A recent study led by an international team of researchers reveals a previously unrealized complexity in cancer development, one that raises concerns and caution about targeting Shp2 in oncological treatments.
The findings were published in the journal Cell Reports. In recent years, much scientific effort and funding have focused on developing drugs that target an enzyme with the unwieldy name of Src homology 2-containing protein tyrosine phosphatase 2 or more briefly, Shp2.
Shp2 is a phosphotyrosine phosphatase; its job is to remove phosphates from protein tyrosine residues, aiding and abetting signal communications within cells. But Shp2 has also been shown to promote the growth and survival of many types of cancers.
Indeed, Shp2 is the first identified oncoprotein in the family of tyrosine phosphatases. Oncoproteins are proteins encoded by an oncogene, which can cause the transformation of a cell into a tumor cell is introduced into it. Drugs that inhibit Shp2, the thinking goes, would attack cancer cells in a way different from other therapies, providing new hope for cancer patients.
But in the new study, researchers at the University of California San Diego, led by senior author Gen-Sheng Feng, PhD, professor of pathology in the UC San Diego School of Medicine and of molecular biology in the Division of Biological Sciences, reveal a previously unrealized complexity in cancer development, one that raises concerns and caution about targeting Shp2 in oncological treatments.
“This finding will have a profound impact in the cancer field, as both the pharmaceutical industry and research labs are putting huge efforts and resources into searching for and making chemical compounds to target Shp2. We believe a new, effective therapeutic strategy must address the secondary tumor-promoting microenvironment generated in response to the primary (Shp2) targeting compound.”
HCC is the most common type of primary liver cancer and the sixth most common type of cancer in the world. It is also among the deadliest. The overall prognosis for survival is grim, with a five-year relative survival rate of just 18.4 percent. The causes and progression of HCC are multifactorial, complex, and poorly understood. Treatment is difficult and limited, making it increasingly urgent to find new therapies.
By creating genetically engineered mouse models and doing single-cell RNA-sequencing, Feng and colleagues found that Shp2 was required by tumor cells for HCC development, which validated and reinforced thinking that Shp2 presented an ideal target for new cancer therapies.
But they also discovered that removing Shp2 from hepatocytes — a major cell type in the liver — allowed the Myc oncogene to dramatically accelerate HCC growth.
They found that inhibiting Shp2 induced an unexpected complex immune-suppressive environment in the liver, which disturbed clearance of tumor-initiating cells in the early stage of disease and exacerbated tumor progression at later stages.
“These unanticipated results may shed light on understanding tumor recurrence, the primary reason why most cancer patients die. Many cancer patients respond well to primary treatment, which often gives patients and doctors an initial sense of excitement or hope. But once a tumor relapses, hope dims and disappointment arises,” said Feng.
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INFUSIONS OF LIDOCAINE COULD HELP MIGRAINE SUFFERERS
Infusions of the local anesthetic lidocaine may provide some pain relief to persons with chronic migraine who have failed to respond to other treatments, according to a recent study.
The findings of the research were published in the journal ‘Regional Anesthesia & Pain Medicine. Intravenous infusions of a local anesthetic such as lidocaine have been suggested as a possible treatment option for people who have a poor quality of life because of chronic migraine which is difficult to treat. The aim is to ‘break the cycle’ of pain, but few studies have looked at the effectiveness of this treatment beyond immediate pain relief.
In this retrospective study, the authors analyzed the hospital records of 609 patients who were admitted with refractory chronic migraine and treated with infusions of lidocaine to assess the short- and medium-term benefits of this approach.
Patients included in the analysis had experienced at least 8 debilitating headache days per month for at least 6 months and failed to respond to or had contradictions to the seven classes of medicine for migraine.
Patients received lidocaine infusions over several days along with other aggressive drug treatments for migraine, such as ketorolac, magnesium, dihydroergotamine, methylprednisolone, and neuroleptics.
Most patients (87.8 percent) experienced rapid pain relief. At the time of admission, the median rating given by patients was 7.0 and this decreased to 1.0 by the time of hospital discharge.
Patients attending follow-up appointments around one month after discharge also reported that the number of headache days that they experienced had fallen. The 266 patients who attended these appointments, which took place between 25 and 65 days after discharge, said that the number of headache days in the last month had fallen from a mean of 26.8 to 22.5. Some patients experienced nausea and vomiting during the treatment but all adverse events experienced were mild.
This is an observational study, and as such, can’t establish cause and the authors also highlight some limitations. Most importantly, not all patients completed follow-up visits, but they add that in their experience these were likely to be patients who responded well. In addition, some patients were included in the analysis more than once because they were admitted on multiple occasions, and while unlikely, it is possible, that hospitalisation itself could have contributed to pain relief.
The authors conclude, “Continuous lidocaine infusions were associated with improvement in acute pain in most patients and a decrease in both average pain and the number of headache days per month that extended out to 1 month. Most patients were acute responders, 43 percent of whom maintained improvement at 1 month and were sustained, responders.
VIRAL INFECTION AFFECTS MATERNAL CARE BEHAVIOUR
As per new research by the Medical University of Vienna, viral infections during pregnancy affect the mother’s brain and her aftercare behavior.
The findings of the research were published in the journal ‘Molecular Psychiatry’. There is ample data from studies in mouse models demonstrating that viral infections during pregnancy can affect the developing brain of the young in utero (in the womb) with lifelong consequences for brain function and behavior.
A preclinical study has now shown, for the first time, that a viral-like immune activation during pregnancy also affects the maternal brain and significantly disrupts maternal care behavior after birth. These results are published by a research group led by behavioral biologist Daniela D. Pollak from the Division of Neurophysiology and Pharmacology at MedUni Vienna’s Center for Physiology and Pharmacology, working together with colleagues from the Division of Molecular Neurosciences at MedUni Vienna’s Center for Brain Research and Columbia University (USA).
In this preclinical study, the researchers used a chemical substance that activates the same receptor pathways as viruses, to trigger the immune system of the mother during pregnancy in a manner that is comparable to the typical course of a viral infection. Once the young had been born, the maternal care behavior of the dams was behaviorally tested.
“Dams who had experienced a viral-like immune activation were less caring towards their young than animals in the control group,” said Daniela D. Pollak, describing the results. “The naturally strong drive to take care of one’s offspring and to keep them safe from harm was much less pronounced corresponding to a significant decline in attachment behavior.”
The researchers not only observed changes in the behavior of the dams but also identified structural, molecular, and functional changes in their brains and were able to discover some of the underlying mechanisms.
Even though animal-model results cannot be directly translated to humans, the study team says it is an indication that viral infections during pregnancy.
AN EPILEPTIC PATIENT UNDERGOES PLASMAPHERESIS
Plasmapheresis is a medical procedure designed to remove some plasma from the blood. During a plasma exchange, unhealthy plasma is swapped for healthy plasma or a plasma substitute, before the blood is returned to the body.
According to the sources, around 200 cases of successful plasmapheresis have been reported worldwide to date. However, for the first time in Paras Hospital, Gurugram has been able to bring an epileptic patient alive using the process of plasmapheresis.
This procedure of the treatment involves withdrawing blood, separating it into plasma and cells, and then transfusing the cells back into the bloodstream of the patient. It is rarely used in epileptic patients but in this case, the doctors decided to proceed with the treatment as the patient had been experiencing recurrent epileptic seizures for the past three days and his respiration and brain functions were becoming compromised that was putting him in grave danger of death.
The 40-year-old, Paramjeet is a resident of Bhiwadi and had no history of epilepsy, however, he began showing some symptoms in April. The indications began with a fever and headache that progressed to seizures later. His family had lost their hopes of his survival as he was brought lifeless when referred to the hospital on April 8, 2022.
The doctors believed that this was caused by an autoimmune condition. In the beginning, he received three plasmapheresis cycles for a week and this treatment improved his brain function along with his respiratory system and other organs. On May 13, 2022, he was discharged from the hospital.
Commenting on this case, Dr. Rajnish Kumar, HOD of the Department of Neurology, Paras Hospital, Gurugram, said, “We’ve seen many epileptic patients die as a result of misdiagnosis or inadequate treatment. We decided to proceed with plasmapheresis after seeing that the patient was not responding to treatment. Fortunately for Paramjeet and us, the treatment worked.”
As per various reports, the treatment is considered costly and may go up to 2000 USD per session abroad. However, due to the cost factor, many charitable organisations support the expenses of patients in India. Discussing the expenses of the treatment, the parents of Paramjeet told The Daily Guardian, “This treatment cost them around Rs 1.5 lakh to Rs 2 lakh which was more affordable than other treatments.” Another case came up in 2018 where 13-year-old Yash, a resident of Gir-Somnath district, had to undergo plasmapheresis due to his kidney failure. The entire cost of treatment was more than Rs 25 lakh and was covered under the school health program.
‘Plasmapheresis is a term used to refer to a broad range of procedures in which extracorporeal separation of blood components results in a filtered plasma product. The filtering of plasma from whole blood can be accomplished via centrifugation or the use of semipermeable membranes.’
A RISE IN THYROID DISORDERS IN INDIA
In India, there is a significant burden of thyroid diseases. According to various researches, 42 million people have thyroid disorders consisting of the five main thyroid diseases hypothyroidism, hyperthyroidism, goitre/iodine deficiency disorders and Hashimoto’s thyroiditis. Thyroid glands are responsible for making hormones that control the metabolism. Any irregularity with the thyroid can lead to various health problems in the longer run. Thyroid disease arises when the thyroid gland produces either too much or too little of these important hormones. May 25 is World Thyroid Day. Thyroid diseases are one of the most common endocrine disorders across the world.
COMMON THYROID DISORDERS
Hypothyroidism (underactive thyroid) is a condition in which the thyroid gland doesn’t produce enough thyroid hormone. In our country, hypothyroidism is the most common thyroid disorder affecting 1 in every 10 men & women. During the initial stage, it may not cause noticeable symptoms. If left untreated, it is associated with various health problems, such as obesity, joint pain, infertility and heart disease. Congenital hypothyroidism occurs when the thyroid gland fails to develop or function properly. The disease occurs in 1 out of 2640 neonates when compared with the worldwide average value of 1 in 3800 subjects.
Hyperthyroidism (overactive thyroid) is the opposite of Hypothyroidism. It occurs when the thyroid gland produces excessive hormone thyroxine. The excess hormones can accelerate the body’s metabolism, causing unintentional weight loss and a rapid or irregular heartbeat. It is estimated that hypothyroidism affects up to 5% of the general population, with a further estimated 5% being undiagnosed. Over 99% of affected patients suffer from primary hypothyroidism.
Goitre is the irregular growth of the thyroid gland due to iodine deficiency or inflammation of the thyroid gland. It is one of the most common thyroid disorders in India affecting more than 1 million cases per year.
Hashimoto’s thyroiditis is an autoimmune disease. The immune system attacks the thyroid which can lead to hypothyroidism. Without proper treatment, the condition can cause serious and even life-threatening complications.
PREVALENCE OF THYROID IS ON THE RISE
Environmental iodine deficiency is the most common cause of all thyroid disorders globally. In India, the number is on the rise owing to factors like the rising awareness of the disease, which means more patients with this condition are being diagnosed and autoimmunity (a common cause of thyroid triggered by stress). It tends to impact women between the ages of 18-35 during their prime reproductive period and this is also the time they tend to suffer the most stress.
The key to thyroid treatment is to help maintain the thyroid hormone levels to normal. Anti-thyroid drugs, Thyroid replacement medication, surgery, etc. are some of the treatment options. However, there are a variety of ways and specific treatments available depending on the cause of your thyroid condition.
TIPS FOR A HEALTHY THYROID
Consume more anti-oxidants & nuts: Since thyroid is very vulnerable to oxidative stress, it is important to increase the intake of anti-oxidants. Include fruits like strawberries, raspberries and colourful vegetables in your diet plan. Also, nuts have high selenium content which is an important component of the thyroid.
Exercise and try to stay lean and fit: Exercise has a whole host of benefits that impact not only your overall health, but can help reduce thyroid symptoms like mood problems, trouble sleeping, and weight gain.
Adequate iodine intake: Iodine is an essential substance in order to maintain thyroid health. Consuming an adequate amount of iodine may help reverse the effects of slow metabolism, as it can help the body make more thyroid hormones.
The writer is Consultant – Endocrinology, Aster CMI Hospital.
UNDERSTANDING BODY SHAMING AND WHY IT OFTEN BEGINS AT HOME
Most parents consider it normal to objectify their kids with verbal usages like mottu (fat), kaali (darker), naata (short) in their regular conversations. A child who is exposed to such humiliating remarks from his/her own family after a point tends to start believing in the statements and gradually becomes conscious of his shortfalls. Soon it begins to affect his self-esteem also and may lead to other disorders like body dysmorphia, depression, anxiety, and more.
Vandana hates being tagged on Facebook family photographs, for her, it reminds her of many horrifying memories and not-so-pleasant childhood. The reason is her elder sister Archana who happens to be fairer and better looking than her. Siblings are often compared to each other based on their academic grades, behaviour, and even their physical appearances. It gets even worse if the child happens to be a girl. Vandana was often reminded of her dusky complexion body and was subjected to mockery at family gatherings. Her mother unfortunately was in the lead of the pack. We are talking about ‘Body Shaming’ an act that involves mocking a person’s physical appearance in a derogatory way. People are usually body shamed for their skin tone; hair growth, height, body weight, and even their vocal tonality are not spared. Most parents consider it normal to objectify their kids with verbal usages like Mottu (fat), Kaali (darker), naata (short) in their regular conversations. A child who is exposed to such humiliating remarks from his/her own family after a point tends to start believing in the statements and gradually becomes conscious of his shortfalls. Soon it begins to affect his self-esteem also and may lead to other disorders like body dysmorphia, depression, anxiety, and more. Statistics reveal that even boys are not spared from body shaming. Gynecomastia for instance is a condition where boys/men develop enlarged breast tissues like women due to hormonal imbalance. And the ones who are suffering from such health conditions are often reluctant to be seen in public without a shirt and even shy away from participating in games and sports.
The truth is that body shaming can happen anywhere and it’s a reality that needs to be dealt with diligence right from childhood. And like all good things that begin in our homes, understanding and handling body shaming should also begin at home. Here are a few points that we all can drive home while dealing with body shaming.
Encourage body acceptance
Body acceptance is all about treating your body with respect and accepting it with its flaws. As parents, it is important to guide your children with the message that nobody is perfect and flawless. Also makes sure they know the truth that the photographs they see of their favourite celebrities on social media are often results of editing and photoshopping.
Avoid conversations about other people›s body
Avoid talking about the physical attributes of other people at home. Most parents tend to make passive comments about other people’s bodies in their daily conversations. A child who listens to such talks begins to consider body-shaming normal and soon becomes a perpetrator himself.
There is a reason why elders insisted on eating all together culture in every family. A dining table conversation often helps children to express their apprehensions to parents and vent out their emotions without letting them clogged within. Talking it out with family often helps young minds manage stress better. Knowing that your family is going to be by your side, come what may be acts as a reassurance and confidence booster for every child. Include topics like ‘body positivity and make the conversation relatable by quoting your own growing-up experiences to them and how you dealt with the situations back then.
Keep a check on your vocabulary
Children are often like blotting paper, they absorb your words and remarks as it is without weighing the pros and cons. In the fits of anger, most parents succumb to using offensive and disapproving words related to body shaming. It not only normalizes the menace but also gives away the wrong notion to the child that it is acceptable to convey negative emotions like anger, aggression, and rage through harsh words.
The writer is Medical Director, Medlounges.
WORLD IBD DAY CELEBRATED IN PGIMER TO RAISE AWARENESS
May 19 is celebrated across the globe as World IBD day. Inflammatory Bowel diseases (IBD) are chronic inflammatory conditions of the intestine and are of two main types: ulcerative colitis and Crohn’s disease. IBD is increasing in India and this increase is largely driven by changes in the diet and westernization of lifestyle. A recent editorial in Lancet Gastroenterology & Hepatology described South Asia (including India) as a new frontier of IBD. Some studies have shown that IBD is as common in North India as in the western world. Genetics, immune response, and changes in the dietary pattern also play a role in the causation of this disease. IBD can affect any age or gender. Usually, these patients have abdominal pain, diarrhoea, and bleeding in the stools. The diagnosis is often delayed because of the lack of awareness about the disease in the community, lack of access to colonoscopy, and confusion about other diseases like haemorrhoids, abdominal tuberculosis, and cancer.
The department of Gastroenterology, PGIMER, Chandigarh celebrated the day to raise awareness about the condition and improve the care and treatment of patients living with IBD. Prof Usha Dutta, Head, Department of Gastroenterology, informed that special lectures were organized where the patients with IBD were educated about the disease, the diagnostic tests, various treatment options, the role of diet, and health maintenance. A quiz was organized where patients were asked questions about their health and the top scorers were given IBD Day Prizes. Prof SK Sinha spoke on the nature and presentation of the disease, Dr. Vishal Sharma spoke about the treatment options of the disease, and Prof Usha Dutta spoke about the diet and lifestyle approaches for IBD. Patients who have inflammatory bowel disease asked questions and doubts about their disease and health, which were answered by experts. The patients were also able to visit stalls that provided patient education material and demonstrated methods to use enema, foam, and suppository therapies, which are a cornerstone in the treatment of this condition . On this occasion an IBD card designed by the Department of Gastroenterology, in association with Colitis and Crohn’s Foundation, India was released. This card will provide a snapshot of the disease state and drug therapies with education material and will help improve various aspects of care including diet, preventive health, and medication. The card is designed with suggestions from other experts from AIIMS, Delhi, DMC, Ludhiana, and SGPGI, Lucknow. The card will be available to clinicians and gastroenterologists across the country for use and will be launched through a web meeting on World IBD day.
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