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PurposeThis study reports the workflow and initial clinical experience of high grade glioma (HGG) radiotherapy on the 1.5 T MR-Linac (MRL), with a focus on the temporal variations of the tumor and feasibility of multi-parametric image (mpMRI) acquisition during routine treatment workflow.Materials and methodsTen HGG patients treated with radiation within the first year of the MRL’s clinical operation, between October 2019 and August 2020, were identified from a prospective database. Workflow timings were recorded and online adaptive plans were generated using the Adapt-To-Position (ATP) workflow. Temporal variation within the FLAIR hyperintense region (FHR) was assessed by the relative FHR volumes (n = 281 contours) and migration distances (maximum linear displacement of the volume). Research mpMRIs were acquired on the MRL during radiation and changes in selected functional parameters were investigated within the FHR.ResultsAll patients completed radiotherapy to a median dose of 60 Gy (range, 54-60 Gy) in 30 fractions (range, 30-33), receiving a total of 287 fractions on the MRL. The mean in-room time per fraction with or without post-beam research imaging was 42.9 minutes (range, 25.0–69.0 minutes) and 37.3 minutes (range, 24.0–51.0 minutes), respectively. Three patients (30%) required re-planning between fractions 9 to 12 due to progression of tumor and/or edema identified on daily MRL imaging. At the 10, 20, and 30-day post-first fraction time points 3, 3, and 4 patients, respectively, had a FHR volume that changed by at least 20% relative to the first fraction. Research mpMRIs were successfully acquired on the MRL. The median apparent diffusion coefficient (ADC) within the FHR and the volumes of FLAIR were significantly correlated when data from all patients and time points were pooled (R=0.68, p

Siderophore-positive bacteria present in the rhizosphere and in bulk soil assist plants by either inhibiting phytopathogen proliferation or increasing plant growth. The bacterial diversity of the Shisham forest ecosystem in the Tarai region of the Western Himalayas was studied and used for siderophore production, taking into account the large-scale dieback and wilt-induced mortality in Dalbergia sissoo (common name: shisham) plantation forests and the importance of soil microbes in tree health. In addition, Pseudomonas, Burkholderia, and Streptomyces were prominent siderophore-positive bacteria in Shisham forests. Pseudomonas species are known for their remarkable siderophore-producing ability. Bacterial siderophores inhibit pathogen growth by rapidly lowering the number of ferric ions in the rhizosphere. The Pseudomonas monteilii strain MN759447 was isolated from a D. sissoo plantation forest at the Agroforestry Research Centre, Pantnagar, Uttarakhand (28°58′N 79°25′E/28.97°N 79.41°E). It produces a significant number of siderophore units (80.36% in total). A two-stage optimization of growth factors was attempted in the strain MN759447 for better siderophore recovery. In the first-stage single-factor experiment, among the five variables studied, only pH, NH4NO3 concentration, and Fe concentration affected siderophore synthesis. In the second stage, an optimization of pH, NH4NO3 concentration, and Fe concentration for improved growth and enhanced siderophore production was carried out using a Box–Behnken design with response surface methodology. By using LC-MS, two derivatives of pseudomonine, salicylic acid, and kynurenic acid were detected as siderophores in the purified XAD-2 methanol extract of the P. monteilii strain MN759447. In addition to siderophore production, the P. monteilii strain MN759447 also exhibited a broad range of antagonistic activity against Aspergillus calidoustus (65%), Fusarium oxysporum (41.66%), Talaromyces pinophilus (65%), and Talaromyces verruculosus (65.1%) that are linked to sissoo mortality. To our knowledge, this is the first report on siderophore-producing bacteria isolated, identified, and characterized from the D. sissoo Roxb. forest habitat. This strain can also be developed as a commercial product.

Introduction: Magnetic resonance imaging-linear accelerator radiotherapy is an innovative technology that requires special consideration for secondary electron interactions within the magnetic field, which can alter dose deposition at air–tissue interfaces. As part of ongoing quality assurance and quality improvement of new radiotherapy technologies, the purpose of this study was to evaluate skin dose modelled from the treatment planning systems of a magnetic resonance imaging-linear accelerator and a conventional linear accelerator, and then correlate with in vivo measurements of delivered skin dose from each linear accelerator. Methods: In this prospective cohort study, 37 consecutive glioma patients had treatment planning completed and approved prior to radiotherapy initiation using commercial treatment planning systems: a Monte Carlo-based algorithm for magnetic resonance imaging-linear accelerator or a convolution-based algorithm for conventional linear accelerator. In vivo skin dose was measured using an optically stimulated luminescent dosimeter. Results: Monte Carlo-based magnetic resonance imaging-linear accelerator plans and convolution-based conventional linear accelerator plans had similar dosimetric parameters for target volumes and organs-at-risk. However, magnetic resonance imaging-linear accelerator plans had 1.52 Gy higher mean dose to air cavities ( P

The lysine demethylase 3A (KDM3A, JMJD1A or JHDM2A) controls transcriptional networks in a variety of biological processes such as spermatogenesis, metabolism, stem cell activity, and tumor progression. We matched transcriptomic and ChIP-Seq profiles to decipher a genome-wide regulatory network of epigenetic control by KDM3A in prostate cancer cells. ChIP-Seq experiments monitoring histone 3 lysine 9 (H3K9) methylation marks show global histone demethylation effects of KDM3A. Combined assessment of histone demethylation events and gene expression changes presented major transcriptional activation suggesting that distinct oncogenic regulators may synergize with the epigenetic patterns by KDM3A. Pathway enrichment analysis of cells with KDM3A knockdown prioritized androgen signaling indicating that KDM3A plays a key role in regulating androgen receptor activity. Matched ChIP-Seq and knockdown experiments of KDM3A in combination with ChIP-Seq of the androgen receptor resulted in a gain of H3K9 methylation marks around androgen receptor binding sites of selected transcriptional targets in androgen signaling including positive regulation of KRT19, NKX3-1, KLK3, NDRG1, MAF, CREB3L4, MYC, INPP4B, PTK2B, MAPK1, MAP2K1, IGF1, E2F1, HSP90AA1, HIF1A, and ACSL3. The cancer systems biology analysis of KDM3A-dependent genes identifies an epigenetic and transcriptional network in androgen response, hypoxia, glycolysis, and lipid metabolism. Genome-wide ChIP-Seq data highlights specific gene targets and the ability of epigenetic master regulators to control oncogenic pathways and cancer progression.

Over the past three decades several randomized trials have enabled evidence-based practice for patients presenting with limited brain metastases. These trials have focused on the role of surgery or stereotactic radiosurgery (SRS) with or without whole brain radiation therapy (WBRT). As a result, it is clear that local control should be optimized with surgery or SRS in patients with optimal prognostic factors presenting with up to 4 brain metastases. The routine use of adjuvant WBRT remains debatable, as although greater distant brain control rates are observed, there is no impact on survival, and modern outcomes suggest adverse effects from WBRT on patient cognition and quality of life. With dramatic technologic advances in radiation oncology facilitating the adoption of SRS into mainstream practice, the optimal management of patients with multiple brain metastases is now being put forward. Practice is evolving to SRS alone in these patients despite a lack of level 1 evidence to support a clinical departure from WBRT. The purpose of this review is to summarize the current state of the evidence for patients presenting with limited and multiple metastases, and to present an in-depth analysis of the technology and dosimetric issues specific to the treatment of multiple metastases.

PurposeWhile several clinical prediction rules (CPRs) of survival exist for patients with symptomatic spinal metastasis (SSM), these have variable prognostic ability and there is no recognized CPR for health related quality of life (HRQoL). We undertook a critical appraisal of the literature to identify key preoperative prognostic factors of clinical outcomes in patients with SSM who were treated surgically. The results of this study could be used to modify existing or develop new CPRs.MethodsSeven electronic databases were searched (1990-2015), without language restriction, to identify studies that performed multivariate analysis of preoperative predictors of survival, neurological, functional and HRQoL outcomes in surgical patients with SSM. Individual studies were assessed for class of evidence. The strength of the overall body of evidence was evaluated using GRADE for each predictor.ResultsAmong 4,818 unique citations, 17 were included; all were in English, rated Class III and focused on survival, revealing a total of 46 predictors. The strength of the overall body of evidence was very low for 39 and low for 7 predictors. Due to considerable heterogeneity in patient samples and prognostic factors investigated as well as several methodological issues, our results had a moderately high risk of bias and were difficult to interpret.ConclusionsThe quality of evidence for predictors of survival was, at best, low. We failed to identify studies that evaluated preoperative prognostic factors for neurological, functional, or HRQoL outcomes in surgical patients with SSM. We formulated methodological recommendations for prognostic studies to promote acquiring high-quality evidence to better estimate predictor effect sizes to improve patient education, surgical decision-making and development of CPRs.

ObjectivesThe aim of this systematic review was to develop International Stereotactic Radiosurgery Society (ISRS) consensus guideline statements for vestibular schwannoma.MethodsA systematic review of the literature was performed up to April 2015.ResultsA total of 55 full-text articles were included in the analysis. All studies were retrospective, except for 2 prospective quality of life studies. Five-year tumour control rates with Gamma Knife radiosurgery (RS), single fraction linac RS, or fractionated (either hypofractionated or conventional fractionation) stereotactic radiation therapy (FSRT) were similar at 81-100%. The single fraction RS series (linac or Gamma Knife) with tumour marginal doses between 12 and 14 Gy revealed 5-year tumour control rates of 90-99%, hearing preservation rates of 41-79%, facial nerve preservation rates of 95-100% and trigeminal preservation rates of 79-99%.There were 6 non-randomized studies comparing single fraction RS versus FSRT. There was no statistically significant difference in tumour control; HR=1.66 (95% CI 0.81, 3.42), p =0.17, facial nerve function; HR = 0.67 (95% CI 0.30, 1.49), p =0.33, trigeminal nerve function; HR = 0.80 (95% CI 0.41, 1.56), p =0.51, and hearing preservation; HR = 1.10 (95% CI 0.72, 1.68), p =0.65 comparing single fraction RS with FSRT.Nine quality of life reports yielded conflicting results as to which modality (surgery, observation, or radiation) was associated with better quality of life outcomes.ConclusionsThere are no randomized trials to help guide management of patients with vestibular schwannoma. Within the limitations of the retrospective series, a number of consensus statements were made.

Abstract Background Clinical target volume (CTV) contouring guidelines are frequently developed through studies in which experts contour the CTV for a representative set of cases for a given treatment site and the consensus CTVs are analyzed to generate margin recommendations. Measures of interobserver variability are used to quantify agreement between experts. In cases where an isotropic margin is not appropriate, however, there is no standard method to compute margins in specified directions that represent possible routes of tumor spread. Moreover, interobserver variability metrics are often measures of volume overlap that do not account for the dependence of disagreement on direction. To aid in the development of consensus contouring guidelines, this study demonstrates a novel method of quantifying CTV margins and interobserver variability in clinician-specified directions. Methods The proposed algorithm was applied to 11 cases of non-spine bone metastases to compute the consensus CTV margin in each direction of intraosseous and extraosseous disease. The median over all cases for each route of spread yielded the recommended margins. The disagreement between experts on the CTV margin was quantified by computing the median of the coefficients of variation for intraosseous and extraosseous margins. Results The recommended intraosseous and extraosseous margins were 7.0 mm and 8.0 mm, respectively. The median coefficient of variation quantifying the margin disagreement between experts was 0.59 and 0.48 for intraosseous and extraosseous disease. Conclusions The proposed algorithm permits the generation of margin recommendations in relation to adjacent anatomy and quantifies interobserver variability in specified directions. This method can be applied to future consensus CTV contouring studies.

Abstract Several cyclin‐dependent kinase 4/6 (CDK4/6) inhibitors are indicated in the treatment of metastatic hormone receptor‐positive (HR)/ human epidermal growth factor receptor 2 (HER2) negative breast cancer which includes palbociclib, ribociclib and abemaciclib. Pelvic radiation therapy (RT) is often indicated for symptomatic or progressive bone metastasis. There are limited data on concurrent use of CDK4/6 inhibitors with pelvic RT with few retrospective studies in the literature involving a small number of patients. The major side effects of these agents include haematological toxicities, while non‐haematological toxicities are less severe. There are concerns for an increased possibility of synergistic toxicity with concurrent use of CDK4/6 inhibitors with pelvic RT. Here we describe an instance of acute grade 3 gastrointestinal toxicity and discuss the relevant literature. A 77‐year‐old lady treated with palliative conventional RT 30 Gy/ 10 fractions concurrently with palbociclib to left hemipelvis and proximal femur, developed severe pancolitis starting 5 days from last RT. She needed inpatient care for 3 weeks and recovered with mesalamine and supportive care. We also postulate a few strategies that can be adopted in patients receiving palliative RT in such a scenario. The agents should be stopped 1 week before, during and for a time (1 week minimally) after RT. A shorter course of 5 fractions (and ablative RT as indicated) can be considered to minimise treatment gaps. Highly conformal techniques (intensity‐modulated radiotherapy/ volumetric‐modulated arc therapy) can significantly reduce bowel dose and should be considered in patients with pre‐existing GI comorbidities or prior GI toxicity with these agents.

Background. T cell exhaustion (TEX) is a state of T cells that is characterized by poor function of effectors and increased expression of inhibitory signals. However, the heterogeneity and prognostic values of TEX in lung adenocarcinoma (LUAD) remain not fully understood. Methods. Based on the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) transcriptomic profiles, we screened differentially expressed lncRNAs, miRNAs, and mRNAs and identified differentially expressed TEXs. Univariate cox and LASSO regression analyses were performed to construct TEX‐related prognostic signature and risk score and validated their expression using real‐time PCR assay. We then investigated the potential mechanism, immune landscape, and antitumor therapy response in LUAD. Results. A total of 315 DE‐lncRNAs, 161 DE‐miRNAs, and 2589 DEGs were screened, and then 80 DE‐TEXGs were identified in LUAD. Based on univariate cox and LASSO regression analyses, CCNA2 and SLC2A1 were identified as TEX‐related prognostic signatures, and the risk score subsequently was calculated. LUAD patients were divided into high‐ and low‐risk groups, and high‐risk groups were involved in poor survival status, immunosuppression, and more sensitive to anti‐CTLA4 therapy. Finally, a TEX‐related ceRNA network was constructed and validated based on DE‐lncRNAs, DE‐miRNAs, and TEX‐related prognostic signatures. Conclusion. We constructed the TEX‐related prognostic signature and its relevant ceRNA network and discovered the molecular mechanism and prognostic values of TEX in LUAD. [ABSTRACT FROM AUTHOR]

Background. Coiled‐coil domain containing 25 (CCDC25) is a receptor for neutrophil extracellular trap (NET) DNA and is involved in various cancers, including CRC. This study aimed to investigate the regulatory role of CCDC25 in CRC using GWAS data, eQTL, transcriptomic profiles, and clinical information of CRC patients. Methods. From open‐source databases, GWAS summary data, eQTL expression profiles, and transcriptomic profiles, as well as clinical information were collected for CRC patients. Mendelian randomization (MR) was used to investigate the causal relationship between CCDC25 and CRC risk. The expression of CCDC25 and its associated differentially expressed genes (DEGs) were identified. We explored the relationship between CCDC25 expression and survival, biological functions, immune cell infiltration, immune checkpoint expression, and response to immunotherapy. Results. High CCDC25 expression reduces the risk of CRC. CCDC25 is downregulated in various cancers, particularly in CRC tumor tissues compared to normal tissues. Metabolic pathways are enriched in groups with high CCDC25 expression, while cancer‐related pathways are enriched in groups with low CCDC25 expression. High CCDC25 expression is also associated with increased infiltration of resting memory CD4+ T cells, elevated levels of most immune checkpoints, and an enhanced response to anti‐PD1 therapy. In addition, 95 DEGs were identified between high‐CCDC25 and low‐CCDC25 groups, and eight genes (FDFT1, ASAH1, ADAM9, CXCL14, SERPINA1, NAT1, EREG, and GSR) were identified as prognostic genes. Conclusion. CDC25 might serve as a candidate diagnostic and prognostic marker for CRC patients. [ABSTRACT FROM AUTHOR]

Breast cancer is the leading cause of death and morbidity among women. A major challenge for clinical management of breast cancer is the dissemination of breast cancer cells from the primary tumor site via lymphatic drainage, resulting in metastatic tumor spread. Recent studies have found that high expression of the microRNA miR‐146a‐5p is associated with better survival outcomes for breast cancer patients. However, the mechanisms for this prognostic benefit are not fully elucidated, including whether or not miR‐146a‐5p plays a role in suppression of lymphatic dissemination. In this study, we investigated the role and uncovered functional mechanisms of miR‐146a‐5p in breast cancer. We found that high expression of miR‐146a‐5p is associated with better clinical outcomes, specifically in the patients with N0 breast cancer. In culture, miR‐146a‐5p overexpression in MCF‐7 breast cancer cells suppressed cell migration and lymphangiogenesis in lymphatic endothelial cells. When implanted in the mammary fat pad of mice, we observed that miR‐146a‐5p overexpressing MCF‐7 suppressed lymphatic dissemination but had no effect on tumor progression in the primary site. This suppression was associated with fewer disseminated cancer cells and reduced lymphangiogenesis in the draining and distal lymph nodes. In conclusion, these results suggest that miR‐146a‐5p can exhibit a protective role against breast cancer metastasis, and it can be a therapeutic target for breast cancer. [ABSTRACT FROM AUTHOR]

Breast cancer (BC), a globally prevalent malignancy, shows significant variability in incidence across different geographical regions. In this study, we examined the expression of the tumor suppressor gene BRCA1 and the tumor marker CA15‐3 in women diagnosed with BC, focusing on different cancer grades. Our research, conducted at the Baqiyat Elah Hospital in Tehran in 2021, involved collecting blood and serum samples from BC patients. These samples underwent BRCA1 gene expression analysis and CA15‐3 tumor marker assessment. Using the AJCC grading system, we categorized BC patients into various grades. Our findings revealed that BRCA1 gene expression was present in 28.57% of patients, while 71.43% showed negative expression. Both BRCA1 expression and CA15‐3 levels significantly increased with advanced cancer stages (P < 0.001). These results suggest the potential utility of BRCA1 gene expression and CA15‐3 tumor marker assessment in BC prognosis and management, particularly concerning staging and disease progression. This study provides valuable insights into the biology of BC and the development of prognostic markers for improved patient outcomes. [ABSTRACT FROM AUTHOR]

The escalating incidence of health issues linked to environmental pollutants, specifically endocrine‐disrupting chemicals (EDCs), has emerged as a dire consequence of modern industrialization. Bisphenol A (BPA), a widespread EDC, is under scrutiny for its potential role in exacerbating bladder cancer via the modulation of cancer‐associated fibroblasts (CAFs). CAFs are integral to the tumor microenvironment, influencing cancer progression through their interactions with immune cells and secretion of various factors and exosomes. By recognizing the critical role of CAFs, this study delves into their utility as therapeutic targets, focusing on the identification of reliable biomarkers within CAFs for bladder cancer. Through weighted correlation network analysis, genes associated with T cell activity were pinpointed, culminating in the creation of a CAFs‐based, immune‐related gene prognostic model. Central to this model is ANPEP, an enzyme whose expression level not only serves as an indicator of T cell infiltration but also implicates a substantial role in the CAF‐mediated immunotherapy responses for bladder cancer. Our investigation posits ANPEP as a linchpin in regulating CAF functions, offering a novel perspective wherein targeting ANPEP may reduce the adverse side effects commonly associated with traditional immunotherapies. Furthermore, ANPEP‐targeted strategies could lessen the tumor mutational burden in bladder cancer patients. Empirical evidence from our proliferation and invasion assays indicates that heightened ANPEP expression is correlated with diminished patient survival. These insights pave the way for tailored immunotherapeutic approaches in bladder cancer treatment, emphasizing the modulation of CAFs by ANPEP. [ABSTRACT FROM AUTHOR]

This article sheds light on three questions: (1) must we apply proportionality review in cases involving economic and social rights recognized under Article 21 of the Constitution of India 1950? (2) If so, how do we apply proportionality review in these cases? And (3) how will this impact the content of these rights and the corresponding obligations placed on the state? The article focuses on the right to housing in India. It argues that courts must apply the proportionality standard of review to check limitations on the right to housing. Applying this standard of review will change the all-things-considered content of the right to housing as beyond conditional, requiring provision of alternate accommodation in all eviction cases that result in homelessness. This article fills a gap in legal doctrine and research with regards to the possibilities for economic and social rights jurisprudence in the age of proportionality. [ABSTRACT FROM AUTHOR]

Introduction. Patients with hormone receptor‐positive (HR+), HER2‐negative (HER2−) breast cancers have the lowest response to neoadjuvant therapy of all subtypes. The role of neoadjuvant endocrine therapy (NET) in clinically node‐positive (cN+), HR+, HER2− patients is evaluated in this meta‐analysis. Methods. This study was performed between January 2010 and August 2022. We evaluated the node pathologic complete response (pCR) and axillary lymph node dissection (ALND) rates after neoadjuvant endocrine therapy (NET). Results. 18,037 HR+, HER2−, cN+ stage II and stage III breast cancer patients within eleven studies received neoadjuvant treatments. 3,707 (20.6%) patients received NET and 14,330 (79.4%) received NAC. The average age of the NET patients was higher than that of the neoadjuvant chemotherapy (NAC) patients (64.1 versus 47.6 years old, p < 0.001). 45.0% and 26.9% of the NET and the NAC groups underwent a lumpectomy. The pooled estimates of node pCR in NET and NAC groups were 8.9% and 14.9%, and the pooled proportion of ALND was 39.1% and 58.5%, respectively. Conclusion. The rate of node pCR was lower among cN+ patients who received NET compared to the NAC group. The rate of ALND among cN+ NET patients was lower than the NAC group, revealing more patients with residual nodal disease do not get ALND in the NET group. Further prospective studies are required to compare survival outcomes as a more reliable surrogate. [ABSTRACT FROM AUTHOR]

Purpose. Endocrine therapy combined with cyclin‐dependent kinase (CDK) 4/6 inhibitors (CDK4/6i) is the preferred treatment for hormone receptor‐positive (HR+)/human epidermal growth factor receptor 2‐negative (HER2–) metastatic breast cancer (MBC). However, there are currently no recommendations for therapeutic strategies after progression on CDK4/6i‐based treatment. This study aimed to examine the efficacy and safety of anlotinib plus chemotherapy in HR+/HER2– MBC after progression on CDK4/6 inhibitors. Methods. We collected data from 32 patients with HR+/HER2– MBC treated with anlotinib plus chemotherapy after progressing on CDK4/6i at Jiangsu Cancer Hospital from March 2020 to October 2023. The median follow‐up was 9.1 months (range, 2.0–19.7 months) as of the data cutoff date in October 2023. The primary endpoint was median progression‐free survival (PFS); secondary endpoints included objective response rate (ORR), disease control rate (DCR), and adverse events. Results. The median PFS (mPFS) of all patients was 7.6 months (95% confidence interval (CI), 5.75–9.45). There was no significant difference in mPFS between patients who responded to prior CDK4/6i treatment and those who did not (8.3 months vs. 6.8 months, p = 0.580). Besides, the ORR was 34.4% and DCR was 93.8%. The most frequently observed adverse events were anemia (50.0%), neutropenia (40.6%), thrombocytopenia (34.4%), and epistaxis (34.4%). Dose interruption or reductions due to adverse events occurred in 2 (6.3%) and 5 (15.6%) patients, respectively. Conclusions. The study preliminarily demonstrates that anlotinib combined with chemotherapy may be an optional recommendation for patients with HR+/HER2– metastatic breast cancer who have progressed after CDK4/6i. [ABSTRACT FROM AUTHOR]

Female breast cancer is the most common and the fifth deadliest cancer worldwide. It is influenced by a combination of genetic, hormonal, and environmental factors. The excision repair cross‐complementation group 3 gene (ERCC3) has recently been identified as a breast cancer susceptibility gene in various cohorts of different geographical and ethnic origin. To explore the role of ERCC3 mutations in breast cancer development and pathological diagnosis, genetic analysis was conducted in 291 patients and 291 controls from mainland China. Bioinformatic analysis and immunohistochemistry (IHC) were performed. A novel ERCC3 mutation p.Y116X was identified in a breast cancer family, while no frequency bias for the genotype and allele of rs754010782 and rs371627165 was observed (all P > 0.05). Bioinformatic analysis revealed that ERCC3 expression was negatively associated with estrogen receptor (ER), progesterone receptor (PR), nontriple‐negative status, and nodal status of breast cancers. ERCC3 amplifications and deep deletions primarily occurred in breast invasive cancer not otherwise specified (NOS) and metaplastic breast cancer, respectively. The decreased ERCC3 expression in tumor tissues of patient with p.Y116X mutation was found by IHC. The ERCC3 mutation p.Y116X may increase breast cancer risk in the Han‐Chinese population. ERCC3 exhibits potential as a biomarker for the pathological diagnosis of breast cancer. [ABSTRACT FROM AUTHOR]

Background. The purpose of this study was to analyze SUMO activating enzyme subunit 1 (SAE1) expression in breast cancer (BC). Through bioinformatics analysis and in vitro experiments, the biological function and possibly associated signal pathways of SAE1 in BC were further analyzed. Methods. Bioinformatics analysis was applied to analyze SAE1 expression in BC and normal breast tissues, its relationship with clinicopathologic characteristics and prognosis in BC patients, and data from the Cancer Genome Atlas database and Gene Expression Omnibus dataset. We performed immunohistochemistry to analyze SAE1 expression in BC tissues and para‐cancer tissues in 79 breast cancer patients. BC cell proliferation was detected with the Cell Counting Kit‐8 and by the colony formation assay. Cell cycle progression was analyzed by flow cytometry, and the expression of cell cycle‐related proteins (E2F1, cyclin D3, and cyclin‐dependent kinase 2) was determined by western blots in SAE1 small interfering RNA (siRNA) transfected cells. The GSE1456 dataset was used to analyze possible signal pathways associated with SAE1 by gene set enrichment analysis (GSEA), and the expression of PI3K/AKT/mTOR pathway‐related proteins (such as p‐PI3K, p‐AKT, and mTOR) in SAE1‐siRNA cells was detected by western blots. Results. The bioinformatics and immunohistochemical results showed that SAE1 mRNA and protein expression in BC tissues were significantly higher than those in normal tissues. The SAE1 overexpression was significantly associated with the tumor size, tumor‐node‐metastasis stage, estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, and whether or not it was a triple‐negative BC. Patients with SAE1 overexpression had a worse overall survival (OS), recurrence‐free survival (RFS), and distant metastasis‐free survival compared with lower expression patients. Multivariate Cox regression analysis showed that SAE1 may be an independent prognostic factor for OS of BC patients. The proliferation and cell cycle process of BC cells were inhibited by SAE1‐siRNA in vitro. The result of GSEA showed that SAE1 was significantly associated with 12 gene sets, including unfolded protein reaction, DNA repair, oxidative phosphorylation, and cell cycle, among others. Additionally, two signal pathways, mTORC1 and PI3K/Akt/mTOR, were significantly correlated with SAE1 overexpression. Western blots confirmed that the expression of PI3K/Akt/mTOR pathway‐related proteins (p‐PI3K, p‐AKT, and mTOR) in BC cells was decreased after knocking down SAE1. Conclusion. SAE1 was highly expressed in BC. Its overexpression was associated with poor BC prognosis. Additionally, it was an independent prognostic factor for BC patients. We demonstrated that in vitro SAE1 knockdown effectively inhibited BC proliferation and its cell cycle process. Furthermore, the biological function of SAE1 may be associated with the PI3K/Akt/mTOR pathway. SAE1 will be a potential target for BC treatment. [ABSTRACT FROM AUTHOR]

Purpose: In Peru, breast cancer (BC) stands as the most predominant malignancy neoplasm among women. Trastuzumab has marked a significant milestone in the management of this disease. It has been shown to improve prognosis in human epidermal growth factor receptor 2 (HER2)–expressing female patients, but its repercussions and efficacy are yet to be analyzed in a context with limited resources. Methods: The study population is made of woman patients aged 18 years and older diagnosed with HER2‐positive BC at Instituto Nacional de Enfermedades Neoplásicas (INEN, Lima, Peru) during 2019–2021 and treated with at least one dose of subcutaneous trastuzumab. We reviewed medical records to register treatment characteristics, adverse events (AEs), disease progression, and survival status. We considered a median follow‐up time of 36 and 45 months for progression and survival status. Results: The majority of patients were over 50 years old (54.29%). Tumor size averaged 19.7 ± 16.1 mm. Lymph nodes were present in 44.78% of patients. Most patients received adjuvant chemotherapy (63.8%) as first‐line treatment. Descriptive analyses of treatment outcomes revealed a 30% toxicity rate, primarily attributed to arthralgia (47.62%), followed by diarrhea, fatigue, and injection site reactions, with relatively lower discontinuation rates compared to larger scale studies. Differences in demographic, clinical, and treatment characteristics were not statistically significant concerning the emergence of AEs (p > 0.05). Progression appeared in nine patients, and the overall survival (OS) rate stood at 98.6% and 92.8%, respectively, during a median follow‐up of 36 and 45 months. Conclusion: The research suggests that subcutaneous trastuzumab is comparable in effectiveness and safety to the intravenous administration. Regional‐specific studies may provide valuable insights into demographic factors influencing treatment outcomes in Peru or other countries. Furthermore, it could represent a more accessible alternative, potentially enhancing patient adherence and optimizing healthcare resource logistics. [ABSTRACT FROM AUTHOR]

Background: Intraoperative radiation therapy (IORT) has gained popularity in recent years as an alternative to external beam whole breast radiation therapy (WBRT) for early‐stage breast cancer. Here, we report 43‐month recurrence and survival outcomes in a multiethnic cohort treated with IORT in a clinical context. Method: Two hundred and eleven patients with low‐risk features were treated with IORT for early‐stage breast cancer from 2014 to 2021. Selection criteria were based on Group Europeen de Curietherapie‐European Society for Therapeutic Radiology and Oncology (GEC‐ESTRO) guidelines: preferably unifocal intraductal carcinoma (IDC), aged > 50, tumor size ≤ 2.0 cm, and without lymph node involvement. All patients received 20 Gy of radiation dose during the lumpectomy. Information on patient and tumor characteristics was collected. Results: The mean age of this cohort was 67.5 years; 95.2% of patients are Jewish, and the rest are Bedouins (4.7%). Most tumors were intraductal carcinoma (97.2%) and stage 1 (94.8%). The mean follow‐up time was 43.4 months. Bedouins had larger tumor sizes (mean 1.21 vs. 1.13 cm) and were younger at diagnosis than Jewish patients (mean 65.4 vs. 67.6 years), although the differences are not significant. The overall recurrence rate was 1.4%. One case of local recurrence (0.5%) and two cases of metastasis (0.9%) were observed during the study period. One patient died from metastasis. Conclusion: Our findings suggest that IORT in selected low‐risk patients can achieve an excellent prognosis with low rates of recurrence and metastasis. [ABSTRACT FROM AUTHOR]

Human epidermal growth factor receptor 2 (HER2)‐low breast cancer (BC) is a subtype of BC that has been recently recognized as a separate clinical entity with distinct clinical and molecular characteristics. It is defined by a low level of HER2 protein expression, which distinguishes it from other more aggressive BC subtypes. Early studies suggest that it may have a more favorable prognosis than HER2‐positive BC, as it is less likely to spread to other parts of the body and may be more responsive to standard BC treatments such as chemotherapy, radiation therapy, and hormone therapy. Given the relative new emergence of HER2‐low BC, there is still much to be learned about this subtype; ongoing research is focused on identifying the underlying genetic mutations that contribute to HER2‐low BC as well as developing targeted therapies that can improve outcomes for patients with this disease. This review is aimed at summarizing the current clinical knowledge on HER2‐low BC, with the aim of creating a better understanding of this entity and paving the way for potential interventions and a new standard of care. [ABSTRACT FROM AUTHOR]

Background: Invasive micropapillary carcinoma (IMPC) of the breast is commonly associated with a poor prognosis due to its high incidence of lymphovascular invasion and lymph node metastasis (LNM). Our study is aimed at investigating the prognostic significance of the expressions of E‐cadherin (E‐cad), N‐cadherin (N‐cad), CD44s, and β‐catenin (β‐cat). In addition, it is aimed at deciphering the consistency of these markers between the IMPC, the invasive breast carcinoma, no‐special type (IBC‐NST), and LNM components in the same IMPC cases. Methods: Sixty‐two IMPC cases with LNM from 1996 to 2018 were analyzed. Immunohistochemical staining was performed separately on the three regions for each patient. Statistical analyses included Kaplan‐Meier, Cox regression, and McNemar's statistical tests. Results: Loss of CD44 expression in IMPC, IBC‐NST, and LNM areas was associated with poor prognosis in overall survival (OS) (p = 0.010, p < 0.0005, p = 0.025). Loss of CD44 expression in the IBC‐NST, gain of N‐cad expression in the IMPC, and loss of β‐cat expression in the LNM areas were indicators of poor prognosis in disease‐free survival (DFS) (p = 0.005, p = 0.041, p = 0.009). Conclusion: Our evaluation of this rare subtype, focusing on the expression of key epithelial–mesenchymal transition (EMT) molecules, revealed that it shares characteristics with the IBC‐NST component within mixed tumors. Notably, contrary to expectations, a reduction in CD44 expression was found to adversely affect both OS and DFS. By conducting staining procedures simultaneously across three regions within the same patient, a novel approach has provided valuable insights into the mechanisms of EMT. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the quality of life (QoL) of patients with cervicofacial nonmelanoma skin cancer (NMSC) using the Brazilian Portuguese‐adapted and validated version of the skin cancer index (SCI). After collecting demographic and clinical data from 182 patients with cervicofacial NMSC, the Brazilian versions of the SCI and the Dermatological Life Quality Index (DLQI) were applied preoperatively (T0) and 4 months postoperatively (T1). Assessments were carried out using the Shapiro–Wilk test, Student's t‐test, Mann–Whitney test, Kruskal–Wallis test, and Spearman's correlation. The QoL was evaluated using the Student's t‐test in paired samples at T0 and T1. Significant results were observed, with an increase in scores on the SCI scale in all its dimensions and a decrease in scores on the DLQI scale, demonstrating better postoperative QoL. The variables that presented significant results on the total scale, which indicated better QoL, were men, without children, income above four minimum wages, from the private sector, did not report pruritus, and scalp lesions. The QoL measurement indicated a change from the baseline and improvement after 4 months postoperatively in all subscales, indicating that surgical treatment increased the QoL of these patients from an emotional, social, and physical appearance point of view. The multivariate analysis produced several statistically significant findings in relation to emotional, social, appearance, and total scores. [ABSTRACT FROM AUTHOR]

Introduction. There is still minimal scientific understanding of effects of fulvic acid (FA) on breast cancer. We investigated the prophylactic, therapeutic, and combined effects of FA in a breast cancer model created using MCF‐7 cell line in severe combined immunodeficiency disease (SCID) mice. Results. Four experimental groups were established as the control group (Group C), prophylaxis group (Group P), therapeutic group (Group T), and prophylaxis + therapeutic group (Group P + T). Tumor growth was observed by the in vivo imaging system and macroscopically in mammary glands of all mice (100%) of Group C, microscopically in only one mouse of Group P (12.5%), in four mice in Group T (50%), but only one animal (12.5%) in Group P + T. Immunohistochemistry (IHC) showed that p53 staining was significantly higher in tissues of Group C compared to other groups (P < 0.05). No difference was found in IHC scores for p53 between Group P and P + T (P > 0.05). Bcl‐2 staining was significantly higher in Group C compared to Group P + T (P = 0.015) and higher in Group P + T compared to Group T (P = 0.021) but no significant difference was found between Group P and others (P > 0.05). Bax staining was significantly higher in Group C compared to others (P < 0.05) but no significant difference was found between FA groups (P > 0.05). Conclusion. Prophylactic FA treatment can prevent tumor formation by inducing variations in the expression of p53, BcL‐2, and Bax proteins in mammary glands of SCID mice before tumor formation. This suggests that FA may be a powerful inhibitory candidate for the prevention of tumorigenesis in breast cancer. [ABSTRACT FROM AUTHOR]