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Topic Review
Protein Kinase C in NSCLC
Despite significant advances, targeted therapy is greatly limited by resistance acquisition, which emerges in nearly all patients receiving treatment. As a result, identifying the molecular modulators of resistance is of great interest. Recent work has implicated protein kinase C (PKC) isozymes as mediators of drug resistance in non-small cell lung cancer (NSCLC). Importantly, previous findings on PKC have implicated this family of enzymes in both tumor-promotive and tumor-suppressive biology in various tissues. Here, we review the biological role of PKC isozymes in NSCLC through extensive analysis of cell-line-based studies to better understand the rationale for PKC inhibition.
  • 978
  • 22 Sep 2021
Topic Review
Normalizing Tumor Vasculature
A basic requirement of tumorigenesis is the development of a vascular network to support the metabolic requirements of tumor growth and metastasis. Tumor vascular formation is regulated by a balance between promoters and inhibitors of angiogenesis. Typically, the pro-angiogenic environment created by the tumor is extremely aggressive, resulting in the rapid vessel formation with abnormal, dysfunctional morphology. The altered morphology and function of tumor blood and lymphatic vessels has numerous implications including poor perfusion, tissue hypoxia, and reduced therapy uptake. Targeting tumor angiogenesis as a therapeutic approach has been pursued in a host of different cancers. Although some preclinical success was seen, there has been a general lack of clinical success with traditional anti-angiogenic therapeutics as single agents. Typically, following anti-angiogenic therapy, there is remodeling of the tumor microenvironment and widespread tumor hypoxia, which is associated with development of therapy resistance. A more comprehensive understanding of the biology of tumor angiogenesis and insights into new clinical approaches, including combinations with immunotherapy, are needed to advance vascular targeting as a therapeutic area. 
  • 978
  • 17 Sep 2021
Topic Review
Breast Cancer-Associated Fibroblasts
Breast cancer-associated fibroblasts (BCAFs) are the CAFs present in breast cancers with genetic and phenotypic characteristics similar to CAFs. CAFs originate from a diverse range of cells, including endothelial cells, adipocytes, pericytes, and MSCs. Although CAFs were derived from endothelial cells and pericytes, the derivation was not tested in breast cancer models similar to other cancers. BCAFs have also been derived from adipocytes that lead to a desmoplastic microenvironment. BCAFs can originate from MSCs, which contribute to angiogenesis through up-regulation of clusterin leading to tumorigenesis. BCAFs possess the fibrillar collagen receptor, DDR2, which rearranges collagen fibers to develop an invasive and metastatic TME. Additionally, integrin α11 in BCAFs interacts with platelet-derived growth factor receptor beta (PDGFRβ) and promotes invasiveness by activating c-Jun N-terminal kinase (JNK) and producing a matricellular protein, tenascin C.
  • 978
  • 14 Jan 2022
Topic Review
Golgi Dynamics in Cancer Metastasis
The Golgi apparatus is at the center of protein processing and trafficking in normal cells. Under pathological conditions, such as in cancer, aberrant Golgi dynamics alter the tumor microenvironment and the immune landscape, which enhances the invasive and metastatic potential of cancer cells. Among these changes in the Golgi in cancer include altered Golgi orientation and morphology that contribute to atypical Golgi function in protein trafficking, post-translational modification, and exocytosis. Golgi-associated gene mutations are ubiquitous across most cancers and are responsible for modifying Golgi function to become pro-metastatic. The pharmacological targeting of the Golgi or its associated genes has been difficult in the clinic; thus, studying the Golgi and its role in cancer is critical to developing novel therapeutic agents that limit cancer progression and metastasis.
  • 978
  • 31 May 2022
Topic Review
C-Terminal CPE in Brain Metastasis from Breast Cancer
Brain metastasis occurs in primary cancers, such as breast cancer, and is correlated with mortality. There are limited options available for treatment, but Clostridium perfringens Enterotoxin (CPE) and its interaction with Claudin-4, a possible diagnostic biomarker for breast cancer, can provide a molecular pathway basis for the development of treatment options for metastatic brain cancer. 
  • 977
  • 22 Sep 2022
Topic Review
Surgical Approaches to Neuroblastoma
Neuroblastoma (NB) is the most commonly occurring soft-tissue malignancy of childhood. Surgery plays an important role in multidisciplinary treatment and its principal aim is a local control of the disease, respecting the integrity of the surrounding structures. There is no unanimous consensus on the best surgical technique, and the operative approach largely depends on the anatomical location and the extension of the mass. To have a complete overview of the different type of treatment, we made a review of the literature from the last twenty years of all the surgical approaches applied for NBs resection, accordingly to the anatomical site.
  • 976
  • 23 Jun 2021
Topic Review
Radiotherapy Considerations for Nasopharyngeal Carcinoma
Radiotherapy is the primary treatment modality for nasopharyngeal carcinoma (NPC). Successful curative treatment requires optimal radiotherapy planning and precise beam delivery that maximizes locoregional control while minimizing treatment-related side effects.
  • 976
  • 06 Feb 2023
Topic Review
Pancreatic Cancer with Mutation
Pancreatic ductal adenocarcinoma (PDAC) is the seventh leading cause of cancer death worldwide; most of cases are sporadic, however about 5% to 10% report a hereditary predisposition. Several hereditary syndromes have been associated with familial pancreatic cancer (FPC) onset, including hereditary breast and ovarian cancer syndrome (HBOC), Lynch syndrome (LS), Familial atypical multiple mole melanoma (FAMMM), Familial adenomatous polyposis (FAP), Li–Fraumeni syndrome (LFS), Peutz–Jeghers syndrome (PJS), and Hereditary pancreatitis (HP).
  • 976
  • 22 Feb 2022
Topic Review
TNBC Histological Subtypes with a Favourable Prognosis
Triple-negative breast cancers (TNBC), as a group of tumours, have a worse prognosis than stage-matched non-TNBC and lack the benefits of routinely available targeted therapy. However, TNBC is a heterogeneous group of neoplasms, which includes some special type carcinomas with a relatively indolent course.
  • 974
  • 29 Mar 2022
Topic Review
DNA-Dependent Protein Kinase Catalytic Subunit
The DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is a key component of the DNA-PK complex that has a well-characterized function in the non-homologous end-joining repair of DNA double-strand breaks. Since its identification, a large body of evidence has demonstrated that DNA-PKcs is frequently overexpressed in cancer, plays a critical role in tumor development and progression, and is associated with poor prognosis of cancer patients.
  • 973
  • 23 Jan 2021
Topic Review
Combination Therapy of Prostate/Breast Cancer
Combinations of radionuclide therapy (RT) and targeted radionuclide therapy (TRT) with other therapies with distinct mechanisms of action represent a promising strategy. As for prostate cancer and breast cancer, the two most prevalent cancer types worldwide, several combination-based therapies have been evaluated. 
  • 973
  • 31 May 2021
Topic Review
SCCHN
Squamous cell carcinoma of the head and neck (SCCHN) is a complex group of malignancies, posing several challenges to treating physicians.
  • 972
  • 02 Jun 2021
Topic Review
Tumor Microenvironment in Basal and Squamous Cell Carcinoma
It is widely known that tumor cells of basal and squamous cell carcinoma interact with the cellular and acellular components of the tumor microenvironment to promote tumor growth and progression. While this environment differs for basal and squamous cell carcinoma, the cellular players within both create an immunosuppressed environment by downregulating effector CD4+ and CD8+ T cells and promoting the release of pro-oncogenic Th2 cytokines. Understanding the crosstalk that occurs within the tumor microenvironment has led to the development of immunotherapeutic agents, including vismodegib and cemiplimab to treat BCC and SCC, respectively.
  • 972
  • 11 May 2023
Topic Review
IDH Mutations in Chondrosarcoma
Chondrosarcomas are malignant cartilage-producing tumours that frequently harbour isocitrate dehydrogenase 1 and -2 (IDH) gene mutations. Several studies have confirmed that these mutations are key players in the early stages of cartilage tumour development, but their role in later stages remains ambiguous. The prognostic value of the IDH mutation in chondrosarcoma seems controversial and (pre)clinical studies that have focused on the direct and indirect targeting of the IDH mutation have not yielded novel treatment strategies.
  • 971
  • 21 Aug 2023
Topic Review
Chromatin Regulator SPEN/SHARP in Cancer
Enzymes, such as histone methyltransferases and demethylases, histone acetyltransferases and deacetylases, and DNA methyltransferases are known as epigenetic modifiers that are often implicated in tumorigenesis and disease. One of the best-studied chromatin-based mechanism is X chromosome inactivation (XCI), a process that establishes facultative heterochromatin on only one X chromosome in females and establishes the right dosage of gene expression. The specificity factor for this process is the long non-coding RNA Xinactivespecifictranscript (Xist), which is upregulated from one X chromosome in female cells. Subsequently, Xist is bound by the corepressor SHARP/SPEN, recruiting and/or activating histone deacetylases (HDACs), leading to the loss of active chromatin marks such as H3K27ac. In addition, polycomb complexes PRC1 and PRC2 establish wide-spread accumulation of H3K27me3 and H2AK119ub1 chromatin marks. The lack of active marks and establishment of repressive marks set the stage for DNA methyltransferases (DNMTs) to stably silence the X chromosome.
  • 970
  • 25 May 2021
Topic Review
Immunotherapy in Glioblastoma
Glioblastoma is the most frequent and the most aggressive brain tumor. Even with the most current treatment, its prognosis remains dismal. Immunotherapies, novel cancer therapies using the patient’s own immune system to fight cancer, have revolutionized the treatment of numerous cancer types and generate great hope for glioblastoma. In this review, we analyze the challenges immunotherapy is facing in glioblastoma, present the different immunotherapy approaches with corresponding key clinical trial findings, and finally discuss limitations and how they might be overcome. Proof of efficacy for immunotherapies remains to be demonstrated in glioblastoma, but novel combinatorial approaches remain promising.
  • 970
  • 29 Mar 2022
Topic Review
The Role of Biomarkers in Adrenocortical Carcinoma
Adrenocortical carcinoma (ACC) is a rare endocrine malignancy arising from the adrenal cortex often with unexpected biological behavior. It can occur at any age, with two peaks of incidence: in the first and between fifth and seventh decades of life. Although ACC are mostly hormonally active, precursors and metabolites, rather than end products of steroidogenesis are produced by dedifferentiated and immature malignant cells.
  • 970
  • 16 Feb 2023
Topic Review
Fructose Consumption and Hepatocellular Carcinoma Promotion
Hepatocellular carcinoma (HCC) accounts for 85% of primary liver cancer, the third most common cause of cancer-related deaths worldwide. Its incidence has been increasing in both men and women. In Western countries, high-calorie diets, mainly rich in carbohydrates such as fructose, represent a significant concern due to their repercussions on the population's health. A high fructose diet is related to the development of Metabolic Associated Fatty Liver Disease (MAFLD), formerly named Non-Alcoholic Fatty Liver Disease (NAFLD), and the progression of HCC since it potentiates the lipogenic pathway and the accumulation of lipids. However, fructose metabolism seems to be different between the stages of the disease, carrying out a metabolic reprogramming to favor the proliferation, inflammation, and metastatic properties of cancer cells in HCC. This review focuses on a better understanding of fructose metabolism in both scenarios: MAFLD and HCC.
  • 969
  • 23 Nov 2021
Topic Review
Cell-Free DNA and Bladder Cancer
Bladder cancer (BC) is the 10th most frequent cancer in the world. The initial diagnosis and surveillance of BC require a combination of invasive and non-invasive methods, which are costly and suffer from several limitations. Cystoscopy with urine cytology and histological examination presents the standard diagnostic approach. Various biomarkers (e.g., proteins, genes, and RNAs) have been extensively studied in relation to BC.
  • 969
  • 24 Nov 2022
Topic Review
Application of Plasma Proteome Signature in Breast Cancer
The prognostic impact of plasma protein biomarkers in breast cancer patients treated with neoadjuvant chemotherapy (NCT) was evaluated using a proteomics approach. Three biomarkers were identified among differentially expressed proteins. The plasma concentration of APOC3 was higher in the pathological complete response (pCR) group, whereas MBL2, ENG, and P4HB were upregulated in the non-pCR group.
  • 968
  • 28 Dec 2021
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