Editorial: metabolic reprogramming in breast cancer

Metabolic reprogramming is an emerging hallmark of breast cancer. A common characteristic of tumor cells is the ability to obtain nutrients from a nutrient-deprived environment and to use them to sustain cancer progression, within crucial metabolic pathways including altered metabolism of glucose, lipids, and amino acids. Also, altered metabolism has been recognized as one of the major mechanisms of resistance to therapies. Important advances have been made to elucidate key mechanisms of metabolic reprogramming which will make possible novel strategies for overcoming breast cancer. However, for metabolic therapy to be effective there is a need to clearly understand the metabolic underpinnings of the different subtypes of breast cancer as well as the role the standard-of-care therapies play in targeting the metabolic phenotype

Decipher the glioblastoma microenvironment: The first milestone for new groundbreaking therapeutic strategies

Glioblastoma (GBM) is the most common primary malignant brain tumour in adults. Despite the combination of novel therapeutical approaches, it remains a deadly malignancy with an abysmal prognosis. GBM is a polymorphic tumour from both molecular and histological points of view. It consists of different malignant cells and various stromal cells, contributing to tumour initiation, progression, and treatment response. GBM’s microenvironment is multifaceted and is made up of soluble factors, extracellular matrix components, tissue-resident cell types (e.g., neurons, astrocytes, endothelial cells, pericytes, and fibroblasts) together with resident (e.g., microglia) or recruited (e.g., bone marrow-derived macrophages) immune cells. These latter constitute the so-called immune microenvironment, accounting for a substantial GBM’s tumour volume. Despite the abundance of immune cells, an intense state of tumour immunosuppression is promoted and developed; this represents the significant challenge for cancer cells’ immune-mediated destruction. Though literature data suggest that distinct GBM’s subtypes harbour differences in their microenvironment, its role in treatment response remains obscure. However, an in-depth investigation of GBM’s microenvironment may lead to novel therapeutic opportunities to improve patients’ outcomes. This review will elucidate the GBM’s microenvironment composition, highlighting the current state of the art in immunotherapy approaches. We will focus on novel strategies of active and passive immunotherapies, including vaccination, gene therapy, checkpoint blockade, and adoptive T-cell therapies

Some interesting features of new massive gravity

A proof that new massive gravity - the massive 3D gravity model proposed by Bergshoeff, Hohm and Townsend (BHT) - is the only unitary system at the tree level that can be constructed by augmenting planar gravity through the curvature-squared terms, is presented. Two interesting gravitational properties of the BHT model, namely, time dilation and time delay, which have no counterpart in the usual Einstein 3D gravity, are analyzed as well.Comment: Submitted to Classical and Quantum Gravit

Trends in stream nitrogen concentrations for forested reference catchments across the USA

To examine whether stream nitrogen concentrations in forested reference catchments have changed over time and if patterns were consistent across the USA, we synthesized up to 44 yr of data collected from 22 catchments at seven USDA Forest Service Experimental Forests. Trends in stream nitrogen presented high spatial variability both among catchments at a site and among sites across the USA. We found both increasing and decreasing trends in monthly flow-weighted stream nitrate and ammonium concentrations. At a subset of the catchments, we found that the length and period of analysis influenced whether trends were positive, negative or non-significant. Trends also differed among neighboring catchments within several Experimental Forests, suggesting the importance of catchment-specific factors in determining nutrient exports. Over the longest time periods, trends were more consistent among catchments within sites, although there are fewer long-term records for analysis. These findings highlight the critical value of long-term, uninterrupted stream chemistry monitoring at a network of sites across the USA to elucidate patterns of change in nutrient concentrations at minimally disturbed forested sites

Land cover evolution of small farms: the Transamazon highway.

The dynamics of land use change in both the mid and long-run were determined for a sample of 132 small farmers located along the Transamazon Highway. On average, four deforestation events occurred after arrival on the property. The average area of deforested land was 10 hectares for each event, totaling 40 of the 50 hectares allowed by law for a typical size plot of 100 hectares. It was observed that small farmers along the Transamazon Highway employ diversified systems of land use including annual crops, perennials and cattle; these show a temporal sequence in accord with household domestic cycles. These results suggest that pasture conversion in Amazon by small farmers is due to domestic dynamics cycle in addition to others variables

Clinical profiles and quality of care of subjects with type 2 diabetes according to their cardiovascular risk: an observational, retrospective study

Background: The European Society of Cardiology (ESC) recently defined cardiovascular risk classes for subjects with diabetes. Aim of this study was to explore the distribution of subjects with type 2 diabetes (T2D) by cardiovascular risk groups according to the ESC classification and to describe the quality indicators of care, with particular regard to cardiovascular risk factors. Methods: The study is based on data extracted from electronic medical records of patients treated at the 258 Italian diabetes centers participating in the AMD Annals initiative. Patients with T2D were stratified by cardiovascular risk. General descriptive indicators, measures of intermediate outcomes, intensity/appropriateness of pharmacological treatment for diabetes and cardiovascular risk factors, presence of other complications and overall quality of care were evaluated. Results: Overall, 473,740 subjects with type 2 diabetes (78.5% at very high cardiovascular risk, 20.9% at high risk and 0.6% at moderate risk) were evaluated. Among people with T2D at very high risk: 26.4% had retinopathy, 39.5% had albuminuria, 18.7% had a previous major cardiovascular event, 39.0% had organ damage, 89.1% had three or more risk factors. The use of DPP4-i markedly increased as cardiovascular risk increased. The prescription of secretagogues also increased and that of GLP1-RAs tended to increase. The use of SGLT2-i was still limited, and only slightly higher in subjects with very high cardiovascular risk. The overall quality of care, as summarized by the Q score, tended to be lower as the level of cardiovascular risk increased. Conclusions: A large proportion of subjects with T2D is at high or very high risk. Glucose-lowering drug therapies seem not to be adequately used with respect to their potential advantages in terms of cardiovascular risk reduction. Several actions are necessary to improve the quality of care

Quality of life and satisfaction of patients after oncoplastic or traditional breast-conserving surgery using the BREAST-Q (BCT module): a prospective study

Introduction: The oncoplastic conservative surgery was developed as a natural evolution of traditional surgery, attempting to improve the therapeutic and aesthetic outcomes where tumor resection could be followed by not-adequate results. Our primary aim is to evaluate how patient satisfaction and quality-of-life after conservative oncoplastic surgery, using BREAST-Q (BCT Module), change pre- and post-operatively. The secondary aim is to compare patient-reported outcome after oncoplastic or traditional conservative surgery. Patients and methods: We enrolled 647 patients who underwent traditional conservative surgery or oncoplastic surgery from January 2020 to December 2022. Only 232 women (35.9%) completed the BREAST-Q questionnaire on a web-based platform, at the preoperative phase and 3 months after treatment. Results: The average score of "Psychosocial well-being" and "Satisfaction with Breasts" 3 months after surgery showed a statistically significant improvement, while the average score for "Physical well-being: Chest" at 3 months showed a worsening compared to the baseline. "Sexual well-being" did not show statistically significant change. A significant difference between the post-operative outcome of oncoplastic surgery and traditional surgery was observed only for Physical well-being (better for traditional surgery). Conclusions: The study showed significant improvement in patient-reported outcomes 3 months after the surgery, except for physical discomfort that increases especially after oncoplastic surgery. Furthermore, our data, as well as many others, point to the appropriateness of using OCS where there is an effective indication, while the perspective of patients cannot find significant superiority over TCS in any of the areas analyzed

ANKRd44 gene silencing: A putative role in trastuzumab resistance in HER2-like breast cancer

Trastuzumab is an effective therapeutic treatment for Her2-like breast cancer; despite this most of these tumors develop resistance to therapy due to specific gene mutations or alterations in gene expression. Understanding the mechanisms of resistance to Trastuzumab could be a useful tool in order to identify combinations of drugs that elude resistance and allow a better response for the treated patients. Twelve primary biopsies of Her2+/hormone receptor negative (ER-/PgR-) breast cancer patients were selected based on the specific response to neoadjuvant therapy with Trastuzumab and their whole exome was sequenced leading to the identification of 18 informative gene mutations that discriminate patients selectively based on response to treatment. Among these genes, we focused on the study of the ANKRD44 gene to understand its role in the mechanism of resistance to Trastuzumab. The ANKRD44 gene was silenced in Her2-like breast cancer cell line (BT474), obtaining a partially Trastuzumab-resistant breast cancer cell line that constitutively activates the NF-kb protein via the TAK1/AKT pathway. Following this activation an increase in the level of glycolysis in resistant cells is promoted, also confirmed by the up-regulation of the LDHB protein and by an increased TROP2 protein expression, found generally associated with aggressive tumors. These results allow us to consider the ANKRD44 gene as a potential gene involved in Trastuzumab resistance