Revitalizing immortalized cancer cell line research with 3D cultures: The time is ripe for transition from 2D to 3D.

Although cardiovascular disease is the leading cause of death globally, therapeutic development in this field is slow. Given the high cost of developing new drugs and running clinical trials for cardiovascular disease, repurposing of drugs with approved safety profiles is an attractive strategy for therapeutic development that can significantly reduce the time and cost investment before phase II clinical trials. In the era of "Omics," various new methods and several large databases have been developed to enable the use of transcriptomics data for drug repurposing. This review summarizes the principles and workflow of signature mapping, which forms the foundation of statistical models used for transcriptome-based drug repurposing. We highlight the features of different analysis pipelines and databases that have been developed for signature mapping. These analysis pipelines prioritize genes that are statistically important, an approach that fundamentally differs from the pharmacological approach of identifying disease-driving and therapeutically targetable pathways. Outcomes of signature mapping pipelines are sensitive to the quality of input data, and results are not always reproducible. Moreover, all widely used RNA-seq databases are derived from cancer research and lack high-quality molecular data for cardiovascular disease. These unmet needs call for interdisciplinary collaboration and large networks of cardiovascular research-oriented biobanks to create the databases needed for transcriptomic-based signature mapping for drug repurposing efforts.

CRISPR-Cas12a biosensing technology advances and applications in precision diagnostics and cancer research.

Electrochemical genosensing finds applications across a wide range of fields, including clinical diagnostics, forensic science, food safety, agriculture, biotechnology, cancer research, defense, environmental monitoring, etc. It focuses on the detection of specific DNA or RNA sequences, often called target sequences, rather than target analytes as in conventional (electro)analysis. Since the groundbreaking contributions dating back to the late 1990s and early 2000s, nearly 500 articles have been published elucidating various important aspects of this research field. This review aims to provide an overview of the current state of knowledge, serving as a comprehensive synthesis of the most recent literature on electrochemical genosensors, published in the last five years. Hopefully, it will also serve as a valuable resource for students, young researchers, scientists, non-academics, or other professionals seeking a consolidated understanding of the key aspects behind this research area, without delving into a collection of individual and scattered studies.

Gene networks have gained considerable relevance in cancer research, enabling the representation of complex biological relationships that provide insights into the mechanisms driving tumor development and progression. The increasing availability of biological data facilitates the construction of clinically relevant gene networks by integrating multiple information sources. Specifically, we consider mutation data, patient survival data, and protein-protein interaction data to identify networks whose genes are recurrently mutated, significantly involved in patient survival, and functionally associated. To this end, we apply multi-objective optimization to simultaneously maximize survival impact, functional association, and mutation coverage. Herein, we introduce MOTEA-GENSU (Multi-Objective Two-archive Evolutionary Algorithm to discover GEne Networks involved in SUrvival), a novel method that employs two collaborative archives and intelligent evolutionary operators to guide the generation of high-quality gene networks. Evaluation across 27 real biological scenarios covering diverse cancer types shows that MOTEA-GENSU outperforms existing methods, achieving superior results in 92.6% of comparisons, with improvements of up to 315.8% over the best-performing competing approach, and consistently surpassing all state-of-the-art methods on average within each evaluated dataset. Biological analysis of the identified networks validates their functional coherence and significant impact on cancer patient survival, revealing clinically relevant networks composed of genes with demonstrated prognostic value.

Porous composite materials driven by carbohydrate-carbohydrate interactions for efficient enrichment of intact glycopeptides in liver cancer cells.

Anti-tumor effect of ardicrenin against MG63 osteosarcoma cells.

The optimal size of circular staplers for esophagojejunostomy remains a subject of debate, with concerns that smaller staplers may increase the risk of postoperative complications and impair quality of life (QoL). The purpose of this study was to evaluate the impact of circular stapler size and anastomotic lumen diameter, measured via postoperative computed tomography (CT) imaging, on patient-reported quality of life following esophagojejunostomy. This prospective observational cohort study included patients who underwent esophagojejunostomy using circular staplers. Anastomotic lumen diameter was measured using postoperative CT imaging. Quality of life was assessed at a 6-month follow-up using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-STO22 and Eastern Cooperative Oncology Group (ECOG) performance status scales. Outcomes were compared across stapler sizes and corresponding lumen diameters. No statistically significant differences in EORTC QLQ-STO22 or ECOG scores were observed between stapler size groups. Additionally, anastomotic lumen diameter showed no correlation with quality-of-life outcomes. Smaller circular staplers, often used due to intraoperative anatomical limitations, do not adversely affect postoperative quality of life. These findings suggest that insisting on larger stapler sizes may be unnecessary and that smaller staplers can be used safely when indicated.

The role of the hedgehog signaling pathway in the regulation of gastrointestinal cancer cell death.

Cancer research increasingly focuses on local drug release in tumorous tissue by using drug carriers. Concurrently, techniques to quantify the associated drug release are under investigation. This study presents a Inertial Cavitation-based Release Estimation (ICbRE) method. The estimation is based on the assessment of inertial cavitation (IC) noise and its correlation to release data. To develop ICbRE, we used poly(lactic-co-glycolic acid) (PLGA) nanocapsules loaded with a fluorescent dye, which were flowed through a tissue-mimicking phantom, and exposed them to focused ultrasound bursts at 550-950 kHz with peak rarefaction pressures (PRP) of 0.22-1.85 MPa, corresponding to mechanical index (MI) values of 0.3-1.9. Cavitation activity was recorded using a passive cavitation detection (PCD) system. By training on acoustic data, we derived weight functions, interpreted as transfer functions, to solve this inverse problem. These weight functions were multiplied by a test set of the acoustic data to estimate payload release. The most accurate estimation showed an absolute error of 0.3% and a standard deviation of 1.9% from the nominal value. Given its precision, we propose the integration of ICbRE into focused ultrasound systems to estimate drug carriers' payload release. In the course of prospective cancer treatments, a drug's released payload may be simultaneously quantified while monitoring the cavitation noise to ensure an effective therapy.

Marine-derived compounds have emerged as a promising frontier in cancer research due to their remarkable structural diversity and broad-spectrum bioactivities. The marine environment, encompassing diverse organisms (e.g., sponges, algae, tunicates, mollusks, and marine microbes), is a prolific source of novel bioactive molecules with potent anti-cancer properties. Key classes of these compounds include alkaloids, polysaccharides, peptides, terpenoids, and polyketides, which exert anti-tumor effects through diverse mechanisms, including the induction of apoptosis, inhibition of angiogenesis, modulation of immune responses, interference with cell cycle progression, and targeting of critical signaling pathways involved in tumorigenesis and metastasis. Notably, marine-derived drugs such as trabectedin, eribulin, and plitidepsin have received regulatory approval for the treatment of various malignancies, demonstrating the translational potential of these natural compounds. Ongoing clinical and preclinical investigations are exploring a wide range of marine metabolites for their cytotoxic, anti-proliferative, and chemosensitizing properties. Advances in marine biotechnology, including genome mining, synthetic biology, and fermentation technologies, have significantly facilitated the discovery, sustainable production, and structural optimization of marine natural products. However, challenges such as low yield, structural complexity, limited water solubility, and poor bioavailability hinder their broader clinical application. The integration of novel drug delivery systems, such as nanoparticles, liposomes, and conjugates, offers a viable solution to overcome these limitations and improve pharmacokinetic profiles. This review provides a comprehensive overview of the mechanisms of action, therapeutic applications, and clinical development of marine-derived anti-cancer compounds. It also emphasizes the need for deeper insights into their molecular targets and the potential for synergistic use with existing chemotherapeutic agents. Future directions should focus on exploring untapped marine biodiversity, developing eco-friendly harvesting strategies, and developing innovative delivery platforms to fully harness the therapeutic promise of the marine pharmacopeia in oncology.

Fragment-based drug design coupled with AI/ML prediction enables identification of novel PARP-1 inhibitors against triple-negative breast cancer.

ReEnSta Alleviates Pain by Reducing Postoperative Swelling and Blood Stasis After Open Surgery.

Despite recent advancements in oncology drug development, patient access to innovative cancer therapies remains inadequate. There is an urgent need for more patient-centric approaches, with meaningful patient input from trial design through to health technology assessment (HTA) consultation. Multi-stakeholder consensus calls for better representation of the diversity of the target population and integration of patients' preferences in clinical cancer research by systematically collecting patient-reported outcomes using standardized methods, and acknowledging trade-offs between survival and long-term wellbeing. Furthermore, the generation of insufficiently robust data for regulatory and HTA decision-making continue to delay patient access to innovation. This could be mitigated through smarter study designs, including smaller, fit-for-purpose randomized studies and prospectively designed trials. Finally, concerted efforts are required to develop and validate novel intermediate/surrogate endpoints that enable earlier assessment of treatment outcomes to facilitate timely, evidence-based decisions that improve the patient experience across the cancer care continuum.

Capecitabine plus oxaliplatin (CAPOX) is a frequently used treatment regimen for colorectal and gastric cancer as postoperative adjuvant chemotherapy. Nausea, vomiting and diarrhea are reported to be the main causes of decreased adherence to CAPOX therapy. The Cancer Institute Hospital, Japanese Foundation for Cancer Research, provides a pharmaceutical outpatient clinic for patients undergoing outpatient chemotherapy. In the present study, dose intensity and severity of side effects of CAPOX therapy as adjuvant chemotherapy after surgery for gastric cancer were evaluated before and after outpatient pharmacy clinic follow-up. This was a retrospective, observational study. Data from consecutive patients who received CAPOX therapy as adjuvant therapy after surgery for gastric cancer from November 2015 to April 2021 were obtained. Two patients were excluded, and 59 patients were included in the analysis. In total, there were 243 prescription recommendations at the pharmacy outpatient clinic. The most common prescription recommendation was prescription of supportive care medications (53.9%, 131 instances), followed by postponement of treatment (10.3%, 25 instances) and dose reduction of each drug (8.2%, 20 instances). The mean relative dose intensity (RDI) was 67.8±20.2% [95% confidence interval (CI), 62.5-73.1%] for capecitabine and 62.2±20.7% (95% CI, 56.9-67.6%) for oxaliplatin. The mean RDI was 72.5±18.8% (95% CI, 61.2-83.7%) before capecitabine dose reduction and 90.4±14.8% (95% CI, 81.4-99.3%) after dose reduction. The pharmacy outpatient clinic maintained RDI and contributed to the continuation of treatment by suggesting supportive care medications and recommending reduction of the dosage of anticancer drugs to the physicians.

The application of electrochemical sensors in medical testing has indeed introduced innovative technical means for the diagnosis, prognosis assessment, and treatment of diseases, particularly in the context of prostate cancer. In prostate cancer research, electrochemical sensors can detect biomarkers such as GNG4, CHGA, and SYP, which are indicative of neuroendocrine differentiation. This capability is crucial for early detection and monitoring of disease progression, as neuroendocrine differentiation is often associated with aggressive, therapy-resistant phenotypes. The high sensitivity of electrochemical sensors allows for the detection of these biomarkers at ultra-low concentrations, even in complex biological samples like blood or tissue lysates. By combining single-cell sequencing with electrochemical detection, the study found that the GNG4 gene plays a key role in the neuroendocrine differentiation process. Its high expression is associated with a reduced risk of biochemical recurrence, but it is also consistent with an increased risk of death and sensitivity to platinum-based chemotherapy drugs. The prognostic model based on electrochemical detection demonstrated high predictive accuracy in multiple independent cohorts, with an average C-index value of more than 0.75, indicating that this model can effectively predict the biochemical recurrence risk of prostate cancer patients. Graphical abstract Fig. 1. Origin and development of NEPC. • Electrochemical sensors can detect biomarkers such as GNG4, CHGA, and SYP. • The high sensitivity of electrochemical sensors allows for the detection of these biomarkers at ultra-low concentrations. • The prognostic model based on electrochemical detection demonstrated high predictive accuracy in multiple independent cohorts.

Ovarian cancer research grants

Bladder cancer research is blossoming in Birmingham.

BackgroundTransdermal estradiol (tE2) is an alternative to luteinizing hormone–releasing hormone (LHRH) agonists as androgen-deprivation therapy in patients with prostate cancer. With tE2, testosterone is suppressed, and the side effects of estrogen depletion due to LHRH agonists and the thromboembolic side effects of oral estrogen are mitigated.MethodsIn this phase 3, noninferiority, randomized trial, we assigned men with locally advanced (M0 and N0 or N+) prostate cancer to receive tE2 patches (100 μg of estradiol every 24 hours) or LHRH agonists. The primary outcome was 3-year metastasis-free survival. The noninferiority margin was 4 percentage points; this corresponded to a target hazard ratio of 1.31, as derived from the observed 3-year metastasis-free survival in the LHRH agonist group. Secondary outcomes included castrate levels of testosterone (<1.7 nmol per liter), overall survival, and safety.ResultsBetween 2007 and 2022, we recruited 1360 patients at 75 U.K. centers. The median age of the patients was 72 years (interquartile range, 68 to 77); 85% had a T3 tumor stage and 65% an N0 nodal stage. Observed 3-year metastasis-free survival was 87.1% with tE2 and 85.9% with LHRH agonists (hazard ratio for confirmed metastasis or death, 0.96; upper limit of the one-sided 95% confidence interval [CI], 1.11, which met the criterion for noninferiority). Among patients continuing the assigned treatment, castrate levels of testosterone were sustained during the first year after randomization in 85% in each group. Observed 5-year overall survival was 81.1% with tE2 and 79.2% with LHRH agonists (hazard ratio for death, 0.90; 95% CI, 0.75 to 1.07). During treatment, hot flashes occurred in 44% of the patients who received tE2 and 89% of those who received LHRH agonists (grade ≥2 events, 8% and 37%, respectively) and gynecomastia in 85% and 42% (grade ≥2 events, 37% and 9%).ConclusionsIn patients with locally advanced prostate cancer, tE2 was noninferior to LHRH agonists for 3-year metastasis-free survival, with a lower incidence of hot flashes but a higher incidence of gynecomastia. (Funded by Cancer Research U.K. and the U.K. Research Institute Medical Research Council; PATCH ClinicalTrials.gov number, NCT00303784; STAMPEDE-1 ClinicalTrials.gov number, NCT00268476.)

Microfluidics has revolutionized cancer research by transforming how we study, diagnose, and test treatments, providing valuable insights into disease mechanisms and therapeutic responses. Through miniaturization, automation, and parallelization, microfluidic devices have standardized analytical assays and enhanced the accuracy and reliability of diagnostic and screening procedures, attracting the interest of pharmaceutical industry, laboratories, and clinicians. The use of advanced biofabrication techniques and biomaterials has further enabled the creation of sophisticated microphysiological devices integrating biomimetic tissue-like structures, closely mimicking the cellular and structural complexity of the native tumor microenvironment. This advanced generation of microfluidic platforms surpass conventional approaches that rely on synthetic, rigid, and planar materials, providing a more realistic representation of cancer biology. Moreover, the incorporation of miniaturized biosensors enabling real-time, multiplex, and precise monitoring of biological processes and biomarker presence overcomes the limitations of traditional screening methods, generating high-resolution data that can directly inform clinical decision-making when translated into practice. Herein, we describe how the convergence of microfluidics, biofabrication, and biosensor technologies is shaping a new paradigm in cancer research, driving advancements in disease modeling, drug screening, and diagnosis. While challenges remain for widespread clinical adoption, this integrated approach holds immense potential to transform cancer management and improve patient outcome.