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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. 
  • 767
  • 23 Nov 2022
Topic Review
Perioperative Treatment for Muscle-Invasive Bladder Cancer
Cisplatin-based neoadjuvant chemotherapy followed by radical cystectomy is the standard of care for muscle-invasive bladder cancer (MIBC). However, less than half of patients are candidates for this treatment, and 50% will develop metastatic disease. Adjuvant chemotherapy could be offered if neoadjuvant treatment has not been administered for suitable patients. It is important to reduce the risk of systemic recurrence and improve the prognosis of localized MIBC. Systemic therapy for metastatic urothelial carcinoma has evolved. Immune checkpoint inhibitors and targeted agents, such as antibody-drug conjugates or FGFR inhibitors, are new therapeutic alternatives and have shown their benefit in advanced disease. Several clinical trials are investigating the role of these drugs, as monotherapy and in combination with chemotherapy, in the neoadjuvant and adjuvant settings with promising outcomes. In addition, the development of predictive biomarkers could predict responses to neoadjuvant therapies.
  • 767
  • 09 Feb 2023
Topic Review
Cancer-Associated Fibroblasts as Tumor Microenvironment Modifiers
Cancer-associated fibroblasts (CAFs) are stromal cells in the tumor microenvironment that are integral to cancer progression. Subtypes of CAFs across a variety of cancers have been revealed, and each play a different role in cancer progression or suppression. CAFs secrete signaling molecules that remodel the extracellular matrix, modulate immune responses and regulate cancer growth and metastasis.
  • 767
  • 04 Apr 2023
Topic Review
Therapy for Hepatocellular Carcinoma
Advanced hepatocellular carcinoma is a prevalent and potentially aggressive disease. For more than a decade, treatment with sorafenib has been the only approved therapeutic approach. Moreover, no agent has been proven to prolong survival following the progression of disease after sorafenib treatment. However, in recent years, this scenario has changed substantially with several trials being conducted to examine the effects of immunotherapy and novel targeting agents. Several immune checkpoint inhibitors have shown promising results in early-stage clinical trials. Moreover, phase III trials with large cohorts have demonstrated remarkable improvement in survival with the use of new targeted therapies in second-line treatment. Treatment regimens involving the combination of two immune checkpoint inhibitors as well as immune checkpoint inhibitors and anti-angiogenic targeted therapies have shown potential to act synergistically in clinical trials. Recently, the combination of atezolizumab and bevacizumab evaluated in a phase III clinical trial has demonstrated survival superiority in the first-line treatment; it is the new considered standard of care.
  • 767
  • 21 Jan 2021
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.
  • 767
  • 12 Jan 2022
Topic Review
Treatment Strategies for KRAS-Mutated Non-Small-Cell Lung Cancer
Activating mutations in Kirsten rat sarcoma viral oncogene homologue (KRAS) are highly prevalent in solid tumours and are frequently found in 35% of lung, 45% of colorectal, and up to 90% of pancreatic cancers. Mutated KRAS is a prognostic factor for disease-free survival (DFS) and overall survival (OS) in NSCLC and is associated with a more aggressive clinical phenotype, highlighting the need for KRAS-targeted therapy. Once considered undruggable due to its smooth shallow surface, a breakthrough showed that the activated G12C-mutated KRAS isozyme can be directly inhibited via a newly identified switch II pocket. This discovery led to the development of a new class of selective small-molecule inhibitors against the KRAS G12C isoform. Sotorasib and adagrasib are approved in locally advanced or metastatic NSCLC patients who have received at least one prior systemic therapy. 
  • 766
  • 28 Mar 2023
Topic Review
Mechanisms of Polyphenols as Treatment Against Neuroblastoma
Neuroblastoma (NB) is an extracranial tumor of the peripheral nervous system arising from neural crest cells. It is the most common malignancy in infants and the most common extracranial solid tumor in children. The treatment for high-risk NB involves chemotherapy and surgical resection followed by high-dose chemotherapy with autologous stem-cell rescue and radiation treatment. However, those with high-risk NB are susceptible to relapse and the long-term side effects of standard chemotherapy. Polyphenols, including the sub-class of flavonoids, contain more than one aromatic ring with hydroxyl groups.
  • 766
  • 06 Apr 2023
Topic Review
CSF ctDNA in CNS Malignancies
The correct characterisation of central nervous system (CNS) malignancies is crucial for accurate diagnosis and prognosis and also the identification of actionable genomic alterations that can guide the therapeutic strategy. Surgical biopsies are performed to characterise the tumour; however, these procedures are invasive and are not always feasible for all patients. Moreover, they only provide a static snapshot and can miss tumour heterogeneity. A liquid biopsy of the CSF can be used to obtain information about the tumour in a less invasive manner. The CSF is a source of cell-free circulating tumour DNA (ctDNA), and the analysis of this biomarker can characterise and monitor brain cancer. Recent studies have shown that ctDNA is more abundant in the CSF than plasma for CNS malignancies and that it can be sequenced to reveal tumour heterogeneity and provide diagnostic and prognostic information. Furthermore, analysis of longitudinal samples can aid patient monitoring by detecting residual disease or even tracking tumour evolution at relapse and, therefore, tailoring the therapeutic strategy.
  • 764
  • 23 Jun 2021
Topic Review
Arginine Metabolism in Oral Tongue Squamous Cell Carcinoma
Arginine is a semi-essential amino acid with a complex metabolism pathway and diverse functionality, which spans well beyond its role in the immune system. Cancers that are ‘arginine auxotrophic’ rely on extracellular arginine as a crucial substrate for proliferation and growth. Capitalizing on this vulnerability, there are numerous clinical trials evaluating the therapeutic benefits of depleting arginine in multiple types of cancer, including those occurring in the head and neck. However, head and neck cancers are different and are nonauxotrophic for arginine. Here, researchers explored the intricacies of arginine metabolism in tongue cancer in order to better understand the therapeutic potential of this biological vulnerability. 
  • 764
  • 13 Dec 2021
Topic Review
Proteomics-Based Interventions in Phytochemical Studies
Proteomic analysis is an unbiased perspective, which is a convenient approach to get a global overview about the effectiveness of bioactive molecules. Phytochemicals such as curcumin (Cur), genistein (Gen), and tanshinone-IIA (Tan IIA) have multifaceted therapeutic potentials and various efforts are in progress to understand the molecular dynamics of their function with different tools and technologies. Cur is an active lipophilic polyphenol with pleiotropic function, and it has been shown to possess various intriguing properties including antioxidant, anti-inflammatory, anti-microbial, anticancer, and anti-genotoxic properties besides others beneficial properties. Similarly, Gen (an isoflavone) exhibits a wide range of vital functions including antioxidant, anti-inflammatory, pro-apoptotic, anti-proliferative, anti-angiogenic activities etc. In addition, Tan IIA, a lipophilic compound, possesses antioxidant, anti-angiogenic, anti-inflammatory, anticancer activities, and so on. The field of proteomics has garnered great momentum mainly attributed to the recent advancement in mass spectrometry (MS) techniques. It is envisaged that the proteomics technology has considerably contributed to the biomedical research endeavors lately. They have also been explored as a reliable approach to understand the molecular intricacies related to phytochemical-based therapeutic interventions. 
  • 764
  • 13 Jan 2023
Topic Review
Prognostic and Predictive Biomarkers in Familial Breast Cancer
Large numbers of breast cancers arise within a familial context, either with known inherited germline mutations largely within DNA repair genes, or with a strong family history of breast and/or ovarian cancer, with unknown genetic underlying mechanisms. These cancers appear to be different to sporadic cases, with earlier age of onset, increased multifocality and with association with specific breast cancer histological and phenotypic subtypes. Furthermore, tumours showing homologous recombination deficiency, due to loss of BRCA1, BRCA2, PALB2 and CHEK2 function, have been shown to be especially sensitive to platinum-based chemotherapeutics and PARP inhibition. 
  • 764
  • 15 Mar 2023
Topic Review
Epothilones with Clinical Significance in Cancer
Epothilone B derivatives such as Ixabepilone and Utidelone are currently used in the clinic for the treatment of advanced breast cancer, their efficacy has been demonstrated in Phase II and III clinical trials.
  • 764
  • 06 Apr 2023
Topic Review
Immunotherapy during the Immediate Perioperative Period
Tumor excision is a necessary life-saving procedure in most solid cancers. However, surgery and the days before and following it, known as the immediate perioperative period (IPP), entail numerous prometastatic processes, including the suppression of antimetastatic immunity and direct stimulation of minimal residual disease (MRD). Thus, the IPP is pivotal in determining long-term cancer outcomes, presenting a short window of opportunity to circumvent perioperative risk factors by employing several therapeutic approaches, including immunotherapy. Nevertheless, immunotherapy is rarely examined or implemented during this short timeframe, due to both established and hypothetical contraindications to surgery. This entry summarizes existing and potential immuno-theraputic approaches to exploit the immediate perioperative period to prevent future metastatic disease.
  • 764
  • 23 Aug 2023
Topic Review
Microbiome in Cancer Development and Treatment
Targeting the microbiome, microbiota-derived metabolites, and related pathways represents a significant challenge in oncology. Microbiome analyses have confirmed the negative impact of cancer treatment on gut homeostasis, resulting in acute dysbiosis and severe complications, including massive inflammatory immune response, mucosal barrier disruption, and bacterial translocation across the gut epithelium. Moreover, recent studies revealed the relationship between an imbalance in the gut microbiome and treatment-related toxicity. Recently, microbiota modulation via probiotic supplementation and fecal microbiota transplantation represents a new trend in cancer patient care, aiming to increase bacterial diversity, alleviate acute and long-term treatment-induced toxicity, and improve the response to various treatment modalities. A more detailed understanding of the complex relationship between the microbiome and host can significantly contribute to integrating a microbiome-based approach into clinical practice. 
  • 764
  • 08 Apr 2024
Topic Review
Cancer-Associated Fibroblasts and T Cells
CAFs release a number of different factors, including chemokines, cytokines, and growth factors, that promote immunosuppression through recruitment of immunosuppressive cells such as T regulatory cells (Tregs) and myeloid cells, upregulation of immune checkpoint molecules on T cells, and regulation of T-cell migration.
  • 763
  • 30 Jun 2021
Topic Review
Selective Internal Radiation Therapy on Hepatocellular Carcinoma
Selective internal radiation therapy (SIRT) is part of the treatment strategy for hepatocellular carcinoma (HCC). Strong clinical data demonstrated the effectiveness of this therapy in HCC with a significant improvement in patient outcomes. Recent studies demonstrated a strong correlation between the tumor response and the patient outcome when the tumor-absorbed dose was assessed by nuclear medicine imaging. Dosimetry plays a key role in predicting the clinical response and can be optimized using a personalized method of activity planning (multi-compartmental dosimetry). Moreover, some patient and tumor characteristics predict a worse outcome, and toxicity related to SIRT treatment of advanced HCC patient selection based on the performance status, liver function, tumor characteristics, and tumor targeting using technetium-99m macro-aggregated albumin scintigraphy can significantly improve the clinical performance of SIRT.
  • 763
  • 12 Apr 2022
Topic Review
Egfr Mutations in Lung Cancer
Epidermal growth factor receptor (EGFR) is a transmembrane protein with cytoplasmic kinase activity that transduces important growth factor signals from the extracellular milieu to cells. Given that more than 60% of non-small cell lung cancers (NSCLC) express EGFR, EGFR has emerged as an important therapeutic target for the treatment of these tumors.
  • 763
  • 27 Jun 2022
Topic Review
Bacterial Causing Pneumonia Post Hematopoietic Stem Cell Transplant
Allogeneic stem cell transplantation is a lifesaving treatment for many malignancies. Post-transplant patients may suffer from graft versus host disease in the acute and/or the chronic form(s). Post-transplantation immune deficiency due to a variety of factors is a major cause of morbidity and mortality. Furthermore, immunosuppression can lead to alterations in host factors that predisposes these patients to infections. Although patients who receive stem cell transplant are at an increased risk of opportunistic pathogens, which include fungi and viruses, bacterial infections remain the most common cause of morbidity.
  • 763
  • 10 Jul 2023
Topic Review
Epithelial-Mesenchymal Transition
Epithelial-mesenchymal transition (EMT) is a crucial and fundamental mechanism in many cellular processes, beginning with embryogenesis via tissue remodulation and wound healing, and plays a vital role in tumorigenesis and metastasis formation. EMT is a complex process that involves many transcription factors and genes that enable the tumor cell to leave the primary location, invade the basement membrane, and send metastasis to other tissues. Moreover, it may help the tumor avoid the immune system and establish radioresistance and chemoresistance. It may also change the normal microenvironment, thus promoting other key factors for tumor survival, such as hypoxia-induced factor-1 (HIF-1) and promoting neoangiogenesis. 
  • 763
  • 21 Feb 2024
Topic Review
Necroptosis: Biological Relevance in Cancer
Necroptosis is a caspase independent form of regulated cell death, investigated as a novel therapeutic strategy to eradicate apoptosis resistant cancer cells. The process can be triggered by a variety of stimuli and is controlled by the activation of RIP kinases family as well as MLKL. The well-studied executor, RIPK1, is able to modulate key cellular events through the interaction with several proteins, acting as strategic crossroads of several molecular pathways. Little evidence is reported about the involvement of RIPK1 in tumorigenesis. Of particular interest is its contradictory role in cancer and its function in cell fate control. Targeting necroptosis might be a novel therapeutic intervention strategy in anticancer therapies as pharmacologically controllable event.
  • 761
  • 26 Feb 2021
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