Pregnant women exposed to chemicals that can increase cancer risk and harm child development

Pregnant women in the U.S. are being exposed to chemicals like melamine, cyanuric acid, and aromatic amines that can increase the risk of cancer and harm child development, according to researchers at UC San Francisco and Johns Hopkins Bloomberg School of Public Health. Melamine and cyanuric acid were found in nearly all study participants' samples, but the highest levels were found in women of color and those with greater exposure to tobacco. Four aromatic amines that are commonly used in products containing dyes and pigments were also found in nearly all pregnant participants. People can be exposed to melamine and aromatic amines in a variety of ways: through the air they breathe, by eating contaminated food or ingesting household dust, as well as from drinking water or by using products that contain plastic, dyes, and pigments. "These chemicals are of serious concern due to their links to cancer and developmental toxicity, yet they are not routinely monitored in the United States," said Tracey J. Woodruff, PhD, a professor of obstetrics, gynecology and reproductive medicine who directs the UCSF Program on Reproductive Health and the Environment, and is the co-senior author of the study published August 30, 2022, in Chemosphere. Melamine and its major byproduct, cyanuric acid, are each high production chemicals that exceed 100 million pounds per year in this country alone. When exposure to these chemicals happens together, they can be more toxic than either one alone. Melamine is found in dishware, plastics, flooring, kitchen counters, and pesticides; cyanuric acid is used as a disinfectant, plastic stabilizer, and cleaning solvent in swimming pools; aromatic amines are found in hair dye, mascara, tattoo ink, paint, tobacco smoke, and diesel exhaust. Melamine was recognized as a kidney toxicant after baby formula and pet food poisoning incidents in 2004, 2007, and 2008 that caused several deaths as well as kidney stones and urinary tract obstruction in some people. Additional animal experiments suggest melamine reduces brain function. Related Stories High consumption of ultra-processed foods linked to increased risk of colorectal cancer in men Gothenburg scientists discover possible new cancer treatment target Study provides a comprehensive view of the genomics of all childhood ALL subtypes For their study, researchers measured 45 chemicals associated with cancer and other risks using new methods to capture chemicals or chemical traces in urine samples from a small but diverse group of 171 women who are part of the National Institutes of Health's Environmental influences on Child Health Outcomes (ECHO) Program. The study period covered 2008 to 2020. The 171 women came from California, Georgia, Illinois, New Hampshire, New York, and Puerto Rico. About one-third (34%) were white, 40% were Latina, 20% were Black, 4% were Asians, and the remaining 3% were from other or multiple racial groups. Prior studies on melamine were conducted among pregnant women in Asian countries or limited to non-pregnant people in the U.S. It's disconcerting that we continue to find higher levels of many of these harmful chemicals in people of color." Jessie Buckley, PhD, study co-senior author, associate professor at Johns Hopkins Bloomberg School of Public Health

Medical latest news Leukemia drug successfully disrupts HER2-positive brain metastasis in animal studies

In animal studies led by researchers at Duke Cancer Institute, a drug approved to treat leukemia successfully disrupted the ability of HER2-positive breast cancer tumors from colonizing the brain. The finding, appearing online Aug. 30 in the journal Cell Reports, provides evidence for human trials and suggests a potential new approach to derail one of the main ways that breast cancer turns deadly. We have made huge strides in treating HER2-positive breast cancers, but when tumors escape the therapies, they often metastasize to the brain." Ann Marie Pendergast, Ph.D., senior author, professor and vice chair of the Department of Pharmacology and Cancer Biology at Duke University School of Medicine Related Stories Abdominal obesity increases risk of pancreatic cancer Study provides a comprehensive view of the genomics of all childhood ALL subtypes Discovery paves the way for specific therapies for common form of childhood brain and spine tumor "When brain metastasis occurs, treatments are unsuccessful either because the tumors have developed resistance, or the therapies cannot penetrate the blood-brain barrier," Pendergast said. "This remains a devastating diagnosis for patients." Pendergast and colleagues looked at how HER2 promotes breast cancer growth, particularly after becoming resistant to targeted treatments that have been highly successful in prolonging lives. The HER2 protein is a driving force in 30% of breast cancers, with approximately 45% of these leading to brain metastases. The researchers focused on a pair of enzymes called ABL1 and ABL2 kinases that regulate the expression of HER2. The researchers found that these kinases play a critical role in creating the conditions that allow HER2 to accumulate on the surface of breast cancer cells, fueling breast cancer tumor metastasis. Experimenting in mice, Pendergast and her team were able to disrupt the ABL kinases using a leukemia drug called asciminib. A kinase inhibitor, the drug is not impeded by the blood-brain barrier in tumor-bearing mice and interferes with the ABL kinases' signaling mechanism. By blocking the ABL signaling network, the therapy keeps the HER2 protein from accumulating in the breast cancer cells and shuts down their process for fueling the proliferation and spread of cancer cells. "These findings support the use of ABL kinase inhibitors for the treatment of HER2-positive brain metastasis," Pendergast said.

Medical latest news State-level economic policy associated with reduction in HIV risk behavior among single mothers

FINDINGS UCLA research finds that a refundable State-level Earned Income Tax Credit (SEITC) of 10% or above the Federal EITC was associated with a 21% relative risk reduction in reported behavior that could put single mothers at high risk for becoming infected with HIV during the previous year. Also, a 10 percentage-point increase in SEITC was linked to a 38% relative reduction in the same reported high-risk behavior the previous year. Related Stories Nasal spray highly effective against HIV and SARS-CoV-2 in animal models Researchers receive $3.25 million NIH grant to better understand the oral manifestations of HIV Scientists receive $3.9 million NIH grant to eradicate HIV from the brain BACKGROUND Previous research has found a relationship between poverty and sexually transmitted infections such as HIV. Poverty, low-wage jobs, income inequality, and other economic structural factors may spread sexually transmitted infections by creating high-risk partner pools, facilitating transactional sex, and undermining women's sexual agency. METHOD The researchers used data from the Behavioral Risk Factor Surveillance System (2002-2018) and state-level data from the University of Kentucky Center for Poverty Research to conduct a multi-state, multi-year analysis. IMPACT These findings demonstrate the impact of anti-poverty policy interventions such as providing cash aid to those in need. In this case, the reduction in HIV risk behavior was what would be expected for two or more hours of intensive HIV risk-reduction counseling, which few low-income single mothers can readily access. Thus, SEITC policy may be a strategy to reduce HIV among women with low socioeconomic status, particularly single mothers. AUTHORS Dr. Kimberly Danae Cauley Narain and Nina Harawa of UCLA.

New treatment may be effective in addressing the long-term effects of preeclampsia

Preeclampsia is a condition that affects the placenta during pregnancy and is dangerous for both the fetus and the mother. Scientists from the Institut Pasteur, Inserm and the CNRS have proposed a new therapy, tested in two rodent models, that corrects the defects identified in placental cells, and restores placental and fetal weight. The treatment successfully lowers blood pressure in the mother and resolves the characteristic preeclampsia symptoms of excess protein in urine and cardiovascular abnormalities. The research was published on July 30 in the journal Redox Biology. Preeclampsia is a placental dysfunction that affects approximately 2 to 8% of pregnant women worldwide. It can have fatal complications, with more than 50,000 maternal deaths each year and indirectly more than a million fetal or perinatal deaths worldwide. The primary symptoms of preeclampsia are arterial hypertension, proteinuria (increased levels of protein in the urine), abnormal coagulation in the placenta, cardiovascular abnormalities in the mother and fetal growth restriction. Preeclampsia can also have long-term effects on the cardiovascular system, brain, liver and kidneys of the mother several years after pregnancy. The current first-line treatment for preeclampsia is limited and involves the preventive use of aspirin for at-risk patients. This treatment reduces the procoagulant state in the placenta and partly relieves pressure on the vascular network. Preeclampsia is characterized by a defective placenta caused by trophoblast dysfunction. Trophoblasts are specific cells in the placenta that help organize and manage the vascular network, allowing the provision of oxygen, nutrients and other elements that are essential for fetal growth. At the molecular level, preeclampsia is characterized by an uncontrolled increase in oxidative stress, with excessive production of various reactive species including reactive oxygen and nitrogen species. There is a genetic component: the first gene to be identified as being implicated in the genetic forms of preeclampsia was the STOX1 transcription factor, which controls the expression of thousands of genes, especially those involved in the production of nitric oxide (NO). In a transgenic mouse model, high accumulation of STOX1 in the placenta induced a preeclampsia-like syndrome. In preeclampsia, nitric oxide, a powerful vasodilator that dilates blood vessels to promote blood flow to the placenta, is mobilized to produce potentially toxic molecules (nitrosative stress) and its levels become insufficient in the placental vascular network, affecting trophoblast function and the vascular network and destabilizing other reactive species. This creates a vicious circle and causes uncontrollable oxidative/nitrosative stress with multiple complications, also affecting maternal blood vessel cells, with potentially fatal consequences. Genetics & Genomics eBook Compilation of the top interviews, articles, and news in the last year. Download a copy today NO is produced by a family of enzymes known as nitric oxide synthases (NOSs). Finding a way of restoring NO production in the placenta via NOSs could represent an effective new therapy to treat preeclampsia. A years-long collaboration between the team led by Dr. Daniel Vaiman (Institut Cochin, Inserm/CNRS/Université Paris Cité) and the team led by Dr. Miria Ricchetti (Department of Developmental & Stem Cell Biology, Institut Pasteur/CNRS) with Dr. Laurent Chatre, and more recently an American team from Mississippi, gave rise to a potential solution. The scientists' research was based on trophoblasts overexpressing STOX1 and on two rodent models of preeclampsia, one mimicking early-onset forms via placental overexpression of STOX1 and the other mimicking late-onset forms by partial occlusion of the lower abdominal aorta. The research revealed a cascade of events that ultimately led the scientists to propose a new therapy. Treating trophoblasts with BH4 (or tetrahydrobiopterin, a cofactor that stabilizes the NOS enzyme producing NO) corrected the defects identified in these cells, restoring production of NO rather than potentially toxic molecules. More importantly, administering BH4 to the two preclinical rodent models restored placental and fetal weight. Finally, in the early-onset STOX1 preclinical model with significant arterial hypertension and proteinuria, the BH4 treatment corrected blood pressure, excess protein in urine, and cardiovascular abnormalities in the mother. The results even suggest that the treatment may be effective in addressing the long-term effects of preeclampsia on mothers (vascular abnormalities in the brain, kidneys, heart and liver). This research is the first step towards the development of a therapy for preeclampsia. The scientists also performed genetic (transcriptomic) analyses of placentas treated with BH4 and showed that it corrects the expression of several genes disrupted by excess STOX1 in a different way from the deregulation induced by aspirin in the placenta. In conclusion, the scientists propose that a treatment combining BH4 and aspirin could be the ultimate therapeutic solution for many cases of preeclampsia. This hypothesis needs to be validated in clinical trials.

Medical latest news news Study shows how COVID-19 pandemic has reversed years of progress in women and children's health

Declines in essential health care utilization during the COVID-19 pandemic in low- and lower-middle-income countries devastatingly impact women and children's health, according to a new study publishing August 30th in the open-access journal PLOS Medicine by Tashrik Ahmed of the World Bank, US, and colleagues. In some of the world's poorest countries, the projected corresponding increases in child and maternal mortality can erase years of progress and cause thousands of preventable deaths. Pandemics can affect health service utilization through numerous pathways. These include limitations in infrastructure, health workforce and supply chains, as well as altered patient behavior that can be attributed to changes in public transportation, mobility restrictions and fear of contracting illness. Early studies of the COVID-19 pandemic predicted that these service disruptions presented a threat to delivery of non-COVID healthcare services. Related Stories Relapse of COVID-19 symptoms and SARS-CoV-2 viral load following nirmatrelvir/ritonavir treatment Immunosuppressive therapies for COVID-19 treatment New study suggests metformin is associated with less severe COVID-19 across prediabetic individuals In the new study, researchers used data on service utilization from 18 countries in Africa and the Middle East to estimate the percent change in health services delivered between March 2020 and June 2021, compared to pre-pandemic levels. Across the countries, they found an average decline in outpatient consultation of 13.1%, and average declines of 2.6% to 4.6% for maternal and child services. The largest service disruptions occurred at the pandemic's start and during months with strict mobility restrictions. Using a mathematical model, the group projected corresponding increases of 3.6% in child mortality and 1.5% in maternal mortality. This work demonstrates how the COVID-19 pandemic has reversed years of progress in the health of women and children, especially those in the most vulnerable communities. As countries tackle multiple crises that continue to restrict service delivery and utilization, these findings can help them promote effective policies to strengthen health systems and recover with greater resilience." Dr. Tashri

Breast MRI may help stratify the risk of second breast cancer

Breast tissue features apparent on MRI are linked with future second breast cancer risk in women with a personal history of breast cancer, according to a study published in Radiology, a journal of the Radiological Society of North America (RSNA). Breast cancer is the most diagnosed cancer and the leading cause of cancer-related death in women worldwide. While advances in treatment and early detection mean that more women are surviving breast cancer, these women face an increased risk of second breast cancers. Breast cancer survivors with dense breasts face an even greater risk of a second cancer. Breast tissue is mostly fatty, with areas of fibrous connective tissue and glandular tissue known collectively as fibroglandular tissue. Women with dense breasts have a greater proportion of fibroglandular tissue and less fatty tissue. This can obscure lesions on mammography and is an independent risk factor for breast cancer. Breast MRI has become the preferred method for imaging women with personal history of breast cancer. Previous studies have shown that breast MRI has a higher cancer detection rate than mammography. Postoperative surveillance breast MRI is increasingly being performed according to the American College of Radiology's annual recommendation for women with dense breasts or those diagnosed with breast cancer before age 50." Su Hyun Lee, M.D., Ph.D., study lead author, Department of Radiology at Seoul National University Hospital in Seoul, Korea Dr. Lee and colleagues studied the link between second cancer risk and background parenchymal enhancement (BPE) at surveillance breast MRI. BPE refers to the brightening, or enhancement, of background tissue on MRI after administration of a contrast agent. The degree of BPE can vary between and within women. It is thought to be related to changes in the blood supply and permeability of breast tissue, which is affected by hormonal status. Breast cancer treatment in the form of radiation therapy, chemotherapy or endocrine therapy can also alter the BPE in the treated breast. Genetics & Genomics eBook Compilation of the top interviews, articles, and news in the last year. Download a copy today BPE on contrast-enhanced breast MRI is a known risk factor for breast cancer. Less is known about the links between BPE at surveillance breast MRI and the risk of second breast cancer. Of the 2,668 women in the study, 109 developed a second breast cancer at a median follow-up of 5.8 years. Mild, moderate, or marked BPE at surveillance breast MRI was independently associated with an increased risk of future second breast cancer compared to minimal BPE. "The results suggest that BPE at postoperative surveillance breast MRI may indicate the response to breast cancer treatment and may be a predictor of the modified risk of second breast cancer after treatment in women with a personal history of breast cancer," Dr. Lee said. The study findings point to a role for BPE measurements in refining screening pathways for women with prior breast cancer, Dr. Lee said. "Our study results may help to stratify the risk of second breast cancer in women with a personal history of breast cancer and to establish personalized imaging surveillance strategies in terms of imaging modality and monitoring interval selection," she said. "For example, women with minimal BPE at surveillance breast MRI may no longer need to undergo contrast-enhanced breast MRI every year if other risk factors are absent." Those other risk factors include younger age at diagnosis, the presence of genetic mutations linked to breast cancer and hormone receptor expression in the initial breast cancer. Areas for future study include the link between BPE changes at screening or preoperative breast MRI and at postoperative surveillance breast MRI and the development of second breast cancer. In the future, Dr. Lee expects that risk models will use mammography, ultrasound and MRI together. This approach, she said, will lead to more tailored surveillance strategies for women with a history of breast cancer.

5 Researchers discover new therapeutic target for triple-negative breast cancer

Breast cancer is categorized into three major subtypes: hormone receptor-positive, HER2-positive, and triple-negative. Although there are targeted therapeutic approaches for the first two, there are limited options for triple negative-breast cancer patients. In a new study, researchers have discovered that the nuclear receptor TLX can potentially be used for therapeutic intervention. Researchers have been able to develop good therapies for both hormone receptor-positive and HER2-positive breast cancer, and the long-term survival of patients diagnosed with these types of cancer is pretty good. On the other hand, triple-negative breast cancer has lacked an obvious target to develop drugs against. We are trying to find new targets because the five-year survival rate is worse than the other types of breast cancer." Erik Nelson (ACPP), associate professor of molecular and integrative physiology The Nelson lab specializes in studying nuclear receptors-;a class of proteins that regulate a host of biological processes. They decided to sort through different nuclear receptors to identify one that could be used to target triple-negative breast cancer. "TLX has previously been characterized in brain and prostate cancer as being a driver of those. However, when we looked at clinical data, we saw that triple-negative breast cancer patients who higher expression of TLX have better survival rates," said Adam Nelczyk, a graduate student in the Nelson lab and lead author of the study. The researchers then carried out experiments in triple-negative breast cancer cell lines to determine whether increased TLX expression could lower the classic hallmarks of cancer: tumor growth, migration, invasion, and metastasis. To measure growth, the researchers layered the cells on plates, allowed them to grow, and then measured the DNA content. They measured migration with a similar set up, but they introduced a scratch between the cells and took time-lapse images to see how quickly cells were able to close the gap. In both these tests, cells that expressed TLX showed lower growth and migration. Related Stories Leukemia drug successfully disrupts HER2-positive brain metastasis in animal studies Gothenburg scientists discover possible new cancer treatment target Discovery paves the way for specific therapies for common form of childhood brain and spine tumor Cancer cells are also notorious for their ability to breach the barriers between tissues, known as invasion, leading to tumors in adjacent tissues as well as tissues that reside far away-;a process called metastasis. To measure this phenomenon in cell lines, the researchers used special gel-coated chambers that mimic the tissue barrier; the cancer cells secrete factors that help them eat their way through. They found that TLX+ cells invaded to a lesser extent. "The decrease in metastasis is particularly important because most mortality is due to the metastatic progression of the disease," Nelson said. The same hallmarks were also measured in mouse models, coupled with RNA sequencing, to measure the changes in TLX expression, and histology studies. The mice were grafted with tumors in their mammary glands. "The data supported our initial findings, showing that mice with increased TLX expression had reduced proliferation," Nelczyk said. Although the results are promising, the mouse models do not completely capture what happens in humans. "The mice we use don't have a full immune system because they have to be able to grow human cells, so they may not recapitulate disease perfectly," Nelson said. "However, together with the patient data, they indicate that TLX is a good drug target. Next, we will have to confirm our findings in humans." Unfortunately, triple-negative breast cancer is a heterogeneous disease, and there are several subcategories. Therefore, the models that the researchers used may not be applicable for the other types of triple-negative cancer. They are hoping to focus on the other subcategories in their future studies. "We want to gain a deeper understanding of what TLX is doing, not just in cancer cells," Nelczyk said. "We have some indications that TLX can also modulate the activity of certain types of immune cells. Since we couldn't get the full picture in our models, that is the primary goal for our next set of studies." Source: