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Cervical cancer has high incidence and mortality rates, especially in less-developed countries. Prevention methods are well established, but there are still barriers preventing some Brazilian women from undergoing a Pap sample. The objective of the study was to evaluate the acceptance, preferences and completion of four screening methods. This has an experimental design (community trial). A total of 164 participants who had never had a Pap sample or had not had one for more than three years were included. The city’s urban area was stratified by census tracts and divided according to income and education levels. Women belonging to the lower-income strata were considered in the study. Random blocks were numbered into five intervention groups (Group 1- Pap sample at the hospital; Group 2- Pap sample in the mobile unit; Group 3- urine self-collection; Group 4- vaginal self-collection; Group 5- woman’s choice). Only 164 women met all of the eligibility criteria (15.3%). Most of them accepted the assigned method (92%), but only 84% of the women completed the collection step. The acceptance rates were as follows: Group 1 (100%), Group 2 (64.5%), Group 3 (100%) and Group 4 (91.4%). In Group 5, the women’s preferences were distributed as follows: examination performed at the hospital, 13 women (33.3%); examination performed at the mobile unit, 11 women (28.2%); urine self-collection, 11 women (28.2%); and vaginal self-collection, 4 women (10.3%). This study suggests that methods that allow cervical sampling collected near the women’s domicile might improve the acceptance and completion of preventive tests. This finding is relevant for the development of new cervical cancer screening strategies.

Background/Objectives: The development of effective oncologic therapies with fewer adverse effects is often limited by the intrinsic and acquired resistance of tumor cells. Hybrid molecules, rationally designed to combine different pharmacophores, represent a promising strategy by providing synergistic effects, dose reduction, and a lower risk of resistance. In this study, the antitumor potential and mechanisms of action of 22 novel hybrid compounds derived from xanthene and pyran scaffolds (SJ022–SJ103) were investigated. The hybrids were initially evaluated through in vitro screening in four breast, three ovarian, and two prostate cancer cell lines, followed by the selection of T-47D, OVCAR-3, and LNCaP cells for detailed assays assessing cytotoxicity, apoptosis, cell cycle distribution, DNA damage, caspase-3/7 activity, morphology, and PI3K/AKT/mTOR pathway modulation. Methods: Cytotoxicity assays were performed in the selected cell lines, while mechanistic studies included apoptosis and cell cycle analysis by flow cytometry, γH2AX detection, Western blotting for PI3K/AKT/mTOR pathway proteins, and 3D spheroid assays. Combinatorial effects with hormone therapies (tamoxifen, fulvestrant, and letrozole) and the AKT inhibitor MK2206 were evaluated. AKT silencing by esiRNA and molecular docking was performed to confirm target engagement. Results: SJ028 demonstrated broad activity across all tested cell lines, whereas SJ064 and SJ078 exhibited higher selectivity. Treatments induced apoptosis, S/G2-M arrest, and DNA damage, accompanied by decreased phospho-AKT levels and stable PI3K and mTOR expression. In 3D models, the hybrids increased caspase-3/7 activity and necrotic core expansion. Co-administration with hormone therapies resulted in synergistic effects in breast and ovarian cancer cells, reducing IC50 values by more than 50% in both parental and resistant models, while combinations with MK2206 were antagonistic across all tumor subtypes. AKT silencing abrogated cytotoxicity, and docking confirmed SJ028 binding to AKT. Conclusions: Xanthene- and pyran-based hybrids—particularly SJ028, SJ064, and SJ078—showed strong antitumor activity through apoptosis induction, cell cycle arrest, and PI3K/AKT pathway modulation. Their preserved efficacy in resistant models and synergistic interactions with hormone therapies contrasted with the antagonism observed with AKT inhibition, highlighting their potential as promising candidates for the treatment of hormone-responsive and -resistant cancers.

Lung cancer is the deadliest cancer worldwide. Tissue biopsy is currently employed for the diagnosis and molecular stratification of lung cancer. Liquid biopsy is a minimally invasive approach to determine biomarkers from body fluids, such as blood, urine, sputum, and saliva. Tumor cells release cfDNA, ctDNA, exosomes, miRNAs, circRNAs, CTCs, and DNA methylated fragments, among others, which can be successfully used as biomarkers for diagnosis, prognosis, and prediction of treatment response. Predictive biomarkers are well-established for managing lung cancer, and liquid biopsy options have emerged in the last few years. Currently, detecting EGFR p.(Tyr790Met) mutation in plasma samples from lung cancer patients has been used for predicting response and monitoring tyrosine kinase inhibitors (TKi)-treated patients with lung cancer. In addition, many efforts continue to bring more sensitive technologies to improve the detection of clinically relevant biomarkers for lung cancer. Moreover, liquid biopsy can dramatically decrease the turnaround time for laboratory reports, accelerating the beginning of treatment and improving the overall survival of lung cancer patients. Herein, we summarized all available and emerging approaches of liquid biopsy—techniques, molecules, and sample type—for lung cancer.

These days, cancer is thought to be more than just one illness, with several complex subtypes that require different screening approaches. These subtypes can be distinguished by the distinct markings left by metabolites, proteins, miRNA, and DNA. Personalized illness management may be possible if cancer is categorized according to its biomarkers. In order to stop cancer from spreading and posing a significant risk to patient survival, early detection and prompt treatment are essential. Traditional cancer screening techniques are tedious, time-consuming, and require expert personnel for analysis. This has led scientists to reevaluate screening methodologies and make use of emerging technologies to achieve better results. Using time and money saving techniques, these methodologies integrate the procedures from sample preparation to detection in small devices with high accuracy and sensitivity. With its proven potential for biomedical use, surface-enhanced Raman scattering (SERS) has been widely used in biosensing applications, particularly in biomarker identification. Consideration was given especially to the potential of SERS as a portable clinical diagnostic tool. The approaches to SERS-based sensing technologies for both invasive and non-invasive samples are reviewed in this article, along with sample preparation techniques and obstacles. Aside from these significant constraints in the detection approach and techniques, the review also takes into account the complexity of biological fluids, the availability of biomarkers, and their sensitivity and selectivity, which are generally lowered. Massive ways to maintain sensing capabilities in clinical samples are being developed recently to get over this restriction. SERS is known to be a reliable diagnostic method for treatment judgments. Nonetheless, there is still room for advancement in terms of portability, creation of diagnostic apps, and interdisciplinary AI-based applications. Therefore, we will outline the current state of technological maturity for SERS-based cancer biomarker detection in this article. The review will meet the demand for reviewing various sample types (invasive and non-invasive) of cancer biomarkers and their detection using SERS. It will also shed light on the growing body of research on portable methods for clinical application and quick cancer detection. [Display omitted] •The wide range application of miRNA as biomarker for cancer diagnostic is addressed.•Application of SERS technology and its potential towards the clinical diagnostics are reviewed critically.•miRNA and its potential application in cancer diagnostic, for invasive and noninvasive sample type are discussed. .•Outlook of miRNA based portable Raman sensing system for biomedical applications are summarized.

Glioblastoma (GBM) is the highest-grade form of glioma, as well as one of the most aggressive types of cancer, exhibiting rapid cellular growth and highly invasive behavior. Despite significant advances in diagnosis and therapy in recent decades, the outcomes for high-grade gliomas (WHO grades III-IV) remain unfavorable, with a median overall survival time of 15–18 months. The concept of cancer stem cells (CSCs) has emerged and provided new insight into GBM resistance and management. CSCs can self-renew and initiate tumor growth and are also responsible for tumor cell heterogeneity and the induction of systemic immunosuppression. The idea that GBM resistance could be dependent on innate differences in the sensitivity of clonogenic glial stem cells (GSCs) to chemotherapeutic drugs/radiation prompted the scientific community to rethink the understanding of GBM growth and therapies directed at eliminating these cells or modulating their stemness. This review aims to describe major intrinsic and extrinsic mechanisms that mediate chemoradioresistant GSCs and therapies based on antineoplastic agents from natural sources, derivatives, and synthetics used alone or in synergistic combination with conventional treatment. We will also address ongoing clinical trials focused on these promising targets. Although the development of effective therapy for GBM remains a major challenge in molecular oncology, GSC knowledge can offer new directions for a promising future.

Background Colorectal cancer (CRC) is the second leading cause of cancer death worldwide. Early detection of precursor lesions or early-stage cancer could hamper cancer development or improve survival rates. Liquid biopsy, which detects tumor biomarkers, such as mutations, in blood, is a promising avenue for cancer screening. Aim To assess the presence of genetic variants in plasma cell-free tumor DNA from patients with precursor lesions and colorectal cancer using the commercial Oncomine Colon cfDNA Assay. Material and methods Cell-free DNA (cfDNA) samples from the plasma of 52 Brazilian patients were analyzed. Eight patients did not have any significant lesions (five normal colonoscopies and three hyperplastic polyps), 24 exhibited precursor lesions (13 nonadvanced adenomas, 10 advanced adenomas, and one sessile serrated lesion), and 20 patients with cancer (CRC). The mutation profile of 14 CRC-associated genes were determined by next-generation sequencing (NGS) using the Oncomine Colon cfDNA Assay in the Ion Torrent PGM/S5 sequencer. Results Thirty-three variants were detected in eight genes ( TP53, PIK3CA, FBXW7, APC, BRAF, GNAS, KRAS, and  SMAD4 ). No variants were detected in the AKT1 , CTNNB1 , EGFR , ERBB2 , MAP2K1 and NRAS genes. All variants were considered pathogenic and classified as missense or truncating. The  TP53  gene harbored the most variants (48.48%), followed by the KRAS  gene (15.15%) and the APC gene (9.09%). It was possible to detect the presence of at least one pathogenic variant in cfDNA in 60% of CRC patients (12/20) and 25% of precursor lesions (6/24), which included variants in three patients with nonadvanced adenoma (3/13 – 23.08%) and three with advanced adenomas (3/10 – 30%). No variants were detected in the eight patients with normal findings during colonoscopy. The detection of mutations showed a sensitivity of 60% and a specificity of 100% for detecting CRC and a sensitivity of 50% and a specificity of 100% for detecting advanced lesions. Conclusion The detection of plasma NGS-identified mutations could assist in early screening and diagnostic of CRC in a noninvasive manner.

High-grade cervical intraepithelial lesions (CIN 2/3) are critical targets for early detection in cervical cancer prevention. MicroRNAs are stable, tissue-specific molecules involved in cancer-related pathways and can be detected in minimally invasive samples, making them suitable for use in the context of liquid biopsies. This exploratory study aimed to identify differentially expressed microRNAs in paired liquid-based cytology (LBC) and plasma samples from women with CIN 2/3, and to evaluate miR-339-3p as a potential biomarker. Samples from 70 women (35 cases with histologically confirmed high-grade lesions and 35 age-matched controls with normal cytology and negative HPV tests) were analyzed using a commercial microRNA panel on the NanoString platform. We identified 57 dysregulated microRNAs in LBC samples and 33 in plasma, with four shared between both matrix types. Among these, miR-339-3p was the only one consistently upregulated and significantly associated with case status. In LBC samples, the area under the curve was 0.65; in plasma, 0.64. Pathway analysis suggested its involvement in apoptosis-related pathways, including PI3K-Akt and p53. Moreover, this study highlights the value of integrating microRNA profiling across local and systemic samples to advance biomarker discovery in cervical cancer.

Identifying significantly mutated genes in cancer is essential for understanding the mechanisms of tumor initiation and progression. This task is a key challenge since large-scale genomic studies have reported an endless number of genes mutated at a shallow frequency. Towards uncovering infrequently mutated genes, gene interaction networks combined with mutation data have been explored. This work proposes Discovering Significant Cancer Genes (DiSCaGe), a computational method for discovering significant genes for cancer. DiSCaGe computes a mutation score for the genes based on the type of mutations they have. The influence received for their neighbors in the network is also considered and obtained through an asymmetric spreading strength applied to a consensus gene network. DiSCaGe produces a ranking of prioritized possible cancer genes. An experimental evaluation with six types of cancer revealed the potential of DiSCaGe for discovering known and possible novel significant cancer genes.

NTRK1, 2, and 3 fusions are important therapeutic targets for NSCLC patients, but their prevalence in South American admixed populations needs to be better explored. NTRK fusion detection in small biopsies is a challenge, and distinct methodologies are used, such as RNA-based next-generation sequencing (NGS), immunohistochemistry, and RNA-based nCounter. This study aimed to evaluate the frequency and concordance of positive samples for NTRK fusions using a custom nCounter assay in a real-world scenario of a single institution in Brazil. Out of 147 NSCLC patients, 12 (8.2%) cases depicted pan-NTRK positivity by IHC. Due to the absence of biological material, RNA-based NGS and/or nCounter could be performed in six of the 12 IHC-positive cases (50%). We found one case exhibiting an NTRK1 fusion and another an NTRK3 gene fusion by both RNA-based NGS and nCounter techniques. Both NTRK fusions were detected in patients diagnosed with lung adenocarcinoma, with no history of tobacco consumption. Moreover, no concomitant EGFR , KRAS, and ALK gene alterations were detected in NTRK -positive patients. The concordance rate between IHC and RNA-based NGS was 33.4%, and between immunohistochemistry and nCounter was 40%. Our findings indicate that NTRK fusions in Brazilian NSCLC patients are relatively rare (1.3%), and RNA-based nCounter methodology is a suitable approach for NRTK fusion identification in small biopsies.

Medulloblastoma is the most common and lethal pediatric malignant brain tumor. It comprises four main molecular subgroups: WNT-activated, SHH-activated, Group 3, and Group 4. Medulloblastoma treatment is surgical resection, craniospinal radiation, and chemotherapy. However, many patients do not respond to therapy, and most suffer severe side effects. Cancer immunotherapy targeting immune checkpoints (IC) (PD-1, PD-L1, and CTLA4) has been getting disappointing outcomes in brain tumors. Nevertheless, other less explored immune checkpoints may be promising candidates for medulloblastoma therapy. In the present study, we aimed to characterize the expression profile of 19 immune checkpoints in medulloblastoma. We analyzed 88 formalin-fixed paraffin-embedded medulloblastomas previously classified for each molecular subgroup and three non-tumoral brain tissue. mRNA levels of 19 immune checkpoint-related genes were quantified using the nCounter (PanCancer Immune Profiling Panel) assay. Further analysis was performed in two larger public microarray datasets, one of which enabled comparisons between tumoral and non-tumoral tissues. Immunohistochemistry of PD-L1 was performed in a subset of cases. Microsatellite instability was also molecularly analyzed. We observed an absence of expression of the canonic ICs, namely (PD-1), (PD-L1), and , as well as , and PD-L1 protein expression was also practically absent. We found higher mRNA levels of , (B7-H3), and , and lower mRNA levels of , , and genes, with significant differences across the four molecular subgroups. Compared to the non-tumor tissues, the expression levels of in all subgroups and in SHH, Group 3, and Group 4 subgroups are significantly higher. The analysis confirmed the expression profile found in the Brazilian cohort, including the lower/absent expression of the canonic ICs. Moreover, it confirmed the overexpression of and in medulloblastomas compared with the non-tumor tissue. Additionally, and CD24 high levels were associated with worse survival. These results highlight the low or absence of mRNA levels of the canonic targetable ICs in medulloblastomas. Importantly, the analysis revealed overexpression of and , which can constitute prognostic biomarkers and attractive immunotherapy targets for medulloblastomas.