Overweight women need frequent mammograms

Women with higher body mass index (BMI) face an increased risk of not detecting their breast tumor until it has become large, they need shorter intervals between mammography screening exams. BMI is a measure of body fat based on height and weight, with overweight defined as a BMI of 25 or more. High BMI is associated with a number of health risks, including diabetes and heart disease. However, BMI is not considered as part of breast cancer screening guidelines.

Researchers set out to identify risk factors associated with tumors not being detected until larger than 2 centimeters (cm), or about the size of a peanut, and to examine the implications for long-term prognosis. The 2-cm size is important because it is one of the parameters used to separate stage I and stage II cancers. In addition, tumor size is known to be strongly associated with prognosis.The researchers followed the patients until history and looked for how disease progression was related to BMI and breast density.

For cancers detected at screening, both BMI and breast density were associated with having a large tumor at diagnosis. However, for interval cancers, or cancers detected within two years of a normal mammogram, only BMI was linked with having a large tumor. Women with higher BMI had worse prognosis than women with lower BMI among interval cancers.

Breast density showed no significant association with disease progression. Besides the larger interval cancers, women with high BMI may have other factors that put them at risk for a worse prognosis, including the molecular composition of the tumors and hormone receptor expression levels that make them harder to treat.
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Vitamin D enhances healing of burns

Patients with severe burns who have higher levels of vitamin D recover more successfully than those with lower levels. Despite improvements in burn care many patients are still at risk of poor recovery. Complications can range from delayed wound healing through to infections. Patients with severe burns are at high risk of infection that may lead to life-threatening sepsis.

Vitamin D is known to have antibacterial actions that may combat infection and therefore aid in wound healing of burn patients. In order to investigate the role of vitamin D in recovery from burn injuries, researchers assessed the recovery progress, over one year, in patients with severe burns and correlated this with their vitamin D levels.

The study found that patients with higher levels of vitamin D had a better prognosis, with improved wound healing, fewer complications and less scarring. The data also showed that burns patients tend to have lower levels of vitamin D. These data suggest that vitamin D supplementation immediately following burn injury may have potent health benefits to the patient, including enhanced antimicrobial activity to prevent infection, and improved wound healing.

Major burn injury severely reduces vitamin D levels and adding this vitamin back may be a simple, safe and cost-effective way to improve outcomes for burns patients. The effectiveness of vitamin D supplementation to improve outcomes in burn patients would need to be verified in clinical trials.

Low vitamin D levels were associated with worse outcomes in burn patients including life threatening infections, mortality and delayed wound healing . It was also associated with worse scarring but vitamin D levels can improve the healing process.
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Gut bacteria may change after severe injury

After a severe traumatic injury, the composition of a patient's intestinal bacteria changes and this could affects patient's prognosis. The gut microbiome experiences a depletion in the presence of some bacteria and an increase in the presence of others came from a small investigation, involving critically injured adults.

Stool samples were collected from each person three times: when they were admitted to the hospital, and then 24 and 72 hours later. The samples were compared with those from 10 other patients who had not sustained traumatic injury.

Samples taken at the time of admission were similar in both groups. But within 24 hours, differences started to show, the investigators found. By 72 hours, three types of bacteria were depleted in the traumatic injury group, relative to the non-injury group, and the levels of two other types of bacteria had risen.

Rapid alterations in intestinal microbiota represent a critical and unrecognized phenomenon that may influence clinical course and outcomes after severe trauma. The intestinal bacterial composition could in some way be critical to patient outcomes after a traumatic injury. This could create the way towards interventions, such as administering probiotic regimens that might improve patient outcomes after injury.
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Liquid biopsy for detecting liver cancer

Researchers have developed a new diagnostic and prognosis method for early detection of hepatocellular carcinoma HCC based on a simple blood sample containing circulating tumor DNA. HCC is the most common type of primary liver cancer in adults and among the leading causes of
cancer mortality in the world.

HCC and nonalcoholic steatohepatitis, have increased, early detection improves prognosis and survival rates, in part due to greater efficacy of localized treatment against systemic treatments. But current detection methods for HCC primarily rely upon imaging and a blood test for a non-specific tumor marker called alpha-fetoprotein AFP which is usually elevated when the disease is significantly advanced.

Non-invasive blood tests or liquid biopsies present a better alternative, there has been little success in developing effective blood-based methods for screening HCC. The only blood test, AFP, has limited clinical utility due to low sensitivity. Many liquid biopsies work by detecting circulating tumor DNA ctDNA which are fragments of genetic material shed into the blood by tumor cells. These biopsies offer several potential advantages over other methods of cancer detection.

ctDNA potentially represents the entire molecular picture of a patient's malignancy while a tumor biopsy may be limited to just the tested portion of the tumor. DNA methylation is a process that can regulate gene expression and extensive DNA methylation of a gene usually leads to a gene being turned off.

 Increased methylation of tumor suppressor genes is an early event in tumor development, suggesting that altered DNA methylation patterns may be a good indicator of an emerging tumor. Researchers looked at hundreds of thousands of methylation profiles of HCC patients and healthy controls.

The researchers identified a specific panel of methylation markers that correlated to HCC, then used a variety of machine learning and statistical methods to examine their efficacy at detecting and assessing HCC in HCC patients and normal controls.
Blood-based HCC diagnosis highly correlated with tumor burden, treatment response and stage of cancer.

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Growing tumors evade anti-tumor immunity

The immunological pressure occurring during tumor progression might be harmful for the tumor to survive but the cancer cells evade the condition by restraining the anti-tumor immune response.

Cancerous tumors often grow so fast that they use up their available blood supply, creating a low-oxygen environment called hypoxia. Cells normally start to self-destruct under hypoxia, but in some tumors, the microenvironment surrounding hypoxic tumor tissue has been discovered to protect the tumor with the help of MicroRNA.

MicroRNAs are small, noncoding RNA molecules that regulate genes by silencing RNA, they have increasingly been implicated in tumor survival and progression. Researchers examined different types of tumor for altered levels of microRNAs. They identified two microRNAs ;miR25 and miR93 whose levels increased in hypoxic tumors.

The team then measured levels of those two microRNAs in the tumors of cancer patients and found that tumors with high levels of miR25 and miR93 led to a worse prognosis in patients compared to tumors with lower levels. The reverse was true for another molecule called cGAS: the lower the level of cGAS in a tumor, the worse the prognosis for the patient.
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DNA sensor and cancer immunotherapy

Tumors stressed by cancer immunotherapy release their mitochondrial DNA into the closer immune cells, causing a host alert system. The chemical alert through the molecule cGAS is an important immune-system sensor for DNA that is in the interior of cells, the cytosol, where DNA should not exist. 

 cGAS connected the innate immune system, which senses initial threats; and the adaptive immune system, which amplifies the anti-tumor response after getting the alert from the innate immune system. The adaptive system battles recurring threats from pathogens. Checkpoints are molecular barriers that cancer cells produce to make themselves undetectable to the immune system. The plan of immunotherapy is to make the cancers detectable.

Current immune checkpoint blockade therapy has been life-extending for many people. The drug targets CD47, a cell surface protein highly expressed in some tumor cells. CD47 signal to block immune cells from killing the cancer cells. cGAS as an innate immune sensor of DNA led to speculation that inhibition of cytosolic DNA sensing could represent a strategy tumor cells used to evade the immune system.

CD47 is found in every cell of the body, and it has long been known that many kinds of cancer cells produce higher amounts of CD47 than healthy cells. CD47 signal helps cancer cells evade detection from the immune system's killer T-cells.

The higher the levels of CD47 found in tumors, the poorer the prognosis for many cancers. Using mouse cells,
the researchers discovered that when cancer cells are stressed by an experimental anti-CD47 immunotherapy, it leaks DNA into nearby dendritic cells, which present antigens to killer T-cells and are considered a bridge between the innate and adaptive immune systems.

 The DNA sensor cGAS sounds the alarm inside those dendritic cells, setting off a signaling cascade that alerts the
immune system and unleashes the cancer-killing T-cells. cGAS is essential for cancer immunotherapy by immune checkpoint blockade. Activating DNA comes from the mitochondria of the cancer cells. Tumor-originated mtDNA was recognized by the DNA sensor cGAS in dendritic cells during anti-CD47 treatment.

 cGAS-STING-IRF3 signaling pathway plays a critical role to drive robust innate and adaptive immune response upon anti-CD47 therapy. Understanding this mechanism of anti-CD47 therapy may make it possible to design new combination strategies to improve current immune checkpoint blockade therapies by modulating the innate sensing of mtDNA.
       

How to treat leukemia effectively

Acute lymphoblastic leukemia is a type of cancer in which the bone marrow produces too many immature white blood cells

Activation of a protein called STAT5 causes competition among others that leads to acute lymphoblastic leukemia ALL.

According to new study, competition among some proteins causes an imbalance that leads to leukemia .

Using a drug that will stop the initial activation of STAT5 and reverse the natural balance of protein will leads to effective treatment of acute lymphoblastic leukemia.

Researchers used innovative methodology by combining mouse models and patience samples in high-throughput DNA sequencing, epigenetic and proteomic analysis and discovered that patients with a high ratio of imbalance proteins of STAT5 to IKAROS or NF-KB had worse prognosis.

Mediterranean diet may reduce the risk of cancer

According to International Journal of Cancer, Mediterranean diet may reduce the risk of estrogen-receptor-negative breast cancer, a postmenopausal form of disease with a poor prognosis.

In Netherlands, 63,573 women ages 55 to 69 tracked their diets for more than 20 years to detect impact of diet on  related disease. In the course of the study, 3354 women developed breast cancer, after excluding previous history and cases of Cancer, 2321 breast cancer cases were analyzed.

Post-menopausal estrogen-receptor-negative breast cancer was 40% less found in women that eat Mediterranean diet regularly.

Mediterranean diet is plant based diet that leads to sound health, strong bones, and prevention of all forms of disease.