Researchers at Saint Louis University have made new progress against advanced melanoma, the most aggressive skin cancer. A retrospective study conducted by them showed that patients with brain metastases respond to high-dose of interleukin-2. The study, which was published in the Journal of Chemotherapy Research and Practice, showed that IL-2 treatment can prolong the overall survival of melanoma patients with brain metastases.

John Richart, MD, associate professor of internal medicine at SLU and principal investigator of the study, said that in the past  IL-2 therapy was not used in patients with melanoma and brain metastases because it was considered futile. The study showed that the presence of brain metastases does not exclude the patient to receive this kind of treatment because it can actually prolong his life.

Melanoma is the third most common cancer that determines brain metastases and according to studies, and it is ranked first in terms of the mortality of skin cancers. Unlike basal cell carcinoma and squamous cell carcinoma, melanoma is associated with a much worse prognosis. Dr Richard explained that the median overall survival of a patient with melanoma and brain metastases is 4 months. However the study conducted by scientists at Saint Louis University showed that treatment with IL-2 may prolong survival to 8 months.

Treatment with IL-2 is administered intravenously in hospital under close monitoring of doctors and require many cycles of six days each. Interleukin-2 kills cancer cells acts by stimulating the immune system;  in fact IL-2 stimulates the immune system to recognize cancer cells and to destroy them.

Although the results are promising (because it was showed that it prolonged survival), however in order to receive the treatment with IL-2, the patient must be in good condition and with a good brain function. Patients with rapidly growing brain injuries or those who show any symptoms of brain injury are excluded from treatment. Until now patients with melanoma and brain metastases were considered ineligible for this treatment because Il-2 was believed to cause cerebral edema, a life threatening complication. In addition, another side effect was neurotoxicity.

Melinda Chu, MD, the first year dermatology resident at SLU and first author of the study, explained that there were no cases of treatment-related mortality and that their study showed that IL-2 can be considered an option for patients with metastatic melanoma and brain. However, researchers added that they need highly skilled staff so that the treatment to be successful.

New treatment for Duchenne muscular dystrophy

Researchers at the University of Alberta have made a step forward in the research of Duchenne muscular dystrophy treatment. According to an article published in the journal PLoS ONE, it seems that researchers led by Toshifumi Yokota, a muscular dystrophy researcher in the Department of Medical Genetics, found a mutation that leads to regrowth of dystrophin protein.

Muscular dystrophies are diseases affecting skeletal muscle and gradually leading to weakness and inability of locomotion. Muscular dystrophies are inherited diseases ( X-linked diseases) that occur mainly in men. There are many forms of dystrophy: Duchenne, Becker, Emery-Dreifuss, mytonic, fascioscapulohumeral, oculopharingeal etc. Muscular dystrophies, it should be noted, do not affect only locomotion but also breathing, heart function, gastrointestinal tract etc.

Duchenne muscular dystrophy

Duchenne muscular dystrophy is an inherited disease caused by a mutation of the DMD gene and affects an average of 1 to 3,500 boys. The first symptoms usually appear in early childhood when the child begins to have difficulty in walking, running, climbing stairs, etc.. Progressive motility disorders occur also in the upper limbs, neck, head, diaphragm and by the age of 12-14 years, children with Duchenne muscular dystrophy are not able anymore to walk and end in a wheelchair. Skeletal abnormalities such as spinal deformity may also appear. Diagnosis is suspected based on signs and symptoms (difficulty in walking, etc.) and is confirmed by muscle biopsy and genetic testing. Muscle biopsy highlights the absence of dystrophin, a protein in muscle fibers, and genetic testing tells if there are mutations (deletions, duplications) in the DMD gene.

All these abnormalities (muscle weakness, chest deformity) lead to breathing problems and gradually many children with Duchenne dystrophy die from respiratory failure or due to cardiomyopathy. There is no cure for Duchenne muscular dystrophy; the treatment is intended only for increasing the survival and improving symptoms (devices to support breathing and corticosteroids to enhance muscle strength).

Toshifumi Yokota, who is a muscular dystrophy is a researcher in the Department of Medical Genetics, along with a team of scientists, discovered a mutation that causes a significant increase in dystrophin protein. They found that laboratory animals carrying this mutation had some unique muscle fibers associated with the regrowth of dystrophin. Yokota said that if they could find the mechanism by which dystrophin regrowths, this could be a therapeutic target for the treatment of Duchenne muscular dystrophy. He added that the discovery is promising but yet there are other research that must be conducted in this regard.

For other readings on Duchenne muscular dystrophy research you can read the follwing :

Duchenne Muscular Dystrophy – diagnosis and treatment

Duchenne Muscular Dystrophy –  causes and symptoms

Researchers Progress Towards Duchenne Muscular Dystrophy Treatment

New findings about Takayasu arteritis

According to an article published in The American Journal of Human Genetics, researchers have made new progress regarding  the genetics of Takayasu arteritis and why some people are more likely to develop this condition.

Takayasu arteritis is a granulomatous vasculitis that usually occurs in Asian women between 20-40 years. Takayasu arteritis is a systemic, rare disease ( that is it can affect all arteries in the body) affecting the aorta and the main branches of the aorta such as the left common carotid artery, brachiocephalic artery, subclavian artery, etc.; because it affects the main arteries of the upper arm this condition is also called pulseless arteritis. This vasculitis can lead to a number of serious complications such as aortic insufficiency, aortic aneurysm or pulmonary hypertension and others.

Not much is known about the etiology of this disease but it is assumed that the factors that trigger the inflammatory process are microorganisms such as streptococci, spirochetes, Mycobacterium tuberculosis, etc.. Researchers also discussed the hypothesis of an autoimmune process that is the formation of autoantibodies and the hypothesis of a genetic component. Until now previous studies have shown that there is an association between Takayasu arteritis and HLA-B and it seems that this link was seen in particular Japanase people. Takayasu arteritis is a vasculitis which means it is an inflammation of the arteries, and this inflammation can lead to several types of lesions such as obstruction, stenosis or aneurysms. It may also be associated with hypertension and heart failure.

Cefalee

Now researchers at the University of Michigan have discovered five genes which are involved in the development of Takayasu arteritis. Senior author Amr Sawalha, MD, associate professor of internal medicine in the division of rheumatology at the UM Medical School, said that the discovery of the genetic components is a fundamental step towards a better understanding of the mechanism of this disease and to develop more effective therapies . These new findings are extremely useful because this disease is devastating but it is little studied and understood, said Dr. Sawalha.

According to new research, there are five areas of risk both in HLA, human leukocyte antigen, and outside HLA.Besides the already established genetic association between HLA-B and Takayasu arteritis, it seems that now researchers at the University of Michigan have discovered other new genetic risk regions: HLA-DQB1/HLA-DRB1, FCGR2A/FCGR3A, and PSMG1. Co-author of the study, Güher Saruhan-Direskeneli, MD, professor of physiology at Istanbul University, explained that they have located the genetic association with IL12B, which encodes a subunit of IL-12 and IL-23. He added that therapies that inhibit IL12/IL23 pathway, that are useful in treating other inflammatory diseases, may be effective in treating this vasculitis.

Recent studies have shown that even a single mutation can make the difference between success or failure of treatment. Now researchers have developed a new technology that can detect even a single DNA mutation that can help diagnose and treat diseases such as tuberculosis or cancer. It seems that these small changes in DNA structure may be due to antibiotic resistance.

Lead author Georg Seelig, a University of Washington assistant professor of electrical engineering and of computer science and engineering, said that they improved previous approaches because their new method requires no complicated reactions and enzymes, they are just using DNA. He added that the the parameters can be modified (temperature and environment ) which means it is suitable for many diagnostic applications.

DNA is actually a nucleic acid that carries the genetic information and is composed of several base pairs. A simple modification (mutations, deletions, insertions) in one of these base pairs is sufficient to trigger important biological consequences. These changes explain why certain diseases occur or why antibiotic resistance appears. Tuberculosis, for example, is an infectious disease caused by Mycobacterium tuberculosis (Gram-positive battery that requires oxygen for survival) is a disease sometimes difficult to treat because, over time, several strains resistant to treatment occured. This resistance to antibiotics is due to small changes in a single gene. Seelig explained that if a person is resistant to treatment, this is due to the presence of a mutation in DNA.

Now researchers can detect these mutations in advance. Seelig and a team of researchers have developed a method that can detect mutations in a single base pair of DNA. This new method allows researchers to look more in detail at variations in long sequences up to 200 base pairs (the current methods can only detect mutations in sequences up to 20 base pairs). Zhang, an assistant professor of bioengineering at Rice University, said: “In terms of specificity, our research suggests that we can do quadratically better, meaning that whatever the best level of specificity, our best will be that number squared.”

This new method involves the use of test probes that bind to the DNA that supposedly contains a mutation. Researchers must create a sequence complementary to the DNA double helix, then mix both sequences in a test tube, where the two base pairs should match up if they are intact. The test probe is designed to emit a fluorescent glow if there is a match between it and the target. If it does not emit fluorescence it means that there is a mutation in the DNA.

For further reading on Tuberculosis treatment : New Drug Candidate for Tuberculosis

According to an article published in the Journal of Medical Virology, herpesvirus-6 could be a possible cause of chronic fatigue syndrome. Herpesvirus-6 is a common virus as most children come into contact with it by the age of 3 ( the infection is transmitted through saliva). The immune system inactivates it, but during childhood herpesvirus-6 infection may as well cause fever and rash. If infection occurs in a immnucompromised patient, then herpesvirus-6 can lead to more serious conditions such as encephalitis, neurological dysfunction, pneumonia, organ failure, etc..

Maria Medveczky, professor of molecular medicine at USF Health and the study’s principal investigator, said that the good thing is that their study showed that the neurological symptoms (chronic pain or long-term fatigue) can be improved with antiviral medication. She added that between 15,000 to 20,000 patients diagnosed with chronic fatigue syndrome may benefit from antiviral therapy.

So far there have been discovered 9 types of herpesvirus (herpes simplex viruses 1 and 2, varicella-zoster virus, Epstein-Barr virus, human cytomegalovirus, human herpesvirus 6, human herpesvirus 7, etc.) that cause a number of signs and symptoms . What is interesting is that after the first contact with the virus, it remains dormant or inactive, which means that at some point it may become active (usually in immunosuppression). HHV-6 however is different from other herpesviruses because it integrates its DNA in telomeres (structures at the end of chromosomes).

In addition, unlike other herpesviruses, it seems that latent HHV-6 genome can be passed on to children, a phenomenon called “chromosomally integrated HHV-6” (CIHHV-6). According to previous studies, approximately 0.8% of the population of the United States of America and the UK is CIHHV-6. It should be noted that most of these individuals are healthy but some of them may be less able to defend themselves against other strains of HHV-6; in addition it seems that some of them have chronic fatigue syndrome.

Studies have shown that the prevalence of CIHHV-6 among CFS patients with significant neurological symptoms is over 2%, which is twice more than in the general population. Therefore, researchers have thought to name this  CFS subtype “inherited Human Herpesvirus 6 Syndrome” (IHS). What is interesting is that the study led by Dr. Medveczky showed that in CIHHV-6 patients with CFS, the virus is active, but responds to valganciclovir, an antiviral drug. What it must be mentioned is that viral RNA levels decreased after treatment for 6 weeks with valgacicovir. The researchers stressed that short term treatment of up to 3 weeks had no effect on the level of viral RNA.

The ‘ABCDE’ rule of melanoma does not apply to children

According to a study led by researchers at the University of California in San Francisco, many children do not meet the classical criteria of melanoma ABCDE, which are the signs of this cancer. Melanoma is a cancer derived from melanocytes and represents about 5% of skin cancers, but its incidence is increasing. It is important to note that melanoma, although the rarest of skin cancer, is responsible for most deaths, the number of deaths from non-melanoma skin data cancers (basal cell carcinoma and squamous cell carcinoma) is four times less.

One of the important factors in the development of melanoma is exposure to sunlight and it has been shown that ultraviolet A and ultraviolet B rays (UVA and UVB) induce mutations in cellular DNA leading to uncontrolled proliferation. The use of sunbeds is also incriminated as a risk factor in the development of melanoma and it was found that the incidence of skin cancers, including melanoma, has increased with the widespread use of sunbeds. In addition it should be noted that sun exposure during childhood is a more important risk factor than sun exposure in adult life. In addition to sun exposure, other risk factors that are associated with melanoma are the skin type (white men and people with pale skin are more prone to make skin cancer), family history of melanoma, the presence of multiple melanocytic nevi etc.

It should be noted that not all melanocytic nevus is melanoma, there are several criteria that indicate malignancy and these are asymmetry (A), irregular borders (B), a change the color (C), diameter greater than 6 mm (D), elevation ( E). Doctors can use a special instrument called dermatoscope that differentiate melanoma from other lesions such as seborrheic keratosis. The aspect of a skin lesion raises suspicion of malignancy but it cannot make the final diagnosis, this requires confirmation by biopsy.

An article recently published in the Journal of the American Academy of Dermatology, shows that many children with melanoma do not meet the classical criteria: ABCDE, which means that the cancer may not be diagnosed in time. A team of researchers from the University of California in San Francisco, led by Kelly M. Cordoro, MD, conducted a retrospective study that included 60 children diagnosed with melanoma and 10 children with ambiguous melanocyte tumors who were diagnosed by age of 20. They were diagnosed in two groups: group A (ages 0-10 years) and group B (aged 11-19 years). It was found that 60% of group A and 40% in group B did not meet the ABCDE criteria. The most common signs were bleeding, amelanosis, variable diameter, de novo development. “Additional ABCD detection criteria (Amelanotic; Bleeding, Bump; Color uniformity; De novo, any Diameter) used together with conventional ABCDE criteria may facilitate earlier recognition and treatment of melanoma in children,” stressed  the authors.

Researchers demonstrate why women respond better to stress

According to popular opinion, women manage stress better than men, and researchers at the University at Buffalo have found a scientific explanation for this. Senior author Zhen Yan, PhD, a professor in the Department of Physiology and Biophysics in the UB School of Medicine and Biomedical Sciences, explained that they examined the molecular mechanism underlying the effect of stress on women and men. He said that the fact that women respond better to chronic stress has already been highlighted by other studies and now their study comes with an explanation for this fact.

The study, which was published in the journal Molecular Psychiatry, shows how female rats manage better stress than males because estrogens have a protective effect on the brain. Experiments on rats have shown that females did not have problems with memory and recognition after episodes of physical stress while males, which were exposed to the same type of stress,  had disturbances in short-term memory. Stressors that researchers used were challenging and stressful, such as working under pressure, which, in general, in humans, determine a sense of frustration.

stress

These memory impairment is due to disturbances in prefrontal cortex. The prefrontal cortex is the brain region involved in the processes of thinking, memory, attention, emotions, decision-making, etc.. The disability to recognize familiar objects appears  due to disturbances in glutamate receptor signaling pathway in the prefrontal cortex. There have been studies that have shown that in young men, repeated stress lead to loss of glutamate receptor. The study led by researchers at the University at Buffalo shows that glutamate receptor in the prefrontal cortex is not affected in females and suggests that it is a target for stress, in other words the glutamate receptor mediates stress response.

What is interesting is that the researchers were able to manipulate the amount of estrogens in the brain and in this way could make that females react to stress as males do, and vice versa. Yan explained that when estrogen signaling in the female brain was blocked, stress has negative effects on them. When estrogen signaling was activated in males, the negative effects of stress were blocked. It appears that aromatase, the enzyme that forms estradiol (female hormone) in the brain is responsible for female stress resilience. “If we could find compounds similar to estrogen that could be administered without causing hormonal side effects, they could prove to be a very effective treatment for stress-related problems in males,” Yan said.

Researchers discover why ovarian cancer disseminates

According to an article published in the American Journal of Pathology, a factor favoring the dissemination and proliferation of ovarian cancer cells is adipose tissue in the abdomen. Researchers at the University of Chicago have conducted several experiments to better understand why ovarian cancer cells disseminate into the abdominal cavity. The results showed that there is actually a two-step model of omental colonization involving on the one hand the attraction of cancer cells in structures containing immune cells and on the other hand adipose tissue promotes the growth and dissemination of cancer cells.

Omentum is a fat tissue that covers peritoneal organs in the abdominal cavity and is composed of several types of cells: fat cells, blood vessels, immune cells, connective tissue and some structures that contain some distinct immune cells called milky spots. The study led by researchers at the University of Chicago is not the first of this kind; previous studies  have suggested that the milky spots of the abdominal cavity attract ovarian cancer cells. Carrie Rinker-Schaeffer, PhD, a professor in the Departments of Surgery (Section of Urology) and Obstetrics and Gynecology at The University of Chicago, said that their study provides a fully integrated model of the relationship between the components of omental tissue and ovarian cancer cells.

Cancer Cells

In the first experiment conducted on laboratory animals, the investigators wanted to see if ovarian cancer cells are more attracted to tissue fat containing milky spots than to tissue that do not contain these structures. They took into account the fact that, in rats, there is a second source of milky spots, namely splenoportal fat. In these way, they discovered that many cancer cell lines and colonize omental and splenoportal fat. In the fat that does not contain these milky spots, there were rarely found ovarian cancer cells.

It seems that omental tissue secretes several factors that attract ovarian cancer cells. The study also showed that those tissues that contain milky spots promotes the growth and dissemination of cancer cells. The colonization of milky spots by ovarian cancer cells is not affected by different immunodeficiencies such as deficit of T cells, B cells and NK (natural killer cells). What is to note is  that between ovarian cancer cells and depletion of adipocytes  there is an inverse relationship. Dr. Rinker-Schaeffer said that their study confirms other research that showed that ovarian cancer cells use lipids stored in adipocytes as a source of energy for growth.