s activity, it lacks some very useful information, such as data on the actual disease, receptor status, invasiveness, metastases or treatment. Given the low rate of mortality in this group, the women reported in this study seem to be a selected set of survivors with a less invasive disease.

Despite these limitations, the study presents for the first time the advantage of intense physical activity over mild activity, suggesting that exceeding the public health recommendations might be better for breast cancer survival, and probably for other health-related issues.

Therefore walking for 30 minutes for 5 days a week might not be enough!

 

  1. Paul T. Williams. Significantly greater reduction in breast cancer mortality from post-diagnosis running than walking. International Journal of Cancer, 2014; DOI: 10.1002/ijc.28740
  2. Hildebrand JS, Gapstur SM, Campbell PT, Gaudet MM, Patel AV. Recreational physical activity and leisure-time sitting in relation to postmenopausal breast cancer risk. Cancer Epidemiology, Biomarkers, and Prevention, October 2013
  3. Lauren E. McCullough, Sybil M. Eng, Patrick T. Bradshaw, Rebecca J. Cleveland, Susan L. Teitelbaum, Alfred I. Neugut, Marilie D. Gammon. Fat or fit: The joint effects of physical activity, weight gain, and body size on breast cancer risk.Cancer, 2012; DOI: 10.1002/cncr.27433

 

 

 

On the road of science: reproducibility, fraud, and authorship for sale

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Argentina 015 
Happy 2014!

This is my first post of the year and I would like to start this New Year reflecting on some concerning habits in science. I will just focus on only three recent articles that undermine the trustfulness of science, but there are many others out there in the jungle of scientific journals.

In a Comment published in Nature last November, Mina Bissell justifies the non-reproducibility of some in vitro experiments1`. Nowadays, “the techniques and reagents are sophisticated, time-consuming and difficult to master”, challenging the ability to reproduce complicated experiments in different laboratories. The solution, for Dr Bissell, “is to consult the original authors thoughtfully […] ask either to go to the original lab to reproduce the data together, or invite someone from their lab to come to yours.” However, this can be true for in vitro assays that are already an artifact, but I hope that it isn’t for in vivo studies used for preclinical studies. This article has opened an intense discussion on scientific reproducibility, as you can read in the comments published this month by Nature2. You can either agree or disagree with her statements, but we are spending words and time on a topic, experimental reproducibility, that shouldn’t be an issue.

Last December, Nature has reported the news regarding duplicated images used on different journals from the same group3.  Professor Fusco at the University of Naples (Italy) and an associate professor from the Academia of Lincei (Italy) are now under investigation by the police and the university. The misconduct has been revealed by Enrico Bucci, a molecular biologist founder of a small startup (BioDigitalValley) aimed at creating a database of all images from Italian papers published since 2000. Running all images on his gel-checking software, he found that out of 300 papers published from Fusco, 53 contained duplicated or cut and paste images, even one from 1985.  Some of the papers have already been retracted; one of them was published on Journal of Clinical Investigation in 2007.  It is highly possible that Fusco is only the first target of this operation that is going to reveal other misconducts. This is quite concerning not only because it is not a right practice, but also because it comes from a country, Italy, where scientific research is well behind and the funding situation is not good; this circumstance is not going to help Italian science. However, fortunately, this fraud has been unmasked.

An article published last November on Science describes a concerning practice in the Chinese scientific community4. Some intermediary agencies sell authorships on papers that have already been accepted for publication, sometimes without the consent or the knowledge of the actual authors. The price for this service varies based on the position in the author’s list. Thus someone can publish a paper not only without doing anything, but also without even knowing the authors. These practices worry the same Chinese scientific community because “hinder China’s growth in original science, damage the reputation of Chinese academics, and dampen the impact of science developed in China”, as asserted by the president of the National Natural Science Foundation of China, Wei Yang in the Editorial published on the same number of Science5.

These are just three examples of the present scientific world. Every month there is at least one retraction, at every meeting there is someone who mistrusts other’s experiments.  Unfortunately we are in a system that gives rewards and funding to sexy science and high Impact Factors publications at the expenses of the truth, the real science, made by simple and reproducible experiments and not artifactual and sexy assays.

Where is science going?

1 Bissell M. Reproducibility: The risks of the replication drive. Nature. 2013 Nov 21;503(7476):333-4.

2 NATURE ’S READERS COMMENT ONLINE.Nature. 2014 Jan 2;505:27.

3 Abbott A. Image search triggers Italian police probe. Nature. 2013 Dec 5;504(7478):18.

4 Hvistendahl M. China’s publication bazaar. Science. 2013 Nov 29;342(6162):1035-9.

5 Yang W. Research Integrity in China. Science. 2013 Nov 29;342(6162):

The life of adult survivors of childhood cancer

Cancer, , , , , , , , ,

DecemberSurvivors of childhood and adolescent cancer have impaired health-related quality of life (HRQQL) and show accelerated aging.

A team from the St. Jude Children’s Hospital analyzed frailty and health-related symptoms in a large cohort of childhood cancer survivors (CCS) and reported them in two consecutive articles published in the Journal of Clinical Oncology in the last two months 1 -2.

In the first study, the participants were 1,662 survivors with more than 10 years from diagnosis. Among the 12 classes of symptoms considered for HRQQL there were cardiac, pulmonary, motor/movement, pain in head, in back/neck, pain involving sites other than head, neck, and back, sensation abnormalities, learning/memory, anxiety, depression, and somatization. 77%of the subjects reported more than one symptom and more than 50% had pain involving sites other than head, neck and back, and disfigurement. The prevalence of the symptoms was higher in this cohort than in the average population of the same age.

In the second study, frailty was defined by the presence of at least two of the following symptoms: low muscle mass, self-reported exhaustion, low energy expenditure, slow walking speed, and weakness. 1,992 survivors where compared to 341 subjects without cancer and 13.1% of women and 2.9% of men were qualified as frail with an average age of 33 years. Frailty was associated with smoking and body mass index in men, while lifestyle choices didn’t affect frailty in women. Also, the kind of cancer treatment, such as cranial radiation therapy (CRT) and abdominal/pelvic radiation in men and only CRT in women, affected the frailty phenotype. As expected in both sex, frailty was associated with increasing age. Frailty is usually reported in people 65 years old or older, therefore such phenotype indicates early aging.

Both these studies highlight the impact of the disease and of the treatments on CCS’ quality of life.  Advances in cancer treatment resulted in an increased number of survivors, who are facing the long term consequences of these treatments.   The importance of these reports is that they are the first reports studying quality of life and aging in such a large cohort of patients. However they present some limitations. For instance, despite the large cohort, the subjects are all from one institution in the United States. Therefore, to find new correlative associations and elucidate the biological causes and mechanisms triggering this phenotype, in the future the study has to be extended to other institutions and other Countries.

Many studies have been published on this cohort of CCS in the last year from the same group of people highlighting different aspects that impair survivors’ quality of life so accurately. If you’re intrigued after reading this post, I would suggest you to do a search on Pubmed to broaden your knowledge.

1 Huang IC, Brinkman TM, Kenzik K, Gurney JG, Ness KK, Lanctot J, Shenkman E, Robison LL, Hudson MM, Krull KR. Association between the prevalence of symptoms and health-related quality of life in adult survivors of childhood cancer: a report from the st Jude lifetime cohort study. J Clin Oncol. 2013 Nov 20;31(33):4242-51. doi: 10.1200/JCO.2012.47.8867. Epub 2013 Oct 14.

2 Ness KK, Krull KR, Jones KE, Mulrooney DA, Armstrong GT, Green DM, Chemaitilly W, Smith WA, Wilson CL, Sklar CA, Shelton K, Srivastava DK, Ali S, Robison LL, Hudson MM. Physiologic Frailty As a Sign of Accelerated Aging Among Adult Survivors of Childhood Cancer: A Report From the St Jude Lifetime Cohort Study. J Clin Oncol. 2013 Nov 18. [Epub ahead of print]

 

Motherhood discrimination in science

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Novembre“The view of my colleagues is that for a man, an engineer is able to do what he is supposed to do, but for a woman, she always has to demonstrate she is able”1.

Nowadays, in the XXI century, women have obtained rights that rank them at the same level as men, but they still experience discrimination in many sectors of the society. While women participation has increased in almost all the professions in the last 20 years, they are still underrepresented in science, engineering, and technology (SET) sectors.

Although the number of women graduating and with high level of education in SET is not decreasing, the number of women at senior positions has reached a deadlock. The reasons for this gender disparity are different (i.e. long working hours, necessity to travel) and perpetuate masculine tradition in these settings.

A recent article by Herman C. et al.1 analyzes women discrimination in the scientific world focusing not on gender disparity, but on motherhood discrimination.  They interviewed women SET professionals working in multinational companies (MNCs) in three European Countries-Italy, France, and The Netherlands-where the proportion of women in SET is equivalent, but the norms for working parents and hour flexibility are different.  They divide the women in three different categories: assimilation, cul de sac, breaking the mould, and lying low.  Women who followed the assimilation strategy are those who accepted the existing structures and continued to work long hours and travel to fulfill their career aspiration. Another group of women who accepted the existing structure are those in the cul de sac category, who had stalled their career and had no more interest in advancing. A third group (breaking the mould), characterized by very ambitious and motivated women, didn’t conform to the existing structure and tried to change the norms to follow their career aspirations.  At last the lying low women retained their ambition, but were pushed away from their career progression by the corporation. They found women in all categories in the three countries with some peculiarity. For instance, In Italy, the assimilation system prevails because there are no norms for hour flexibility, therefore women have to conform to the system or quit the corporation. On the other hand, the lying low strategy has been institutionalized in France and is common in The Netherlands, where the norms for hour flexibility and part-time made this possible.

Despite the environment, many women returned to work part time and this, together with their new status as “mothers”, undermined their career opportunities. The same companies expressed their concern about their female employees coming back after maternity leave and failing to achieve higher levels of management. Although some women were still able to progress and achieve their career goals, these situations were considered exceptional.

In this study, the authors present for the first time an analysis of motherhood discrimination over women discrimination. As pointed out by the study, the situation can be different based on the Country, company norms and managers. To have a broader spectrum of the actual situation, the analysis has to be extended to different Countries and companies.

Women SET professionals have to face first gender discrimination, and then later in their career also motherhood discrimination, thus making their progression and life very hard. Studies, discussions, blogs on this topic underscore the “exceptionality” of successful mothers in SET sectors, and, I believe, in many others. How many studies do we need before this situation is going to change?

As a new mom, I would like to quote an interviewed woman in the study described here.

“I take care of my children first, because they won’t wait for me to grow up…”

Source

1Herman C, Lewis S, and Humbert AL. Women Scientists and Engineers in European Compnies: Putting Motherhood under the Microscope. Gender, Work and Organization, Vol.20 No.5 Sept 2013

The first cancer drug for neoadjuvant treatment is on its way

Cancer, , , , , , , ,

October 2013At the beginning of September a group of experts, the FDA’s Oncologic Drugs Advisory Committee (ODAC), recommended accelerated approval of the Genentech’s drug Perjeta (Pertuzumab) for neoadjuvant treatment of early stage Her-2 positive breast cancers.

The Committee voted 13 to 0 with one abstention for the approval of Perjeta in combination with other two drugs, docetaxel and trastuzumab, another Genentech drug against Her-2. The FDA will return a verdict before the end of October. If approved, Perjeta is going to be the first nation’s cancer drug used to treat cancer patients before surgery with the purpose of shrinking the tumor to make it operable and allow breast conserving surgery.

Perjeta was approved by FDA in 2012 to treat metastatic HER-2 positive breast cancers after surgery. It is an antibody that binds to the Her-2 receptor inhibiting its activity by preventing the binding with other members of the Her-2 family.

The panel of experts based their decision on three clinical trials, two Phase II trials (NEUROSPHERE and TRYPHAENA) involving early breast cancer patients, and a Phase III trial (CLEOPATRA) with metastatic breast cancer patients. The NEUROSPHERE and TRYPHAENA were both conducted on patients with early stage Her-2 positive breast cancer, using two different regimen of chemotherapy.  NEUROSPHERE used Perjeta and Herceptin in combination with docetaxel, and TRYPHAENA used Perjeta and Herceptin in combination with anthracycline. The pathological complete response (pCR) was improved in both trials in patients using Perjeta in combination with the other drugs.  The increased efficacy of Perjeta combined with Herceptin is probably due to the binding of the two antibodies to two different regions of the Her-2 receptor, thus synergistically inhibiting its activation.

20% of breast cancer patients are Her-2 positive and those are the ones who are going to benefit from this treatment. This kind of tumor is very aggressive with 6,000 women dying every year in the US, mainly because of its inoperability. This drug will help to decrease the tumor volume, thus making it operable.

Genentech is part of the big Swiss pharmaceutical company Roche. Genentech has spent more than 30 years studying breast cancer leading to the commercialization of the first drug approved to treat Her-2 positive breast cancers, Herceptin. Genentech is going to lose the patent exclusivity for Herceptin in 2014 in Europe and 2018 in the US. Probably this market will be replaced by Perjeta…

This drug will treat breast cancer and Genentech’s budget.

The frightening effect of the word “cancer”

Cancer, , , , , ,

Did you know that Ductal Carcinoma In Situ (DCIS), noninvasive breast cancer, breast lesion or abnormal cells have all the same meaning? A very recent study from a team of the University of California San Francisco (UCSF) describes the impact of complicated medical terminology on patient treatment preference.

september 2013Since medical terms may sometimes sound too complicated and cryptic, health care provider’s communication with their patients is critical for a full understanding of medical conditions, diagnosis and treatments. In the research letter published on JAMA Internal Medicine on August 26th, Ozanne M. et al.1 explored the effect of Ductal Carcinoma In Situ (DCIS) terminology on the choice of patient treatment.

DCIS is the most common type of non-invasive breast cancer, accounting for the 20-25% of newly diagnosed breast cancers in the United States. It is treated with mastectomy or lumpectomy, with or without radiation therapy, and with or without adjuvant hormonal therapy2. In some low-grade cases, the progression may occur in a very long time frame (5 to 40 years), with no relevant clinical significance during patient’s life. Therefore, in these cases a watchful waiting period has been proposed instead of a treatment, even if it might be difficult to convince of this a patient who has just discovered to have “cancer”.

The team of doctors from UCSF hypothesized that without using the word cancer, the women diagnosed with DCIS might be more prone to non-invasive approaches. They surveyed 394 healthy women with no history of breast cancer and presented them 3 scenarios to describe the diagnosis of DCIS: noninvasive breast cancer, breast lesion or abnormal cells. To all of them was presented the same outcomes and options of treatment (surgery, medication, or active surveillance). They found that when DCIS was described as a high risk condition (breast lesion, or abnormal cells) instead of a cancer, more that 66% of women chose non-surgical treatments, whereas when the term noninvasive cancer was used only 53% of the participants chose a non-surgical option.

As pointed out in the original article, the current study has some limitations, being performed on a restricted cohort of educated and well insured women, different from the cohort of DCIS patients, and without taking into account specific factors, such as tumor grade and age. Although this analysis was performed on healthy women who didn’t have cancer, it suggests that many patients may prefer noninvasive therapies, when allowed to carefully consider risks and treatments, pointing out the importance of the terminology used by health care providers.

Too often, people are confused after leaving their physician’s office and this is something that should not happen, especially when dealing with serious and heterogeneous diseases, such as cancer. Hopefully this study is not a drop in the bucket and will be taken into consideration in the future, leading to a careful elucidation of the puzzling medical dictionary.

1              Omer, Z. B., Hwang, E. S., Esserman, L. J., Howe, R. & Ozanne, E. M. Impact of Ductal Carcinoma In Situ Terminology on Patient Treatment Preferences. JAMA Intern Med, doi:10.1001/jamainternmed.2013.84051731962 [pii] (2013).

2              Virnig, B. A., Wang, S. Y., Shamilyan, T., Kane, R. L. & Tuttle, T. M. Ductal carcinoma in situ: risk factors and impact of screening. J Natl Cancer Inst Monogr 2010, 113-116, doi:10.1093/jncimonographs/lgq024lgq024 [pii] (2010).

 

Cancer is a family affair

Cancer, , , ,

A recent study describes the relationship between Family History of cancer and cancer risk for the same type or for a different type of cancer on a wide network of cases collected in Switzerland and Italy. 

When someone is diagnosed with cancer, members of the family start periodical check-up, frightened by the idea that cancer could easily affect other relatives.   Although approximately only the 7%  of cancers are hereditary with known mutations that imprint the risk of cancer in the genes, scientists often refer to familial cancer. Indeed some type of tumors commonly spread in certain families. However, there are no other hereditary factors -other than gene mutations- known to drive the disease.

An interesting  study published in the Journal  “Annals of Oncology” by Turati et al. 1 last July tries to elucidate the relationship between Family History of cancer (FH) and cancer risk. The researchers provide a quantitative association of FH and risk of developing the same type or a different type of tumor in a cohort of 23000 individuals (11000 controls and 12000 cancer cases) collected in Switzerland and Italy between 1999 and 2009.  They analyzed 13 cancer types (mouth and pharynx, nasopharynx, esophagus, stomach, colorectum, liver, pancreas, larynx, breast, womb, ovaries, prostate and kidneys) and incorporated several information, such as sociodemographic characteristics, lifestyle, dietary habits, and personal medical history.

In all cases, they found higher risk of developing cancer when a first degree relative had a history of the same type of cancer. Interestingly, the researchers found a plethora of associations between cancers of different origin: esophageal cancer and FH of oral and pharyngeal cancer, breast cancer and FH of colorectal and of hemolymphopoietic cancer, ovarian cancer and FH of breast cancer, prostate cancer and FH of bladder cancer.  Some associations were stronger if analyzed in subjects before 60 years old (colorectal and FH of ovarian cancer and prostate cancer or endometrial cancer and FH of stomach cancer).

august 2013Some of these associations were already known. For example, subjects with BRCA1/2 mutations have increased risk of developing breast and ovarian cancer, as well as prostate, colon and pancreatic cancers.  However, as they properly point out in their article, these mutations are associated with an increased risk, but “they are too rare to account for a substantial proportion of common cancers”. They may predispose to cancer, but other factors might concur in the development of a familial cancer. For instance, intrinsic factors, such as genetic polymorphisms occurring in the same family, or extrinsic factors, such as the environment and lifestyle habits, could affect the spread of cancer.  Indeed, alcohol and tobacco are associated with increased risk of developing tumors. In some cases, cancer incidence was found higher in males than in women, in part due to a largest consumption of alcohol and tobacco  among men in the past. These trends might change in the future. On one hand, women now consume as much alcohol and tobacco as men do, leading to a potential higher incidence of cancer in the female population. On the other hand, the anti-tobacco advertisements might have a positive effect and tobacco might  be a limited issue in the future.

Family history of cancer has been studied for a long time, but lack of complete information limited rigorous epidemiological studies. The present study incorporates information about lifestyle and subjects’ characteristics for adjustment purposes which haven’t been considered previously, leading to better insights on how cancer can spread in some families. More analyses of this kind are needed in other population datasets to make a wide correlation between family history and risk of cancer.

We need to be aware that if cancer occurs in one member of a family, in some cases there might be either a genetic or an environmental factor that can predispose other members of the family.  We need to know, to prevent it.

1. Turati, F. et al. Family history of cancer and the risk of cancer: a network of case-control studies. Ann Oncol, doi:mdt280 [pii] 10.1093/annonc/mdt280 (2013).