Effects of Sulfonylureas on Tumor Growth.


Type 2 diabetes mellitus patients are at higher cancer risk, probably because of hyperinsulinemia and insulin growth factor 1 pathway activation. The effects of antidiabetic drugs on cancer risk have been described and discussed in several studies suggesting opposite effects of the biguanide metformin and sulfonylureas on cancer incidence and mortality. The anticancer mechanisms of metformin have been clarified, and some clinical studies, particularly in breast cancer patients, have been published or are currently ongoing; however, data about the effects of sulfonylureas on cancer growth are less consistent. The aims of this work are to review preclinical evidence of second-generation sulfonylureas effects on tumor growth, to clarify the potential mechanisms of action, and to identify possible metabolic targets for patient selection. Most evidence is on the adenosine triphosphate-sensitive potassium channels inhibitor glibenclamide, which interacts with reactive oxygen species production thus inducing cancer cell death. Among diarylsulfonylureas, next-generation DW2282 derivatives are particularly promising because of the proapoptotic activity in multidrug-resistant cells.

 

Source: The Oncologist.

 

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Alopecia With Endocrine Therapies in Patients With Cancer.


Abstract

Background. Whereas the frequency of alopecia to cytotoxic chemotherapies has been well described, the incidence of alopecia during endocrine therapies (i.e., anti-estrogens, aromatase inhibitors) has not been investigated. Endocrine agents are widely used in the treatment and prevention of many solid tumors, principally those of the breast and prostate. Adherence to these therapies is suboptimal, in part because of toxicities. We performed a systematic analysis of the literature to ascertain the incidence and risk for alopecia in patients receiving endocrine therapies.

Methods. An independent search of citations was conducted using the PubMed database for all literature as of February 2013. Phase II–III studies using the terms “tamoxifen,” “toremifene,” “raloxifene,” “anastrozole,” “letrozole,” “exemestane,” “fulvestrant,” “leuprolide,” “flutamide,” “bicalutamide,” “nilutamide,” “fluoxymesterone,” “estradiol,” “octreotide,” “megestrol,” “medroxyprogesterone acetate,” “enzalutamide,” and “abiraterone” were searched.

Results. Data from 19,430 patients in 35 clinical trials were available for analysis. Of these, 13,415 patients had received endocrine treatments and 6,015 patients served as controls. The incidence of all-grade alopecia ranged from 0% to 25%, with an overall incidence of 4.4% (95% confidence interval: 3.3%–5.9%). The highest incidence of all-grade alopecia was observed in patients treated with tamoxifen in a phase II trial (25.4%); similarly, the overall incidence of grade 2 alopecia by meta-analysis was highest with tamoxifen (6.4%). The overall relative risk of alopecia in comparison with placebo was 12.88 (p < .001), with selective estrogen receptor modulators having the highest risk.

Conclusion. Alopecia is a common yet underreported adverse event of endocrine-based cancer therapies. Their long-term use heightens the importance of this condition on patients’ quality of life. These findings are critical for pretherapy counseling, the identification of risk factors, and the development of interventions that could enhance adherence and mitigate this psychosocially difficult event.

 

Source: The Oncologist.

 

 

Aiming for a Better Understanding and Management of Cancer-Related Fatigue.


Cancer-related fatigue (CRF) is a serious symptom of patients with cancer and deteriorates their daily quality of life. Whereas fatigue is a common problem in the general population, with a prevalence of about 30%, up to 99% of patients with cancer have fatigue of more intense severity. CRF is directly related to the biology of cancer, but it can also be caused by anticancer treatment. We reviewed current evidence about the potential pathophysiological mechanisms causing CRF. Clinical methods to determine the presence and severity of CRF and potential treatment options to reduce CRF will be discussed. After reading this review, the reader will have knowledge of the current understanding of CRF and will be able to give evidence-based advice to patients with CRF.

 

Source: The Oncologist.

Witnessing hateful people in pain modulates brain activity in regions associated with physical pain and reward.


How does witnessing a hateful person in pain compare to witnessing a likable person in pain? The current study compared the brain bases for how we perceive likable people in pain with those of viewing hateful people in pain. While social bonds are built through sharing the plight and pain of others in the name of empathy, viewing a hateful person in pain also has many potential ramifications. In this functional Magnetic Resonance Imaging (fMRI) study, Caucasian Jewish male participants viewed videos of (1) disliked, hateful, anti-Semitic individuals, and (2) liked, non-hateful, tolerant individuals in pain. The results showed that, compared with viewing liked people, viewing hateful people in pain elicited increased responses in regions associated with observation of physical pain (the insular cortex, the anterior cingulate cortex, and the somatosensory cortex), reward processing (the striatum), and frontal regions associated with emotion regulation. Functional connectivity analyses revealed connections between seed regions in the left anterior cingulate cortex and right insular cortex with reward regions, the amygdala, and frontal regions associated with emotion regulation. These data indicate that regions of the brain active while viewing someone in pain may be more active in response to the danger or threat posed by witnessing the pain of a hateful individual more so than the desire to empathize with a likable person’s pain.

 

Lymph node micrometastasis in gastrointestinal tract cancer—a clinical aspect.


Abstract

Lymph node micrometastasis (LNM) can now be detected thanks to the development of various biological methods such as immunohistochemistry (IHC) and reverse transcription-polymerase chain reaction (RT-PCR). Although several reports have examined LNM in various carcinomas, including gastrointestinal (GI) cancer, the clinical significance of LNM remains controversial. Clinically, the presence of LNM is particularly important in patients without nodal metastasis on routine histological examination (pN0), because patients with pN0 but with LNM already in fact have metastatic potential. However, at present, several technical obstacles are impeding the detection of LNM using methods such as IHC or RT-PCR. Accurate evaluation should be carried out using the same antibody or primer and the same technique in a large number of patients. The clinical importance of the difference between LNM and isolated tumor cells (≤0.2 mm in diameter) will also be gradually clarified. It is important that the results of basic studies on LNM are prospectively introduced into the clinical field. Rapid diagnosis of LNM using IHC and RT-PCR during surgery would be clinically useful. Currently, minimally invasive treatments such as endoscopic submucosal dissection and laparoscopic surgery with individualized lymphadenectomy are increasingly being performed. Accurate diagnosis of LNM would clarify issues of curability and safety when performing such treatments. In the near future, individualized lymphadenectomy will develop based on the establishment of rapid, accurate diagnosis of LNM.

Source: International Journal of Clinical Oncology

Microbes ‘cheaper, fairer’ for boosting yields than GM.


Speed read

  • Microbes may offer a more equitable choice for smallholder farmers
  • Improvements in technology must continue to get them from the lab to the field
  • Melon yields in Honduras have already benefited from microbes.

Adapting microbes that dramatically increase crop yields while reducing demand for fertilisers and pesticides through selective breeding or genetic engineering could be cheaper and more flexible than genetically modifying plants themselves, says an author of a report.
 
Microbes, such as beneficial bacteria, fungi and viruses, could be produced locally for smallholder 
farmers to significantly improve food security and incomes in developing regions, believes Ann Reid, director of the American Academy of Microbiology and co-author of a report published by the organisation last month (27 August).
 
“Genetic modification of crop plants, which has seen a huge investment, is closed to all but the biggest agricultural companies,” she tells SciDev.Net.
 
“Optimisation of microbes could be done at the level of the local community college and is much more obtainable for a smallholder farmer.”
 
Her comments echo the findings of the report — the product of an expert meeting in 2012 — which underscored the significant impact microbes could have on food production by increasing crops’ absorption of nutrients, resistance to disease and environmental stresses, and even improving flavour.
 

“Optimisation of microbes could be done at the level of the local community college and is much more obtainable for a smallholder farmer.”

Ann Reid, American Academy of Microbiology

As well as to accentuate naturally occurring traits such as the secretion of pest-killing toxins or nitrogen-fixation, the modification of microbes is often needed to allow them to be grown in large numbers out of their natural environment.
 
For example, researchers in Colombia could only produce large quantities of a fungus that improves the nutrient absorption of cassava once they bred a strain of that fungus that was capable of growing on carrot roots.
 
Recent technological developments in rapid DNA sequencing, imaging and computer modelling can help provide further solutions, as well as building a greater understanding of the complex environment that microbes themselves need to flourish, the report says.
 
These advances raise the possibility that, within two decades, microbes could increase food production by a fifth and reduce fertiliser demands by the same proportion, it finds.
 
But to achieve this ambitious goal, the research community must engage in curiosity-driven basic research, develop even cheaper sequencing techniques, and establish a process to move discoveries from the lab to the field, it says.
 
Reid adds that, unlike genetic modification, which requires farmers to regularly buy improved seeds, microbes may be able to stay in the soil indefinitely.
 
But larger universities are still needed to drive more-complex areas of investigation, which inevitably requires funding, she says. “We wanted to get the word out that this could be a big-bang-for-your- buck area for funding agencies.”
 
Matteo Lorito, a professor of plant pathology at the University of Naples, Italy, agrees that sophisticated research centres must be involved in identifying and selecting suitable microbes and techniques.
 
But once this groundwork has been done, growing microbes will require as little as a fermenting tank, he says.
 
The impact of this approach is already being seen in areas such as Honduras, where melon yields have been improved by 15 per cent by applying a fungus that boosts the plants’ defence mechanisms.
 
Other crops such as maize, tomatoes and wheat could see rises in production of more than 50 per cent from such techniques, he believes.
 
But Ken Giller, professor of plant production systems at the Netherland’s Wageningen University, says that much more work needs to be done, particularly on how to get the microbes into the soil, before farmers will benefit, he says.
 
“Molecular biology has been incredibly important in understanding biology in general, which has helped when thinking about solutions [for food production],” he tells SciDev.Net.
 
“But in terms of the manipulation of these processes to make an impact in the field, we have yet to make any great inroads

1,600-Year-Old Goblet Shows that the Romans Were Nanotechnology Pioneers.


Researchers have finally found out why the jade-green cup appears red when lit from behind

The colorful secret of a 1,600-year-old Roman chalice at the British Museum is the key to a super­sensitive new technology that might help diagnose human disease or pinpoint biohazards at security checkpoints.

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The glass chalice, known as the Lycurgus Cup because it bears a scene involving King Lycurgus of Thrace, appears jade green when lit from the front but blood-red when lit from behind—a property that puzzled scientists for decades after the museum acquired the cup in the 1950s. The mystery wasn’t solved until 1990, when researchers in England scrutinized broken fragments under a microscope and discovered that the Roman artisans were nanotechnology pioneers: They’d impregnated the glass with particles of silver and gold, ground down until they were as small as 50 nanometers in diameter, less than one-thousandth the size of a grain of table salt. The exact mixture of the precious metals suggests the Romans knew what they were doing—“an amazing feat,” says one of the researchers, archaeologist Ian Freestone of University College London.

The ancient nanotech works something like this: When hit with light, electrons belonging to the metal flecks vibrate in ways that alter the color depending on the observer’s position. Gang Logan Liu, an engineer at the University of Illinois at Urbana-Champaign, who has long focused on using nanotechnology to diagnose disease, and his colleagues realized that this effect offered untapped potential. “The Romans knew how to make and use nanoparticles for beautiful art,” Liu says. “We wanted to see if this could have scientific applications.”

When various fluids filled the cup, Liu suspected, they would change how the vibrating electrons in the glass interacted, and thus the color. (Today’s home pregnancy tests exploit a separate nano-based phenomenon to turn a white line pink.)

Since the researchers couldn’t put liquid into the precious artifact itself, they instead imprinted billions of tiny wells onto a plastic plate about the size of a postage stamp and sprayed the wells with gold or silver nanoparticles, essentially creating an array with billions of ultra-miniature Lycurgus Cups. When water, oil, sugar solutions and salt solutions were poured into the wells, they displayed a range of easy-to-distinguish colors—light green for water and red for oil, for example. The proto­type was 100 times more sensitive to altered levels of salt in solution than current commercial sensors using similar techniques. It may one day make its way into handheld devices for detecting pathogens in samples of saliva or urine, or for thwarting terrorists trying to carry dangerous liquids onto airplanes.

The original fourth-century A.D. Lycurgus Cup, probably taken out only for special occasions, depicts King Lycurgus ensnared in a tangle of grapevines, presumably for evil acts committed against Dionysus, the Greek god of wine. If inventors manage to develop a new detection tool from this ancient technology, it’ll be Lycurgus’ turn to do the ensnaring.

Can ‘powdered rain’ make drought a thing of the past?


The lack of water is a growing, global problem that seems intractable.

While the UN estimates that a large majority of the water we use goes on irrigation, researchers have been working on a range of ideas that make the water we use in agriculture last longer.

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There has been a great deal of excitement and some dramatic headlines in recent weeks about a product that is said to have the potential to overcome the global challenge of growing crops in arid conditions.

“Solid Rain” is a powder that’s capable of absorbing enormous amounts of water and releasing it slowly over a year so that plants can survive and thrive in the middle of a drought.

A litre of water can be absorbed in as little as 10 grams of the material, which is a type of absorbent polymer originally pioneered by the US Department of Agriculture (USDA).

Back in the 1970s, USDA developed a super-absorbent product made from a type of starch nicknamed the “super slurper“.

The most widely used, commercial application of this technology has been in disposable nappies, or diapers as they are quaintly termed in the US.

But a Mexican chemical engineer called Sergio Jesus Rico Velasco saw more in the product than dry bottoms.

He developed and patented a different version of the formula that could be mixed in with soil to hold water that could then slowly feed plants.

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Ground water

He formed a company to sell Solid Rain and it has quietly been selling the product in Mexico for around 10 years. The company says that the government there tested Solid Rain and found that crop yields could increase by 300% when it was added to the soil.

According to Edwin Gonzalez, a vice president with the Solid Rain company, the product is now attracting wider interest because of growing concerns about the scarcity of water.

“It works by encapsulating the water, and our product lasts 8 to 10 years in the ground, depending on the water quality – if you use pure water, it lasts longer,” he told BBC News.

The company recommends using about 50kgs per hectare – though it’s not cheap, at $1,500 (£960) for that amount.

Mr Gonzalez was at pains to point out that Solid Rain was all natural and would not damage the land even if it was used for several years.

“Our product is not toxic; it’s made from a bio-acrylamide. After it disintegrates, the powder-like substance becomes part of the plant – it is not toxic,” he said.

Science uncertain

But not everyone is convinced that Solid Rain is a significant solution to the problem of drought.

Dr Linda Chalker-Scott from Washington State University says that these types of products have been known to gardeners for several years now.

“They’re hardly new, and there’s no scientific evidence to suggest that they hold water for a year, or last for 10 years in the soil,” she told BBC News.

“An additional practical problem is that gels can do as much harm as good. As the gels begin to dry out, they soak up surrounding water more vigorously. That means they will start taking water directly from plant roots,” she added.

Dr Chalker-Scott says that research she carried out in Seattle with newly transplanted trees showed that wood chip mulching was just as effective as adding powdered materials and gels to the soil. And it was significantly cheaper.

However, Edwin Gonzalez says Solid Rain is different.

“There are other competitors that last three or four years. The ones that don’t last as long are the ones that have sodium – they don’t absorb as much. The potassium ones, like ours, are seen as the better products,” he said

Despite the fact that the science may not be entirely certain about the benefits of products like this, Edwin Gonzalez says his company has been inundated with enquiries from dry spots including India and Australia.

And he’s also had several orders from the UK, where the lack of water is usually not a problem.

Source:BBC

Soon, a jacket which charges your phone.


What if you had a jacket which served a dual purpose — beat the summer heat and simultaneously charged your mobile?

Santipada GonChaudhary, a Kolkata-based scientist, and his team is designing a jacket, especially for traffic police and those who work in the sun for long hours.

Apart from being fitted with cooling elements, the jacket will have a solar cell in the pocket with a connecting lead that can be used for charging a mobile. Solar cells varying between 2.5-3 inches in size would be embedded in each shirt to generate around 400 watts of energy, sufficient to charge mobile phones.

“A prototype will be ready in a few months. The design and the components have been procured. We are now integrating the solar cells. Once the prototype is ready we will give it to a company for mass production. It should cost around Rs. 1600,” he said.

He said the jacket will be two layered — in the inner layer there will be six small fans embedded with a soft blade which can be twisted.

The buttons on the shoulder, which is an accessorising element, will have solar cells that can be rotated, enhancing cooling. The jackets, he said would be of cotton.

Besides the jacket we have also prepared a solar umbrella which will have solar cell on the top and just beneath a fan which can rotate. “This should cost around Rs. 800.”

Source: HT

Blood-Based Prenatal Genetic Tests Greeted with Skepticism.


 

Newer prenatal tests for genetic abnormalities, touted by some as alternatives to amniocentesis, are getting wider use and presenting familiar problems.

Four companies have entered the market, selling products that range in price from $800 to almost $3000, according to a report in the Wall Street Journal. The tests (or “screenings,” as one national genetics group would like to call them) use fetal DNA from the mother’s blood rather than relying on amniocentesis.

The tests’ accuracy has been established in clinical trials, but in real-world practice “the numbers usually tend to be not quite as good,” according to one expert. False-positives could lead to unneeded abortions, and false-negatives may become apparent only much later in the pregnancy.

“Positive results should be confirmed with invasive testing,” according to one company official. Another says, “it is important to understand [the new tests] don’t replace invasive tests yet.”

Source:Wall Street Journal story