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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.
  • 789
  • 09 Aug 2021
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.
  • 788
  • 02 Nov 2020
Topic Review
Novel hybrid IGP before Esophagectomy
Esophagectomy has a high rate of anastomotic complications thought to be caused by poor perfusion of the gastric graft, which is used to restore the continuity of the gastrointestinal tract. Ischemic gastric preconditioning (IGP), performed by partially destroying preoperatively the gastric vessels either by means of interventional radiology or surgically, might improve the gastric conduit perfusion. Both approaches have downsides. The timing, extent and mechanism of IGP remain unclear. A novel hybrid IGP method combining the advantages of the endovascular and surgical approach was introduced in this study. IGP improves unequivocally the mucosal and serosal blood-flow at the gastric conduit fundus by triggering new vessels formation. The proposed timing and extent of IGP were efficacious and might be easily applied to humans. This novel minimally invasive IGP technique might reduce the anastomotic leak rate of patients undergoing esophagectomy, thus improving their overall oncological outcome.
  • 788
  • 23 Oct 2020
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.
  • 788
  • 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. 
  • 788
  • 05 Jun 2023
Topic Review
Gold Nanoparticles for Cancer Theragnosis
Research on cancer theragnosis with gold nanoparticles (AuNPs) has rapidly increased, as AuNPs have many useful characteristics for various biomedical applications, such as biocompatibility, tunable optical properties, enhanced permeability and retention (EPR), localized surface plasmon resonance (LSPR), photothermal properties, and surface enhanced Raman scattering (SERS). AuNPs have been widely utilized in cancer theragnosis, including phototherapy and photoimaging, owing to their enhanced solubility, stability, biofunctionality, cancer targetability, and biocompatibility.
  • 787
  • 02 Nov 2020
Topic Review
Next-Generation Target for Cancer Immunotherapy
The most successful strategies for solid cancer immunotherapy have centered on targeting the co-stimulatory and co-inhibitory T cell molecules that regulate T cell activation. Although immunotherapy that targets surface receptors such as CTLA-4 and/or PD-1 with recombinant antibodies has been a game changer for cancer treatment, a sizeable subset of patients still fail to respond to, and even fewer patients are cured by, these therapy regimens. The identification of alternate and potentially additive immune checkpoint candidates is intended to improve immunotherapies for a large number of cancer patients. Therefore, we focused on checkpoints located inside immune cells as suitable targets for future cancer drugs. We demonstrated, in recent years, the crucial T lymphocyte-intrinsic role of the orphan nuclear receptor NR2F6 as an intracellular checkpoint in fine-tuning adaptive immunity. NR2F6 induced an anti-inflammatory signal in the T cell compartment.
  • 787
  • 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.
  • 786
  • 23 Jun 2021
Topic Review
Protein SUMOylation in Human Hepatocellular Carcinoma
Small ubiquitin-like modifier (SUMO) is a highly conserved post-translational modification protein, mainly found in eukaryotes. They are widely expressed in different tissues, including the liver. As an essential post-translational modification, SUMOylation is involved in many necessary regulations in cells. It plays a vital role in DNA repair, transcription regulation, protein stability and cell cycle progression. Increasing shreds of evidence show that SUMOylation is closely related to Hepatocellular carcinoma (HCC). 
  • 786
  • 15 Nov 2021
Topic Review
SARS-CoV-2 Vaccination: The Real Turning Point
The SARS-CoV-2 vaccine has recently emerged as the main weapon to fight the COVID-19 pandemic. The various candidate anti-SARS-CoV-2 vaccines can be grouped according to the technological platform used to their development in order to elicit a protective immune response.
  • 786
  • 02 Jun 2022
Topic Review
The Effects of Radiation on Toll-Like Receptors
Toll-like receptors (TLRs) are indispensable for the activation, maintenance and halting of immune responses. TLRs can mediate inflammation by recognizing molecular patterns in microbes (pathogen-associated molecular patterns: PAMPs) and endogenous ligands (danger-associated molecular patterns: DAMPs) released by injured or dead cells. For this reason, TLR ligands have attracted much attention in recent years in many cancer vaccines, alone or in combination with immunotherapy, chemotherapy and radiotherapy (RT). 
  • 786
  • 18 Apr 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.
  • 786
  • 20 Nov 2023
Topic Review
BRAF Mutation in Cutaneous Melanoma
In advanced melanoma, BRAF mutation testing is critical in predicting treatment response with targeted therapy (i.e., BRAF/MEK inhibitors). Certain features were identified in melanomas that harbor BRAF mutations (e.g., primary lesions located on the trunk, diagnosed in patients <50, visibly pigmented tumors and, at times, with ulceration or specific dermatoscopic features). For select advanced melanoma patients, delays in determining mutational status present a significant barrier to the prompt initiation of treatment.  This can adversely impact patient outcomes, especially in the metastatic setting due to a rapidly progressive disease. Treatment in these cases needs to start promptly by a medical oncologist. Ordering BRAF testing by preceding members of the treating team will allow medical oncologists to initiate treatment at the first visit. According to poor survival outcomes, we propose that patients with thick tumors (>4.0 mm) or >2 mm tumors with ulceration (i.e., stage ≥IIB) should potentially be considered for systemic therapy, thus justifying reflex BRAF testing.
  • 785
  • 22 Sep 2021
Topic Review
Endostatin and Cancer Therapy
Endostatin constitutes one of the most studied peptides with inhibitory effect on angiogenesis. This peptide is a 20 kDa C-terminal cleavage fragment from the α1 chain of type XVIII collagen, which is an extracellular matrix protein recognized for its anti-atherosclerotic effect as well as a potent inhibitor of angiogenesis. Endostatin has been artificially synthesized in a recombinant human form with the addition of nine extra amino acids that confer greater stability, solubility, and antiangiogenic effect. The endostatin mechanism of action is not completely understood. Evidence shows that this molecule exerts its angiostatic effect through multiple mechanisms involving elements of the extracellular matrix, as well as proteins and signaling cascades related to endothelial cell migration and proliferation.
  • 785
  • 10 Mar 2023
Topic Review
Polycomb-like Proteins in Gene Regulation and Cancer
Polycomb-like proteins (PCLs) are a crucial group of proteins associated with the Polycomb repressive complex 2 (PRC2) and are responsible for setting up the PRC2.1 subcomplex. In the vertebrate system, three homologous PCLs exist: PHF1 (PCL1), MTF2 (PCL2), and PHF19 (PCL3). Although the PCLs share a similar domain composition, they differ significantly in their primary sequence. PCLs play a critical role in targeting PRC2.1 to its genomic targets and regulating the functionality of PRC2. However, they also have PRC2-independent functions. In addition to their physiological roles, their dysregulation has been associated with various human cancers.
  • 785
  • 15 Jun 2023
Topic Review
Immunmodulatory Treatment Strategies of HCC
Hepatocellular carcinoma (HCC) still represents a human tumor entity with very limited therapeutic options, especially for advanced stages. Here, immune checkpoint modulating drugs alone or in combination with local ablative techniques could open a new and attractive therapeutic “door” to improve outcome and response rate for patients with HCC.
  • 784
  • 05 May 2021
Topic Review
Risk Factors for Pancreatic Cancer
Pancreatic cancer is one of the most aggressive malignant neoplastic diseases. The incidence and mortality rates of this disease vary depending on geographical area, which might be explained by the different exposure to risk factors. Currently, the risk factors for pancreatic cancer fall into two broad categories, namely extrinsic and intrinsic factors. Extrinsic factors include alcohol consumption, smoking, a diet rich in saturated fats, and viral infections such as chronic infection with hepatitis B and C viruses. The pathophysiological mechanisms explaining how these hepatotropic viruses contribute to the development of pancreatic cancer are not fully elucidated. The common origin of hepatocytes and pancreatic cells in the multipotent endodermal cells, the common origin of the blood vessels and biliary ducts of the pancreas and the liver, or chronic inflammatory changes may be involved in this interaction.
  • 784
  • 19 Apr 2022
Topic Review
An Alternative Model of Cancer-Related Fatigue
The most notable framework previously proposed to describe complex disease processes is the biopsychosocial model, an inter-disciplinary model that looks at the interconnection between biology, psychology, and socioenvironmental factors. While the biopsychosocial model has played a crucial role in counteracting biological reductionism and progressing towards a more holistic philosophy of human health, it lacks the granularity necessary to understand how various factors contribute to disease. In contrast, the 3P model can be utilized to describe the complex biological and psychological processes underlying cancer-related fatigue. The 3P model postulates that predisposing factors place patients at risk of developing baseline fatigue (e.g., 1. biobehavioral: age, biological sex, genetic variants, metabolomics, inflammation, body composition, nutritional quality, circadian disruption, and co-morbidities; 2. psychosocial: depressed mood, anxiety, insomnia, and perceived stress); precipitating factors spur the onset of fatigue (e.g., changes in metabolism and inflammation due to cancer and/or chemotherapy and treatment-related factors: systemic therapy and radiotherapy); and perpetuating factors worsen fatigue or cause it to become chronic (e.g., poor sleep, physical inactivity, and poor diet). The 3P model has been suggested for better understanding fatigue and successfully applied to other chronic conditions including sleep and pain. 
  • 784
  • 29 Apr 2022
Topic Review
Immunotherapy Drugs and Combinations of HNCSCC
Cutaneous squamous cell carcinoma (CSCC) is the second most common non-melanoma skin cancer. A majority of patients present with localized disease, but some can present with locally advanced or metastatic disease. Most of these advanced cases occur in the anatomical head and neck region and are associated with more aggressive disease, necessitating prompt and effective treatment. Prior to the emergence of immunotherapy, systemic treatment options were limited to platinum-based chemotherapy and salvaged with targeted epidermal growth factor therapy. These therapies were associated with poor efficacy and increased toxicity in an often frail, older population. Immunotherapy has dramatically improved outcomes in this patient population due to its favorable side effect profile, durable treatment response, and improved overall outcomes. 
  • 784
  • 29 Jan 2023
Topic Review
Immune Checkpoints as Biomarkers of Gastric Cancer
To increase the effectiveness of anticancer therapy based on immune checkpoint (IC) inhibition, some ICs are being investigated in addition to those used in clinic. Increased expression of the most studied ICs—PD-L1, B7-H3, and B7-H4—is associated with poor survival; their inhibition is clinically significant. Expression of IDO1, CD155, and ADAM17 is also associated with poor survival, including gastric cancer (GC). The available data indicate that CD155 and ADAM17 are promising targets for immune therapy. However, the clinical trials of anti-IDO1 antibodies have been unsatisfactory. Expression of Galectin-3 and -9, CEACAM1 and Siglec-15 demonstrates a contradictory relationship with patient survival. In conclusion, in many cases it is important to analyze the expression of other participants of the immune response besides target IC. The PD-L1, B7-H3, B7-H4, IDO1 and ADAM17 may be considered as candidates for prognosis markers for GC patient survival.
  • 783
  • 29 Mar 2022
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