Biopeer

Light-activated molecules found effective at killing cancerous cells

Researchers at Florida State University (FSU) found that certain kinds of molecules, when exposed to light, have the potential to kill cancer cells without damaging the healthy ones. The researchers' method of killing cancer cells was to induce a type of cell death called apoptosis, in which a cell sustains so much damage that both strands of the cellular DNA are broken and the cell can no longer repair itself.  "We have found that a group of cancer-killing molecules known as lysine conjugates can identify a damaged spot, or ‘cleavage,’ in a single strand of DNA and then induce cleavage on the DNA strand opposite the damage site," said Igor V. Alabugin, associate professor of chemistry biochemistry, FSU. "This ‘double cleavage’ of the DNA is very difficult for the cell to repair and typically leads to apoptosis."

An international research team, led by Yoram Palti at the Technion-Israel Institute of Technology, suggests that low-intensity electric fields can disrupt the division of cancer cells and slow the growth of brain tumors. The researchers used low-intensity alternating electric fields that jiggle electrically charged particles in cells back and forth hundreds of thousands of times per second in laboratory experiments. The study also involved a small human trial of 10 brain cancer patients with recurrent glioblastoma multiforme (GBM). The researchers observed that the brain tumors in these patients progressed to advanced stages much slower than usual, and the patients also lived considerably longer with a median survival time of 62 weeks. This electric-field treatment poses little danger because it does not damage healthy brain cells. The researchers are now working on another human trial with a control group to investigate the possibility of combining the electric-field therapy with low-dose chemotherapy.

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Green tea found effective for treating inflammatory skin disease

Researchers at the Medical College of Georgia found that skin disorders such as psoriasis and dandruff could be treated with green tea. The researchers studied an animal model for inflammatory skin diseases and found that those animals treated with green tea showed slower growth of skin cells. The researchers observed that a chemical in the green tea suppressed inflammation by regulating the expression of Caspase-14, a protein in genes that regulates the life cycle of a skin cell. "That marker guides cells by telling them when to differentiate, die off and form a skin barrier," said Stephen Hsu, an oral biologist at the Medical College of Georgia School of Dentistry. "In people with psoriasis, that process is interrupted and the skin cells don’t die before more are created and the resulting lesions form."  The traditional treatment of ultraviolet light and medication is effective in controlling lesions, but may cause squamous cell carcinoma – the second most common form of skin cancer. So green tea treatment may prove to be a potential alternative.

Scientists from the U.S., France and Japan discovered what causes acne rosacea, a common inflammatory skin ailment that affects people over 30,  also known as adult acne. The study, published in Nature Medicine, found that that people with rosacea have high levels of the anti-microbial peptide cathelicidin in the skin, and the proteins that the cathelicidin produces are different than those produced by people without rosacea. An enzyme called stratum corneum tryptic enzyme (SCTE) is another contributor to rosacea. The scientists found that over-production of two inflammatory proteins leads to high levels of a third protein that causes rosacea symptoms. "It's like having lost of gasoline and a match," said Richard L. Gallo, professor of medicine and chief of the Division of Dermatology, University of California. "Antibiotics tend to alleviate the symptoms of rosacea in patients because some of them work to inhibit these enzymes. Our findings may modify the therapeutic approach to treating rosacea, since bacteria aren't the right target."

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Radiofrequency ablation found 100% effective at killing small kidney tumors

Researchers from the Wake Forest University Baptist Medical Center found that a minimally invasive treatment was 100% successful in eradicating small malignant kidney tumors. Doctors followed 104 patients with renal cell carcinomas (RCC), who underwent CT-guided radiofrequency ablation (RFA) for a total of 125 kidney tumors ranging in size from 0.6 cm to 8.8 cm. Researchers found that 95 small and 14 large tumors were completely eradicated by a single treatment, and seven more were eradicated after a second treatment. "This is the largest treatment group to date of patients with biopsy-proven renal malignancies," said Ronald J. Zagoria, M.D., professor of radiology at Wake Forest. "The results – a high cure rate and low complication rate – establish that at institutions with experience doing this procedure, this is an alternative method for treating small renal malignancies in patients who are not good surgical candidates."  The researchers believe renal cell carcinomas can be reliably and safely eradicated with percutaneous RFA regardless of their location in the kidney.

A pilot study conducted by researchers at Duke University Comprehensive Cancer Center found that a combination of the drugs interferon alpha and sorafenib works better than isolated drug treatment for patients with renal cell carcinoma. The study comprised of 40 patients, out of whom two had complete responses (the tumors were destroyed) and 33% had significant tumor shrinkage. "Most tumors that respond to either therapy alone begin growing again after about five or six months," said Jared Gollob, M.D., an oncologist at Duke. "By using interferon alpha and sorafenib in combination, we not only increased the response rate, but found we could double the amount of time that these patients could survive without their tumors growing." The results of the study suggest that the efficiency of drugs like sorafenib and interferon alpha could be further improved to treat this deadly cancer.

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Schizophrenic hallucinations linked to structural abnormalitites in the brain

Researchers have found both structural and functional abnormalities in specific brain regions of schizophrenic patients who experience chronic auditory hallucinations. “The results showed abnormalities in specific areas of the brain associated with the capacity to process human voices,” said Luis Martí-Bonmatí, M.D., Ph.D., of Dr. Peset University Hospital in Valencia, Spain. The researchers studied 31 right-handed men, 21 with schizophrenia and 10 healthy controls. The researchers used morphological MRI to show abnormalities in brain structure and functional MRI to gauge brain response to various emotional and neutral stimuli. The schizophrenic men showed functional abnormalities and corresponding gray matter deficits. “We hope that by evaluating combined structural and functional abnormalities in the brains of these patients, we may uncover biological markers to find candidates for specific treatments and better monitor patient response to those treatments,” added Dr. Martí-Bonmatí. The results of the MRIs may help doctors understand the pathological abnormalities associated with schizophrenia, which has been one of the greatest challenges in psychiatry.

Researchers at Johns Hopkins University have genetically engineered the first mouse that models both the anatomical and behavioral defects of schizophrenia, a complex and debilitating brain disorder. According to the online report in the Proceedings of the National Academy of Sciences, the researchers developed mice that make a regular DISC1 protein and an incomplete, shortened form of the DISC1 protein, which is an effect of having the DISC1 gene mutation associated with schizophrenia. The short form of the protein attaches to the full-length one, disrupting its normal duties. As the mice matured they showed behavioral defects as observed in schizophrenia patients. “The animals can also be bred with other strains of genetically engineered mice to try to pinpoint additional schizophrenia genes,” said Akira Sawa, M.D., Ph.D., associate professor of psychiatry and neuroscience at Johns Hopkins.

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Cancer patients benefit from white blood cell boosters

A multi-institutional study, led by researchers from the University of Rochester School Of Medicine and Dentistry and the Duke University Comprehensive Cancer Center, found that cancer patients who received drugs to stimulate the growth of infection-fighting white blood cells were less likely to die from chemotherapy-related complication. The researchers compiled 17 trials involving more than 3,000 cancer patients receiving chemotherapy of varying intensity to treat several different types of cancers. "Patients taking a drug known as granulocyte colony-stimulating factor early in their chemotherapy were about half as likely to develop dangerously low white blood cell counts with fever, and half as likely to die from infection," said Nicole M. Kuderer, M.D., lead author of the study. "This study represents an important part of the effort to better treat this common complication in cancer patients receiving chemotherapy." The results of this study showed that white blood cell boosters also benefit cancer patients who receive more common chemotherapy doses.

A study conducted at the Indiana University School of Medicine found that testicular cancer patients who do not respond to commonly used therapies may be cured with aggressive chemotherapy and a stem cell treatment. The study team looked at 184 patients with metastatic testicular cancer and demonstrated that the disease can be curable with a high-dose chemotherapy and stem cell transplant using cells harvested from the patient before the initial chemotherapy infusion. "The message for patients is that through research, diligence and new technologies, there is hope," said Lawrence Einhorn, professor of medicine at Indiana University Melvin and Bren Simon Cancer Center. The results of this study brought new hope for patients who are treated with this therapy. “This is new medicine and it tells patients that cures are on the horizon,” said Stephen D. Williams, M.D., director of the Indiana University Simon Cancer Center and a co-author of the paper.

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Cell treatment provokes immune system to fight cancer

Immunovative Therapies, an Israeli biopharmaceutical company, has developed an immunotherapy drug designed to stimulate the immune system to destroy cancer cells. “We provoke these cells, so that they become very ‘angry’ immune cells that are highly stimulated. Then we infuse them into the patient," said Michael Har-Noy, CEO of Immunovative Therapies. "The patient's immune system sees these new ‘angry’ cells as a great danger to the body, and rallies to the defense to eliminate the threat, releasing an array of inflammatory cytokines, in what is a bit like the fight or flight response of adrenaline." The drug, AlloStim, has been successfully tested in animal trials. Phase I and II clinical trials on patients with advanced blood cancer will begin at the end of this year, or the start of 2008.

Researchers at the Ohio State University have isolated compounds called glucosinolates from broccoli, which might help prevent or slow the progress of bladder cancer. “We’re starting to look at which compounds in broccoli could inhibit or decrease the growth of cancerous cells,” said Steven Schwartz, study co-author and professor of food science and technology at Ohio State University. The researchers found that during chewing and digestion, glucosinolates morph into nutritional powerhouses called isothiocyanates, compounds believed to play a role in inhibiting cancer. The scientists now will be working to find how isothiocyanates affect progression and proliferation to slow down the growth of cancer at its preliminary stage.

Researchers at the Ohio State University Comprehensive Cancer Center (the OSU CCC - James) found that blood tests for thyroid cancer can detect persistent or recurrent disease even before doctors can find any trace of a tumor. “We were surprised to find that even with relatively low thyroglobulin levels, and even when there is no sign of a tumor, about 80% of patients had a recurrence of their cancer within three to five years,” said Richard T. Kloos, associate professor of internal medicine and of radiology at OSU CCC – James.

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Scientists develop cancer-fighting virus

Scientists at the ESMO Conference Lugano (ECLU) in Switzerland announced the results of a clinical trial of NV1020, a virus developed from herpes simplex virus. NV1020 is safe to normal tissue, but deadly to cancer. "It doesn’t replicate in normal, healthy cells, so our hope is that it will help fight cancers without causing side-effects in the rest of the body," said Dr. Axel Mescheder, vice president of MediGene in Mumbai. After six months of treatment, liver masses in colorectal cancer patients almost disappeared. "In the current study, the scientists are testing the treatment in patients with colorectal cancer that have not responded to chemotherapy and where the cancer has spread to the liver," said Dr. Mescheder. "We are hoping to extend overall survival."

Researchers at the University of Athens reported that a meta-analysis of five major breast cancer trials confirmed that a combination treatment with the antibody trastuzumab and chemotherapy improves survival in women with operable HER2 positive breast cancer. Researchers compared disease-free survival, overall survival and the risk of locoregional and distant recurrence of breast cancer in women treated after breast surgery with adjuvant chemotherapy alone or chemotherapy and trastuzumab. "Taken together, these results confirm that the administration of trastuzumab in combination with chemotherapy should be the standard choice for the treatment of women with HER2 positive early stage disease, especially those with limited cardiovascular comorbidities," said Issa Dahabreh, from the University of Athens.

Scientists at the German Cancer Research Center discovered that the antibiotic griseofulvin can force cancer cells into cell death. Cancer cells can manage to divide chromosomes correctly, despite having too many centrosomes, through a "trick" of aggregating centrosomes into an alignment that mimics the alignment of two centrosomes in healthy cells. Griseofulvin interferes with this "trick" and puts cancer cells out of action. "Even though griseofulvin is not yet the ideal molecule for use in cancer treatment we were able to show clearly that this approach may contribute to fighting cancer," said Alwin Krämer, head of the Clinical Cooperation Unit Molecular Hematology/Oncology at the German Cancer Research Center.

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Scientists discover how cancer tumors evade the immune system

Researchers at the University of Southern California (USC) believe that the way a cancer tumor avoids the immune system might become its greatest vulnerability. Genetic mutation in cancerous cells results in an 'immune signature' that evades the body's natural defenses and allows cancer tumors to grow. The study, which looked at human colorectal and breast cancers, indicated that determining a tumor’s ‘immune signature’ could help diagnose and treat specific cancers. “The implication is that once you know the mechanism by which tumors evade the immune system, you can match that tumor to available therapies,” said Alan L. Epstein, professor of pathology at USC’s Keck School of Medicine. Epstein used real time PCR to screen tumors and identified 14 pro-immunity genes and 11 key anti-immunity genes. The result of this study holds promise for cancer treatment and may lead to better understanding of the immune system for most forms of cancer.

A study published in the July 3 issue of the Proceedings of the National Academy of Sciences showed that an over-expressed gene found at the site of a variety of tumors plays an active role in the development of two types of brain cancer. Wei Zhang, senior author of the paper, used a gene transfer delivery system in a mouse model to show that the gene IGFBP2 influenced the tumorigenesis of astrocytoma and oligodendrogliom – two different forms of glioma. “We hope IGFBP2 will provide an effective target for treatment of this devastating disease,” said Zhang.

A study conducted at the M.D. Anderson Cancer Center in Houston, Texas, found that patients with inoperable non-small cell lung cancer (NSCLC) can expect an increase in overall survival if they receive an initial high dose of chemotherapy before their treatment begins. Out of 265 patients with NSCLC, 127 patients received the induction therapy with chemoradiation. Those patients showed significant increase in overall survival. “This study raises questions about how we approach our treatment processes and further research will be needed to find the best way to increase survival in these patients,” said Eugene H. Huang, radiation oncologist and lead author of the study.

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Sea-squirt derived drug shows potent anti-tumor activity

A study at the Instituto Nazionale Tumori in Milan, Italy, found that a sea-squirt derived drug called trabectedin (ecteinascidinin-743) shows anti-tumor activity in more than half of the patients with a specific type of cancer. The researchers studied the effect of trabectedin on 51 patients with advanced pre-treated myxoid liposarcomas. They found two patients' tumors disappeared completely and 24 patients showed a partial response. According to the researchers,  “If the results of this analysis are reproduced in ongoing prospective studies, myxoid sarcoma would represent a uniquely sensitive subgroup to trabectedin treatment in the heterogeneous family of soft-tissue sarcoma.” The scientists are now studying the selective mechanism of the action of trabectedin and forming prospective studies to assess the drug in preoperative and metastatic conditions.

Leire García Navarro, a researcher in the School of Pharmacy at the University of Navarra, discovered a new treatment which slows the growth of colon and liver cancers. The researcher used genetic therapy with non-viral vectors to transfer genetic material to cancerous cells. Because it's non-viral, the treatment can be applied repeatedly as it does not generate immunity. Ms. Navarro prepared a new pharmaceutical format called 'lipopolyplex,' which aids the genetic material in penetrating damaged cells and allows drug release in tumorous organs. Experimentation with this new drug in mice showed a slower rate of tumor growth than in animals subjected to other procedures.

Dr. John Maris, of The Children's Hospital of Philadelphia, reviewed new approaches to treatments for children whose neuroblastoma has relapsed in an aggressive form in the June 23 issue of the Lancet. Neuroblastoma can range from a relatively easy cancer to treat, to a very aggressive cancer. Dr. Maris argues that pre-defining a patient's risk level could help oncologists design the best treatment, avoiding the twin pitfalls of under-treating or over-treating any given child. “Our goal is to match the most appropriate treatment with precise molecular targets in biological pathways, so we can intervene to stop neuroblastoma in its tracks,” said Maris.

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Progress made in liver cancer tracing

American researchers have found a way to trace liver cancer using blood DNA tests. For their study, the researchers used information from a cancer-screening program conducted earlier in Taiwan. The Taiwanese program, which was carried out between 1991 and 1992, covered 12,000 male and 11,900 female subjects who had been giving blood samples regularly before the diagnosis. The American researchers performed screenings and found changes linked with cancer in serum DNA as a biomarker to pinpoint tumor suppressor gene changes which might predict liver cancer. This is the first time that an attempt has been made to use a biomarker to detect early stage liver carcinoma and their findings were extremely optimistic.

Meanwhile, Progen announced the success of its liver cancer trials, which exceeded expectations. The pharmaceutical company carried out stage 1 tests of the Phase 2 trials on subjects who had had their liver cancer operated on and removed surgically. They randomly divided the subjects into three groups, giving them either 160 mg or 250 mg of PI-88 over a period of 36 weeks. They found that those who were given 160 mg of PI-88, showed a marked reduction in the recurrence of cancer. The first stage trials were conducted to find out the adequate dosage of PI-88 and its effectiveness. Due to the success of these trials, the researchers have decided against a stage 2 of these trials and are now planning to conduct a global Phase 3 trial at the end of the year.

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