Tag: 31/1/24

Categories : CancerTags :

ER+ Tumours Driving Surge in Breast Cancer Diagnoses among Younger Women

On By ModernMedia
Photo by National Cancer Institute on Unsplash

Diagnoses of breast cancer have increased steadily in women under age 50 over the past two decades, with steeper increases in more recent years, according to a study published in JAMA Network Open. The surge is driven largely by increases in the number of women diagnosed with oestrogen-receptor positive (ER+) tumours.

While overall trends show increases, however, some decreases have occurred in specific tumour types and among specific groups of women. Such changes in disease rates in young women observed over time – analysed by age, race, tumour type, tumour stage and other factors – may offer clues to possible prevention strategies.

“For most women, regular breast cancer screening does not begin until at least age 40, so younger women diagnosed with breast cancer tend to have later-stage tumours, when the disease is more advanced and more difficult to treat,” said senior author Adetunji T. Toriola, MD, PhD, a professor of surgery and co-leader of the Cancer Prevention and Control Program at Siteman Cancer Center, based at Barnes-Jewish Hospital and Washington University School of Medicine. “This research offers a way to begin identifying the factors driving these increasing rates, with the goal of finding ways to slow or reverse them. It also could help identify young women who are at high risk of developing early-onset breast cancer, so that we can design interventions to evaluate in clinical trials to see if we can lower that risk.”

The research team analysed data from over 217 000 U.S. women diagnosed with any type of breast cancer from 2000 through 2019. In 2000, the incidence of breast cancer among women ages 20 to 49 was about 64 cases per 100 000 people. Over the next 16 years, that rate slowly went up, increasing at about 0.24% per year. By 2016, the rate had reached about 66 cases per 100 000. But after 2016, for reasons researchers do not yet understand, the trend line made a steep uphill turn, suddenly increasing at 3.76% per year. By 2019 the rate had reached 74 cases per 100 000.

An additional intriguing aspect of the data is that the increase in breast cancer incidence is due almost entirely to an increase in tumours that are ER+ according to Toriola, who is also a William H. Danforth Washington University Physician-Scientist Scholar. These tumours have proteins on their surfaces that bind to oestrogen, which fuels tumour growth. In fact, the incidence of tumours without the oestrogen receptor decreased over the 20 years of data analysed in the study.

“We need to understand what is driving the specific increase in oestrogen-receptor positive tumours,” Toriola said. “We also hope to learn from the decrease in oestrogen-receptor negative tumours. If we can understand what is driving that rate down, perhaps we can apply it in efforts to reduce or prevent other breast tumour types.”

The researchers also found higher rates of breast cancer among Black women, especially among those ages 20 to 29. Black women in this age group have a 53% increased risk of breast cancer compared with white women of the same age group. A higher risk for Black women also continues from ages 30 to 39, but the increased risk is smaller, at about 15% greater risk compared with white women of the same age range. Then, from ages 40 to 49, the rate for Black women drops below that of white women.

Toriola said his group is evaluating breast tumour tissue from cancer patients of different ages and races to see if there are molecular differences that could shed light on what is driving cancer to develop more in young Black women. Of note, Hispanic women in the study had the lowest incidence of breast cancer of any group.

The researchers also showed an increase in diagnoses of stage 1 and stage 4 tumours, and a decrease in diagnoses of stage 2 and stage 3 tumours. Toriola said such data suggest that improvements in screening over the past two decades, and perhaps greater awareness of family history and genetic risk factors for breast cancer, have led to many tumours being caught earlier. But it also suggests that when stage 1 tumours are missed in younger women, the tumours tend not to be found until they reach stage 4.

The researchers also found differences in breast cancer risk by year of birth. Toriola said the most dramatic difference was a greater than 20% increased risk of breast cancer among women born in 1990 compared with women born in 1955.

“We are hopeful this study will offer clues to prevention strategies that will be effective in younger women, especially younger Black women, who are at particularly high risk of developing breast cancer before age 40,” Toriola said.

Source: Washington University School of Medicine in St. Louis

Categories : Obstetrics & GynaecologyTags :

New Study Sheds Light on Placenta Accreta Spectrum Disorder

On By ModernMedia
Photo by Jonathan Borba on Unsplash

A new UCLA-led study published in American Journal of Obstetrics & Gynecology may change the way clinicians and scientists understand, diagnose and treat placenta accreta spectrum disorder, a serious condition in which the placenta fails to separate from the uterus at birth. Researchers previously believed that certain overly invasive placental cells, called trophoblasts, were responsible for keeping the connection intact.

But this new research, which identifies genetic and cellular changes within single cells where the placenta and uterus join, shifts the focus to how the structural support of tissues, and the blood vessels of the uterus, can cause a “loss of normal boundary limits” between the placenta and the uterus.

“We utilized two new techniques in single-cell analysis to create an atlas of cells involved in placenta accreta to better understand this increasingly prevalent disorder that can have devastating implications for maternal and neonatal health,” said Dr Yalda Afshar, a maternal-foetal medicine specialist and researcher at the David Geffen School of Medicine at UCLA, and the first and corresponding author.

“This work revealed a subset of genes differentially expressed in placenta accreta spectrum disorder, which provides the basis for the ‘permissive environment’ for the placenta to attach to the uterine lining,” said Dr Deborah Krakow, a maternal-foetal medicine specialist and researcher, chair of the Department of Obstetrics and Gynecology at the David Geffen School of Medicine at UCLA, and the paper’s senior author.

The research showed that the decidua, the layer of the uterine lining that forms during pregnancy, and blood vessels, are sending different signals to the placenta when a pregnant person has placenta accreta.

In placenta accreta, the placenta is stuck on too tight, which becomes the reason for many of the maternal complications of placenta accreta.

“Our goal was to characterize the intimate relationship between the maternal and fetal tissue at the site of accreta or malfunction,” Afshar said.

“The genes and signaling pathways we identified go beyond providing a better understanding of the mechanism of the disease; they may be used as targets to help us refine diagnostic tests, track disease progression over time, and discover new, more effective therapies.”

The incidence of placenta accreta spectrum (PAS) disorders has increased dramatically in recent decades, the cause of which is not certain, though cesarean deliveries, is one of several risk factors.

Today, incidence is estimated at 1 in 272 births in the U.S., up from 1 in about 30 000 pregnancies in the 1960s, researchers say.

For this study, the research team performed multiple placental biopsies on 12 placentas, six with PAS disorder and six controls, conducting single-cell RNA analysis on 31 406 individual cells.

The researchers also applied spatial transcriptomics to 36 regions of interest: 12 in PAS-adherent, 12 in PAS-nonadherent, and 12 in controls.

Spatial transcriptomics allow researchers to precisely measure and map the gene activity within a single tissue sample.

“At the end of the day, understanding the biology of pregnancy and pregnancy-related diseases, like accreta, is inspired by only one thing – finding ways to improve the care we can provide to pregnant people and their families,” said Afshar, a physician-scientist who manages the care of many patients with placenta accreta spectrum disorders at UCLA Health.

Source: University of California – Los Angeles Health Sciences

Categories : Diet and Nutrition Immune SystemTags :

Switching to Vegan or Keto Diets Impacts Immune System

On By ModernMedia
Photo by Pixabay: https://www.pexels.com/photo/broccoli-161514/

Researchers at the National Institutes of Health observed rapid and distinct immune system changes in a small study of people who switched to a vegan or a ketogenic (“keto”) diet. They found that the vegan diet prompted responses linked to innate immunity while the keto diet prompted responses associated with adaptive immunity. Metabolic changes and shifts in the participants’ microbiomes were also observed. More research is needed to determine if these changes are beneficial or detrimental and what effect they could have on nutritional interventions for diseases such as cancer or inflammatory conditions.

Scientific understanding of how different diets impact the human immune system and microbiome is limited. Therapeutic nutritional interventions, which involve changing the diet to improve health, are not well understood, and few studies have directly compared the effects of more than one diet. The keto diet is a low-carbohydrate diet that is generally high in fat. The vegan diet eliminates animal products and tends to be high in fibre and low in fat.

The study was conducted by researchers from the NIH’s National Institute of Allergy and Infectious Diseases (NIAID) and National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at the Metabolic Clinical Research Unit in the NIH Clinical Center.

The 20 participants were diverse with respect to ethnicity, race, gender, body mass index (BMI), and age. Participants sequentially ate vegan and keto diets for two weeks, in random order. Each person ate as much as desired of one diet (vegan or keto) for two weeks, followed by as much as desired of the other diet for two weeks. People on the vegan diet, which contained about 10% fat and 75% carbohydrates, chose to consume fewer calories than those on the keto diet, which contained about 76% fat and 10% carbohydrates. Throughout the study period, blood, urine, and stool were collected for analysis.

The effects of the diets were examined using a “multi-omics” approach that analysed multiple data sets to assess the body’s biochemical, cellular, metabolic, and immune responses, as well as changes to the microbiome.

Participants remained on site for the entire month-long study, allowing for careful control of the dietary interventions. Switching exclusively to the study diets caused notable changes in all participants.

The vegan diet significantly impacted pathways linked to the innate immune system, including antiviral responses. On the other hand, the keto diet led to significant increases in biochemical and cellular processes linked to adaptive immunity, such as pathways associated with T and B cells.

The keto diet affected levels of more proteins in the blood plasma than the vegan diet, as well as proteins from a wider range of tissues, such as the blood, brain and bone marrow. The vegan diet promoted more red blood cell-linked pathways, including those involved in heme metabolism, which could be due to the higher iron content of this diet.

Additionally, both diets produced changes in the microbiomes of the participants, causing shifts in the abundance of gut bacterial species that previously had been linked to the diets.

The keto diet was associated with changes in amino acid metabolism – an increase in human metabolic pathways for the production and degradation of amino acids and a reduction in microbial pathways for these processes – which might reflect the higher amounts of protein consumed by people on this diet.

The distinct metabolic and immune system changes caused by the two diets were observed despite the diversity of the participants, which shows that dietary changes consistently affect widespread and interconnected pathways in the body. More study is needed to examine how these nutritional interventions affect specific components of the immune system. According to the authors, the results of this study demonstrate that the immune system responds surprisingly rapidly to nutritional interventions. The authors suggest that it may be possible to tailor diets to prevent disease or complement disease treatments, such as by slowing processes associated with cancer or neurodegenerative disorders.

Source: NIH/National Institute of Allergy and Infectious Diseases

Categories : Gastrointestinal Respiratory DiseasesTags :

Gut Microbiome Composition Affects Sensitivity to Respiratory Viruses

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Gut Microbiome. Credit Darryl Leja National Human Genome Research Institute National Institutes Of Health

The composition of microbiota found in the gut influences how susceptible mice are to respiratory virus infections and the severity of these infections, according to Georgia State University researchers. The findings, published in the journal Cell Host & Microbe, report that segmented filamentous bacteria, a bacterial species found in the intestines, protected mice against influenza virus infection when these bacteria were either naturally acquired or administered.

This protection against infection also applied to respiratory syncytial virus (RSV) and severe acute SARS-CoV-2. To maintain this protection, the study noted that segmented filamentous bacteria required immune cells in the lungs called basally resident alveolar macrophages.

In this study, the researchers investigated how differences in specific microbial species can impact outcomes of respiratory virus infections and how they might do so, which hasn’t been well defined previously.

They studied mice with discrete microbiome differences and mice differing in only the presence or absence of segmented filamentous bacteria.

Viral titers in the lung were measured several days after infection and varied significantly depending on the nature of the microbiome of the different animal groups.

“These findings uncover complex interactions that mechanistically link the intestinal microbiota with the functionality of basally resident alveolar macrophages and severity of respiratory virus infection,” said Dr. Andrew Gewirtz, co-senior author of the study and Regents’ Professor in the Institute for Biomedical Sciences at Georgia State.

The study found that in segmented filamentous bacteria-negative mice, basally resident alveolar macrophages were quickly depleted as respiratory virus infection progressed.

However, in segmented filamentous bacteria-colonised mice, basally resident alveolar macrophages were altered to resist influenza virus infection depletion and inflammatory signaling.

The basally resident alveolar macrophages disabled influenza virus, in large part by activating a component of the immune system referred to as the complement system.

“We find it remarkable that the presence of a single common commensal bacterial species, amidst the thousands of different microbial species that inhabit the mouse gut, had such strong impacts in respiratory virus infection models and that such impacts were largely attributable to reprogramming of basally resident alveolar macrophages,” said D. Richard Plemper, co-senior author of the study, Regents’ Professor and director of the Center for Translational Antiviral Research at Georgia State.

“If applicable to human infections, these findings will have major implications for the future risk assessment of a patient to advance to severe disease.”

“We find it highly unlikely that segmented filamentous bacteria is the only gut microbe capable of impacting the phenotype of alveolar macrophages, and consequently, proneness to respiratory virus infection,” Gewirtz said.

“Rather, we hypothesize that gut microbiota composition broadly influences proneness to respiratory virus infection. Microbiota mediated programming of basally resident alveolar macrophages may not only influence the severity of acute respiratory virus infection, but may also be a long-term post-respiratory virus infection health determinant.”

Source: Georgia State University

Categories : Exercise Obstetrics & GynaecologyTags :

Vegan Diet in Pregnancy may Increase Preeclampsia and Low Birth Weight Risks

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Photo by Anna Hecker on Unsplash

Women who follow vegan diets during pregnancy may face higher risks of developing preeclampsia and of giving birth to newborns with lower birth weight, suggests a recent study published in Acta Obstetricia et Gynecologica Scandinavica.

For the study, 65 872 women identified themselves as omnivorous, 666 as fish/poultry vegetarians, 183 as lacto/ovo vegetarians, and 18 as vegans. Based on a questionnaire completed mid-pregnancy, investigators found that protein intake was lower among lacto/ovo vegetarians (13.3%) and vegans (10.4%) compared with omnivorous participants (15.4%). Micronutrient intake was also much lower among vegans, but when dietary supplements were considered, no major differences were observed.

Compared with omnivorous mothers, vegan mothers had a higher prevalence of preeclampsia (a pregnancy complication characterised by high blood pressure), and their newborns weighed an average of 240 g less.

“Further research is needed regarding possible causality between plant-based diets and pregnancy and birth outcomes, to strengthen the basis for dietary recommendations,” the authors wrote.

Source: Wiley