Alcohol And Cancer

Even moderate alcohol consumption can increase the risk of cancer.

Consuming alcoholic beverages, even in moderation, may increase your risk of developing certain cancers, according to a new statement released by the American Society of Clinical Oncology (ASCO).

"People typically don't associate drinking beer, wine, and hard liquor with increasing their risk of developing cancer in their lifetimes," Dr. Bruce Johnson, president of the ASCO, an organization of cancer doctors, said in a statement.

Consuming just 1 alcoholic drink a day increases breast cancer risk, report finds…

…Ashton said that moderate alcohol consumption is defined as up to an average of one drink a day for women (or seven drinks per week) and two drinks a day for men (or 14 drinks a week). She added that this can also cause confusion because of the various types of alcohol available.

For wine, a standard serving size is considered to be 5 ounces. For beer, 12 ounces is considered a standard serving size. Meanwhile, for hard liquor, 1.5 ounces is considered a standard serving. Ashton adds that if you pour more than these standard serving sizes, it counts for more than one drink.

Ashton said alcohol consumption has been shown to be a causative factor in a wide range of cancers, including cancer of the head and neck, esophagus, breast and colon. It may also be associated with liver cancer, according to Ashton.

On the other hand, we are sometimes told about cardiovascular benefits to moderate wine consumption for example.  I’m not an alcohol drinker myself.  Listen to your doctor’s advice about this.

Heavy Metal Music Toxicity?

By Flickr user Wok - http://www.flickr.com/photos/wok/12916031/, CC BY 2.0, https://commons.wikimedia.org/w/index.php?curid=887535

It would appear that lovers of “heavy metal” music (HMML) have certain “alterations” of brain function, compared to fans of classical music (CML), and we can assume these alterations are not good because the authors of this study conclude that “The results may partly explain the disorders of behavioral and emotional cognition in HMML compared with CML and are consistent with our predictions. These findings may help provide a basic understanding of the potential neural mechanism of HMML.”

Assuming these findings can be replicated and are of relevance, the question is whether they are cause or effect. Does listening to “heavy metal” cause the alterations, or is it that people already having the alterations (for whatever reason) are prone to be HMML?  Or both – some people are predisposed to be HMML because of their neural wiring, but then listening to the music creates positive feedback to reinforce the differences?  Abstract:

The aim of this study was to investigate the spontaneous neural activity and functional connectivity (FC) in heavy metal music lovers (HMML) compared with classical music lovers (CML) during resting state. Forty HMML and 31 CML underwent resting-state functional MRI scans. Fractional amplitude of low-frequency fluctuations (fALFF) and seed-based resting-state FC were computed to explore regional activity and functional integration. A voxel-based two-sample t-test was used to test the differences between the two groups. Compared with CML, HMML showed functional alterations: higher fALFF in the right precentral gyrus, the bilateral paracentral lobule, and the left middle occipital gyrus, lower fALFF in the left medial superior frontal gyrus, an altered FC in the default-mode network, lower connectivity between the right precentral gyrus and the left cerebellum-6 and the right cerebellum-3, and an altered FC between the left paracentral lobule and the sensorimotor network, lower in the right paracentral lobule and the right inferior temporal gyrus FC. The results may partly explain the disorders of behavioral and emotional cognition in HMML compared with CML and are consistent with our predictions. These findings may help provide a basic understanding of the potential neural mechanism of HMML.

Obesity, Hypoxia, And Breast Cancer

Public Domain, https://commons.wikimedia.org/w/index.php?curid=1273807

Hypoxia – oxygen deprivation – in tumor tissue can promote cancer development, including breast cancer.  A factor stimulated by hypoxia can affect metastasis through neovascularization (new blood vessel formation).  Obesity can increase hypoxia in adipocytes (fat cells), promoting a favorable environment for tumor cells in breast fat tissue; adipocytes have been shown to enhance expression of the aforementioned factor that promotes blood vessel formation for tumors. More evidence showing the consequences of the obesity epidemic, and the consequences of the media effort to normalize obesity.  Abstract:

OBJECTIVE:The development of breast cancer cells is linked to hypoxia. The hypoxia-induced factor HIF-1α influences metastasis through neovascularization. Hypoxia seems to decrease the responsiveness to hormonal treatment due to loss of estrogen receptors (ERs). Obesity is discussed to increase hypoxia in adipocytes, which promotes a favorable environment for tumor cells in mammary fat tissue, whereas, tumor cells profit from good oxygen supply and are influenced by its deprivation as target regions within tumors show. This review gives an overview of the current state on research of hypoxia and breast cancer in human adipose tissue.METHODS:A systematic literature search was conducted on PubMed (2000-2016) by applying hypoxia and/or adipocytes and breast cancer as keywords. Review articles were excluded as well as languages other than English or German. There was no restriction regarding the study design or type of breast cancer. A total of 35 papers were found. Eight studies were excluded due to missing at least two of the three keywords. One paper was removed due to Russian language, and one was dismissed due to lack of adherence. Seven papers were identified as reviews. After applying exclusion criteria, 18 articles were eligible for inclusion.RESULTS:Two articles describe the impairment of mammary epithelial cell polarization through hypoxic preconditioning. A high amount of adipocytes enhances cancer progression due to the increased expression of HIF-1α which causes the loss of ER α protein as stated in four articles. Four articles analyzed that increased activation of HIF's induces a series of transcriptions resulting in tumor angiogenesis. HIF inhibition, especially when combined with cytotoxic chemotherapy, holds strong potential for tumor suppression as stated in further four articles. In two articles there is evidence of a strong connection between hypoxia, oxidative stress and a poor prognosis for breast cancer via HIF regulated pathways. Acute hypoxia seems to normalize the microenvironment in breast cancer tissue and has proven to affect tumor growth positively as covered in two articles.CONCLUSION:This review indicates that the development of breast cancer is influenced by hypoxia. A high amount of adipocytes enhances cancer progression due to the increased expression of HIF-1α.

Aspirin Against Preeclampsia

By Nephron - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=10874506

Preeclampsia is a disorder of pregnancy featuring high blood pressure and other physical manifestations, and which is linked to poor outcomes for mother and child.  Aspirin – a drug with an impressive array of health benefits (including cardiovascular and decreased risk of colorectal cancer, besides its typical use for pain, fever, and inflammation) now has shown to have preventive properties against preeclampsia.  Abstract:

Aspirin is currently the most widely prescribed treatment in the prevention of cardiovascular complications. The indications for the use of aspirin during pregnancy are, however, the subject of much controversy. Since the first evidence of the obstetric efficacy of aspirin in 1985, numerous studies have tried to determine the effect of low-dose aspirin on the incidence of preeclampsia, with very controversial results. Large meta-analyses including individual patient data have demonstrated that aspirin is effective in preventing preeclampsia in high-risk patients, mainly those with a history of preeclampsia. However, guidelines regarding the usage of aspirin to prevent preeclampsia differ considerably from one country to another. Screening modalities, target population, and aspirin dosage are still a matter of debate. In this review, we report the pharmacodynamics of aspirin, its main effects according to dosage and gestational age, and the evidence-based indications for primary and secondary prevention of preeclampsia.

Problems With Cancer Model Systems

Patient-derived xenografts (PDXs) – where human tumors are transplanted into immunodeficient mice to test for therapeutic approaches – are popular research models in cancer research.  The underlying premise is that the transplanted tissue will “faithfully represent” the original human tumor, but here is a paper suggesting otherwise, showing significant genetic changes that occur.  This of course puts into question how effective the model system is.  It is important to know the limitations of a model system and strive for improvement; it is also important to use the tools at hand.  There is currently no perfect model system for human cancer.  Human cancer cells in culture are a very useful model, but cells in culture are not a human tumor, and the cells of course change over time, so they are not “faithfully representing” the original tumor; various 3-D cell culture models, organoids, etc. are useful but also come with caveats; animal models (transgenics, xenografts, dietary or chemical challenges on wild-type mice) are also useful, but we remember that mice are not humans, and as we see in this paper, transplanted human tissue can change over time.  There is always a hurdle going from therapies tested in model systems to their efficacy in actual human patients, and the variability between models and humans is one major cause for this.  But we must do the best we can with the tools we currently have at hand.  With all their faults, PDXs can yield valuable data; we just need to be careful with the interpretation – and always look toward developing a better model system.  Abstract:

Patient-derived xenografts (PDXs) have become a prominent cancer model system, as they are presumed to faithfully represent the genomic features of primary tumors. Here we monitored the dynamics of copy number alterations (CNAs) in 1,110 PDX samples across 24 cancer types. We observed rapid accumulation of CNAs during PDX passaging, often due to selection of preexisting minor clones. CNA acquisition in PDXs was correlated with the tissue-specific levels of aneuploidy and genetic heterogeneity observed in primary tumors. However, the particular CNAs acquired during PDX passaging differed from those acquired during tumor evolution in patients. Several CNAs recurrently observed in primary tumors gradually disappeared in PDXs, indicating that events undergoing positive selection in humans can become dispensable during propagation in mice. Notably, the genomic stability of PDXs was associated with their response to chemotherapy and targeted drugs. These findings have major implications for PDX-based modeling of human cancer.

Uber-fiber dish

Here is a recipe for a dish that will boost everyone's fiber intake. Why should you care about fiber? Read this and this.

For the last couple of years, our family has been trying to increase the fiber intake not only by having more veggies and fruit, but also by buying high-fiber breads, pasta and flour.

This recipes calls for whole wheat spaghetti (or any other whole wheat pasta) and lots of chickpeas

Ingredients:
Whole wheat pasta, boiled
Buffalo wing sauce (to taste)
3-4 stalks of celery, cut thinly
2 cans (15 oz) of chickpeas (drained and mashed)
one sweet onion, peeled, sliced thinly
one red (or any other color) pepper, sliced thinly
3-5 garlic cloves, pressed
3 Tbsp olive oil

Preparation:
Boil the pasta according to the package directions. I usually prepare industrial amounts and freeze in batches. For this recipe, I thawed one of these endless pasta portions.

Heat the oil in a pan and add onion and pepper; mix occasionally, and keep under cover to soften and preserve the liquid. When the veggies are soft, add the garlic. Mix and cook with the garlic for a minute. Mix the veggies with the pasta.

Next, prepare the chickpeas: mix the mashed beans with the chopped celery and add Buffalo wing sauce to taste. To serve, scoop some pasta and some chickpeas on the plate, or mix together. The result is delightfully spicy!

CRISPR For HIV Treatment?

This paper is an analysis of the future potential of the CRISP gene editing method as a therapeutic approach against HIV infection.  It needs to be noted that there is nothing on the horizon, and methodologies, including delivery of the system to the relevant infected cells, needs to be worked out.  Nevertheless, I provide the abstract here for interested individuals who wish to delve deeper into the topic:

The huge success of current antiretroviral therapy is mediated by a triple effect: (i) Halting progression to AIDS in infected persons; (ii) reducing the risk of transmission to contacts (treatment as prevention); and (iii) minimizing the risk of HIV acquisition treating uninfected persons at risk (pre-exposure prophylaxis). However, UNAIDS has estimated that only 70% of infected people globally are diagnosed, only 53% are treated, and overall 44% have undetectable viral load, which is the necessary request for ensuring any antiretroviral benefit. Thus, with 37 million people currently living with HIV worldwide and more than 2 million new infections per year, the prospects for global HIV eradication are far on the horizon. Over the past couple of years, rapid development has been seen for technologies enabling modification of gene expression, either by direct inhibition by RNA interference (RNAi) or by genomic modification at DNA level. In particular, genome-editing endonucleases have significantly improved our ability to make precise changes in the DNA of eukaryotic cells. Notably, firstgeneration genome-editing technologies (i.e., ZFNs and TALENs) have been replaced by clustered regularly interspaced short palindromic repeats (CRISPR/Cas9), which work with a short guide RNA (gRNA) to hybridize to a target DNA site and recruit the Cas9 endonuclease. Once integrated into the host genome, HIV gene expression is regulated by the LTR promoter. Hypothetically, gene editing of the HIV promoter might have the potential to deactivate viral transcription by the introduction of mutations or fragment excision. HIV gene therapy progressed very slowly until recent breakthroughs in gene-editing methods using CRISPR/Cas9 (Liao et al. Nat Commun 2015;6:6413). Using a shorter version of the Cas9 endonuclease ensembled into an adenoviral vector, critical segments of thAQ!e viral DNA genome spanning between the LTR and gag regions were successfully removed in HIV transgenic mice. Excision was confirmed in all examined tissues as well as in circulating lymphocytes and resulted in a drastic reduction of HIV-RNA (Kaminski et al. Gene Ther 2016;23:690-5). Moreover, using latently infected CD4+ T lymphocytes from HIV-infected persons, lentiviral-delivered CRISPR/Cas9 precisely removed the entire HIV genome spanning between the 50 and 30 LTRs of integrated HIV proviral DNA (Kaminski et al., Sci Rep 2016;6:22555), providing a proof of concept of the high potential of genome-editing technologies. Before moving to the clinic, the CRISPR/Cas9 technology must solve several major issues in the HIV scenario. First, generation of resistance is a major concern. Mutations may occur surrounding the targeted site and result in the selection of strains that are no longer recognized nor cleaved by CRISPR (Badia et al. Curr Opin Virol 2017;24:46-54). The efficacy of the anti-HIV CRISPR/Cas9 strategy is highly dependent on the gRNA sequence, yet some mutant viral strains show poor or no cleavage at all. Higher CRISPR/Cas9 pressure could delay but not eliminate viral replication when using a combination of distinct gRNAs targeting distinct HIV proviral genes. In this case, although the reading frame may remain unaltered, an accumulation of insertions and/or deletions may occur in the target sequence, rendering new viral strains insensitive to CRISPR/Cas9 cleavage. Finally, double-strand breaks resulting from CRISPR/Cas9 activity and subsequent cellular non-homologous end joining machinery may introduce mutations in sequences that are no longer recognized by the gRNA, and therefore not susceptible to Cas9 cleavage. A second consideration is a need for developing safe and effective mechanisms of delivery. Adenoviral vectors have long been studied in gene therapy and represent an ideal viral vector for transduction at different tissues. However, the packaging size of adenoviral vectors is a limiting factor, especially for CRIPSR/Cas9. Third, HIV has a genome of about 10 kb while a gRNA generally only targets 20 bp of the DNA molecule, which means that there are thousands available targeting sites for the provirus in latently infected cells. To date, there is no platform established solely for gRNA candidate evaluation in HIV provirus eradication. A final consideration is an access to all tissues and cells potentially harboring the HIV provirus, including reservoirs as the central nervous system. In this regard, efforts are being focused in the development of Cas9/gRNA nanoparticle formulations. To overcome these problems, a group in Florida recently developed human transgenic cells that may be used for gene-editing studies and as platform for high-throughput screen of HIV provirus disrupters (Huang et al. Sci Rep 2017;7:5955). Of note, Cas9 protein instead of a Cas9 plasmid was used. Compared to a plasmid introduction, Cas9 protein agents could be easily quantitatively applied and standardized, mimicking better real clinic scenarios. In summary, RNAi-based technologies have widely dominated gene therapy research during the past decade, with overall slow progress. However, the advent of new gene-editing technologies, and especially the CRISPR/Cas9 system, has revolutionized the field. In the HIV context, CRISPR/Cas9 applications might go further than those of RNAi, for example, enabling excision of segments of integrated proviral DNA from latently infected cells and allowing complete provirus elimination, or it may be used to reverse HIV latency. Although important challenges still need to be overcome, a promising pathway to HIV cure seems to have been found.

The Real Headless Horseman: Obesity

By John Quidor - aQHCpcwsbaMXQA at Google Cultural Institute maximum zoom level, Public Domain, https://commons.wikimedia.org/w/index.php?curid=22126482

For Halloween, we need to remember that much of the “treats” that children are getting are extremely unhealthy. Most treats are sugar/fat/high fructose corn syrup laden candy.  As a once-a-year event, this might be fine (in moderation), but with childhood obesity and metabolic syndrome on the rise, and colon cancer diagnosed at ever-younger ages (possibly due to weight problems), consuming such junk food should not be a habit.  It’s not “The Headless Horseman” stalking the land, but the obesity epidemic, and fewer and fewer of us are as slim as Ichabod Crane.

Do Bacteria Run The Show?

http://www.hypothesisjournal.com/wp-content/uploads/2016/11/HJ479_Fig1.png

Are humans merely vehicles for accomplishing the objectives of bacteria (and life in general) to spread itself?  Here is a hypothesis paper that suggests that prokaryotes (e.g., bacteria) have followed a two-pronged strategy to shape higher eukaryotes (e.g., humans) to achieve the end of spreading bacteria worldwide and spacewide: via the mitochondria (derived from an ancient prokaryote and symbiosis) and the microbiome. Of course, we are not talking about conscious strategies; there is no anthropomorphizing of bacteria!  But the end result of selection and the general tendency of life to find ways of spreading has led to this conclusion. Abstract:

Beyond considering that humans are not just composed of eukaryotic cells but also of a huge number of microbes playing pivotal roles in the overall organism functioning, in this article it is additionally suggested to look at eukaryotic cells as a kind of evolved community of bacteria-derived individuals. Mitochondria are fundamental organelles for energy production, but also for driving cell fate. Although it is perfectly established that mitochondria are phylogenetically linked to bacteria, with theories suggesting they survived in a symbiotic parasitism within an ancestral eukaryotic cell, we alternatively encourage their consideration as the main orchestrators of eukaryogenesis. Bacteria gradually evolved into mitochondria, while the social interrelationship and architecture of a prokaryotic community transformed into eukaryotic cells. Last but not least, given the role of bacteria on Panspermia, and by converging mitochondrion and microbiome potential to respectively modulate cell and whole organism functioning, we wonder whether superior animals and in particular humans might be so far the most evolved product coming from two main bacterial socio-evolutive strategies engaged in an attempt to endure living matter expansion.

Conclusion:

In conclusion, independently of whether humans are simply a “clothing”, a subject hijacked by the host or the final refined product resulting from the convergence of two different microbial socio-evolutive strategies, it might be worth giving more consideration to the fact that the ultimate “aim” of bio-evolution is not humans but the perpetuation of living matter. Humans could be just a piece of the whole biosphere puzzle and might not be necessarily the most important nor the end result. We may simply be the most sophisticated living matter approach, intentional or not, engaged in an attempt to endure a goal of bioevolution that is panspermia (38-44,113-116).

Load And Resistance Training Results

Take home point: to build muscle only, one can use both heavy or lighter resistance.  To build strength, heavy is required.  Thus, if you want both, tend to train on the heavy side – but caveat emptor about injury risk and of course it is your responsibility to get medical consultation before starting any sort of physical activity program.  

Abstract:

The purpose of this paper was to conduct a systematic review of the current body of literature and a meta-analysis to compare changes in strength and hypertrophy between low- versus high-load resistance training protocols. Searches of PubMed/MEDLINE, Cochrane Library and Scopus were conducted for studies that met the following criteria: 1) an experimental trial involving both low- (≤60% 1 RM) and high- (>60% 1 RM) load training; 2) with all sets in the training protocols being performed to momentary muscular failure; 3) at least one method of estimating changes in muscle mass and/or dynamic, isometric or isokinetic strength was used; 4) the training protocol lasted for a minimum of 6 weeks; 5) the study involved participants with no known medical conditions or injuries impairing training capacity. A total of 21 studies were ultimately included for analysis. Gains in 1RM strength were significantly greater in favor of high- versus low-load training, while no significant differences were found for isometric strength between conditions. Changes in measures of muscle hypertrophy were similar between conditions. The findings indicate that maximal strength benefits are obtained from the use of heavy loads while muscle hypertrophy can be equally achieved across a spectrum of loading ranges.