Search Results (47)

Background/Objectives: The Notch signaling pathway regulates cell fate, proliferation, and differentiation, and its dysregulation has been implicated in various cancers, including breast cancer. MicroRNAs (miRNAs) are critical post-transcriptional regulators that can modulate Notch pathway components. The aim of this study was to identify miRNAs that may potentially regulate the expression of Notch pathway-related genes across five molecular subtypes of breast cancer in Polish women. Methods: Tumor and adjacent normal tissue samples were collected from 405 patients with five breast cancer subtypes: luminal A (n = 130), HER2-negative luminal B (n = 100), HER2-positive luminal B (n = 96), non-luminal HER2-positive (n = 36), and triple-negative breast cancer (n = 43). Gene expression was profiled using mRNA microarrays and validated with RT-qPCR and ELISA. Candidate regulatory miRNAs were identified by miRNA microarrays and confirmed using the miRDB database. Results: APH1A, CTBP1, DTX1, HEY1, HEY2, JAG2, NOTCH4, TLE2, and TLE4 were consistently dysregulated across all breast cancer subtypes. Overexpression of HEY1 and JAG2 may be driven by decreased levels of miR-145, miR-98, and miR-381. Conversely, downregulation of TLE4 may be associated with elevated expression of miR-196a and miR-155. No regulatory miRNAs meeting the selection criteria were identified for APH1A, CTBP1, DTX1, HEY2, NOTCH4, or TLE2. Conclusions: The consistent alterations suggest the presence of a shared Notch-driven oncogenic signature in breast cancer, potentially driving cell proliferation, stemness, and resistance to therapy. These findings enhance our understanding of Notch signaling in breast cancer and propose novel miRNA–Notch interactions as candidate targets for therapeutic intervention. Full article

To mitigate potential interference in a coexisting system, an ultra-wideband (UWB) antenna with triple-band-notched characteristics is proposed. Based on transmission line theory, three notched bands are achieved by utilizing the open- or short-circuited properties of microstrip line resonators and slot resonators. Each antenna element consists of a patch etched with three half-wavelength slots and a one-wavelength strip. Measurement results demonstrate that the antenna exhibits excellent rejection performance at the three designated frequency bands. Furthermore, the effects of array configuration and element deflection angle on mutual coupling are investigated using a 2 × 1 face-to-face multiple-in, multiple-out (MIMO) array. Finally, a two-element MIMO array with high isolation was fabricated and measured. Experimental results show that an isolation level better than 24.6 dB is maintained across the operating band. Full article

Background/Objectives: Chondrosarcoma (CS), the most common malignant bone tumor in adults, exhibits a poor prognosis due to high rates of post-surgical recurrence and metastasis, and resistance to chemotherapy. CS’s abundant expression of aspartyl-asparaginyl-β-hydroxylase (ASPH), which drives invasive tumor growth via Notch and PI3K/mTOR activation, opens opportunities for treatment in combination with standard Doxorubicin (DOX) chemotherapy. We hypothesized that the small molecule inhibitor SMI1182, which targets the catalytic domain of ASPH, and BEZ235, which targets PI3K/mTOR, could enhance the chemotherapeutic effects of DOX. Human CS1 (Grade 3) and CDS11 (Grade 2) conventional CS cell lines were treated with broad dose ranges of DOX, BEZ235, or SMI1182 as mono- or combination therapy to assess their anti-tumor effects on cell viability, toxicity, and motility. Methods: Mechanistic studies included the analysis of ASPH expression, Notch signaling, and insulin/IGF/IRS pathway activation through mTOR. DOX, BEZ235, or SMI1182 treatments caused dose-dependent cell loss and cytotoxicity. Results: SMI1182 and BEZ235, with or without DOX, significantly reduced directional motility. Combined treatments had additive cytotoxic effects linked to the reduced expression of ASPH, Notch transcription factors, and insulin receptor substrate type I, which positively regulates both ASPH and Notch. Conclusions: Triple-drug treatment with DOX, SMI1182, and BEZ235 could potentially improve disease-free survival with CS by the simultaneous targeting of multiple upstream mediators of aggressive malignant tumor cell behavior. Full article

Understanding cancer etiology requires replicating the tumor microenvironment (TME), which significantly differs from standard in vitro cultures due to nutrient limitations, acidic pH, and oxidative stress. To address this, a microfluidic bioreactor (µBR) with an expanded culture surface was designed to optimize exosome enrichment and glioblastoma cell behavior. Using response surface methodology (RSM), key parameters—including medium exchange volume and interval time—were optimized, leading to about a six-fold increase in exosome concentration without artificial inducers. Characterization techniques (SEM, AFM, DLS, RT-qPCR, and ELISA) confirmed significant alterations in exosome profiles, cancer stemness, and epithelial-mesenchymal transition (EMT)-related markers. Notably, EMT was induced in the µBR system, with a six-fold increase in HIF-1α protein despite normoxic conditions, suggesting activation of compensatory signaling pathways. Molecular analysis showed upregulation of SOX2, OCT4, and Notch1, with SOX2 protein reaching 28 ng/mL, while it was undetectable in traditional culture. Notch1 concentration tripled in the µBR system, correlating with enhanced stemness and phenotypic heterogeneity. Immunofluorescent microscopy confirmed nuclear SOX2 accumulation and co-expression of SOX2 and HIF-1α in dedifferentiated CSC-like cells, demonstrating tumor heterogeneity. These findings highlight the µBR’s ability to enhance stemness and mimic glioblastoma’s aggressive phenotype, establishing it as a valuable platform for tumor modeling and therapeutic development. Full article

Breast cancer is one of the most commonly diagnosed cancers and is the second leading cause of cancer-related deaths among women in the United States. Despite a decrease in mortality associated with breast cancer, there has been a steady increase in its incidence. Development of the mammary gland is normally regulated by such pathways including Wnt, Hedgehog, estrogen and Notch signaling. However, the deregulation of these pathways gives rise to tumor development, and upregulated Wnt activity along with high levels of beta-catenin is correlated with poor prognosis of breast cancer. In addition, beta-catenin-dependent Wnt signaling is enriched in triple-negative breast cancers and is associated with reduced overall survival in breast cancer patients. Various studies have investigated the ability of naturally occurring plant-based agents to reduce incidence and morbidity of breast cancer by regulating critical cell survival pathways to reverse or inhibit the occurrence of clinical disease. The present review focuses on summarizing the role of commonly consumed dietary phytochemicals and their role in regulating Wnt/β-catenin pathway against the development of breast cancer. Full article

Triple-negative breast cancer (TNBC) is the most aggressive and malignant type of breast cancer with limited treatment options and poor prognosis. One of the most significant impediments in TNBC treatment is the high heterogeneity of this disease, as highlighted by the detection of several molecular subtypes of TNBC. Each subtype is driven by distinct mutations and pathway aberrations, giving rise to specific molecular characteristics closely connected to clinical behavior, outcomes, and drug sensitivity. This review summarizes the knowledge regarding TNBC molecular subtypes and how it can be harnessed to devise tailored treatment strategies instead of blindly using targeted drugs. We provide an overview of novel targeted agents and key insights about new treatment modalities with an emphasis on the androgen receptor signaling pathway, cancer stem cell-associated pathways, phosphatidylinositol 3-kinase (PI3K)/AKT pathway, growth factor signaling, and immunotherapy. Full article

Triple-negative breast cancer (TNBC) accounts for approximately 20% of all breast cancer cases and is characterized by a lack of estrogen, progesterone, and human epidermal growth factor 2 receptors. Current targeted medicines have been unsuccessful due to this absence of hormone receptors. This study explored the efficacy of Tulbaghia violacea, a South African medicinal plant, for the treatment of TNBC metastasis. Extracts from T. violacea leaves were prepared using water and methanol. However, only the water-soluble extract showed anti-cancer activity and the effects of this water-soluble extract on cell adhesion, invasion, and migration, and its antioxidant activity were assessed using MCF-10A and MDA-MB-231 cells. The T. violacea extract that was soluble in water effectively decreased the movement and penetration of MDA-MB-231 cells through the basement membrane in scratch and invasion tests, while enhancing their attachment to a substance resembling an extracellular matrix. The sample showed mild-to-low antioxidant activity in the antioxidant assy. Nuclear magnetic resonance spectroscopy revealed 61 chemical components in the water-soluble extract, including DDMP, 1,2,4-triazine-3,5(2H,4H)-dione, vanillin, schisandrin, taurolidine, and α-pinene, which are known to have anti-cancer properties. An in-depth examination of the transcriptome showed alterations in genes linked to angiogenesis, metastasis, and proliferation post-treatment, with reduced activity in growth receptor signaling, angiogenesis, and cancer-related pathways, such as the Wnt, Notch, and PI3K pathways. These results indicate that T. violacea may be a beneficial source of lead chemicals for the development of potential therapeutic medicines that target TNBC metastasis. Additional studies are required to identify the precise bioactive chemical components responsible for the observed anti-cancer effects. Full article

The transmission spectrum of a twin-waveguide cavity is systematically analyzed based on coupled mode theory, using the transfer matrix method (TMM). The results show that the traveling-wave transmission spectra of the twin-waveguide cavity is entirely determined by the coherent coupling effect involving the parameters of the effective refractive indices of the upper and lower waveguides, the coupling length Lc, and the ratio of the cavity length L to the coupling length (L/Lc). Filters with single, double, or triple-notch filtering could be obtained by choosing an appropriate L/Lc value. When the facet reflection is taken into consideration, the traveling-wave transmission spectrum is modified by the Fabry––Perot (FP) resonance, making it a standing-wave transmission spectrum. As a result, resonance splitting has been observed in the transmission spectrum of twin-waveguide resonators with high facet reflectivity. Further analysis shows that such an abnormal resonance phenomenon can be attributed to the destructive interference between the two FP resonance modes of the upper and lower waveguide through coherent coupling. In addition, narrow bandwidth amplification has also been observed through asymmetric facet reflections. Undoubtedly, all these unique spectral characteristics should be beneficial to the twin-waveguide cavity, achieving many more functions and being widely used in photonic integration circuits (PICs). Full article

A group of 27 patients diagnosed with metastatic triple-negative breast cancer (mTNBC) was randomly distributed into two groups and underwent different lines of metronomic treatment (mCHT). The former group (N 14) received first-line mCHT and showed a higher overall survival rate than the second group (N 13), which underwent second-line mCHT. Analysis of one patient still alive from the first group, diagnosed with mTNBC in 2019, showed a complete metabolic response (CMR) after a composite approach implicating first-line mCHT followed by second-line epirubicin and third-line nab-paclitaxel, and was chosen for subsequent molecular characterization. We found altered expression in the cancer stemness-associated gene NOTCH-1 and its corresponding protein. Additionally, we found changes in the expression of oncogenes, such as MYC and AKT, along with their respective proteins. Overall, our data suggest that a first-line treatment with mCHT followed by MTD might be effective by negatively regulating stemness traits usually associated with the emergence of drug resistance. Full article

This paper presents a triple-input and four-output type voltage-mode universal active filter based on three current-feedback operational amplifiers (CFOAs). The filter employs three CFOAs, two grounded capacitors, and six resistors. The filter structure has three high-input and three low-output impedances that simultaneously provide band-reject, high-pass, low-pass, and band-pass filtering functions with single-input and four-output type and also implements an all-pass filtering function by connecting three input signals to one input without the use of voltage inverters or switches. The same circuit configuration enables two unique filtering functions: low-pass notch and high-pass notch. Three CFOAs with three high-input and low-output impedance terminals enable cascading without voltage buffers. The circuit is implemented using three commercial off-the-shelf AD844 integrated circuits, two grounded capacitors, and six resistors and further implemented as a CFOA-based chip using three CFOAs, two grounded capacitors, and six resistors. The CFOA-based chip has lower power consumption and higher integration than the AD844-based filter. The circuit was simulated using OrCAD PSpice to verify the AD844-based filter and Synopsys HSpice for post-layout simulation of the CFOA-based chip. The theoretical analysis is validated and confirmed by measurements on an AD844-based filter and a CFOA-based chip. Full article

This study introduces a monopole 4 × 4 Ultra-Wide-Band (UWB) Multiple-Input Multiple-Output (MIMO) antenna system with a novel structure and outstanding performance. The proposed design has triple-notched characteristics due to CSRR etching and a C-shaped curve. The notching occurs in 4.5 GHz, 5.5 GHz, and 8.8 GHz frequencies in the C-band, WLAN band, and satellite network, respectively. Complementary Split-Ring Resonators (CSRR) are etched at the feed line and ground plane, and a C-shaped curve is used to reduce interference between the ultra-wide band and narrowband. The mutual coupling of CSRR enables the MIMO architecture to achieve high isolation and polarisation diversity. With prototype dimensions of (60.4 × 60.4) mm², the proposed antenna design is small. The simulated and measured results show good agreement, indicating the effectiveness of the UWB-MIMO antenna for wireless communication and portable systems. Full article

Spectrum sensing is an important aspect in cognitive radio (CR) networks as it involves the identification of unused frequency spectra, which saves both bandwidth and energy. The design of a compact super-wideband (SWB) multi-input multi-output (MIMO)/diversity antenna with triple-band-notched features is presented for spectrum sensing in CR systems. The MIMO antenna comprises four identical semi-elliptical-shaped monopole resonators, which are orthogonally positioned and excited individually via tapered coplanar waveguide feed lines. Also, a mirror-slot analogous to the radiator is etched in the ground conductor of each antenna element to achieve SWB characteristics. In order to avoid interference with the SWB, the antenna radiator is loaded with a staircase-shaped slit and a pair of concentric slits, arranged like a complementary split-ring resonator. The antenna resonates from 1.2 to 43 GHz, exhibiting a bandwidth ratio of 36:1. In the MIMO antenna, the antenna elements are located orthogonally, and the isolation > 18 dB and envelope correlation coefficient < 0.01 are realized in the resonating band. The antenna offers a peak gain of 4 dBi, and a sharp reduction in gain at notch frequencies (3.5 GHz, 5.5 GHz, and 8.5 GHz) is achieved. The size of the MIMO antenna is 52 mm × 52 mm. The proposed compact-size antenna features a high bandwidth ratio and straightforward design procedure, and can be simply integrated into contemporary RF equipment. The presented SWB MIMO antenna outperforms SWB antenna designs reported in the open literature, which featured one or two notched bands, whereas it has three notched bands. Also, the three notches in the SWB are achieved without the use of any filters, which simplifies the antenna development process. Full article

Triple negative breast cancer (TNBC) is a very aggressive subtype of breast cancer that lacks estrogen, progesterone, and HER2 receptor expression. TNBC is thought to be produced by Wnt, Notch, TGF-beta, and VEGF pathway activation, which leads to cell invasion and metastasis. To address this, the use of phytochemicals as a therapeutic option for TNBC has been researched. Plants contain natural compounds known as phytochemicals. Curcumin, resveratrol, and EGCG are phytochemicals that have been found to inhibit the pathways that cause TNBC, but their limited bioavailability and lack of clinical evidence for their use as single therapies pose challenges to the use of these phytochemical therapies. More research is required to better understand the role of phytochemicals in TNBC therapy, or to advance the development of more effective delivery mechanisms for these phytochemicals to the site where they are required. This review will discuss the promise shown by phytochemicals as a treatment option for TNBC. Full article

In this paper, a novel ultra-wideband UWB antenna element with triple-band notches is proposed. The proposed UWB radiator element operates from 2.03 GHz up to 15.04 GHz with triple rejected bands at the WiMAX band (3.28–3.8 GHz), WLAN band (5.05–5.9 GHz), and X-band (7.78–8.51 GHz). In addition, the radiator supports the Bluetooth band (2.4–2.483 GHz). Three different techniques were utilized to obtain the triple-band notches. An alpha-shaped coupled line with a stub-loaded resonator (SLR) band stop filter was inserted along the main feeding line before the radiator to obtain a WiMAX band notch characteristic. Two identical U-shaped slots were etched on the proposed UWB radiator to achieve WLAN band notch characteristics with a very high degree of selectivity. Two identical metallic frames of an octagon-shaped electromagnetic band gap structure (EBG) were placed along the main feeding line to achieve the notch characteristic with X-band satellite communication with high sharpness edges. A novel UWB multiple-input multiple-output (MIMO) radiator is proposed. The proposed UWB-MIMO radiator was fabricated on FR-4 substrate material and measured. The isolation between every two adjacent ports was below −20 dB over the FCC-UWB spectrum and the Bluetooth band for the four MIMO antennas. The envelope correlation coefficient (ECC) between the proposed antennas in MIMO does not exceed 0.05. The diversity gains (DG) for all the radiators are greater than 9.98 dB. Full article

The key elements used for receiving and processing signals in communication systems are the bandpass filters. Initially, a common operating mechanism was applied for the design of broadband filters, i.e., by cascading low-pass filters or high-pass filters using multiple line resonators with length quarter-half- or full-wavelength with central frequency, but using these approaches, the design topology becomes expensive and complex. The above mechanisms can be possibly overcome using a planar microstrip transmission line structure due to its simple design fabrication procedure and low cost. So, pointing out the above problems in bandpass filters such as low-cost, low insertion loss, and good out-of-band performance, this article presents a broadband filter with multifrequency suppression capability at 4.9 GHz, 8.3 GHz, and 11.5 GHz using a T-shaped shorted stub-loaded resonator with a central square ring coupled to the basic broadband filter. Initially, the C-shaped resonator is utilized for the formation of a stopband at 8.3 GHz for a satellite communication system, and then a shorted square ring resonator is added to the existing C-shaped structure for the realization of two more stopbands at 4.9 GHz and 11.5 GHz for 5G (WLAN 802.11j) communication, respectively. The overall circuit area covered with the proposed filter is 0.52 λg × 0.32 λg (λg is the wavelength of the feed lines at frequency 4.9 GHz). All the loaded stubs are folded in order to save the circuit area, which is an important requirement of next-generation wireless communication systems. The proposed filter has been analyzed using a well-known transmission line theory, even–odd-mode, and simulated with the 3D software HFSS. After the parametric analysis, some attractive features were obtained, i.e., compact structure, simple planar topology, low insertion losses of 0.4 dB over the entire band, good return loss greater than 10 dB, and independently controlled mutli stopbands, which make the proposed design unique and can be used in various wireless communication system applications. Finally, a Rogers RO-4350 substrate is selected for the fabrication of the prototype using an LPKF S63 ProtoLaser machine and then measured using a ZNB20 vector network analyzer for matching the simulated and measured results. After testing the prototype, a good agreement was found between the results. Full article