Breast cancer is a major global health issue, causing high incidence and mortality rates as well as psychological stress for patients. Chemotherapy resistance is a common challenge, and the Aldo-keto reductase family one-member C3 enzyme is associated with resistance to anthracyclines like doxorubicin. Recent studies have identified celecoxib as a potential treatment for breast cancer. Virtual screening was conducted using a quantitative structure–activity relationship model to develop similar drugs; this involved backpropagation of artificial neural networks and structure-based virtual screening. The screening revealed that the C-6 molecule had a higher affinity for the enzyme (−11.4 kcal/mol), a lower half-maximal inhibitory concentration value (1.7 µM), and a safer toxicological profile than celecoxib. The compound C-6 was synthesized with an 82% yield, and its biological activity was evaluated. The results showed that C-6 had a more substantial cytotoxic effect on MCF-7 cells (62%) compared to DOX (63%) and celecoxib (79.5%). Additionally, C-6 had a less harmful impact on healthy L929 cells than DOX and celecoxib. These findings suggest that C-6 has promising potential as a breast cancer treatment.
Acute lymphoblastic leukemia (ALL) is a significant concern in both pediatric and adult demographics. Despite 156 approved cancer therapies based on small molecules, a mere five apply to all types of leukemia. Unfortunately, adherence to these treatments is low due to adverse side effects. Consequently, there is an urgent need to identify more effective treatment options for ALL. This study presents a potential solution. We have designed over fifty analogs of carbamazepine, utilizing a combination of ligand-based and structure-based drug design methodologies. Among these analogs, we identified the CR80 analog, which demonstrated predicted binding values of -8.66 kcal/mol against beta-tubulin, a favorable LogP, and IC50 values suitable for in vitro evaluation. The CR80 compound was synthesized with a yield of 50% and subsequently assessed in vitro against the U-937 cell line. It obtained an IC50 value of 0.8 micromolar to 1 micromolar and a selectivity index of two, thus marking it as a promising candidate for in vivo studies.
1 January 2024 in International Journal of Microbiology
PCR and its variants (RT‐PCR and qRT‐PCR) are valuable and innovative molecular techniques for studying nucleic acids. qPCR has proven to be highly sensitive, efficient, and reproducible, generating reliable results that are easy to analyze. During the COVID‐19 pandemic, qPCR became the gold standard technique for detecting the SARS‐CoV‐2 virus that allowed to confirm the infection event, and those asymptomatic ones, and thus save millions of lives. In‐house multiplex qPCR tests were developed worldwide to detect different viral targets and ensure results, follow the infections, and favor the containment of a pandemic. Here, we present the detailed fundamentals of the qPCR technique based on fluorogenic probes and processes to develop and optimize a successful multiplex RT‐qPCR test for detecting SARS‐CoV‐2 that could be used to diagnose COVID‐19 accurately.
This paper presents a temperature study of cellular spheroids of the line MCF-07 under a hyperthermia (HT) treatment. A 3D printed culture plate embedded with optical fiber Bragg grating (FBG) sensors was designed to perform real-time temperature measurements of the spheroids. The proposed culture plate preserves the fiber sensors' integrity and functionality while remaining immune to the high electromagnetic interference scenario. A custom microwave applicator was designed to eliminate direct contact between the heating element and the samples, while considering the culture plate material's permittivity to ensure efficient heating. The heating setup maintains the samples' temperature within the HT range, which is crucial for predicting treatment outcomes. The sensors embedded in the designed culture plate achieved an accuracy within 0.31 ${}^\mathrm{C}$ . Initial observations of the temperature effects on spheroids are discussed, highlighting the potential of this approach to understand how temperature variations within the HT range affect cell cultures.
Breast cancer remains the most common cancer among women worldwide, and recurrence rates stay high despite current treatments, especially for those with negative estrogen receptor status, where therapies are less effective, and prognosis is worse. Identifying molecules with predictive value for therapy response and prognosis is therefore crucial. In this context, FOXA1 could serve as a potential biomarker to predict the progression of ER-negative tumors. A search was conducted to answer the question, “What is the prognostic value of FOXA1 expression in breast cancer, estrogen receptor negative?” using various databases. Controlled vocabulary and Boolean operators were employed. Only studies reporting overall survival and disease-free survival, defined as the time from evaluation to death or relapse, were included. We identified seven articles evaluating FOXA1 and its relationship with disease-free survival (DFS) or overall survival (OS) in patients with ER-negative breast cancer. Our data indicate that higher FOXA1 expression is associated with improved overall survival (HR = 0.61, CI = 0.45–0.83, p < 0.002) and better disease-free survival (HR = 0.69, CI = 0.51–0.93, p < 0.02). These findings suggest that FOXA1 is linked to a favorable prognosis in terms of overall survival and disease-free survival. Further studies are needed to assess the role of FOXA1 in response to chemotherapy. PROSPERO registration number: CRD42024453750