Search Results (312)

Breast cancer is one of the most common malignancies worldwide, affecting 2.3 million and causing 670,000 deaths in women annually. However, data indicate that the risk of developing breast cancer decreases with pregnancy at a young age, and each subsequent pregnancy further reduces the risk by approximately 10%. One of the characteristics inherent in both the mammary gland epithelium in pregnant women and luminal epithelial adenocarcinomas is the increased expression of NIS—the sodium/iodide symporter, whose defective cytoplasmic forms possess pro-oncogenic properties. Therefore, the analysis of the degree of influence of pregnancy on NIS expression in breast cancer cells is of medical interest. The aim of this study is to conduct a comparative morphological analysis of NIS expression in breast cancer cells according to the number of pregnancies of each patient. This study included 161 patients with triple-negative breast cancer who visited the P.A. Herzen Moscow Oncology Research Institute from 2020 to 2023. Immunohistochemical examination was performed using antibodies to NIS. The gravidity status of women was determined based on provided medical documentation. The degree of NIS expression was assessed using a modified Gainor scale. Statistical analysis was performed using mean and standard deviation (SD) depending on the normality of the distribution (Lilliefors test: p > 0.20); a p-value ≤ 0.05 was considered statistically significant. The degree of correlation between variables was assessed using Kendall’s tau rank correlation coefficient. A weak to moderate negative correlation (τ: −0.369) was found between the number of pregnancies and the degree of NIS expression in triple-negative breast cancer cells. In patients with triple-negative breast cancer, a weak to moderate negative correlation was found between the degree of NIS expression and gravidity status. The discovered phenomenon is likely due to the terminal differentiation of the mammary gland epithelium that occurs during pregnancy. This may potentially indicate the suppression of pro-oncogenic properties of atypical cells developed from the epithelium that has undergone terminal differentiation. Full article

Purpose: To investigate the efficacy of a novel test for diagnosing colour vision deficiencies using reflexive eye movements measured using an unmodified tablet. Methods: This study followed a cross-sectional design, where thirty-three participants aged between 17 and 65 years were recruited. The participant group comprised 23 controls, 8 deuteranopes, and 2 protanopes. An anomaloscope was employed to determine the colour vision status of these participants. The study methodology involved using an Apple iPad Pro’s built-in eye-tracking capabilities to record eye movements in response to coloured patterns drifting on the screen. Through an automated analysis of these movements, the researchers estimated individuals’ red–green equiluminant point and their equivalent luminance contrast. Results: Estimates of the red–green equiluminant point and the equivalent luminance contrast were used to classify participants’ colour vision status with a sensitivity rate of 90.0% and a specificity rate of 91.30%. Conclusions: The novel colour vision test administered using an unmodified tablet was found to be effective in diagnosing colour vision deficiencies and has the potential to be a practical and cost-effective alternative to traditional methods. Translation Relevance: The test’s objectivity, its straightforward implementation on a standard tablet, and its minimal requirement for patient cooperation, all contribute to the wider accessibility of colour vision diagnosis. This is particularly advantageous for demographics like children who might be challenging to engage, but for whom early detection is of paramount importance. Full article

Background and Objectives: Urothelial carcinoma of the urinary bladder is a heterogeneous disease with diverse morphological and molecular characteristics. This study aims to analyze the expression of HER2 in 100 consecutive cases of muscle-invasive bladder carcinoma (MIBC), with a special attention to the different histological subtypes and consensus molecular variants determined by IHC methods. Materials and Methods: A retrospective single-center study was conducted on 100 consecutive cases of MIBC (2021–2024). HER2 status is assessed by immunohistochemistry (IHC) (scores 0, 0+, 1+, 2+, 3+), and the results are compared with the published data. Results: We have established that over half of the tumors (~60%) show some level of HER2 expression, with strong expression (3+) present in 25%. There are significant differences among the IHC-based molecular variants: luminal tumors, including papillary tumors, exhibit a frequent HER2 overexpression, whereas those with a basal immunophenotype (e.g., squamous, sarcomatoid variants) are almost entirely HER2-negative. The micropapillary subtype and some other rare subtypes can also express HER2. Conclusions: HER2 is an important biomarker with heterogeneous expression in urothelial carcinoma of the bladder. The present study showed that the frequency and level of HER2 expression vary substantially among different histopathological subtypes and molecular variants. In therapeutic terms, interest in HER2 as a target is growing—new antibody–drug conjugates show a promising activity even in cases with low HER2 expression, which will likely lead to the integration of HER2-directed therapies and routine testing in the future. Full article

Background: Inflammatory Bowel Disease (IBD), comprising Crohn’s disease and ulcerative colitis, requires accurate assessment over time. Imaging techniques play a crucial role in diagnosis, monitoring disease activity, and guiding therapeutic response. This review summarizes the current evidence on radiologic imaging techniques in IBD, focusing on intestinal ultrasound (IUS), computed tomography enterography (CTE), magnetic resonance enterography (MRE), and other emerging technologies. Methods: A literature review was conducted using PubMed, EMBASE, Scopus, and the Cochrane Library, encompassing publications up to 31 October 2024. Results: IUS offers a non-invasive tool for assessing bowel wall thickness, vascularity, and complications. CTE and MRE provide detailed visualization of luminal and extraluminal disease, with MRE preferred for routine monitoring due to the absence of ionizing radiation. Standardized indices and scoring systems aid in objective disease activity assessment. Emerging technologies like Positron Emission Tomography (PET)/MRI and radiomics show promise in combining metabolic and morphological information for complex cases. Conclusions: Imaging has a central role in IBD management, with IUS, CTE, and MRE demonstrating high diagnostic accuracy. Radiomics and Artificial Intelligence (AI) are paving the way for precision imaging. Integrating advanced imaging techniques, scoring systems, and AI-driven analytics represents a transformative step toward more effective and individualized care for patients with IBD. Full article

As a reflective display technology, electrowetting displays (EWDs) have the advantages of a paper-like appearance, fast response speed, and full-color capability. However, the use of an overdriving voltage to improve the response speed of EWDs can cause fluctuations in display luminance, which manifest as glitches in the luminance change curve. In order to eliminate this luminance instability phenomenon, a new driving pulse is proposed, which consists of an overdriving phase, a switching phase, and a driving phase. Firstly, a simplified equivalent circuit model is proposed to apply a target voltage in the driving phase without break down of the hydrophobic insulating layer. Secondly, a COMSOL (Version 6.3) two-dimensional model is established to simulate the oil contraction process and conduct comparisons, so as to ensure the effectiveness of the overdriving pulse. Then, the overdriving phase is applied to improve oil response speed, and a linear function is used in the switching phase to alleviate glitch phenomena. Moreover, the influences of overdriving voltage, overdriving time, and linear switching time on the luminance curve are analyzed by charge trapping theory in order to obtain optimal performance. The experimental results show that the glitch phenomenon is eliminated effectively, and the luminance of the EWD is increased by 1.02% and 1.96% compared with the step switching pulse and PWM pulse, respectively, while the response time is shortened by 1.82% and 8.05% compared with the step switching pulse and PWM pulse, respectively. Full article

Background/Objectives: This study aimed to profile the molecular variants of muscle-invasive bladder cancer (MIBC) based on immunohistochemical analysis and to make a correlation with morphological characteristics in a series of 100 consecutive patients. Methods: A retrospective single-center study was conducted on 100 consecutive cases of MIBC (2021–2024). A selected immunohistochemical (IHC) panel (including CK5/6, CK20, and p16) was applied in all cases to classify the tumors into known molecular variants (luminal papillary, luminal non-specified, luminal unstable, stroma-rich, basal/squamous, neuroendocrine-like). Results: Seven molecular subtypes are identified: basal (33%), luminal papillary (24%), luminal unstable (16%), luminal non-specified (10%), basoluminal (double-positive) (9%), neuroendocrine-like (double-negative with neuroendocrine morphology) (6%), and stroma-rich (2%). This distribution largely matches published data (Consensus Classification and The Cancer Genome Atlas (TCGA)), with minor differences (e.g., a lower share of the stroma-rich variant). A strong correlation is found between the histological subtypes of some tumors and their molecular variant (χ², p < 0.001): for example, all cases of urothelial carcinoma with squamous differentiation are basal, micropapillary tumors are entirely luminal, and small-cell carcinomas are neuroendocrine-like. Conclusions: The results demonstrate that the morphological subtype of urothelial carcinoma largely predetermines the molecular profile. Combining classic histopathology with IHC-based profiling allows for a more complete characterization of the tumor and aids prognosis and personalized treatment in MIBC. Full article

Mammals exhibit unique and highly variable mechanisms for the establishment and maintenance of pregnancy. Ruminants (e.g., sheep, cows, and goats) have novel mechanisms whereby the conceptus (embryo and its extra-embryonic membranes) signals for the establishment of pregnancy and exhibits unique metabolic pathways favoring conceptus development. Embryos of ruminants reach the spherical blastocyst stage at 5 to 10 mm in diameter and then elongate rapidly to elongated filamentous conceptuses of greater than 250 mm as they make contact with the uterine luminal epithelium (LE) for implantation. During conceptus elongation the trophectoderm cells secrete interferon tau (IFNT), a novel pregnancy recognition signal for ruminants to ensure maintenance of a functional corpus luteum (CL) to secrete progesterone (P4) required for pregnancy. P4 induces uterine epithelia cells to express the endogenous Jaagsiekte Retrovirus (enJSRV) that may transactivate toll-like receptors 7 and 8 in the conceptus trophectoderm to induce secretion of IFNT, a classical viral–antiviral mechanism. IFNT silences expression of receptors for estradiol (E2) and oxytocin (OXTR), which abrogates the mechanism whereby oxytocin from CL and posterior pituitary would otherwise induce large pulses of prostaglandin F_2α (PGF) by uterine epithelia to cause regression of the CL and its secretion of P4. IFNT has another novel role in silencing expression of not only ESR1 and OXTR, but all classical interferon-stimulated genes in the uterine LE and superficial glandular epithelium (sGE), but with P4 increasing expression of genes for transport of nutrients such as glucose and arginine into the uterine lumen to support conceptus development. Ruminant conceptuses convert glucose to fructose, a novel hexose sugar that cannot be transported back to the maternal circulation. Fructose is converted to fructose-1-PO4 for metabolism, not via the pathway for glycolysis but via the novel fructolysis pathway uninhibited by low pH, citrate, or ATP as is the case for glycolysis. Thus, fructose and its metabolites support the pentose cycle, hexosamine biosynthesis pathway, one-carbon metabolism, and the citric acid cycle for all cells of the conceptus. Arginine is another key nutrient transported into the uterine lumen by the uterine LE/sGE in response to P4 and IFNT. Arginine is metabolized to generate nitric oxide, polyamines, and creatine, essential for conceptus growth and development, while enhancing production of IFNT as a novel pregnancy recognition signal, and upregulating expression of genes in the uterine LE/sGE for transport of nutrients. Fructose is the major hexose sugar supporting major metabolic pathways required for conceptus growth and development in ruminants. Full article

This review provides an overview of the cross-sectional imaging features of gastrointestinal (GI) metastases presenting with a linitis plastica (LP) pattern and illustrates these findings through a series of cases from various primary tumors. It also addresses key diagnostic challenges, with particular attention to differential diagnosis. The term linitis plastica (LP) refers to the macroscopic appearance of a hollow organ with diffuse mural tumor infiltration, leading to loss of parietal distensibility. Although rare, primary LP can occur throughout the gastrointestinal (GI) tract. First described in the stomach—the most common site—it is typically associated with undifferentiated adenocarcinoma composed of poorly cohesive cells, often with signet ring morphology. Beyond primary GI tumors, LP-like metastases may also arise from extragastrointestinal primaries, most notably breast carcinoma (particularly the lobular subtype), as well as urinary bladder and prostate carcinomas. LP-like GI metastases typically manifest as circumferential, enhancing wall thickenings with exaggerated zonal anatomy and luminal narrowing. Due to diffuse parietal tumor infiltration—often with mucosal preservation—the submucosa and serosa appear disproportionately thickened and show greater enhancement relative to the muscularis propria (MP). This specific imaging appearance is known as the malignant target sign, which must be distinguished from the benign target sign, where the most prominent low-density layer corresponds to edematous submucosa. Additional key features include homogeneous enhancement with loss of layer differentiation on delayed-phase imaging and a concentric ring pattern on MR. Secondary findings may also be present, such as intestinal obstruction and concomitant peritoneal carcinomatosis (PC). Gastrointestinal metastases with an LP pattern present a significant diagnostic challenge, as they can mimic both primary tumors and benign inflammatory or infectious conditions. Accurate diagnosis is critical because management strategies differ substantially. Since the mucosa is often spared, endoscopy and superficial biopsies may yield false-negative results. Therefore, while immunohistochemistry (IHC) remains essential for confirmation, radiologists play a pivotal role in raising suspicion for LP-like GI metastases and recommending deep, extensive biopsies to obtain adequate representative tissue. Furthermore, in cases of an unknown primary tumor, recognition of the LP pattern can provide important clues to the potential site of origin. Full article

This study presents a novel method for high-precision detection and quantitative evaluation of the spatial relationship between cells and amyloid-$\beta$ (A$\beta$) in time-lapse brightfield microscopy images. Achieving accurate detection of non-fluorescent cells and A$\beta$ deposits requires high-quality video images free from noise, distortion, and frame-to-frame luminance flicker. To this end, we employ a robust preprocessing pipeline that combines multi-frame integration with vignetting correction to enhance image quality and reduce luminance variability across frames. Key preprocessing steps include background correction via two-dimensional polynomial fitting, temporal smoothing of luminance fluctuations, histogram matching for luminance normalization, and dust artifact removal based on intensity thresholds. This enhanced imaging approach enables accurate identification of A$\beta$ aggregates, which typically appear as jelly-like structures and are difficult to detect under standard brightfield conditions. Furthermore, we introduce a quantitative index to assess the spatial relationship between cells and A$\beta$ concentrations, facilitating detailed analysis under varying A$\beta$ levels. Full article

Background: Breast cancer, particularly the luminal subtype, often responds to endocrine therapies. However, 20–30% of patients develop resistance, resulting in more aggressive disease. Long non-coding RNAs (lncRNAs) are implicated in cancer progression and treatment resistance. Objective: This study aimed to evaluate the role of the lncRNA insulin-like growth factor 2 antisense (IGF2-AS) in tamoxifen-resistant breast cancer and assess its potential as a therapeutic target. Methods: Two tamoxifen-resistant breast cancer cell lines (TAMR-V and TAMR-H) were used to assess IGF2-AS expression via qPCR. Knockdown experiments with siRNA evaluated the role of IGF2-AS in cell proliferation, invasion, and migration. Next-generation sequencing (NGS) analyzed gene expression differences between the cell lines. Kaplan–Meier survival analysis determined the clinical significance of IGF2-AS expression in breast cancer patients. Results: IGF2-AS expression was significantly upregulated in TAMR-V and TAMR-H cell lines compared to control MCF-7 cells. Knockdown of IGF2-AS reduced cell proliferation and invasion in TAMR-V cells but did not significantly affect TAMR-H cells, indicating a cell line-specific role in tamoxifen resistance. NGS revealed differential gene expression profiles between TAMR-V and TAMR-H cells, suggesting variability in resistance mechanisms. Survival analysis demonstrated that higher IGF2-AS expression was associated with poorer prognosis in breast cancer patients, including those with hormone-positive and triple-negative subtypes. Conclusions: IGF2-AS is upregulated in tamoxifen-resistant breast cancer and promotes cell proliferation and invasion in a cell line-specific manner. Its differential expression in TAMR-V and TAMR-H cells highlights the complexity of resistance mechanisms, suggesting IGF2-AS as a potential therapeutic target for overcoming tamoxifen resistance. Full article

Carcinomas originate from polarized epithelia, displaying luminal and basal orientations with distinct biological properties. Regardless of tissue of origin, many carcinomas show luminal or basal traits that are reflected in molecular profiles and are associated with different clinical behaviors and outcomes. Traditionally, cancers have been classified by histology and anatomical site, but accumulating evidence indicates that luminal/basal subtyping reflects shared biological programs that transcend organ boundaries. Breast cancer was the first model in which these subtypes were defined, revealing clear prognostic and therapeutic implications. Subsequent studies have identified similar subtypes in bladder, lung, prostate, pancreatic, and head and neck carcinomas, where basal phenotypes are consistently associated with aggressive disease and distinct vulnerabilities to treatment. In this review, we synthesize advances from the last decade (2010–2024) on the basal-like subtype across epithelial tumors. We summarize key studies applying luminal/basal subtyping in large cohorts of carcinomas and in single tissue tumor types. By integrating these findings, we aim to clarify the current understanding of luminal and basal subtypes in epithelial tumors and outline their potential to refine cancer classification, improve prognostic accuracy, and guide therapeutic decision-making. This perspective supports a biology-driven framework for cancer classification and treatment, moving beyond traditional histological boundaries. Full article

The endoplasmic reticulum (ER) maintains protein homeostasis through chaperone-mediated folding and ER-associated degradation (ERAD). Disruption of this quality control, particularly involving the ER chaperone GRP94, contributes to diseases such as hypercholesterolemia, cancer, and immune disorders, where defective GRP94-dependent folding and the trafficking of client proteins like PCSK9, integrins, and Toll-like receptors drive pathology. Here, we characterize NSC637153 (cp153), a small molecule identified in a drGFP-based ERAD dislocation screen, as a selective probe of GRP94-dependent processes. cp153 inhibits the dislocation of ERAD substrates, preferentially affecting luminal clients, increases PCSK9 secretion, and promotes LDLR degradation. Unlike ATP-competitive HSP90 inhibitors, cp153 does not induce HSP70 or destabilize AKT, suggesting that it perturbs GRP94 function by interfering with client interaction or folding. The identification of cp153 provides a useful tool to for probing GRP94’s role in protein folding, trafficking, ER quality control, and disease-relevant signaling pathways, and supports the development of client-selective GRP94-targeted therapies. Full article

Obesity and inflammatory bowel disease (IBD) are two chronic conditions whose prevalence continues to rise globally. Emerging evidence suggests a bidirectional interplay between them, mediated by shared pathophysiological pathways. This narrative review explores the mechanisms Ilinking obesity to IBD development and progression, focusing on the role of adipose tissue dysfunction. Both diseases exhibit intestinal dysbiosis, low-grade systemic inflammation, and impaired epithelial barrier integrity, contributing to immune activation. Visceral adiposity, particularly mesenteric fat, acts as an immunometabolic organ producing cytokines and adipokines that may exacerbate intestinal inflammation. In Crohn’s disease, mesenteric fat expansion, or “creeping fat”, is associated with transmural inflammation, fibrosis, and luminal narrowing. Epidemiological data on obesity as a risk factor for IBD remain inconsistent due to methodological heterogeneity and confounders. Similarly, the impact of obesity on IBD outcomes, including disease activity, phenotype, and the need for surgery, is debated. While mesenteric surgical approaches like Kono-S anastomosis showed initial promise in reducing recurrence, recent randomized trials offer conflicting results. Finally, metabolic drugs such as statins, metformin, and GLP-1 receptor agonists have demonstrated anti-inflammatory properties with potential utility in IBD management. Prospective studies are warranted to elucidate the clinical significance of obesity and metabolic dysfunction in IBD and evaluate targeted therapeutic strategies. Full article

Luminous, hot, massive stars can lose mass both through quasi-steady winds driven by line-scattering of the star’s continuum luminosity, and through transient eruptions identified as Luminous Blue Variables (LBVs). This paper compares and contrasts the processes involved in steady vs. eruptive mass loss, with an emphasis on their dependence on the star’s proximity to the classical Eddington limit. For winds, I examine the role of the iron opacity bump in initiating a quasi-continuum-driven outflow, which can induce atmospheric turbulence in O-stars, an envelope inflation cycle in LBVs, or enhanced wind mass loss in WR stars. In contrast, the giant eruptions of eruptive LBVs like $\eta$ Carinae require a sudden addition of energy to the stellar envelope, like that which can occur from stellar mergers. The positive net energy imparted to a substantial fraction (>10%) of the stellar mass leads to sudden ejection that closely follows an analytic exponential similarity solution. Moreover, the rapid rotation and enhanced luminosity of the post-merger star drive a super-Eddington wind. Due to equatorial gravity darkening, this wind is stronger over the poles, sculpting a bipolar structure in the ejected mass, consistent with observations of $\eta$ Carinae’s Homunculus nebula. Full article

Background: Breast cancer, one of the most researched cancers in oncology, remains the primary cause of cancer-related mortality in women. Its biological complexity, which includes phenotypic, genetic, and microenvironmental aspects, makes modeling and treatment quite difficult. The need for more physiologically realistic models is highlighted by the comparison of two-dimensional (2D) cell cultures with 3D breast-cancer-derived spheroids, which discloses how important pathways such as epidermal growth factor receptor (EGFR) and insulin-like growth factor I receptor (IGF-IR) influence cell behavior and extracellular matrix (ECM) macromolecular expression. Methods: The purpose of this study was to utilize novel 3D cell platforms to assess the effect of inhibiting the EGFR and IGF-IR pathways, alone or in combination, on the functional properties and the expression levels of certain matrix metalloproteinases (MMPs) which are implicated in breast cancer progression (i.e., triple-negative and luminal A breast cancer subtypes) and related with the EGFR and IGF-ΙR molecular network, as also demonstrated through STRING analysis. Results: Our results demonstrated potential crosstalk between EGFR and IGF-IR signaling, which influences cell proliferation and spheroid growth, dissemination, and migration. Significant phenotypic changes proposed between 2D and 3D cell cultures, and alterations in the expression of MMPs, were also recorded. Conclusions: Both breast cancer cell lines retained acknowledged characteristics across the tested models while also exhibiting new, condition-dependent properties. Overall, our findings enhance our understanding on the interplay between the EGFR and IGF-IR pathways and underscore the value of 3D models in revealing key biological processes underlying distinct breast cancer phenotypes. Full article