Sunday, August 5, 2018
Saturday, August 4, 2018
Cancer cells are weaker when made more acidic
Cancer cells function less well and are less able to multiply when their internal environment is made more acidic.
This was the conclusion that researchers in the United States and Spain came to after they used a computer model to study the conditions that affect metabolic pathways in cancer cells.
The model showed that cancer cells need an internal environment that is more alkaline than that of healthy cells for their metabolism to function properly.
It also helped identify some enzymes that work with the more alkaline environment to promote cancer.
The findings could lead to new cancer drugs that target these molecules, according to a paper now published in the journal Nature Communications.
“This work is still very academic,” explains study co-author Miquel Duran-Frigola, a computational chemist at the Institute for Research in Biomedicine in Barcelona, Spain, “but we believe that some of the targets identified are ready to be tested in animals, thus allowing us to move into more advanced preclinical trial stages.”
Systems biology
The study is an example of the type of research that is going on in the field of systems biology, which uses complex computer models and big data to help us understand the “organizational principles of life.”
The researchers brought together a large amount of biochemical and genetic data to develop a molecular model of cancer cell metabolism.
They used the model to explore the response of “almost 2,000 metabolic enzymes” to changes in the internal pH of the cell.
The pH scale is a measure of acidity. An acidic environment has a low pH and an alkaline, or basic, environment has a high pH. A pH of 7 is neutral — it is neither acid nor alkaline.
Healthy cells have a slightly alkaline internal environment with a pH of around 7.2. Cancer cells are more alkaline and have an internal pH that is higher than 7.2.
“By reconstructing and integrating enzymatic pH-dependent activity profiles into cell-specific genome-scale metabolic models,” note the authors, “we develop a computational methodology that explores how intracellular pH […] can modulate metabolism.”
Promising results
Using the computer model, the team showed that when its insides remain in the favored alkaline pH zone, the cancer cell is able to proliferate. This condition also favors other functions that the cell relies on, such as “glycolysis and adaptation to hypoxia.”
But a lower, more acidic pH in the cancer cell “disables these adaptations and compromises tumorcell growth,” note the authors.
The team also used the model to identify metabolic targets that showed “predicted amplified anticancer effects” when the cancer cell’s internal environment became more acidic.
Some of the targets have already shown promising results in tests using real breast cancer cells.
“Understanding the link between metabolic pathways that work better under different pHs can give us an idea about the mechanisms used by cancer to survive at basic pH.”Miquel Duran-Frigola
Mass hysteria: An epidemic of the mind?
An outbreak of fatal dancing fits among members of the same community, men suddenly gripped by the sickening fear of losing their genital organs, and teenagers having mysterious symptoms after watching an episode of their favorite TV series — these are all instances of what we often refer to as “mass hysteria.”
They danced together, ceaselessly, for hours or days, and in wild delirium, the dancers collapsed and fell to the ground exhausted, groaning and sighing as if in the agonies of death. When recuperated, they […] resumed their convulsive movements.”
This is a description of the epidemic of “dancing plague” or “dancing mania” as given by Benjamin Lee Gordon in Medieval and Renaissance Medicine.
These events were spontaneous outbursts of uncontrollable dancing motions that gripped people in communities across Europe in the Middle Ages.
Those affected would often reportedly be unable to stop dancing until they were so worn out and exhausted that they died. These events are typically cited as some of the first known instances of what would come to be referred to as “mass hysteria.”
Mass hysteria is a phrase that is used so often and so imprecisely to refer to anything from giving in to fashion fads to participating in riots and raves that it has become something of a fluid concept, synonymous with anything with a negative connotation that involves the participation of a large group of people.
However, though sometimes contested as a useful, valid concept, mass hysteria — in its more restrictive sense — lives at the intersection of psychology and sociology.
As such, it has received some rigorous attention from specialists over the years.
What is mass hysteria?
In order to provide a clearer definition of mass hysteria, to outline it as an event of potential clinical interest, and to distance it from any unduly negative connotations, researchers have actually advised referring to the phenomenon as “collective obsessional behavior.”
Specialists who have taken an interest in this phenomenon say that it is a type of “psychogenic illness” — that is, a condition that begins in the mind, rather than in the body. Physiological symptoms, however, are often not illusory but very much real.
Mass hysteria is also described as a “conversion disorder,” in which a person has physiological symptoms affecting the nervous system in the absence of a physical cause of illness, and which may appear in reaction to psychological distress.
Because mass hysteria, or collective obsessional behavior, can take so many different forms, it is very difficult to provide a clear definition for it, or to characterize it with confidence.
In a seminal article he published on this topic, Prof. Simon Wessley — from King’s College London in the United Kingdom — also notes that mass hysteria has been used to describe such “[a] wide variety of crazes, panics, and abnormal group beliefs” that defining it is particularly tricky.
Still, he suggests that in characterizing a phenomenon as an instance of mass hysteria, we should aim to guide ourselves by five principles:
- that “it is an outbreak of abnormal illness behavior that cannot be explained by physical disease”
- that “it affects people who would not normally behave in this fashion”
- that “it excludes symptoms deliberately provoked in groups gathered for that purpose,” such as when someone intentionally gathers a group of people and convinces them that they are collectively experiencing a psychological or physiological symptom
- that “it excludes collective manifestations used to obtain a state of satisfaction unavailable singly, such as fads, crazes, and riots”
- that “the link between the [individuals experiencing collective obsessional behavior] must not be coincidental,” meaning, for instance, that they are all part of the same close-knit community
Prof. Wessley also believes that mass hysteria should not be confused with “moral panic.” This is a sociological concept that refers to the phenomenon of masses of people becoming distressed about a perceived — usually unreal or exaggerated — threat portrayed in catastrophizing terms by the media.
Different types of mass hysteria?
In his article, Prof. Wessley goes even further, arguing that — based on the instances of mass hysteria documented in specialized literature — this phenomenon actually refers to two “syndromes” with somewhat different characteristics.
He calls these two types of collective obsessional behavior “mass anxiety hysteria” and “mass motor hysteria.”
The first kind, he says, is marked by physiological symptoms consistent with those experienced in the case of anxiety. These can include: abdominal pain, chest tightness, dizziness, fainting, headaches, hyperventilation, nausea, and heart palpitations.
The second kind of mass hysteria, on the other hand, is characterized by seizure-like events (pseudoseizures), apparent partial paralysis (pseudoparesis), or other symptoms that alter a person’s motor function in a specific way.
Are women most affected?
Medical sociologist Robert Bartholomew has reviewed some of the most prominent cases of mass hysteria in his book Little Green Men, Meowing Nuns and Head-Hunting Panics.
His research seems to indicate one thing: that instances of mass hysteria are most prominently experienced by groups of women.
But why would that be the case? And does it mean that women are somehow “hardwired” to fall prey to such mass “epidemics?” Some researchers argue that women may be more exposed to collective obsessional behavior because they are typically exposed to more stressful situations.
Physical symptoms of disease could provide a nonconfrontational way out of an overwhelming situation. Bartholomew notes, for example, that in a stressful or even abusive work context, mass hysteria and its accompanying symptoms can provide a means of putting up resistance and forging a way out.
Similarly, Christian Hempelmann — from Texas A&M University-Commerce — who has taken an interest in mass hysteria, suggests that these group manifestations are effective and nonconfrontational.
“The way […] to get out of [an oppressive situation] is to show symptoms of disease and to be allowed not to have to endure the situation any longer,” he believes.
However, the word “hysteria” itself is fraught with problems and has a “bumpy,” highly controversialhistory. It is derived from the Greek word “hystera,” meaning “uterus,” thereby attaching the condition specifically to women.
Uses of the word have historically been so imprecise, and the term has gained such negative connotations — used to describe any violent outburst of emotion — that it was “retired” by the American Psychiatric Association in 1952.
“Hysteria” is no longer used to describe any existent psychological condition, and more specific terms are instead employed to refer to a wide range of conditions that fell, in the past, under the large umbrella of this name.
As a consequence of this, any claims that mass hysteria could be a phenomenon that applies most prominently to women becomes questionable, especially considering the heterogeneous nature of such events and how difficult it is to categorize them.
Recent instances of mass hysteria
Though occurrences of mass hysteria have been documented throughout history, they do not seem to have become less common with the passage of time and the advent of technology that supports the rapid flux of information.
A number of intriguing events involving collective experiences of psychological and physiological symptoms have been referred to as instances of mass hysteria over the past 50 years or so. And some of the most recent occurrences have even been tied to the perils of social media.
Laughter epidemics and penis panics
In 1962, in a village in Tanganyika — now Tanzania — a girl at a boarding school suddenly started laughing…and was unable to stop. Her laughing fit quickly produced a “laughing epidemic” among her schoolmates, which became of such magnitude that the school had to be shut down.
Upon sending all the girls home, the epidemic spread to the wider community, and it only began to fade after 2 years from the start of the outbreak.
Notoriously, in Singapore in 1967, hundreds of men became convinced that eating pork meat taken from a series of vaccinated pigs would lead to penis shrinkage or disappearance, and potentially death.
This “penis panic,” or “koro,” required a concerted effort from the country’s government to educate the male population about their genital organs to convince them that their conviction was not, and could not, be true.
In autumn 2001, children in elementary and middle schools across the United States experienced a strange symptom: their skin would break out in rashes, but only while they were in school. At home, their symptoms would promptly disappear.
In the media, this phenomenon was linked to the impact of the tragic events of September 11, and the children’s symptoms were taken as a mass psychosomatic reaction to the feelings associated with trauma that permeated the U.S. at the time.
The impact of mass media and social media?
More recently, in 2006, teenagers in Portugal started to present to hospital with dizziness, rashes, and breathing difficulties.
After the doctors could find no physical cause for these symptoms, some investigative work found an intriguing parallel: these were the same symptoms that were experienced by a character in a popular soap opera for young people, Strawberries With Sugar (Morangos com Açúcar, in Portugese).
This is why the phenomenon came to be known as the “strawberries with sugar virus.”
Finally, the most fresh instance of alleged mass hysteria took place as recently as 2012, when teenage girls from the small town of LeRoy, NY, started to exhibit symptoms similar to those seen in Tourette’s syndrome — such as uncontrollable jerks of the limbs and verbal outbreaks — though the doctors were unable to find a clear cause for them.
This epidemic started when a girl posted a video of herself on YouTube, in which she documented an episode of such symptoms. Until recently, this girl had shown no sign of Tourette’s.
The video went viral, and many more teenage girls started to display the same symptoms. A teenage boy and a 36-year-old woman were also “infected.”
When the woman explained that she started having these symptoms after she learned of the girl’s story on Facebook, this led to speculation about social media’s potential role in advancing mass hysteria in the present day.
So, is mass hysteria an epidemic of the mind, leading to symptoms in the body, which is spread via social contact? This question is still under debate, but if it is so, the advent of social media is a likely vehicle for the spread of such “viruses.”
In any case, instances of reported mass hysteria do highlight one consideration: that it is just as important to preserve our inner well-being as it is to look after our physical health.
And the messages we ingest — through what we read, watch, or hear — may affect our well-being in unsuspected ways.
Daiichi Sankyo, Glycotope in deal for 1st-in-class antibody-drug conjugate
Daiichi Sankyo and Glycotope have signed a licensing agreement to develop an antibody-drug conjugate that enables tumor-specific binding to TA-MUC1.
The terms of the agreement give Daiichi Sankyo exclusive rights to develop and commercialize Glycotopes investigational tumor-associated TA-MUC1 antibody, gatipotzumab, as an antibody-drug conjugate (ADC).
Glycotope will receive an upfront payment and is eligible for further milestone payments and royalties. The licensing agreement will also give Daiichi Sankyo the right to research and develop gatipotuzumab as an ADC worldwide and to conduct all clinical trials and non-clinical studies in all countries, said Glycotope representative, Chris Gardner.
Gardner continued, The agreement is part of Glycotopes immuno-oncology strategy. Glycotope is partnering products from early pre-clinical to advanced clinical stage while bringing forward its in-house pipeline.
ADC to target tumors
According to Jennifer Brennan, Daiichi Sankyo spokesperson, ADCs are targeted cancer medicines that deliver cytotoxic chemotherapy to cancer cells through a linker that is attached to a monoclonal antibody. This antibody then binds to a target expressed in cancer cells.
Gatipotuzumab ADC is a potential first-in-class TA-MUC1-targeting antibody-drug conjugate. With the licensing of gatipotuzumab for the purposes of combining with its ADC platform, Daiichi Sankyo now has seven novel ADCs in development within its investigational ADC franchise said Brennan.
He continued, Daiichi Sankyos proprietary ADC linker-payload technology will be applied to gatipotzumab antibody to potentially directly deliver the payload to cancer cells that express the TA-MUC1 antigen, which is extensively expressed in many tumor types including ovarian, lung and breast.
The ADC will target ovarian, lung and breast cancer tumors. This licensing agreement is set to build on the previous option from 2017, where Daiichi Sankyo and Glycotopesigned an option agreement to develop an ADC PankoMab-GEX, the former name of gatipotuzumab.
Amgen Breaks Ground On Next-Gen Biomanufacturing Plant In Rhode Island
“Biologics manufacturing is a complex science and has long been a competitive advantage for Amgen,” said Robert A. Bradway, chairman and chief executive officer at Amgen. “We are working to extend that advantage even further with a next-generation biomanufacturing plant in Rhode Island that will produce medicines to serve patients around the world suffering from serious illnesses.”
A next-generation biomanufacturing plant incorporates multiple innovative technologies into a single facility, and therefore is built in half the construction time with approximately one half of the operating cost of a traditional plant. Next-generation biomanufacturing plants require a smaller manufacturing footprint and offer greater environmental benefits, including reduced consumption of water and energy and lower levels of carbon emissions. Within the plant, the equipment is portable, smaller and some components are disposable, which provides greater flexibility and speed when manufacturing different medicines simultaneously. This eliminates costly and complex retrofitting inherent in standard facilities and allows Amgen to respond to changing demands for its medicines with increased agility, ultimately impacting the speed at which a medicine is available for patients.
“We are thrilled that Amgen has selected Rhode Island as the location for this plant that will be the first-of-its-kind in the United States,” said Governor Gina M. Raimondo. “This is more proof that Rhode Island is now successfully competing for economic development opportunities with global companies thanks to our highly skilled workforce, robust academic institutions and exceptional quality of life. Rhode Island is proud to support Amgen in its commitment to developing innovative medicines.”
Amgen expects to invest up to $200 million in the approximately 120,000 square foot next-generation manufacturing plant in Rhode Island. This plant is anticipated to create approximately 150 additional highly-skilled manufacturing positions.
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