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Topic Review
miRNA as a Therapy Target in Breast Cancer
Most miRNAs are found inside the cell but also migrate in body fluids such as blood, urine, saliva, or breast milk. Thus, these short RNA particles are considered diagnostic and therapeutic markers, especially in cancer, neurology, or cardiology. It is noteworthy that miRNA dysregulation is common in many cancer cases as they can act as both tumor suppressors or oncogenes. miRNA as a therapy target is gaining extensive attention due to its various effects on cancer development. For example, supplementation of miRNA mimics (miR-15a) in prostate cancer cell lines induced apoptosis and blocked cell proliferation. Another study showed that miR-99a reduced breast cancer cell proliferation, invasion, and migration in vitro and in vivo. Numerous studies showed that targeting miRNA with its antagonists might lead to tumor suppression and efficient, personalized cancer therapy. Significantly, miRNA-targeted therapy may influence a single gene and whole cellular pathways, which can be particularly beneficial. Specifically, the latest approach in miRNA therapeutics is mainly based on two strategies, i.e., the inhibition of oncogenic miRNAs and, hence, the restoration of the expression of tumor-suppressing genes that they target, or restoring the expression of tumor-suppressing miRNAs and consequently inhibiting the oncogenes that they target. Downregulation of tumor miRNA suppressors leads to the overexpression of their target oncogenes. To restore the expression of tumor-suppressing miRNAs, promising areas are the mimic miRNAs. They are small, chemically modified (2′-O’methoxy) double-stranded RNA molecules that mimic the endogenous mature miRNA molecules.
  • 799
  • 30 Nov 2023
Topic Review
The Innate Immune Microenvironment in Metastatic Breast Cancer
The immune system plays a fundamental role in neoplastic disease. In the era of immunotherapy, the adaptive immune response has been in the spotlight whereas the role of innate immunity in cancer development and progression is less known. The tumor microenvironment influences the terminal differentiation of innate immune cells, which can explicate their pro-tumor or anti-tumor effect. Different cells are able to recognize and eliminate no self and tumor cells: macrophages, natural killer cells, monocytes, dendritic cells, and neutrophils are, together with the elements of the complement system, the principal players of innate immunity in cancer development and evolution. Metastatic breast cancer is a heterogeneous disease from the stromal, immune, and biological point of view and requires deepened exploration to understand different patient outcomes. 
  • 798
  • 23 Nov 2022
Topic Review
Immune Evasion in Ewing Sarcoma and Osteosarcoma
Immunogenicity of the tumor environment can be enhanced by altering macrophage differentiation and polarization or by administering activating cytokines. Additional tumor microenvironment-directed approaches could be designed to interfere with the immunosuppressive mechanisms active in the immunological deserts, e.g., blocking immunosuppressive extracellular vesicles (EVs) or immunosuppressive metabolic mechanisms, or probably both. This can be achieved by engineering bifunctional TCR or CAR transgenic T cells that could simultaneously manipulate the tumor microenvironment (TME) and target tumor-specific cell surface antigens. Moreover, epigenetic activation of gene expression from non-coding sequences may provide targetable neo-epitopes even in immune inert malignancies.
  • 798
  • 13 Jan 2023
Topic Review
Molecular and Genetic Factors of Prostate Cancer
Prostate cancer is one of the most malignant types of cancer in men. It can spread to distant sites, including bones, lymph nodes, lungs, liver, and brain.
  • 798
  • 14 Feb 2023
Topic Review
Gut Microbiome in Hepatocellular Carcinoma
Hepatocellular carcinoma (HCC) is the most common type of liver cancer, accounting for approximately 85–90% of all cases of liver cancer worldwide. The gut microbiome can serve as a potential non-invasive biomarker for early HCC detection and may also impact the effectiveness of immunotherapy in cancer treatment.
  • 798
  • 13 Oct 2023
Topic Review
Factors Affecting Local Control Following SBRT for Liver Metastases
The utilization of stereotactic body radiation therapy for the treatment of liver metastasis has been widely studied and has demonstrated favorable local control outcomes. However, several predictive factors play a crucial role in the efficacy of stereotactic body radiation therapy, such as the number and size (volume) of metastatic liver lesions, the primary tumor site (histology), molecular biomarkers (e.g., KRAS and TP53 mutation), the use of systemic therapy prior to SBRT, the radiation dose, and the use of advanced technology and organ motion management during stereotactic body radiation therapy (SBRT). These prognostic factors need to be considered when clinical trials are designed to evaluate the efficacy of SBRT for liver metastases.
  • 798
  • 14 Nov 2023
Topic Review
AI Applications in Pancreatic Ductal Adenocarcinoma
Pancreatic ductal adenocarcinoma (PDAC) stands out as the predominant malignant neoplasm affecting the pancreas, characterized by a poor prognosis, in most cases patients being diagnosed in a nonresectable stage. Image-based artificial intelligence (AI) models implemented in tumor detection, segmentation, and classification could improve diagnosis with better treatment options and increased survival. 
  • 798
  • 05 Mar 2024
Topic Review
Circulating Tumour Cell Enrichment Technologies
Circulating tumour cells (CTCs) are the precursor cells for the formation of metastatic disease.
  • 797
  • 15 Mar 2021
Topic Review
Anti-PD-1/PD-L1 Based Combination Immunotherapy
Thirty to fifty percent of hepatocellular carcinomas (HCC) display an immune class genetic signature. In this type of tumor, HCC-specific CD8 T cells carry out a key role in HCC control. Those potential reactive HCC-specific CD8 T cells recognize either HCC immunogenic neoantigens or aberrantly expressed host’s antigens, but they become progressively exhausted or deleted. These cells express the negative immunoregulatory checkpoint programmed cell death protein 1 (PD-1) which impairs T cell receptor signaling by blocking the CD28 positive co-stimulatory signal. The pool of CD8 cells sensitive to anti-PD-1/PD-L1 treatment is the PD-1dim memory-like precursor pool that gives rise to the effector subset involved in HCC control. 
  • 797
  • 28 Apr 2021
Topic Review
The Microrna-143/145 Cluster in Tumors
The establishment and spreading of cancer involve the acquirement of many biological functions including resistance to apoptosis, enhanced proliferation and the ability to invade the surrounding tissue, extravasate from the primary site, survive in circulating blood, and finally extravasate and colonize distant organs giving origin to metastatic lesions, the major cause of cancer deaths. Dramatic changes in the expression of protein coding genes due to altered transcription factors activity or to epigenetic modifications orchestrate these events, intertwining with a microRNA regulatory network that is often disrupted in cancer cells. microRNAs-143 and -145 represent puzzling players of this game, with apparently contradictory functions. They were at first classified as tumor suppressive due to their frequently reduced levels in tumors, correlating with cell survival, proliferation, and migration. More recently, pro-oncogenic roles of these microRNAs have been described, challenging their simplistic definition as merely tumor-suppressive. Here we review their known activities in tumors, whether oncogenic or onco-suppressive, and highlight how their expression and functions are strongly dependent on their complex regulation downstream and upstream of cytokines and growth factors, on the cell type of expression and on the specific tumor stage. 
  • 797
  • 23 Jun 2021
Topic Review
Treatment of Malignant Pleural Mesothelioma
Malignant pleural mesothelioma (MPM) is a rare malignancy characterized by very poor prognosis and lack of treatment options. Immunotherapy has rapidly emerged as an effective tool for MPM, particularly for tumors of non-epithelioid histology. At the same time, comprehensive genomic sequencing may open the way to new-generation targeted-drugs able to hit specific MPM molecular vulnerabilities. These innovations will possibly enrich, but also dramatically complicate, the elucidation of treatment algorithms. Multidisciplinary integration is urgently needed.
  • 797
  • 23 Jun 2021
Topic Review
Tumor Microenvironment and Early-Stage Lung Cancer
Lung cancer is the leading cause of cancer-related death worldwide, accounting for more than 1.8 million fatalities each year. It is also the second most frequent type of malignancy, with more than 2.2 million cases diagnosed annually. Recent advances in cancer biology and genomics research have the potential of revealing more biomarkers for diagnostic, prognostic, and targeted therapies. A new source of biomarkers are the non-coding RNAs, especially miRNAs.
  • 797
  • 23 May 2022
Topic Review
Utilizing Cytomegalovirus T Cells in Adoptive Cell Therapy
Infection with cytomegalovirus (CMV) is highly prevalent in the general population and largely controlled by CD8pos T cells. Intriguingly, anti-CMV T cells accumulate over time to extraordinarily high numbers, are frequently present as tumor-resident ‘bystander’ T cells, and remain functional in cancer patients. Consequently, various strategies for redirecting anti-CMV CD8pos T cells to eliminate cancer cells are currently being developed. This includes conveying the advantageous characteristics of anti-CMV T cells in adoptive cell therapy. Chimeric antigen receptors (CARs) and T cell receptors (TCRs) were transduced into anti-CMV CD8pos T cells to improve the in vivo persistence of CAR/TCR-engineered T cells. Moreover, anti-CMV T cells were activated ex vivo, expanded, and reinfused into glioblastoma patients to directly target CMV peptide epitopes expressed in a subset of glioblastomas.
  • 797
  • 14 Aug 2023
Topic Review
PET Radiomics
PET radiomics is a new medical imaging field exploiting image features to develop novel diagnostic, predictive and prognostic multiparametric models to support personalized clinical decisions and improve individualized treatment selection.
  • 796
  • 25 Mar 2021
Topic Review
EUS in PanNENs Management
Pancreatic neuroendocrine neoplasms (PanNENs) are relatively rare, but their incidence has increased significantly in the last decades. Precise diagnosis and prognostic stratification are crucial for proper patient management. Endoscopic ultrasound (EUS) is the modality of choice for diagnosis of solid pancreatic tumors, showing a higher tumor detection rate than other imaging modalities, especially for small size lesions. EUS also serves as a guide for preoperative sampling and other interventions. EUS-tissue acquisition is a safe and highly accurate technique for cyto/histological diagnosis of PanNENs with a well-demonstrated correlation between Ki-67 proliferation index values and tumor grading on EUS and surgical specimens according to the WHO 2017 classification. Furthermore, the possibility of a preoperative EUS-guided fine needle tattooing or fiducial markers placement may help the surgeon to locate small and deep tumors, thus avoiding formal pancreatic resections in favor of parenchymal-sparing surgery. Finally, locoregional ablative treatments using either ethanol injection or radiofrequency ablation have been proposed in recent studies with promising results in order to control symptoms or reduce tumor burden in selected patients unfit for surgery with functioning or non-functioning PanNENs.
  • 796
  • 09 Aug 2021
Topic Review
Molecular Biomarkers in Prostate Cancer
There is clinically relevant molecular heterogeneity in prostate cancer (PCa), but this biological diversity has had only a minimal impact on clinical practice. Treatment outcomes in patients with localised PCa are often highly variable, even among patients stratified to the same risk group or disease state based on standard clinical and pathological parameters. In recent years, the development of gene panels has provided valuable data on the differential expression of genes in patients with PCa. Nevertheless, there is an urgent need to identify and validate prognostic and predictive biomarkers that can be applied across clinical scenarios, ranging from localised disease to metastatic castration-resistant PCa. The availability of such tools would allow for precision medicine to finally reach PCa patients.
  • 796
  • 16 Aug 2021
Topic Review
Oxidative Stress, Inflammation and Colorectal Cancer
Colorectal cancer (CRC) represents the second leading cause of cancer-related deaths worldwide. The pathogenesis of CRC is a complex multistep process. Among other factors, inflammation and oxidative stress (OS) have been reported to be involved in the initiation and development of CRC. Although OS plays a vital part in the life of all organisms, its long-term effects on the human body may be involved in the development of different chronic diseases, including cancer diseases. Chronic OS can lead to the oxidation of biomolecules (nucleic acids, lipids and proteins) or the activation of inflammatory signaling pathways, resulting in the activation of several transcription factors or the dysregulation of gene and protein expression followed by tumor initiation or cancer cell survival. In addition, it is well known that chronic intestinal diseases such as inflammatory bowel disease (IBD) are associated with an increased risk of cancer, and a link between OS and IBD initiation and progression has been reported. 
  • 796
  • 05 Jun 2023
Topic Review
Genomically-Guided Precision Radiation Treatment
Genetic information is seldom incorporated in formulating radiation treatment recommendations for patients with cancer, even though genetic information is now well established to be prognostic and predictive of cancer outcomes and response to systemic therapy. With the increasing accessibility to and use of genetic testing, tumor, and germline genetic data have the potential to inform clinical decisions by improving the efficacy of radiation treatment and ensuring the safety of treatment delivery.
  • 796
  • 20 Nov 2023
Topic Review
Metastatic Cancer Therapeutic Pan-resistance
Metastatic spread represents the leading cause of disease-related mortality among cancer patients. Many cancer patients suffer from metastatic relapse years or even decades after radical surgery for the primary tumor. This clinical phenomenon is explained by the early dissemination of cancer cells followed by a long period of dormancy. Although dormancy could be viewed as a window of opportunity for therapeutic interventions, dormant disseminated cancer cells and micrometastases, as well as emergent outgrowing macrometastases, exhibit a generalized, innate resistance to chemotherapy and even immunotherapy. This therapeutic pan-resistance, on top of other adaptive responses to targeted agents such as acquired mutations and lineage plasticity, underpins the current difficulties in eradicating cancer. In the present review, we attempt to provide a framework to understand the underlying biology of this major issue.
  • 795
  • 02 Nov 2020
Topic Review
Immunotherapeutic Strategies Targeting PD-1/PD-L1 Axis in NSCLC
Treatment strategies targeting programmed cell death 1 (PD-1) or its ligand, PD-L1, have been developed as immunotherapy against tumor progression for various cancer types including non-small cell lung cancer (NSCLC). The recent pivotal clinical trials of immune-checkpoint inhibiters (ICIs) combined with cytotoxic chemotherapy have reshaped therapeutic strategies and established various first-line standard treatments. The therapeutic effects of ICIs in these clinical trials were analyzed according to PD-L1 tumor proportion scores or tumor mutational burden; however, these indicators are insufficient to predict the clinical outcome. Consequently, molecular biological approaches including multiomics analyses have addressed other mechanisms of cancer immune escape and have revealed an association of NSCLC containing specific driver mutations with distinct immune phenotypes. NSCLC has been characterized by driver mutation-defined molecular subsets and the effect of driver mutations on the regulatory mechanism of PD-L1 expression on the tumor itself.
  • 795
  • 12 Jan 2022
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