Breaking News
January 18, 2018 - A new strategy proposed for drug discovery
January 17, 2018 - Lactation May Lower T2D Risk in Younger Women
January 17, 2018 - New Atopic Dermatitis Yardstick provides practical guidance and management insights
January 17, 2018 - New biodegradable pressure sensor could help monitor serious health conditions
January 17, 2018 - HSS orders Sectra’s 3D pre-operative planning solution for improving patient outcomes
January 17, 2018 - Study identifies six new genes regions associated with diabetes
January 17, 2018 - Women do not receive timely diagnosis for heart disease
January 17, 2018 - AbbVie’s Upadacitinib Shows Positive Results as Monotherapy in Phase 3 Rheumatoid Arthritis Study, Meeting All Primary and Key Secondary Endpoints
January 17, 2018 - Should President Trump’s Physical Include a Cognitive Screen?
January 17, 2018 - Could gene therapy someday eliminate HIV?
January 17, 2018 - Researchers identify new anti-inflammatory drug target
January 17, 2018 - Loxo Oncology Initiates Rolling Submission of New Drug Application to U.S. Food and Drug Administration for Larotrectinib for the Treatment of TRK Fusion Cancers
January 17, 2018 - Trunk Imaging Tied to Higher Nephrectomy Risk
January 17, 2018 - Campaigners incensed at failings in Africa AIDS war
January 17, 2018 - Research opens door to development of new treatment for type 2 diabetes
January 17, 2018 - Bariatric surgery extends lifespan in obese patients, shows study
January 17, 2018 - Bristol-Myers Squibb Receives FDA Approval for Opdivo (nivolumab) as Adjuvant Therapy in Patients with Completely Resected Melanoma with Lymph Node Involvement or Metastatic Disease
January 17, 2018 - Ewww Moments in the ER: That’s Improbable!
January 17, 2018 - Methods from optogenetics, machine learning should help improve treatment options for stroke patients
January 17, 2018 - Booze may help or harm the heart, but income matters
January 17, 2018 - Three-dimensional organization of genome plays key role in gene expression, cell fate
January 17, 2018 - Scientists identify six new gene regions that may help treat type 1 diabetes
January 17, 2018 - Top nutrients needed to boost mood and energy levels on Blue Monday
January 17, 2018 - Scientists develop unique technique to map elasticity of cell components
January 17, 2018 - Obesity surgery reduces the risk of death by half finds new study
January 17, 2018 - Raw Meat Not the Safest Choice for Your Dog or for You
January 17, 2018 - Men who lack HSD17B4 gene may be more susceptible to treatment-resistant prostate cancer
January 17, 2018 - High-Dose Aspirin Preferred for Kawasaki’s
January 17, 2018 - Study suggests risk management approach to combat EMS fatigue
January 17, 2018 - A new therapy against obesity
January 17, 2018 - Doctors warn against holding your nose and closing your mouth to contain a sneeze
January 17, 2018 - Measles outbreak alarms public health officials
January 17, 2018 - FDA Slaps Class Warning on Gadolinium Contrast Agents
January 17, 2018 - Distinct human mutations can alter the effect of medicine
January 17, 2018 - ASIT biotech’s new article presents clinical results of gp
January 17, 2018 - Alternative tobacco use by adolescents associated with greater odds of future cigarette smoking
January 17, 2018 - A High-Salt Diet Produces Dementia In Mice
January 17, 2018 - Scientists provide insights into crucial interaction for DNA repair
January 17, 2018 - Sanofi and Regeneron Announce Positive Topline Pivotal Results for PD-1 Antibody Cemiplimab in Advanced Cutaneous Squamous Cell Carcinoma
January 17, 2018 - Morning Break: Pfizer Kills AD/PD Pipeline; Trump Affirms His Mental Health; Humira Pricing Strategy
January 17, 2018 - Researchers see gene influencing performance of sleep-deprived people
January 17, 2018 - Fast food triggers the immune system making it hyperactive
January 17, 2018 - Scientists find increased risk of HIV outbreaks in Ukraine due to war-related migration
January 17, 2018 - New universal flu vaccine moves to clinical trial phase and could be a reality soon
January 17, 2018 - Cocaine de-addiction breakthrough shows promise
January 17, 2018 - FDA Accepts New Drug Application for Seysara (sarecycline) for the Treatment of Moderate to Severe Acne
January 17, 2018 - Robotic Telestenting; BP Cuff Smartwatch; Medicare Bundled Care
January 17, 2018 - New cellular approach found to control progression of chronic kidney disease
January 17, 2018 - Lamprey genes provide clues to repair spinal cord damage, finds study
January 17, 2018 - Tissue-based soft robot could lead to advances in bio-inspired robotics
January 17, 2018 - Mostly the healthy and wealthy Americans use mobile phone apps to track sleep habits
January 17, 2018 - FDA Alert: Varubi (rolapitant) Injectable Emulsion: Health Care Provider Letter
January 16, 2018 - NeuroBreak: Rough Days for Neuroscience Research; Another Migraine Drug Advances
January 16, 2018 - The ‘greatest pandemic in history’ was 100 years ago – but many of us still get the basic facts wrong
January 16, 2018 - Serena Williams Shares Childbirth Ordeal
January 16, 2018 - The Artificial Brain as Doctor
January 16, 2018 - Type 2 diabetes has hepatic origins
January 16, 2018 - Expert discusses how to identify, support individuals with drug or alcohol addiction in workplace
January 16, 2018 - Starting menstruation early increases risk of cardiovascular disease and stroke in later life
January 16, 2018 - CapsoVision receives CE Mark approval for use of CapsoCam Plus System in pediatric patients
January 16, 2018 - Researchers develop new dynamic statistical model to follow gene expressions over time
January 16, 2018 - Alzheimer’s ‘looks like me, it looks like you’
January 16, 2018 - By the Numbers: Physicians’ Economic Impact
January 16, 2018 - Sound Health | NIH News in Health
January 16, 2018 - Modifying baby formula doesn’t prevent type 1 diabetes in children
January 16, 2018 - Energy drinks dangerous for kids
January 16, 2018 - When you need a breast screening, should you get a 3-D mammogram?
January 16, 2018 - Johns Hopkins gets approval to perform HIV positive to HIV positive living donor kidney transplants
January 16, 2018 - The Salk Institute and Indivumed collaborate for cutting-edge cancer research
January 16, 2018 - Study reveals negative long-term effects of heavy cannabis use on brain function and behavior
January 16, 2018 - Many gym-goers injure themselves by pushing harder to be better than friends
January 16, 2018 - Risankizumab Meets All Primary Endpoints Reporting Positive Results in Fourth Pivotal Phase 3 Psoriasis Study
January 16, 2018 - Federal Junk Food Tax Feasible, Study Says
January 16, 2018 - Do girls have stronger teeth than boys?
January 16, 2018 - New high-sensitivity blood tests could aid faster diagnosis and treatment for heart attack
January 16, 2018 - How fatal mitochondrial diseases may strike offspring of families with no history of the conditions
January 16, 2018 - TherapeuticsMD Announces FDA Acceptance of New Drug Application and Prescription Drug User Fee Act (PDUFA) Date for TX-004HR
January 16, 2018 - Morning Break: Food Pharmacies; Obamacare Sign-ups Dip; Top Pot Studies
January 16, 2018 - Blood pressure declines 14 to 18 years before death
January 16, 2018 - ViLim Ball technology helps reduce uncontrollable shaking hands
Russian scientists uncover previously unknown effect of leukemia drug

Russian scientists uncover previously unknown effect of leukemia drug

image_pdfDownload PDFimage_print

Researchers from RUDN University and Institute of Biomedical Chemistry of the Russian Academy of Sciences have identified an alternative mechanism for the effective antitumor drug — an enzyme called L-asparaginase. Some isoenzymes of L-asparaginase block the growth of telomeres (region of repetitive nucleotide sequences at each end of a chromosome) on DNA molecules, and this limits the number of divisions of a cancer cell. This effect is reported in the Biochemical and Biophysical Research Communications.

“L-asparaginase enzyme has been used for the treatment of acute lymphoblastic leukemia (cancer of the hematopoietic system) in children for more than 35 years. In recent years, data on its effectiveness in NK/T-cell lymphomas (atype of skin cancer) have been published. We performed a meta-analysis of explored these findings in one of our recent articles”– said one of the authors of the paper, Vadim Pokrovsky, professor of the Department of Biochemistry (RUDN).

The antitumor effect of this enzyme first became known in the 1950s, when scientists noticed that the serum of guinea pig blood with a high content of L-asparaginase stops the development of leukemia in mice. This enzyme is present in a large number of bacteria, fungi, protozoa and even plants. For medical purposes, it is extracted from Escherichia coli (E. coli): the gene encoding L-asparaginase is inserted into the producer strain so that the enzyme can be obtained to produce commercial batches.

The antitumor effect of the enzyme is associated with the breaking down of asparagine. Asparagine is one of the amino acids, of which proteins are built. When L-asparaginase cleaves asparagine, many cells that are sensitive to the deficiency of this amino acid are killed. Above all, this refers to tumor cells that are unable to synthesize this amino acid independently.

RUDN University scientists, in collaboration with their colleagues from the laboratory of medical biotechnology (V.N. Orekhovich Institute of Biomedical Chemistry) and the laboratory of combined therapy of tumors (N.N. Blokhin Oncology Research Institute) discovered and investigated another, previously unknown effect of L-asparaginase. To do this, they used the strain of L-asparaginase obtained from another microorganism, Rhodospirillum rubrum. Amino acid substitutions were introduced into this strain, and this allowed to alter its biological properties.

It turned out that L-asparaginase can also inhibit (block) telomerase — an enzyme responsible for elongation of terminal DNA regions(telomeres), the length of which determines the possible number of cell divisions. Thus, scientists have discovered that L-asparaginase is capable of limiting the number of divisions of a cancer cell.

The work was divided into several steps. First, scientists isolated L-asparaginase and demonstrated its ability to inhibit telomerase in cancer cells. At the second stage, the same effect was reproduced in vivo. Researchers took human tumor cell cultures and transplanted them to athymic mice (mice with absence of T-cell immunity, which prevents human tumors from growing in mice). The desired effect was reproduced in model organisms: tumor growth was suspended, and this effect correlated with the shortening of telomeres and telomerase inhibition.

The researchers hope to obtain new enzymes with a stronger antitumor effect, which can be realized due to the presence of a dual mechanism described above. Along with the shortening of telomeres, L-asparaginase might possess other effects that are not yet known to science.

“The search for alternative effects of L-asparaginase, additional potential targets of this and other enzymes would allow us to design new enzyme-based drugs. That is, one enzyme will act immediately on a few metabolic targets of the tumor cell,” — Pokrovsky concluded.

Tagged with:

About author

Related Articles