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Breast Cancer spreads more aggressively at night

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I finally got an account, just so I could post these links.

From the ScienceAlert article on the Nature article:

"The researchers ran experiments where they gave some mice jet lag by changing the light-dark routine. Messing with the circadian rhythm led to a massive decrease in the concentration of circulating tumor cells in mice. 

In another experiment, the researchers tested whether giving the mice hormones that were similar to those found in the body when mice are awake would affect the number of circulating tumor cells when the mouse was at rest. 

They injected mice with testosterone, insulin (a hormone that makes it possible to turn sugar into energy), and dexamethasone (a synthetic chemical that acts like cortisol, the stress hormone). 

The researchers found a "marked reduction" in the number of circulating tumor cells in a blood sample taken during the rest period (when the tumor would normally be most aggressive).

"Our research shows that the escape of circulating cancer cells from the original tumor is controlled by hormones such as melatonin, which determine our rhythms of day and night," says Zoi Diamantopoulou, the study's first author and a molecular oncology researcher at ETH Zurich."


ScienceAlert article

The metastatic spread of breast cancer accelerates during sleep

medline and medline reacted
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Thank you. Very interesting indeed!

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Tumors might grow faster at night

October 6, 2014
Weizmann Institute of Science
A hormone that keeps us alert also suppresses the spread of cancer, researchers have discovered. The study suggests, therefore, that nighttime is the right time for cancer to grow and spread in the body, and that administering certain treatments in time with the body's day-night cycle could boost their efficiency.

They emerge at night, while we sleep unaware, growing and spreading out as quickly as they can. And they are deadly. In a surprise finding that was recently published in Nature Communications, Weizmann Institute of Science researchers showed that nighttime is the right time for cancer to grow and spread in the body. Their findings suggest that administering certain treatments in time with the body's day-night cycle could boost their efficiency.

This finding arose out of an investigation into the relationships between different receptors in the cell -- a complex network that we still do not completely understand. The receptors -- protein molecules on the cell's surface or within cells -- take in biochemical messages secreted by other cells and pass them on into the cell's interior. The scientists, led by Dr. Mattia Lauriola, a postdoctoral fellow in the research group of Prof. Yosef Yarden of the Weizmann Institute's Biological Regulation Department, working together with Prof. Eytan Domany of the Physics of Complex Systems Department, focused on two particular receptors. The first, the epidermal growth factor receptor, EGFR, promotes the growth and migration of cells, including cancer cells. The second binds to a steroid hormone called a glucocorticoid (GC). Glucocorticoids play a role in maintaining the body's energy levels during the day, as well as the metabolic exchange of materials. It is often called the stress hormone because its levels rise in stressful situations, rapidly bringing the body to a state of full alert.

With multiple receptors, the cell receives all sorts of messages at once, and some of these messages can take precedence over others. In the experiment, Lauriola and Yarden found that cell migration -- the activity promoted by the EGF receptor -- is suppressed when the GC receptor is bound to its steroid messenger.

Since the steroid levels peak during waking hours and drop off during sleep, the scientists asked how this might affect the second receptor -- EGFR. Checking the levels of this activity in mice, they found that there was a significant difference: This receptor is much more active during sleep and quiescent during waking hours.

How relevant are these findings for cancers, particularly those which use the EGF receptors to grow and spread? To find out, the scientists gave Lapatinib -- one of the new generation of cancer drugs -- to mouse models of cancer. This drug, used to treat breast cancer, is designed to inhibit EGFR, and thus to prevent the growth and migration of the cancer cells. In the experiment, they gave the mice the drug at different times of day. The results revealed significant differences between the sizes of tumors in the different groups of mice, depending on whether they had been given the drug during sleep or waking hours. The experimental findings suggest that it is indeed the rise and fall in the levels of the GC steroids over the course of 24 hours that hinder or enable the growth of the cancer.

The conclusion, say the scientists, is that it could be more efficient to administer certain anticancer drugs at night.

"It seems to be an issue of timing," says Yarden. "Cancer treatments are often administered in the daytime, just when the patient's body is suppressing the spread of the cancer on its own. What we propose is not a new treatment, but rather a new treatment schedule for some of the current drugs."

Story Source:

Materials provided by Weizmann Institute of Science. Note: Content may be edited for style and length.

Journal Reference:

  1. Mattia Lauriola, Yehoshua Enuka, Amit Zeisel, Gabriele D’Uva, Lee Roth, Michal Sharon-Sevilla, Moshit Lindzen, Kirti Sharma, Nava Nevo, Morris Feldman, Silvia Carvalho, Hadas Cohen-Dvashi, Merav Kedmi, Nir Ben-Chetrit, Alon Chen, Rossella Solmi, Stefan Wiemann, Fernando Schmitt, Eytan Domany, Yosef Yarden. Diurnal suppression of EGFR signalling by glucocorticoids and implications for tumour progression and treatment. Nature Communications, 2014; 5: 5073 DOI: 10.1038/ncomms6073

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People might be reluctant to consider treatments during the night because we are told me need 8 hours of uninterrupted sleep, but this might not be necessary at all, some believe biphasic sleeping is a more natural sleep pattern:

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New research shows that the stress transmitter norepinephrine causes you to “neurologically wake up more than 100 times a night, but the moment is so brief that the sleeper will not notice”.

Is norepinephrine an etiological factor in some types of cancer?

I examine evidence that the signaling molecule norepinephrine (NE) is an etiological factor in some types of cancer. In support of this hypothesis, I cite the following 7 lines of evidence:
(i) rodent studies of tumorigenesis in the context of NE manipulation;
(ii) human studies of tricyclic antidepressant use and cancer rate;
(iii) existence of pheochromocytoma, a cancer of the adrenal glands;
(iv) cancer rate in families with individuals who have bipolar disorder;
(v) hypertension and cancer risk; (vi) excessive body weight and cancer risk; and
(vii) psychological stressors and cancer risk.
Three aspects of the body's NE system are consistent with it playing an etiological role in various types of cancer:
(i) NE circulates in the blood and can thereby access organ systems throughout the body, in addition to direct peripheral release by the sympathetic nervous system and being released within the brain;
(ii) many of the body's organs possess NE receptors on the outer surface of at least some of their cells;
(iii) by binding to its extracellular receptors, NE affects intracellular second messenger systems that could influence carcinogenesis.
Most importantly, use of existing pharmaceutical drugs that either lower the level of NE (such as clonidine) or block NE receptors may lower the probability of an individual developing cancer, and this hypothesis could be tested immediately by an epidemiologist through examination of existing medical records.

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Sleeping on the right side may prevent cancer and tumor growth at night because this sleeping position reduces the activity of the sympathetic nervous system and plasma norepinephrine.

Pasma norepinephrine concentrations showed the lowest value when participants were in the right lateral decubitus position.

The right lateral decubitus position attenuate sympathetic nerve activity.

A left lateral body position increases pulmonary vein stress.

The right lateral decubitus position leads to the highest vagal modulation and parasympathetic nervous system activity.

The supine position leads to the lowest vagal modulation.