Lutathera for treating gastroenteropancreatic neuroendocrine tumours

The U.S. Food and Drug Administration had approved Lutathera (lutetium Lu 177 dotatate) for the treatment of a type of cancer that affects the pancreas or gastrointestinal tract called gastroenteropancreatic neuroendocrine tumors (GEP-NETs). This is the first time a radioactive drug, or radiopharmaceutical, has been approved for the treatment of GEP-NETs. Lutathera is indicated for adult patients with somatostatin receptor-positive GEP-NETs.

GEP-NETs are a rare group of cancers with limited treatment options after initial therapy fails to keep the cancer from growing. GEP-NETs can be present in the pancreas and in different parts of the gastrointestinal tract such as the stomach, intestines, colon and rectum. Lutathera is a radioactive drug that works by binding to a part of a cell called a somatostatin receptor, which may be present on certain tumors. After binding to the receptor, the drug enters the cell allowing radiation to cause damage to the tumor cells.

The approval of Lutathera was supported by two studies. The first was a randomized clinical trial in 229 patients with a certain type of advanced somatostatin receptor-positive GEP-NET. Patients in the trial either received Lutathera in combination with the drug octreotide or octreotide alone. The study measured the length of time the tumors did not grow after treatment (progression-free survival).

Progression-free survival was longer for patients taking Lutathera with octreotide compared to patients who received octreotide alone. This means the risk of tumor growth or patient death was lower for patients who received Lutathera with octreotide compared to that of patients who received only octreotide.

The second study was based on data from 1,214 patients with somatostatin receptor-positive tumors, including GEP-NETS, who received Lutathera at a single site in the Netherlands. Complete or partial tumor shrinkage was reported in 16 percent of a subset of 360 patients with GEP-NETs who were evaluated for response by the FDA.

Patients initially enrolled in the study received Lutathera as part of an expanded access program. Expanded access is a way for patients with serious or immediately life-threatening diseases or conditions who lack therapeutic alternatives to gain access to investigational drugs for treatment use.

Common side effects of Lutathera include low levels of white blood cells (lymphopenia), high levels of enzymes in certain organs (increased GGT, AST and/or ALT), vomiting, nausea, high levels of blood sugar (hyperglycemia) and low levels of potassium in the blood (hypokalemia).

Serious side effects of Lutathera include low levels of blood cells (myelosuppression), development of certain blood or bone marrow cancers (secondary myelodysplastic syndrome and leukemia), kidney damage (renal toxicity), liver damage (hepatotoxicity), abnormal levels of hormones in the body (neuroendocrine hormonal crises) and infertility.

Lutathera can cause harm to a developing fetus; women should be advised of the potential risk to the fetus and to use effective contraception. Patients taking Lutathera are exposed to radiation. Exposure of other patients, medical personnel, and household members should be limited in accordance with radiation safety practices.
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How immune system's organ regenerates

A molecule called BMP4 that plays a key role in the thymus's extraordinary natural ability to recover from damage. Dr. Jarrod Dudakov of Fred Hutchinson Cancer Research Center, one of the study's leaders, talks about the importance of the thymus, the discoveries he and his colleagues have made about how it regenerates. The researchers hope to translate their work into new therapies to improve the function of the immune system in old age and make immunotherapies more effective.

The thymus is like a boot camp for new recruits to the immune system. From their birthplace in the bone marrow, immature white blood cells go to the thymus to mature into disease-killing machines. A healthy, active thymus gets you a diverse set of different T cells, each equipped to recognize and kill a slightly different foreign target. Thus, the organ is critical for a strong immune system that's ready to prevent any threat.

The thymus is sensitive to damage from everything from infections to life stress, it is also naturally resilient. Its power to bounce back from injury, however, fades with age, and it can take a serious hit from certain aggressive cancer therapies. BMP4, the molecule identified in the team's new study, is only the second known driver of natural thymic regeneration.

 The researchers found that BMP4 is produced by certain cells lining the inside of the organ. That molecule signals other cells of the thymus to turn on genes that promote development and repair.
Now, the team is working to figure out whether there's a master trigger that activates the whole regeneration process and then translate that knowledge into new therapies that help patients.
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How immune system react to junk food

The immune system reacts similarly to a high fat and high calorie diet as to a bacterial infection. This is shown by a recent study led by the University of Bonn. Particularly disturbing: unhealthy food seems to make the body's defenses more aggressive in the long term. Even long after switching to a healthy diet, inflammation towards innate immune stimulation is more pronounced. These long-term changes may be involved in the development of arteriosclerosis and diabetes, diseases linked to Western diet consumption.

The scientists placed mice for a month on western diet- high in fat, high in sugar, and low in fiber. The animals consequently developed a strong inflammatory response throughout the body, almost like after infection with dangerous bacteria. The unhealthy diet led to an unexpected increase in the number of certain immune cells in the blood of the mice, especially granulocytes and monocytes. This was an indication for an involvement of immune cell progenitors in the bone marrow.

Bone marrow progenitors for major immune cell types were isolated from mice fed a western diet or healthy control diet and a systematic analysis of their function and activation state was performed.
Genomic studies show that the western diet had activated a large number of genes in the progenitor cells. The genes affected included those responsible for proliferation and maturation. Fast food makes the body to activate strong immune system. When the researchers offered the rodents their typical cereal diet for another four weeks, the acute inflammation disappeared.

What did not disappear was the genetic reprogramming of the immune cells and their precursors, many of the genes that had been switched on during the fast food phase were still active after four weeks. It has only recently been discovered that the innate immune system has a form of memory. After an infection, the body's defenses remain in an alarm state, so that they can respond more quickly to a new attack-this is "innate immune training." In the mice, this process was not triggered by a bacterium, but by an unhealthy diet.

The scientists were further able to identify the responsible "fast food sensor" in immune cells. They examined blood cells from 120 subjects. In some of the subjects, the innate immune system showed a particularly strong training effect. In these subjects, the researchers found genetic evidence of the involvement of a so-called inflammasome. Inflammasomes are key intracellular signaling complexes that recognize infectious agents and other harmful substances and subsequently release highly inflammatory messengers.

The activation by Western diet changes the way in which the genetic information is packaged. The genetic material is stored in the DNA and each cell contains several DNA strands, which together are about two meters long. However, they are typically wrapped around certain proteins in the nucleus and thus many genes in the DNA cannot be read as they are sinaccessible.

Unhealthy eating causes some of these normally hidden pieces of DNA to unwind, similar to a loop hanging out of a ball of wool. This area of the genetic material can then be read much easier as long as this temporary unwrapping remains active. The inflammasome triggers such epigenetic changes, the immune system consequently reacts even to small stimuli with stronger inflammatory responses.

These inflammatory responses can in turn accelerate the development of vascular diseases or type 2 diabetes. In arteriosclerosis for example, the typical vascular deposits, the plaques, consist largely of lipids and immune cells. The inflammatory reaction contributes directly to their growth, because newly activated immune cells constantly migrate into the altered vessel walls.

When the plaques grow too large, they can burst, leading to blood clotting and are carried away by the bloodstream and can clog vessels causing stroke or heart attack. Wrong nutrition can thus have dramatic consequences. In recent centuries, average life expectancy has steadily increased in Western countries. This trend is currently being broken for the first time: Individuals born today will live on average shorter lives than their parents.
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Cancer survivors age faster and die younger

Childhood cancer survivors naturally age faster and are more likely to die sooner than those who have not had the disease, according to a new study. The research also showed that survivors are three to six times more likely to develop cancer again. Researchers from the Mayo Clinic in Rochester, Minnesota, found that hormonal/gland disorders (endocrinopathies), heart problems, lower bone mineral density, lung scarring (pulmonary fibrosis) and secondary cancers are more likely to occur in childhood cancer survivors later in life.

Frailty to bones and joints may also occur at an earlier age than the general population due to the damage caused by chemotherapy and radiotherapy to normal healthy tissues. The cancer and harsh treatments diminishes 'physiological reserve', the capacity in organs and biological body systems given to us at birth. These are the body's natural resilience to overcome internal and external biological stressors.

Other findings showed that childhood cancer survivors' estimated life expectancy is 30 percent lower than that of the general population. Also, the risk of frailty among bone marrow transplant recipients is around eight times as high as that of their siblings. Radiation therapy is associated with dementia, memory loss and secondary bone marrow cell and blood cancers, while long-term steroid treatment is linked to a higher risk of cataracts, osteoporosis, nerve damage and infection.
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Natural immune suppressor responsible for early death in leukemia patients

Patients diagnosed with the most common form of leukemia who also have high levels of an enzyme known to suppress the immune system are most likely to die early. High levels of this enzyme, indoleamine 2,3 dioxygenase, or IDO, at diagnosis also identify those who might benefit most by taking an IDO inhibitor along with their standard therapy.

A review of patients with acute myeloid leukemia, or AML, found increased IDO expression in the bone marrow biopsy, performed to diagnose their disease, correlated with lower overall survival rates and early mortality. It also indicates that IDO expression should routinely be measured when the diagnostic bone marrow biopsy is performed, Everyone has the IDO gene, it's the cancer cells in this scenario that activate the disabler of the immune response that is also used by the fetus and solid tumors.

 Stem cells in the bone marrow are supposed to mature into a variety of cells that enable human blood and immune system function. Instead in AML, stem cells get stuck in an in-between, undifferentiated state called blasts.In leukemia, stem cells get limboed in the blast state so you don't get any maturation. That means there are low platelets so you get clotting problems, you have low neutrophils so you have infections, you have less red blood cells so you get anemic.

Bleeding is a major cause of death for patients and often, significant gum bleeding is the first indicator. The patients who died at six months had a high expression of IDO while the blasts produced relatively little IDO in the patients who lived five years or more. During pregnancy, cells in the placenta trigger an isolated suppression of the mother's immune system so it won't reject the genetically foreign fetus. They showed that IDO locally disables the mother's immune system by degrading tryptophan, an amino acid essential to survival of T cells , orchestrators of the immune system's response.

Later work would show that tumors - and leukemia - also use IDO to hide from the immune response. Conversely, some organ transplant patients who inexplicably express higher levels of IDO, have lower rejection rates of their new organ. Induction therapy is given to get the patient into remission, and is typically followed by more chemotherapy to ensure it stays dormant.
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Prevymn for intravenous infusion

 Food and Drug Administration FDA has approved Prevymis (letermovir) once-daily tablets for oral use and injection for intravenous infusion. Prevymis is indicated for prophylaxis (prevention) of cytomegalovirus CMV infection and disease in adult CMV-seropositive recipients [R+] of an allogeneic hematopoietic stem cell transplant HSCT. CMV is a common and potentially serious viral infection in allogeneic HSCT recipients. CMV-seropositive patients who undergo an HSCT are at high risk for CMV reactivation. Any level of CMV infection is associated with increased mortality in HSCT patients.

 In this study, the incidence of bone marrow suppression in the Prevymis group was comparable to the placebo group. The median time to engraftment was 19 days in the Prevymis group and 18 days in the placebo group. Prevymis is contraindicated in patients receiving pimozide or ergot alkaloids. Increased pimozide concentrations may lead to QT prolongation and torsades de pointes. Increased ergot alkaloids concentrations may lead to ergotism.

Prevymis is contraindicated with pitavastatin and simvastatin when co-administered with cyclosporine. Significantly increased pitavastatin or simvastatin concentrations may lead to myopathy or rhabdomyolysis. The concomitant use of Prevymis (letermovir) and certain drugs may result in potentially significant drug interactions, some of which may lead to adverse reactions (Prevymis or concomitant drugs) or reduced therapeutic effect of Prevymis or the concomitant drug.

 Consider the potential for drug interactions prior to and during Prevymis therapy; review concomitant medications during Prevymis therapy; and monitor for adverse reactions associated with Prevymis and concomitant medications.This findings demonstrate that letermovir is a significant and welcomed advance in the prevention of clinically significant CMV infection and lowers mortality in this highly vulnerable patient population.

The recommended dosage of Prevymis is 480 mg administered once daily, initiated as early as Day 0 and up to Day 28 post-transplantation (before or after engraftment), and continued through Day 100 post-transplantation. If Prevymis is co-administered with cyclosporine, the dosage of oral or intravenous Prevymis should be decreased to 240 mg once daily. Prevymis is available as 240 mg and 480 mg tablets, which may be administered with or without food. Prevymis is also available as 240 mg and 480 mg injection for intravenous infusion via a peripheral catheter or central venous line at a constant rate over one hour.
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Calquence for treating Mantle cell lymphoma

Mantle cell lymphoma is an aggressive cancer. The U.S. Food and Drug Administration has approved Calquence (acalabrutinib) for the treatment of adults with mantle cell lymphoma who have received at least one prior therapy.

For patients who have not responded to treatment or have relapsed, Calquence provides a new treatment option that has shown high rates of response for some patients in initial studies. Mantle cell lymphoma is a rare and fast-growing type of non-Hodgkin lymphoma.

Mantle cell lymphoma is a cancer of the lymph system, which is part of the body’s immune system and is made up of lymph tissue, lymph nodes, the spleen, thymus, tonsils and bone marrow. By the time mantle cell lymphoma is diagnosed, it usually spread to the lymph nodes, bone marrow and other organs.

Calquence is a kinase inhibitor that works by blocking an enzyme needed by the cancer to multiply and spread.
The trial measured how many patients experienced complete or partial shrinkage of their tumors after treatment. In the trial, 40 percent of the patients had a complete response and 41 percent for partial response.

Common side effects of Calquence include headache, diarrhea, bruising, fatigue, muscle pain, reduced levels of red blood cells and neutrophils in the blood. Serious side effects include bleeding, infections and irregular heartbeat.

Additional cancers, known as second primary malignancies, have occurred in some patients taking Calquence. Women who are breastfeeding should not take Calquence because it may cause harm to a newborn baby.
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Fat cells for treating leukemia

Killing cancer cells indirectly by powering up fat cells in the bone marrow could help acute myeloid leukemia patients. Researchers discovered that boosting adipocytes, or fat cells, located in the bone morrow suppressed cancerous leukemia cells.

The production of healthy red blood cells is critical for those with acute myeloid leukemia but is sometimes overlooked as conventional treatments focus on killing the leukemia cells alone. Patients with this disease suffer from anemia and infection due to the failure of healthy blood production.

A drug used to moderate diabetes that induces fat cell production in the bone marrow was used for leukemia patients and was found to help foster red blood cell production as well as suppress leukemic disease.

The drug suppressed the cancer cells and bolstered the healthy cells, allowing them to regenerate in the new drug-induced environment. The drug activates blood regeneration and may provide benefits for those waiting for bone marrow transplants by activating their healthy cells.
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Blood cancer destroys bone marrow

Healthy bone marrow stromal
cells were made to transfer their power-generating mitochondria to other cancer cells, effectively feeding the acute myeloid leukaemia AML and supporting the leukaemia to grow.

AML act in a parasitic way by generating oxygen-deprived conditions in the bone marrow which stimulates the transfer of healthy mitochondria from the non-cancerous cells to the leukaemia cells.

An enzyme found in the AML cell membrane was shown to be responsible for creating the conditions necessary for mitochondrial transfer to occur. Researchers established that the enzyme called NOX-2 generated superoxide which drives this transfer.

The transfer takes place through AML-derived tunnelling nanotubes TNTs which link the cancer cells directly to the surrounding healthy cells.
Furthermore by inhibiting NOX-2, researchers showed a reduction in mitochondrial transfer took place which limited how much energy the AML cells could generate and resulted in slower cancer growth.
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Bone marrow concentrate improves joint transplant

Biologic joint restoration using donor tissue instead of traditional metal and plastic may be an option for active patients with joint defects. Recovery from a biologic joint repair takes a long time compared to traditional replacement, successful biologic restoration allows patients to return to full activity.

However, in some cases, the transplanted bone does not heal correctly. Researchers found in a group of patients that treating donor grafts with bone marrow aspirate concentrate BMC before surgery improves bone integration and aids recovery. Surgeons performing biologic joint restoration surgeries typically wash the donor bone to remove the marrow as a pretreatment before implanting the graft.

Once implanted, the recipient's bone has to grow into the donor bone for the surgery to be successful. This graft integration involves a long process called creeping substitution that can take more than a year to complete.

The researchers reviewed biologic knee replacement outcomes related to BMC use in humans. To pretreat a graft with BMC, the patient's bone marrow is collected at the beginning of the procedure, it is processed in the operating room using a centrifuge to make a powerful concentrate containing the patient's cells and proteins.

 The resulting BMC is used to saturate the donor bone before it is implanted into the patient's joint. donor grafts pretreated with BMC were associated with earlier and better bone integration. This means that pretreatment with BMC reduces the risk of bone graft failure and improves the patients' chances for long term success.

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Aliqopa for treating follicular lymphoma

Aliqopa drug (copanlisib) is for the treatment of adults with relapsed follicular lymphoma who have received systemic therapies. For patients with relapsed follicular lymphoma, the cancer often comes after multiple treatments.

Follicular lymphoma is a slow-growing type of non-Hodgkin lymphoma, a cancer of the lymph system. The lymph system is part of the body’s immune system and is made up of lymph tissue, lymph nodes, the spleen, thymus, tonsils and bone marrow.

Aliqopa is a kinase inhibitor that works by blocking several enzymes that promote cell growth. Common side effects of Aliqopa include high blood sugar levels, diarrhea, fatigue, high blood pressure, low levels of certain white blood cells, nausea, lower respiratory tract infections, and low levels of blood platelets.

Serious side effects include infections, high blood sugar levels, hypertension, inflammation of the lung tissues, low neutropenia and severe skin reactions. Women who are pregnant or breastfeeding should not take Aliqopa because it may cause harm to a developing fetus or newborn baby.
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Bone marrow protein may be used for stem cell transplant

Bone marrow contains hematopoetic stem cells, the precursors to every blood cell type. These cells become after bone marrow transplants, bone marrow injury and during systemic infection, creating new blood cells, including immune cells.

Del-1 is a protein that plays a role in gum disease, it regulate the production of blood cells. Targeting it could be an effective way to improve stem cell transplants for both donors and recipients. Modulate levels of Del-1 in patients with certain blood cancers can enhance immune cell production.

Because the hematopoetic stem cell niche is so important for the creation of bone marrow and blood cells and because Del-1 is a soluble protein and is easily manipulated, it could be a target in many potential applications.

The researchers' investigations revealed that Del-1 was expressed by at least three cell types in the bone marrow that support hematopoetic stem cells: endothelial cells, CAR cells and osteoblasts.

Using mice deficient in Del-1, they found that the protein promotes proliferation and differentiation of hematopoetic stem cells, sending more of these progenitor cells down a path toward becoming myeloid cells, such as macrophages and neutrophils, rather than lymphocytes, such as T cells and B cells.

In bone marrow transplant experiments, researchers discovered that the presence of Del-1 in recipient
bone marrow is required for the transplanted stem cells to engraft in the recipient and to facilitate the process of myelopoesis, the production of myeloid cells.

When the researchers mimicked a systemic infection in mice, animals deficient in Del-1 were slower to begin making myeloid cells again compared to those with normal Del-1 levels.

The scientists see potential applications in bone marrow and stem cell transplants, for both donors and recipients. In donors, blocking the interaction between Del-1 and hematopoetic stem cells could enhance the mobilization of those progenitors into the bloodstream. This could be helpful for increasing donor cell numbers for transplantation.

Transplant recipients, on the other hand, may need enhanced Del-1 interaction to ensure the transplanted cells engraft and begin making new blood cells more rapidly. People undergoing chemotherapy who develop febrile neutropenia, associated with low levels of white blood cells, might benefit from the role of Del-1 in supporting the production of immune-related blood cells such as neutrophils.
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Duzallo drugs for treating gout

Duzallo is a prescription medicine that contains two medicines, a URAT1 inhibitor called lesinurad and a xanthine oxidase inhibitor called allopurinol. It is used to lower uric acid levels in the blood of people with gout.

Active ingredients are lesinurad and allopurinol. Inactive ingredients: crospovidone, hydroxypropyl cellulose, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, iron oxide red, iron oxide yellow, titanium dioxide, and triacetin.

Duzallo can cause serious side effects, like kidney problems. People taking Duzallo may have kidney problems such as a sudden decrease in kidney function (acute kidney failure).
Duzallo can affect bone marrow and cause low red blood cells, white blood cells and platelets.

Other side effects are: skin rash; blistering of the skin, mouth, nose, and genitals, painful red or purple skin that looks burned and peels off, joint pain; swollen glands red, painful, watery eyes; persistent itching; hives, fever, loss of appetite, weight loss, fatigue, nausea, heartburn and diarrhea
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Besponsa for treatment of acute lymphoblastic leukemia

Food and Drug Administration approved Besponsa for the treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia. ALL.

B-cell precursor ALL is a rapidly progressing type of cancer in which the bone marrow makes too many B-cell lymphocytes, an immature type of white blood cell.

Besponsa is a targeted therapy that is thought to work by binding to B-cell ALL cancer cells that express the CD22 antigen, blocking the growth of cancerous cells.

Women who are pregnant or breastfeeding should not take Besponsa because it may cause harm to a developing fetus or a newborn baby.

Side effects of Besponsa include low levels of platelets, low levels of certain white blood cells, infection, low levels of red blood cells, fatigue, severe bleeding, fever, nausea, headache, low levels of white blood cells with fever, liver damage, abdominal pain, high levels of bilirubin in the blood,
decrease in blood cell and platelet production, infusion-related reactions and problems with the heart’s electrical pulses.
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Vitamin C can stop the spread of blood cancer

Faulty stem cells in bone marrow often multiply, increasing the growth of fatal tumours. The diseases can lead to anaemia and bleeding as abnormal stem cells multiply in the bone marrow and interfere with blood cell production.

Vitamin C can kill and prevents the spread of the tumours. Vitamin C found in high levels in kale, oranges and peppers could prevents blood cancer but it is impossible to get the required amount through fruits and vegetables in high quantities.

High quantities of vitamin C required for killing the tumours can be given by injecting cancer patients intravenously, the patients can get up to 500 times the amount they would get through eating fruit and vegetables.

Vitamin C prevents the breakdown of glucose, the mitochondria - the strength of the cancer cells are unable to gain vital energy it needs to grow with vitamin C injection.

Researchers discovered that vitamin C suppressed the growth of leukaemia cancer stem cells from human patients implanted into the mice. Combining vitamin C with a cancer drug is more effective in cancer treatment.
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Testicular macrophages guard fertility

At birth, human immune system differentiate between native cells pathogenic cells. But in males, sperm develop at puberty, the sperm may be recognized as foreign cells by some elements of the immune system.

Testicular macrophages are immune cells that rush to the defense of sperm. By releasing specific molecules, these guardians of fertility prevent other immune system agents from getting to the testes.

Macrophages migrate to sites of infection and phagocytose pathogens. They also modulate immune system activity to ensure proper organ function and regeneration.

They may arise from embryonic progenitors or bone marrow cells in adults. The testis is divided into two compartments; one of testicular macrophage is in the interstitial spaces, where testosterone-producing Leydig cells are located.

These interstitial macrophages are of embryonic origin: they are present at birth. The other is peritubular - it is located on the surface of the seminiferous tubules that house sperm cell precursors.

Each macrophage population has distinctive cellular markers. The researchers used a new cell tracing method to follow the movement of peritubular macrophages from the bone marrow to the testes in mice.

They discovered that these macrophages only appear two weeks after the birth of mice, the same duration in human. Once they have been established in the testes, macrophages remain there for the rest of their lives.
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Vyxeos for Acute Myeloid Leukemia

Food and Drug Administration has approves Vyxeos (daunorubicin and cytarabine) Liposome for Injection for Certain Types of Poor-Prognosis Acute Myeloid Leukemia

The drug is for the treatment of adults with two types of acute myeloid leukemia (AML): newly diagnosed therapy-related AML (t-AML) or AML with myelodysplasia-related changes (AML-MRC).

Vyxeos is a fixed-combination of chemotherapy drugs daunorubicin and cytarabine. Vyxeos combines two commonly used chemotherapies into a single formulation that may help some patients live longer than if they were to receive the two therapies separately.

Acute myeloid leukemia AML is a rapidly progressing cancer that forms in the bone marrow and results in an increased number of white blood cells in the bloodstream. It occurs as a complication of chemotherapy or radiation in patients treated for cancer five years after treatment.

Patients who have a history of serious hypersensitivity to daunorubicin, cytarabine or any component of the formulation should not use Vyxeos.
Patients taking Vyxeos should be monitored for hypersensitivity reactions and decreased cardiac function.

Common side effects of Vyxeos are: hemorrhage, fever with low white blood cell count, rash, swelling of the tissues, nausea, inflammation of the mucous membranes, diarrhea, constipation, musculoskeletal pain, fatigue, abdominal pain, shortness of breath, headache, cough, decreased appetite, abnormal heart rhythm, lung infection, blood infection, sleep disorders and vomiting.
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Dangers of stress

A stressful life increases the thickness of the artery walls, leading to high blood pressure and heart disease.

It also increases the production of cortisol. Researchers used high-tech MRI scanners to examine the brains, hearts and bone marrow of nearly 300 patients.

They discovered that people with higher activity in the amygdala region of the brain, the part associated with stress, were 59 percent more likely over the next 3.7 years to develop heart failure.

Stress has been linked to illnesses like cancer, lung disease, bone loss and cirrhosis of the liver.


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Malaria can cause bone loss

Malaria caused by Plasmodium parasites is a life-threatening infectious disease that kills at least half a million people annually while causing over 200 million new infections.

Common complications are: cerebral malaria, respiratory distress and severe anemia, often leading to death. The majority of patients recover from disease, however, there is increasing evidence to suggest that survivors experience long-term 'hidden' pathologies due to infection.

Now, the Laboratory of Malaria Immunology Team at the Immunology Frontier Research Center (IFReC), Osaka University, headed by Professor Cevayir COBAN, have used mouse malaria models to show that robust immune activation and invasion of parasite by-products into the bone marrow during and after malaria infection leads to an adverse balance in bone homeostasis.

Researchers discovered that Plasmodium products continuously accumulate in the bone marrow niche which turns the bone noticeably black in color, and results in it being "eaten-up" by bone resorbing cells known as osteoclasts, eventually disrupting bone homeostasis.

 Side effects of malaria infection on bone can be reversed by taking oral supplementation with alfacalcidol, a vitamin D3 analog, could completely prevent bone loss. Anti-malarial drugs combined with bone therapy may be beneficial in improving bone health in malaria-infected individuals.

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Impacts of proteins on immune system

Different genetic make-up can impact on the activity of the immune system and our ability to fight cancer.

Proteins are made up of thousands of smaller units called amino acids, which are attached to one another in long chains.

Proteins do most of the work in cells and are required for the structure, function, and regulation of the body's tissues and organs.

 A protein called ULBP6 leads to the removal of damaged cells. There are two types of this protein found in different people.

The ULBP6 protein is found on the surface of damaged cells, including several types of cancer cells, and acts as a signal to white cells in our immune system that the damaged cell should be killed.

There are two major types of protein in the population and people who inherit a certain subtype have been shown to have a poor outcome after stem cell transplantation, a procedure used to treat leukemia, which is commonly referred to as bone marrow treatment.

The two types of ULBP6 differ only by two amino acids out of a total of around 180 and it has important influence on patient outcomes. One form of ULBP6
 forms a very strong bond indeed with its receptor NKG2D on the immune system.

This shows why transplants work less well in some people, which is an important step on the path to developing better transplant therapy for more people living with blood cancer.

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