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Topic Review
Timing of Metastatic Colorectal Cancer
Colorectal cancer (CRC) is the third most frequently diagnosed cancer worldwide, where ~50% of patients develop metastasis, despite current improved management. Genomic characterisation of metastatic CRC, and elucidating the effects of therapy on the metastatic process, are essential to help guide precision medicine. Multi-region whole-exome sequencing was performed on 191 sampled tumour regions of patient-matched therapy-naïve and treated CRC primary tumours (n = 92 tumour regions) and metastases (n = 99 tumour regions), in 30 patients. Somatic variants were analysed to define the origin, composition, and timing of seeding in the metastatic progression of therapy-naïve and treated metastatic CRC. High concordance, with few genomic differences, was observed between primary CRC and metastases. Most cases supported a late dissemination model, via either monoclonal or polyclonal seeding. Polyclonal seeding appeared more common in therapy-naïve metastases than in treated metastases. Whereby, treatment prompted for the selection of distinct resistant clones, through monoclonal seeding to distant metastatic sites. Overall, this study reinforces the importance of early clinical detection and surgical excision of the CRC tumour, whilst further highlighting the clinical challenges for metastatic CRC with increased intratumour heterogeneity (either due to early dissemination or polyclonal metastatic spread) and the underlying risk of future therapeutic resistance in treated patients.
  • 988
  • 20 Oct 2020
Topic Review
Hypoxia-Driven Effects in Cancer
Hypoxia, a common feature of solid tumors, greatly hinders the efficacy of conventional cancer treatments such as chemo-, radio-, and immunotherapy. The depletion of oxygen in proliferating and advanced tumors causes an array of genetic, transcriptional, and metabolic adaptations that promote survival, metastasis, and a clinically malignant phenotype. At the nexus of these interconnected pathways are hypoxia-inducible factors (HIFs) which orchestrate transcriptional responses under hypoxia. We discuss mechanisms and pathways, such as HIF signaling, mitochondrial dynamics, exosomes, and the unfolded protein response, that contribute to hypoxia-induced phenotypic changes.
  • 988
  • 02 Jun 2021
Topic Review
The HIF-1α and Gastric Cancer
Gastric cancer is one of the most aggressive tumors in the clinic that is resistant to chemotherapy. Gastric tumors are rich in hypoxic niches, and high expression of hypoxia-inducible factor-1α is associated with poor prognosis. Hypoxia is the principal architect of the topographic heterogeneity in tumors. Hypoxia-inducible factor-1α (HIF-1α) reinforces all hallmarks of cancer and donates cancer cells with more aggressive characteristics at hypoxic niches. HIF-1α potently induces sustained growth factor signaling, angiogenesis, epithelial–mesenchymal transition, and replicative immortality. Hypoxia leads to the selection of cancer cells that evade growth suppressors or apoptotic triggers and deregulates cellular energetics. HIF-1α is also associated with genetic instability, tumor-promoting inflammation, and escape from immunity. 
  • 988
  • 17 Jun 2022
Topic Review
Proanthocyanidins and Anthocyanins in Nicotine-Induced NSCLC Treatment
In traditional medicine, different parts of plants, including fruits, have been used for their anti-inflammatory and anti-oxidative properties. Plant-based foods, such as fruits, seeds and vegetables, are used for therapeutic purposes due to the presence of flavonoid compounds. Proanthocyanidins (PCs) and anthocyanins (ACNs) are the major distributed flavonoid pigments in plants, which have therapeutic potential against certain chronic diseases. PCs and ACNs derived from plant-based foods and/or medicinal plants at different nontoxic concentrations have shown anti-non-small cell lung cancer (NSCLC) activity in vitro/in vivo models through inhibiting proliferation, invasion/migration, metastasis and angiogenesis and by activating apoptosis/autophagy-related mechanisms.
  • 988
  • 02 Aug 2022
Topic Review
Carbonic Anhydrase IX for Cancer Immunotherapy
Carbonic anhydrases are metalloenzymes that reversibly catalyze the hydration of carbon dioxide, generating bicarbonate ions and protons. Several tumors, such as clear cell renal cell carcinoma (ccRCC), glioblastoma, triple-negative breast cancer, ovarian cancer, colorectal, and others overexpress carbonic anhydrase isoform IX (CAIX). The CAIX enzyme is constitutively overexpressed in the vast majority of clear cell renal cell carcinoma (ccRCC) and can also be induced in hypoxic microenvironments, a major hallmark of most solid tumors. CAIX expression is restricted to a few sites in healthy tissues, positioning this molecule as a strategic target for cancer immunotherapy.
  • 987
  • 29 Mar 2022
Topic Review
Biomarkers for Hepatocellular Carcinoma Diagnosis/Prognosis
Hepatocellular carcinoma (HCC) causes many deaths worldwide, and current treatments have limitations. Immunotherapies have shown the most promising clinical outcomes for advanced HCC. However, there are many patients with HCC who still respond poorly to these treatments. Circulating biomarkers that can easily be obtained through blood sampling are promising in predicting treatment responses, since they are minimally invasive and enable us to constantly monitor disease progression. 
  • 986
  • 28 Sep 2021
Topic Review
Structure Dynamics and Signaling of the Neurokinin-1 Receptor
Substance P (SP), the first isolated neuropeptide, belongs to the family of tachykinin peptides and is the natural ligand of neurokinin-1 receptors (NK-1R), also named SP receptors. The undecapeptide activates the receptor after specifically binding to the protein and triggers intracellular signals leading to different biochemical events and subsequent physiological responses. 
  • 986
  • 21 Oct 2022
Topic Review
Adjuvant Therapy for Renal Cell Carcinoma
Renal cell carcinoma (RCC) is the third most common genitourinary cancer accounting for approximately 180,000 deaths worldwide in 2020. Although over two-thirds of patients initially present localized disease, up to 50% of them may progress to metastatic disease. Adjuvant therapy aims to reduce the recurrence risk and improve outcomes in several types of cancers but is currently an unmet need in RCC. RCC led to the evaluation of these target therapies in an early setting with conflicting results for disease-free survival and no overall survival (OS) benefit. 
  • 986
  • 02 Mar 2023
Topic Review
Hemoptysis in Cancer Patients
Hemoptysis in cancer patients is a potentially serious symptom that requires detailed evaluation by oncologists and emergency department physicians. Timely diagnosis and appropriate management are crucial to address both the immediate concern of bleeding and the broader implications for the patient's cancer care. As hemoptysis in cancer patients indicates the presence of complications or progression of the disease, investigating the underlying cause using appropriate diagnostic procedures such as imaging studies (CT scans, bronchoscopy) and laboratory tests is vital, as it can significantly impact treatment choices and potentially alter the patient's overall prognosis. Risk stratification for cancer patients presenting with hemoptysis will support a personalized treatment approach that ensures that each patient receives tailored and effective care and identifies patients who are at a higher risk of deterioration, warranting more aggressive diagnostic and treatment plans and close, continuous monitoring for these patients.
  • 986
  • 12 Oct 2023
Topic Review
Tumor-Nerves Interactions
The interaction between neurons and a tumor are bilateral and promote metastasis on one hand, and the formation of new nerve structures (neoneurogenesis) on the other. Substances such as neurotransmitters and neurotrophins being the main actors in such interplay, it seems reasonable to expect that alternative splicing and the different populations of protein isoforms can affect tumor-derived neurogenesis. 
  • 985
  • 23 Jun 2021
Topic Review
Impact of Hesitancy on Cancer Care and COVID-19
The COVID-19 pandemic disrupted the optimal management of outpatient appointments, scheduled treatments, and hospitalizations for cancer patients because of hesitancy among patients and health-care providers. Travel restrictions and other factors likely affected medical, surgical, and radiation treatments during the COVID-19 pandemic. Cancer patients were more likely to be affected by severe illness and complications if they contracted COVID-19. A compromised immune system and comorbidities in cancer patients may have contributed to this increased risk. Hesitancy or reluctance to receive appropriate therapy or vaccination advice might have played a major role for cancer patients, resulting in health-care deficits. 
  • 985
  • 16 Jun 2023
Topic Review
Common Cardiotoxicity Manifestations
Common cardiotoxicity complications include new or worsening left ventricular ejection fraction (LVEF), QT interval prolongation, myocardial ischaemia, hypertension, thromboembolic disease, cardiac device malfunction and valve disease. Baseline electrocardiogram (ECG) and transthoracic echocardiogram (TTE) are routinely performed for all patients commenced on cardiotoxic treatment, while other imaging modalities and biochemical markers have proven useful for monitoring. Management mainly includes early risk stratification and prompt identification of cardiovascular complications, with patient-specific surveillance throughout treatment.
  • 985
  • 16 Oct 2023
Topic Review
AXL Receptor in Breast Cancer
Breast cancer was one of the first malignancies to benefit from targeted therapy, i.e., treatments directed against specific markers. Inhibitors against HER2 are a significant example and they improved the life expectancy of a large cohort of patients. Research on new biomarkers, therefore, is always current and important. AXL, a member of the TYRO-3, AXL and MER (TAM) subfamily, is, today, considered a predictive and prognostic biomarker in many tumor contexts, primarily breast cancer. Its oncogenic implications make it an ideal target for the development of new pharmacological agents; moreover, its recent role as immune-modulator makes AXL particularly attractive to researchers involved in the study of interactions between cancer and the tumor microenvironment (TME). All these peculiarities characterize AXL as compared to other members of the TAM family.
  • 984
  • 24 Nov 2020
Topic Review
Ovarian clear cell carcinoma (CCC)
Ovarian clear cell carcinoma (CCC) exhibits unique characteristics, including slow growth, glycogen accumulation in the cytoplasm, and poor prognosis for stress resistance. Several molecular targeting agents have failed to treat ovarian CCC. Recent reports have identified metabolic alterations through HNF1B, which is highly expressed in ovarian CCC. The Warburg effect, GSH synthesis, and mitochondrial regulation occur in CCC. The metabolic behaviors of ovarian CCC resemble the evolution of life to survive in stressful environments. Understanding the fundamental biology of ovarian CCC might help in the development of novel therapeutic strategies. 
  • 984
  • 08 Jun 2021
Topic Review
Colorectal cancer and bone tissue
Colorectal cancer (CRC) is the third most common cancer worldwide. There is a need for the early diagnosis of CRC for a better prognostic outcome. It is, therefore, crucial to understand the CRC pathogenesis in all its aspects. In many cases, one of the main causes of cancer-related deaths is the presence of metastases. In this context, an often overlooked aspect is the metastatic tropism, since CRC, like other cancers, is more prone to metastasize some organs rather than others. Beyond the liver and lung, and differently from other types of cancers, a not usual site of CRC metastases is the bone. However, it may assume a crucial role in the development and the outcome of the disease. Therefore, this review aims to discuss the complex relations between bone markers and CRC pathogenesis, suggesting the use of these molecules as potential targets for therapeutic purposes. Different osteogenic molecules, some of whom are growth factors and are implicated in the different osteogenic pathways, have been proved to also be involved in CRC progression. Some of them are oncogenes, while others oncosuppressors, and in a future perspective, some of them may represent new potential CRC biomarkers.
  • 983
  • 04 Aug 2020
Topic Review
Small Extracellular Vesicles
Small Extracellular Vesicles are lipid bilayer structures ranging in size from 15 to 10,000 nm, are released from almost all cells (normal and cancerous) present in body fluids, and they are considered as delivery vehicles responsible for local and distant cellular communication.
  • 983
  • 17 Dec 2020
Topic Review
Immunosuppression in Colorectal Cancer
More emerging studies are exploring immunotherapy for solid cancers, including colorectal cancer. Besides, checkpoint blockade immunotherapy and chimeric antigen receptor (CAR) -based immune cell therapy have being examined in clinical trials for colorectal cancer patients. However, immunosuppression that leads to the blockage of normal immunosurveillance often leads to cancer development and relapse.
  • 983
  • 12 Jan 2021
Topic Review
Biliary Tract Cancer Management
Biliary tract cancers (BTC) comprise a group of malignancies originating in the epithelium of the biliary tract. These include cholangiocarcinoma (CCA) and gallbladder carcinoma (GBC). Intrahepatic cholangiocarcinoma or iCCA refers to tumors proximal to the second-order ducts, while extrahepatic cholangiocarcinoma or eCCA refers to tumors arising more distally (perihilar CCA, between second-order ducts and cystic duct and distal CCA, distal to cystic duct). Perihilar CCA represents 50% of the total CCAs, with distal lesions comprising 40% and the final 10% being intrahepatic. BTC are often diagnosed at advanced stages and have a grave outcome due to limited systemic options. Gemcitabine and cisplatin combination (GC) has been the first-line standard for more than a decade. Second-line chemotherapy (CT) options are limited. Targeted therapy or TT (fibroblast growth factor 2 inhibitors or FGFR2, isocitrate dehydrogenase 1 or IDH-1, and neurotrophic tyrosine receptor kinase or NTRK gene fusions inhibitors) have had reasonable success, but <5% of total BTC patients are eligible for them. The use of immune checkpoint inhibitors (ICI) such as pembrolizumab is restricted to microsatellite instability high (MSI-H) patients in the first line. The success of the TOPAZ-1 trial (GC plus durvalumab) is promising, with numerous trials underway that might soon bring targeted therapy (pemigatinib and infrigatinib) and ICI combinations (with CT or TT in microsatellite stable cancers) in the first line.
  • 983
  • 20 May 2022
Topic Review
Representative Applications of Conjugated Nanomedicine
Chemotherapy is one of the standard methods for the clinical treatment of malignant tumors. Due to the heterogeneity of tumors and the complexity of their pathological mechanisms, a single chemotherapeutic drug is usually unable to eradicate cancer cells. It may also encounter some problems, such as toxic side effects induced by high doses of drugs and obtaining multidrug resistance (MDR) after repeated treatment. These problems then increase the likelihood of cancer metastasis or recurrence. The emergence of the combination of multiple antineoplastic drugs makes up for the deficiency of single drug application. Accordingly, the overall treatment benefit of the multidrug combination is usually higher than that of single drug administration by virtue of different therapeutic mechanisms. More importantly, the drug dose used during synergistic therapy usually decreases and the unfavorable side effects could be weakened under the premise of the same or better therapeutic efficacy. Thereinto, conjugated nanomedicine, as an important type of nanomedicine, can not only possess the targeted delivery of chemotherapeutics with great precision but also achieve controlled drug release to avoid adverse effects. Meanwhile, conjugated nanomedicine provides the platform for combining several different therapeutic approaches (chemotherapy, photothermal therapy, photodynamic therapy, thermodynamic therapy, immunotherapy, etc.) with the purpose of achieving synergistic effects during cancer treatment.
  • 982
  • 09 Aug 2022
Topic Review
Peptide Receptor Radionuclide Therapy
The PRRT (Peptide Receptor Radionuclide Therapy) is a promising modality treatment for patients with inoperable or metastatic neuroendocrine tumors (NETs). Progression-free survival (PFS) and overall survival (OS) of these patients are favorably comparable with standard therapies. The protagonist in this type of therapy is a somatostatin-modified peptide fragment ([Tyr3] octreotide), equipped with a specific chelating system (DOTA) capable of creating a stable bond with β-emitting radionuclides, such as yttrium-90 and lutetium-177.
  • 982
  • 04 Oct 2021
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