Scientists at UC San Diego, UC Santa Barbara and MIT have developed nanometer-sized “nanoworms” that can cruise through the bloodstream without significant interference from the body’s immune defense system and—like tiny anti-cancer missiles—home in on tumors.

Their discovery, detailed in this week’s issue of the journal Advanced Materials, is reminiscent of the 1966 science fiction movie, the Fantastic Voyage, in which a submarine is shrunken to microscopic dimensions, then injected into the bloodstream to remove a blood clot from a diplomat’s brain.

Using nanoworms, doctors should eventually be able to target and reveal the location of developing tumors that are too small to detect by conventional methods. Carrying payloads targeted to specific features on tumors, these microscopic vehicles could also one day provide the means to more effectively deliver toxic anti-cancer drugs to these tumors in high concentrations without negatively impacting other parts of the body.

“Most nanoparticles are recognized by the body’s protective mechanisms, which capture and remove them from the bloodstream within a few minutes,” said Michael Sailor, a professor of chemistry and biochemistry at UC San Diego who headed the research team. “The reason these worms work so well is due to a combination of their shape and to a polymer coating on their surfaces that allows the nanoworms to evade these natural elimination processes. As a result, our nanoworms can circulate in the body of a mouse for many hours.”

“When attached to drugs, these nanoworms could offer physicians the ability to increase the efficacy of drugs by allowing them to deliver them directly to the tumors,” said Sangeeta Bhatia, a physician, bioengineer and a professor of Health Sciences and Technology at MIT who was part of the team. “They could decrease the side effects of toxic anti-cancer drugs by limiting their exposure of normal tissues and provide a better diagnosis of tumors and abnormal lymph nodes.”

The scientists constructed their nanoworms from spherical iron oxide nanoparticles that join together, like segments of an earthworm, to produce tiny gummy worm-like structures about 30 nanometers long—or about 3 million times smaller than an earthworm. Their iron-oxide composition allows the nanoworms to show up brightly in diagnostic devices, specifically the MRI, or magnetic resonance imaging, machines that are used to find tumors.

“The iron oxide used in the nanoworms has a property of superparamagnetism, which makes them show up very brightly in MRI,” said Sailor. “The magnetism of the individual iron oxide segments, typically eight per nanoworm, combine to provide a much larger signal than can be observed if the segments are separated. This translates to a better ability to see smaller tumors, hopefully enabling physicians to make their diagnosis of cancer at earlier stages of development.”

In addition to the polymer coating, which is derived from the biopolymer dextran, the scientists coated their nanoworms with a tumor-specific targeting molecule, a peptide called F3, developed in the laboratory of Erkki Ruoslahti, a cell biologist and professor at the Burnham Institute for Medical Research at UC Santa Barbara. This peptide allows the nanoworms to target and home in on tumors.

“Because of its elongated shape, the nanoworm can carry many F3 molecules that can simultaneously bind to the tumor surface,” said Sailor. “And this cooperative effect significantly improves the ability of the nanoworm to attach to a tumor.”

The scientists were able to verify in their experiments that their nanoworms homed in on tumor sites by injecting them into the bloodstream of mice with tumors and following the aggregation of the nanoworms on the tumors. They found that the nanoworms, unlike the spherical nanoparticles of similar size that were shuttled out of the blood by the immune system, remained in the bloodstream for hours.

“This is an important property because the longer these nanoworms can stay in the bloodstream, the more chances they have to hit their targets, the tumors,” said Ji-Ho Park, a UC San Diego graduate student in materials science and engineering working in Sailor’s laboratory.

Park was the motivating force behind the discovery when he found by accident that the gummy worm aggregates of nanoparticles stayed for hours in the bloodstream despite their relatively large size.

While it’s not clear yet to the researchers why, Park notes that “the nanoworm’s flexibly moving, one dimensional structure may be one the reasons for its long life in the bloodstream.”

The researchers are now working on developing ways to attach drugs to the nanoworms and chemically treating their exteriors with specific chemical “zip codes,” that will allow them to be delivered to specific tumors, organs and other sites in the body.

“We are now using nanoworms to construct the next generation of smart tumor-targeting nanodevices,” said Ruoslahti. We hope that these devices will improve the diagnostic imaging of cancer and allow pinpoint targeting of treatments into cancerous tumors.”

News source

The removal through endoscopy of tumours that affect only the superficial layers of the oesophagus can avoid complete extirpation of this part of the digestive tract. The technique, carried out at the University Hospital of Navarra for the last three years, was presented at the VI International Course on Therapeutic Endoscopy in the Digestive System, organized by the Digestive System Service at this hospital. Specifically, more than 90% of patients treated for this ailment at the University Hospital of Navarra have not needed the extirpation of the oesophagus.
400 specialists from ten different countries attended the course, focusing on the therapeutic possibilities of endoscopy in the digestive system. Treatment using digestive endoscopy, without having to carry out surgery, is increasing. These applications are less aggressive than surgical operations and are undertaken at out-patient clinics in about 99% of the cases, which usually enables the patient to go home after the walk-in/walk-out treatment, explained Doctor Miguel Ángel Muñoz Navas, Director of the Digestive System Service at the University Hospital of Navarra.

As is known, endoscopy is a technique carried out using a tube-like instrument which contains a light and a lens at its tip. The tube has, moreover, a duct for carrying other instruments with which, amongst other operations. biopsies, extirpation of polyps, injection of contrasting fluids, insertion of prostheses and clips, coagulation of bleedings, extraction of stones from the biliary or pancreatic zone and the draining of abscesses may be undertaken. There are also exists an ecoendoscope, which is one incorporating an ecograph at its end. While in a normal ecography the transducer of the ecograph is outside the body, ecoendoscopy provides better quality images of a lesion that is close to the digestive tract. From the digestive tract we can observe lesions in its vicinity and access them.

Extirpation of oesophageal tumours

As regards the technique for the extirpation of distal tumours of the oesophagus undertaken at the University Hospital of Navarra, Doctor Muñoz explained that this was effective when the carcinoma occurs at surface layers. “The oesophagus is made up of three layers: mucous, sub-mucous and muscular. When the tumour is located in the mucous, we can take it out completely in most cases and thus avoid extirpation of the oesophagus. Until recently patients with this ailment – although affecting only the primary layers – were recommended the total extirpation of the oesophagus, which involved surgery with a high morbidity risk and even death”.

In any case, according to the Director of the Digestive System Service at the University Hospital of Navarra, Doctor Miguel Ángel Muñoz Navas, sometimes a surgical operation is inevitable. “There are times when you have to operate but there are others when a solution with endoscopy can be tried. But, in this case, monitoring of the patient has to be undertaken. It could be the case that we extirpate a tumour with endoscopy and the anatomopathology shows up the fact that the cancer is more infiltrated than had been thought from the biopsies or the ecoendoscopy. In these cases a surgical operation is required. Our experience has shown that more than 90% of patients that we have treated with this technique have not needed subsequent surgery”.

Extirpation of oesophageal tumours using endoscopy is not a very widespread treatment, in part due to its complexity. Nevertheless, it is a real possibility – and scientifically recognised – avoiding the extirpation of the oesophagus. Moreover, the technique can be applied in a walk-in/walk- out manner.

Surgery through natural orifices

Amongst other advances within the sphere of therapeutic digestive endoscopy, on the course organised by the Digestive System Service at the University Hospital of Navarra, surgical operations have been carried out using natural orifices, known as NOTES (natural orifice transluminal endoscopic surgery). Access can be through the buccal cavity, the anus, the vagina and the urinary bladder, the most commonly used routes being oral and vaginal. With the same endoscopy we usually use we can get to the stomach, perforate it and enter the abdominal cavity in order to, for example, extirpate a vesicle or deal with other lesions. Currently in this type of surgery, endoscopy and laparoscopy are being combined.

Endoscopic treatment has also been used in obesity cases. For patients with morbid obesity who do not respond to dietetic treatment, it is common to have recourse to bariatric surgery. This can be aggressive and, from time to time, news stories appear about patients who have died as a consequence of such operations. Such mortality is due, in part, to the fact that these patients are in a bad state of health generally and may have other diseases associated with obesity. They are beginning to work with the possibility of reducing the size of the stomach via endoscopy and of short-circuiting the intestinal loops.

Another novel application presented at the course involves therapeutic endoscopy in the biliary and pancreatic ducts. Despite the small diameter of these ducts, a new technology enables them to be accessed in order to examine them directly and to apply therapeutic techniques.

The Digestive System Service at the University Hospital of Navarra has presented a technique for draining the vesicle directly into the stomach by means of ecoendoscopy; as the Director of the Service explains: when the vesicle is very inflamed it is not possible to carry out surgery and it is less aggressive to access the organ by perforating the stomach and draining the contents of the vesicle into the stomach.

In the session devoted to the diagnostic application of endoscopy, the possibilities of carrying out direct microscopy were considered. Although it does not substitute biopsy, this technique is a complement in deciding where to take samples or in being more certain that a lesion found during examination is a malignant tumour or not.

News source

Millions of post-menopausal women use hormone replacement therapy (HRT) as a method to reduce symptoms associated with menopause. In a recent University of Missouri study, researchers found that one of the hormones used in HRT, a synthetic progestin, could be a major factor in promoting breast cancer. At the same time, the researchers have compelling evidence that using an antibody that prevents new blood vessel formation in tumors, or a small molecular drug, known as PRIMA, with similar properties as the antibody may be effective in treating or preventing the negative effects of progestin.

In a study published in the journal, Cancer Research, MU scientist Salman Hyder and his research team found that exposing tumor cells to progestin caused an increase in a growth factor that is involved in the formation of new blood vessels in tumors. Increasing the blood supply allows the tumors to expand as the availability of nourishment increases. However, when they used an antibody that inhibits the growth factor, the tumor shrank. Hyder’s team found similar results using PRIMA, which re-activated a protein known as p53. When p53 was activated within tumor cells, the number of breast cancer cells reduced significantly.

“As women age, many develop tiny lesions in their breasts,” said Hyder, professor of biomedical sciences in the College of Veterinary Medicine and the Dalton Cardiovascular Research Center. “The majority of the time, these lesions never expand. We think this might be due to a specific protein, p53, that, under normal circumstances, prevents tumor cells from living. We found in our study that when the protein is active, it reduces the number of breast cancer cells in the body by inhibiting the growth factor that supplies blood vessels to the tumor. However, when the cells of these lesions are exposed to progestin in a body that does not have an active p53 protein, we found that the cells might start expanding and turn into tumors.”

The synthetic progestin Hyder’s team studied is known as medroxyprogesterone acetate (MPA), which is commonly used in HRT. Using an animal model, Hyder introduced MPA to the animals that were carrying human breast cancer cells. When the breast cancer cells were exposed to MPA, they began growing at an accelerated rate. Later, when the research team exposed the cells to the antibody known as 2C3, or PRIMA – both of which block formation of new blood vessels in tumors – the tumor cells failed to grow and spread in response to the MPA.

“Since MPA is a synthetic hormone, it stays in the body longer,” Hyder said. “Unfortunately, while the drug is used to protect the uterus from the harmful effects of estrogens in HRT formulations, it is hurting the breast.”

The Women’s Health Initiative estimated a 26 percent jump in the number of breast cancer cases among women ingesting estrogen and progestin. Hyder believes that a large number of these women might also have a p53 protein that is not active and, therefore, not able to inhibit MPA-induced growth factor that helps to proliferate the tumor cells. Hyder cautioned that these studies are at an early stage and a lot of work remains to link progestin use firmly with progression of breast cancers in women.

News source

A new breast cancer study comparing Herceptin with Tykerb aims to develop a new model for global cancer research. The trial, dubbed ALTTO (Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization), will track all care and data collection in a standardized format, regardless of where patients are being treated.

News source

A new study reveals that mobile phones (cell phones) may eventually be responsible for more human deaths than smoking or asbestos. Dr. Vini Khurana, an award-winning cancer expert (14 awards) from Australia, has published some grim study results. Khurana added that government and mobile phone companies should do whatever they can to immediately reduce people’s exposure to radiation.

Khurana, who carried a 15-month critical review of the link between mobile phones and malignant brain tumors, said using mobiles for more than a decade could more than double a person’s risk of developing brain cancer. He added that a ‘solid scientific study’ needs to be carried out on people who have been regular heavy users of mobiles for at least ten years.

Many say mobile phones have not been around long enough for us to make any firm conclusions about their safety. As most tumors (cancers) take about ten years to develop it has been hard to conclude one way or the other. However, we are now reaching a time when certain studies may soon give us some more compelling pointers.

Even so, as a result of previous studies, governments around the world have started telling their people to keep mobile phone usage down to a minimum. The French government has told its children not to use them, while the German government has told its citizens to use them as little as possible. Even the European Environment Agency has advised people to keep exposure down to a minimum.

While Khurana agrees that mobile phones can save lives in emergencies, he states that there is now a significant and growing body of evidence for a link between mobile phone use and the development of some brain tumors. As we move into the next decade Khurana says this evidence will become a reality.

He says that the incidence of brain tumors will grow significantly over the next decade, by which time there is not much that can be done for those who become ill.

Khurana says that the mobile phone danger to public health may be greater than that of asbestos and/or smoking. There are three times as many people globally who use mobiles regularly than there are regular smokers, Khurana points out.

According to the Mobile Operators Association, Khurana’s study does not present a balanced analysis.

News source