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Giorgiana Pavaloiu

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2340

Aspirin reduces the risk of cancer

A new study led by researchers at the University of California, San Francisco, could change the approach†of prevention and treatment of cancer. In the article published in the journal†PLoS†Genetics, they explain the mechanism by which aspirin has anti-cancer effect. According to the study, aspirin slows the accumulation of DNA mutations in the abnormal cells and thus decreases the risk of†premalignant†conditions.

Carlo†Maley, PhD, a member of the UCSF Helen Diller Family Comprehensive Cancer Center, explained that aspirin and NSAIDs, which are drugs widely available and cost-effective, have cancer prevention effect by decreasing the rate of mutation.†Maley, along with†gastroenterologist†and geneticist Brian Reid, MD, PhD, of the Fred Hutchinson Cancer Research Center, investigated 13 patients with Barrett’s esophagus ( which is considered a†premalignant†lesions) that were followed for 6 to 19 years. Of these, some were beginning to take aspirin daily for several years and then stopped and others started to take aspirin for the first time. The aim of the study was to see which is the mutation rate in these patients †at different times. The researchers found that patients taking aspirin had accumulated new mutations on average 10 times slower than patients who had not taken aspirin for years.

Aspirin

Maley†points out that this is the first study that measures the genome-wide mutation rates of the pre-malignant tissue from patients for more than a decade and the first to assess how aspirin affects these mutation rates.†We already know that cancer arises through successive accumulation of mutations in certain tissues more quickly than others and that the same tumor express several types of mutations. The accumulation of mutations within cells lead†to tumor growth and the presence of several types of mutations can cause resistance to treatment.

Now researchers want to test a hypothesis that explains the results of the study: that aspirin may decrease the risk of cancer by reducing inflammation, as it is a known fact that inflammation is associated with cancer.†Maley†said that less inflammation could lead to a lower risk of cancer. In the study, in almost in all cases except one, the mutation rate was low even in periods when patients were not taking aspirin. These results confirm that the few cases of Barrett’s esophagus lead to cancer††although Barrett’s esophagus is considered a†premalignant†lesion. Researchers found that in the patient who later on developed cancer of the esophagus,†a population of cellular “clones” with a great number of mutations†appeared just before he started taking aspirin.

2871

Obesity may be linked to increased cortisol levels after eating

According to an observational study on obesity, it appears that overweight and obese men secrete large amounts of stress hormones after eating, which might make them more susceptible to this metabolic disorder. Obesity and overweight are global health issues as in 2008 WHO estimated that there are over 500 millions obese people and the incidence is increasing. Obesity is often correlated with metabolic syndrome which includes (besides obesity, quantified by waist circumference), diabetes, elevated triglycerides, low HDL cholesterol and hypertension. These all together greatly increase cardiovascular risk, that is the risk of angina, heart attack, stroke or other complications (lower limb peripheral arterial disease).

Obese People

Obese People

Because obesity is a serious public health problem, researchers have thought of ways to reduce this phenomenon. One way to do this is to identify hormonal differences between the obese and lean people in certain situations such as after eating. Previous studies have highlighted the fact that in stressful situations cortisol is secreted in greater amounts in obese people than lean people. Cortisol is a steroid hormone secreted by the adrenal gland in stressful situations, along with adrenaline and noradrenaline. This hormone is absolutely necessary in humans in order to be able to deal with stressful situations but excess levels of this hormone may lead to numerous metabolic disorders. It was found that this hormone is also secreted after eating and researchers wanted to see if indeed cortisol levels are increased in obese humans after they eat.

What scientists found was that obese and overweight people have a higher level of cortisol in saliva than lean people after they have meal. Salivary cortisol is increased by 51% in obese compared to 5% in lean people. Study lead author Anne Turner, Ph.D., senior lecturer at Deakin University in Melbourne, Australia, said that this research shows that if you have excess fat deposits this exposes you to increased amounts of stress hormones every time you eat. She added that this disorder makes obese or overweight people to have an increased risk of developing related stress-diseases.

In their study, researchers measured salivary cortisol levels every 15 to 30 minutes before eating (meal included margarine, cheese, bread, meat, tomatoes, ) and for 90 minutes after eating. Turner said:†“Greater exposure of the body to cortisol may in turn, increase our risk of developing stress-related diseases such as cardiovascular disease, type 2 diabetes, depression and anxiety”. She said that this is one of the reasons why we should keep fit.

2189

New findings about Bone Cancer

Researchers at The Wellcome Trust Sanger Institute, the Royal National Orthopaedic Hospital and UCL Cancer Institute, have made a discovery that could improve the diagnosis of a common type of bone cancer. They found that a gene involved in the production of cartilage (COL2A1) is linked to the development of chondrosarcoma, which is a cancer-derived cartilage and the second most common malignant bone cancer.

The study also reveals new findings about an important signaling pathway that contributes to the development of bone cancer (Indian Hedgehog pathway). Although a therapy targeting this signaling pathway has already been developed, new research may lead to new therapeutic options for patients with bone cancer. Dr Patrick Tarpey, joint first author from the Wellcome Trust Sanger Institute, said they investigated the genetic profile of patients with this type of cancer and that their study highlights the importance of characterizing all types of cancer in order to develop improved diagnosis and treatment strategies. To see the role of gene mutations in the development of chondrosarcoma, †researchers analyzed functioning regions in 49 patients with chondrosarcoma. They found that 40% of these patients had mutations in COL2A1 gene.

Bones Cancer

Bones Cancer

COL2A1 gene is involved in the production of collagen, which is part of the cartilage. The study led by researchers at UCL Cancer Institute reveals for the first time that a collagen gene may be in the center of bone cancer development. Researchers believe that the increased activity of COL2A1 in cartilage cells can lead to the formation of mutations that can cause cancer.

According to the study, it appears that other types of bone cancer do not have mutations in the COL2A1 gene, which means that the high frequency of this mutation in chondrosarcoma could become a useful marker in the diagnosis and differentiation from other types of bone cancer. Dr Sam Behjati, joint first author from the Wellcome Trust Sanger Institute, said that the frequency of this mutation in chondrosarcoma is very interesting.

Also, researchers have made new discoveries about the signaling pathways involved in the development of chondrosarcoma. It seems that the two biological pathways, IHH and RB1, contribute to the occurrence of this type of cancer. It should be noted that there are already drugs that target IHH which are used to treat other types of cancer, which means it could be useful for patients with chondrosarcoma.

Chondrosarcomas†usually occur in patients over 40 years†and prognosis of these tumors varies depending on location, size and tumor grading. Standard treatment consists of surgical removal of the tumor, as radiotherapy and chemotherapy do not bring benefits.

3476

Berger’s Disease

Berger’s disease or IgA nephropathy is the most common glomerulonephritis in adults and is characterized by deposits of IgA antibodies in glomeruli. This disease can occur primary, without a known cause, or it can occur secondary to other conditions such as liver disease, gastrointestinal, cutaneous or respiratory infections. It can be associated with Henoch-Sch√∂nlein purpura (HSP), which is characterized by purpuric rash, joint pain and abdominal pain. IgA nephropathy is a disease with a slow evolution towards chronic renal failure with exacerbations during infectious episodes.

Berger’s disease is a kidney disease that occurs due to accumulation of IgA antibodies in glomeruli. It seems that an important role in the onset of the disease is represented by the immune system as it has been found that the Ig A nephropaty can occur after kidney transplantation. Moreover the IgA subclass (Ig A1) which is stored in the kidneys does not come from mucosa associated lymphatic tissue ( MALT) but from the bone marrow. IgA deposition in glomerulus†leads to injury, impaired glomerular basement membrane permeability and finally glomerulosclerosis.

Berger's disease

Berger’s disease

Symptoms

Usually, the disease is manifested by macroscopic hematuria that occurs after upper respiratory tract infection, gastrointestinal, skin or urinary infection. Hematuria (red blood cells in the urine) may be accompanied by proteinuria (proteins in the urine) that can be nephritic (below 3.5 g / day) or nephrotic (over 3.5 g / day). Macroscopic hematuria may disappear but microscopic hematuria persist and never goes away which is a hallmark of the disease. It can also manifest as acute nephritic syndrome with hematuria, edema and hypertension.

Berger’s disease diagnosis

Symptoms and signs such as recurrent hematuria, accompanied by edema and hypertension, are suggestive of Berger’s disease. Urine exams and blood tests show hematuria, proteinuria, inflammatory syndrome and other abnormalities. But for the diagnosis to be confirmed a renal biopsy is required.

Berger disease treatment

Berger’s disease treatment varies according to the symptoms and the clinical condition of the patient because there are situations when the disease is discovered incidentally (so the patient is asymptomatic) and situations when the patient presents to the physician in acute renal failure or chronic renal failure. Depending on the level of proteinuria there may be administered converting enzyme inhibitors, corticosteroids and immunosuppressants. In addition, studies have shown that long-term treatment with omega-3 fatty acids delays kidney failure.†Converting enzyme inhibitors (enalapril, captopril) or angiotensin II receptor blockers†(irbesartan, candesartan) lower blood pressure and have the advantage that they have nephroprotective†effects because they decrease proteinuria.

2393

Basal Cell Carcinoma is on the rise

Latest research shows that indoor tanning has increased the incidence of basal cell carcinoma ( BCC ), one of the most common forms of non-melanoma skin cancer. In general, skin cancer occurs in older people due to skin aging, but lately dermatologists have observed that basal cell carcinoma occurs more and more in younger people. And this increased incidence in young people seems to be due to indoor tanning.

An analysis conducted by Yale dermatologist Dr. David J. Leffell, Informed Susan T. Mayne, the C.-EA Winslow Professor of Epidemiology and cancer epidemiologist of the Yale School of Public Health (YSPH) shows that between 1990 and 2004 the number of patients up to 40 years with basal cell carcinoma jumped. This increase has been reported in both men and in women with about 40-50%. These data were confirmed by other studies that have shown similar increases in women under 40 years between (1976 and 2003).

 tanning

Tanning

To investigate the relationship between basal cell carcinoma and indoor tanning, postdoctoral researcher Leah M. Ferrucci, and colleagues from the Yale Cancer Center and the Yale School of Medicine, conducted a case control study that included 376 non-Hispanic, Caucasian BCC patients under the age of 40. They were asked about their exposure to the UV rays ( indoor tanning); their responses were then compared with those of a control group consisting of patients with benign, non-UV-related skin conditions.

The results were interesting: it was found that those who were tanning even once had a 69% higher risk of basal cell carcinoma than do those who have never been to the solarium. Although this demonstrates the correlation and not a causal relationship, however, it is suggestive. It also found that the risk of basal cell carcinoma increases as solar exposure is higher. Also, it was shown that†this cancer frequently appeared mostly on the torso and limbs, where exposure to ultraviolet rays in indoor tanning is higher.

It is a†well-known†fact that UV rays are causing cancer. In 2009, the International Agency for Research on Cancer (IARC) included†devices that emit UV rays as a type 1 carcinogen, along with smoking, asbestosis and X-rays.†Ferrucci said there was a clear increase in both non-melanoma skin cancers and melanomas in patients with a history of indoor tanning.†Mayne said that the mechanism by which UV rays lead to skin cancer is plausible. “We’re just looking at it in a new exposure setting. This is about as compelling evidence for causation as you can get in the setting of epidemiologic research.”

2492

Abatacept and adalimumab have the same efficacy and safety in rheumatoid arthritis

According to recent studies presented at EULAR 2013, the Annual Congress of the European League against Rheumatism, abatacept (ABA) has the same efficacy and safety as adalimumab (ADA). Rheumatoid arthritis is an autoimmune disease characterized by joint deformity, but besides joints there can be affected other organs such as the skin, lungs, eyes and others. Statistics show that 1 in 100 people suffer from rheumatoid arthritis, women are affected more frequently than men, and the disease usually occurs at forty or fifty years.

Abatacept, which is part of biological DMARDs (Disease-modifying antirheumatic drugs), reduces co-stimulation of T cells and thus decreases inflammation, pain and damage progression in rheumatoid arthritis. Adalimumab is a TNF inhibitor but the effect is similar because it decreases inflammation, pain and disease progression.

rheumatoid arthritis

RA

The study that showed similarity between ADA and ABA is called AMPLE and was a phase IIIb clinical trial that included 646 biologic-na√Įve†patients with rheumatoid arthritis who were divided to receive either the ADA or ABA (with a dose of methotrexate). Lead author of the study Dr. Michael Schiff, University of Colorado, USA, said that there were not controlled, randomized trials comparing the efficacy of two different biological DMARD therapy using biological treatment with methotrexate, which is the most prescribed drug in rheumatoid arthritis. He said that the study showed that the two drugs had the same efficacy and safety in terms of clinical, radiographic and functional outcomes.

“This robust data set demonstrates that subcutaneous abatacept and adalimumab†are equally efficacious in clinical, functional and radiographic outcomes”, Dr. Schiff said. He†added that the study is a step forward for patients because it shows that other treatment is as effective as adalimumab.

Patients with active RA and an inadequate response to methotrexate ABA received 125 mg weekly or 40 mg of ADA twice a week, along with a dose of methotrexate. Clinical effectiveness and radiographic progression inhibition of the disease were comparable between the two groups. It should be noted that the radiological aspect of the disease was evaluated with†a score called the van der Heijde modified Total Sharp Score (mTSS).

Rates of adverse events and serious adverse events were similar in both groups, though it must be said that several side†effects were observed in the group receiving abatacept. It was also found that there were fewer discontinuations of treatment due to adverse reactions in the ABA group than in the ADA group.

2259

Hormonal therapy shows promise in endomentrial cancer treatment

According to a study led by G.O. Discovery Lab team and collaborators at University of California, Los Angeles, the†microenvironment†may represent the new target for treating endometrial cancer. An important role in the pathogenesis of cancer is †played by progesterone, the female hormone that helps maintaining the menstrual cycle and pregnancy. This hormone is used as a treatment for endometrial cancer because it kills cancer cells indirectly by binding to a receptor in the surrounding connective tissue.

The standard treatment for endometrial cancer is hysterectomy, radiation and chemotherapy. Progesterone can be administered if patients want to preserve their fertility, but by the moment biomarkers that predict which tumors will respond to hormone therapy and which not have not been found.

endometrial cancer

endometrial cancer

Although endometrial cancer is regulated by hormones like breast or prostate cancer, however in treating endometrial cancer, hormonal therapies are not used to block the hormone signaling but rather to stimulate specific hormone receptors. Although it is not known exactly what mechanism underlies this treatment, however it is known that some patients will respond to treatment with progesterone. Study senior author Dr. Sanaz Memarzadeh, an assistant professor of obstetrics and gynecology and director of the GO Discovery Lab at UCLA, said it is not known from the beginning which patients will respond to hormonal treatment and which have resistant tumors. Due to this fact, progesterone is not †widely used in clinical practice although might help some patients.

Memarzadeh, who also is a researcher at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research and UCLA’s Jonsson Comprehensive Cancer Center, said that when scientists see under the microscope tumors, they focus on tumor cells and neglect the stroma, that is the†microenvironment. Their study showed that virtually all anti-tumor effects of progesterone are actually mediated by stroma, even if this represents only a small part of the tumor.

Memarzadeh and his team of researchers made many laboratory experiments and demonstrated that if you remove the progesterone receptor, the hormone therapy has no effect. A promising finding is that in hormone resistant endometrial cancer model, tumor cells become sensitive when progesterone receptors are reactivated.†Researchers will now apply the discovery in patients with†endometrial†cancer to see if it has the same effect in humans. Besides, they hope to discover biomarkers that predict which patients will respond to hormonal therapy and who do not. In addition, they want to find and test drug to combat resistance to progesterone.

2595

Immunotherapy offers new hope in the fight against cancer

The fight against cancer seems to be moving more recently to immunotherapy. Stanford University Medical Center researchers are confident that the immune response is the key to eradicate cancer and now they trying to find ways to destroy malignant tumors.

Our immune system’s ability to fight microorganisms lies on the capacity to differentiate the body’s own cells ( self) from the foreign ones ( non-self). Normally the immune system does not react against the body’s own cells, a phenomenon called immune tolerance. Trying to kill cancer cells by immune system cells is quite difficult since the tumor cells are simply cells in the body that made bad choices regarding growth and proliferation. Often even if the initial cancer cells are destroyed by the immune system, then it happens that certain immune cells called regulatory T cells, or Tregs,† recognize cancer cells as self and stop their destruction.

Cercetare

Cercetare

But now researchers have made progress and found that the initial immune response against cancer may be more persistent. Experiments on animals made by Ronald Levy, MD, professor of oncology at the School of Medicine and pioneer in the field of cancer immunotherapy, and Postdoctoral Scholar Aurelien Marabel, MD, showed that anti-cancer immune response may be more persistent. This is possible by blocking Tregs by antibodies †injected directly into the tumor. Levy said that these monoclonal antibodies target and destroy these regulatory T cells related to tumor.

Levy and his team of researchers implanted human lymphoma cells under the skin of rats †or injected the cells directly into the bloodstream. Then after cancer appearred , rats were treated with a combination of two highly specific monoclonal antibodies that were linked to regulatory T cells. It should be noted that some of the anti-Treg†antibodies are already used in cancer therapy, such as ipilimumab which is used in the treatment of metastatic melanoma. However there are side effects for these anti-Treg†antibodies because they are injected in large doses into the blood and inhibits not only tumor cells but also the rest of the cells in the body.

However, Levy and his team used much lower doses to be injected directly into the tumor so that adverse effects would not occur. They believe that by injecting antibodies into the tumor, the immune system from all over the body is activated to fight the cancer. It was found that the triple of therapy: two anti-Tregs antibodies plus the injection†of a molecules that activate the anti-cancer immune response, was very effective in rats with distant metastases. Levy said that the study results could change the way we use the immune system to fight cancer.

2399

Minimally invasive laser-based surgery for Epilepsy

According to the Mayo Clinic researchers, patients with epilepsy can now benefit from a new minimally invasive laser-based method. Preliminary results, presented at the American Academy of Neurology, show that this new method has a quicker recovery time than open surgery while the benefits are similar.

The standard treatment for patients with epilepsy who do not respond to medical treatment is surgery. Surgical treatment consists of removal of the area of the brain that cause seizures. It should be noted that surgery is a solution when the location of the crisis is clearly identified, and the procedure is called temporal lobectomy†(when the crisis are located in the temporal lobe). This type of surgery is successful in about 80% of patients, but recovery time is quite slow, that is patients need several days of hospitalization and one to three months before returning to daily activities.

Epilepsy

Epilepsy

The new technique developed by researchers at Mayo Clinic is promising because it shortens recovery time and does not involve additional risks of open surgery. Co-author W. Richard Marsh, MD, a Mayo Clinic neurosurgeon, said that although it is still under investigation, the new method can change how epilepsy surgery is done. So far this minimally invasive laser-based method†was tested on only 14 patients, but the results are positive. Five of the patients undergoing this new procedure had localized seizures occurring in the hippocampus. The most significant difference was that relating to recovery: all five required only one night in the hospital, and daily activity was resumed after only a week. Three of the patients who had mesial temporal sclerosis, a type of epilepsy that gives over 50 epileptic seizures a month, also had positive results: a few months after the procedure, two of the patients were seizure-free and one had only short auras. The minimally invasive laser-based method also resulted in improvements in patients who had localized hypothalamic hamartoma epilepsy syndrome.

This new procedure is performed under general anesthesia in a stereotactic frame. Neurosurgeons made a small hole in the skull in order to place a laser-tipped catheter with which burn a small portion of the hippocampus that causes seizures. An intraoperative MRI and another after surgery are performed to correctly identify the location and to confirm the extension of the lesion. However, patients will be investigated for one year using neuropsychological tests and MRI scans to see the differences between this new procedure and temporal lobectomy.

2419

Eculizumab proves effective in treating atypical hemolytic uremic syndrome

A new treatment for patients with atypical hemolytic uremic syndrome ( aHUS) was tested by researchers at Emory University. According to an article published in the New England Journal of Medicine, it seems that eculizumab, a monoclonal antibody, is effective in the management of this life-threatening inflammatory disease.
Hemolytic uremic syndrome, which is a thrombotic microangiopathy that causes blood clots in small vessels, is characterized by thrombocytopenia, hemolytic anemia and uremia. It mostly affects children up to 7 years old and is the most common cause of acute renal failure in children. The hemolytic uremic syndrome is often associated with enteric infections (E. coli, Shigella, Salmonella, etc.), but it can occur in other situations such as after certain drugs, tumors, after transplantation, etc..

Eculizumab

Eculizumab

A few days after enteric infection multiple organ impairment can occur such as hepatosplenomegaly, petechiae, hypertension. These symptoms can sometimes be complicated with acute renal failure, convulsions, cardiac arrhythmias, hepatitis and even death.†So far atypical hemolytic uremic syndrome (aHUS) has been treated with plasma exchange or infusion, but not all patients respond to this treatment. The rate of kidney failure or even death occurs in 30-40% of cases during the first clinical episode. In addition, in the first year, up to 65% of patients treated with plasma exchange or infusion develop renal or die.

Eculizumab, the new treatment tested for hemolytic uremic syndrome, blocks the production of inflammatory proteins by binding to complement C5 protein. FDA has approved eculizumab as previous studies have shown that this monoclonal antibody is useful for the treatment of paroxysmal nocturnal hemoglobinuria and now studies show its effectiveness in the treatment of aHUS.

There were conducted two phase 2 clinical trials that included 37 patients who did not responded to plasma exchange or infusion or had no platelet count decrease >25% for 8 weeks during standard treatment. After being treated for 26 weeks, it was found that patients who received eculizumab had an increase in platelet count and TMA (thrombotic microangiopathy) event-free status.†The study results also showed that eculizumab significantly improved patient status: hematological measurements were normalized and platelet increased from baseline.

Other improvements were made on kidney function: 4 of 5 patients receiving dialysis were able to discontinue dialysis after treatment with eculizumab. It should be noted that there were no cases of severe toxicity or adverse reactions to treatment. Principal investigator Larry Greenbaum, MD, PhD, said:†“This study showed that eculizumab is effective in treating patients with this chronic, life-threatening disease, and we were pleased to be one of the participating sites.”