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Cancers, Volume 10, Issue 2 (February 2018)

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Cover Story (view full-size image) Pancreatic ductal adenocarcinoma (PDAC) is characterized by a very dense and highly organized tumor [...] Read more.
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Open AccessFeature PaperArticle Respiratory-Gated Proton Beam Therapy for Hepatocellular Carcinoma Adjacent to the Gastrointestinal Tract without Fiducial Markers
Received: 29 January 2018 / Revised: 16 February 2018 / Accepted: 19 February 2018 / Published: 21 February 2018
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Abstract
The efficacy of proton beam therapy (PBT) for hepatocellular carcinoma (HCC) has been reported, but insertion of fiducial markers in the liver is usually required. We evaluated the efficacy and toxicity of respiratory-gated PBT without fiducial markers for HCC located within 2 cm
[...] Read more.
The efficacy of proton beam therapy (PBT) for hepatocellular carcinoma (HCC) has been reported, but insertion of fiducial markers in the liver is usually required. We evaluated the efficacy and toxicity of respiratory-gated PBT without fiducial markers for HCC located within 2 cm of the gastrointestinal tract. From March 2011 to December 2015 at our institution, 40 patients were evaluated (median age, 72 years; range, 38–87 years). All patients underwent PBT at a dose of 60 to 80 cobalt gray equivalents (CGE) in 20 to 38 fractions. The median follow-up period was 19.9 months (range, 1.2–72.3 months). The median tumor size was 36.5 mm (range, 11–124 mm). Kaplan–Meier estimates of the 2-year overall survival, progression-free survival, and local tumor control rates were 76%, 60%, and 94%, respectively. One patient (2.5%) developed a grade 3 gastric ulcer and one (2.5%) developed grade 3 ascites retention; none of the remaining patients developed grade >3 toxicities (National Cancer Institute Common Terminology Criteria for Adverse Events ver. 4.0.). This study indicates that PBT without fiducial markers achieves good local control without severe treatment-related toxicity of the gastrointestinal tract for HCC located within 2 cm of the gastrointestinal tract. Full article
(This article belongs to the Special Issue Proton and Carbon Ion Therapy)
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Open AccessReview Recommendations and Choices for BRCA Mutation Carriers at Risk for Ovarian Cancer: A Complicated Decision
Received: 7 December 2017 / Revised: 14 February 2018 / Accepted: 16 February 2018 / Published: 21 February 2018
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Abstract
Current ovarian cancer screening guidelines in high-risk women vary according to different organizations. Risk reducing surgery remains the gold standard for definitive treatment in BRCA mutation carriers, but research advancements have created more short-term options for patients to consider. The decisions involved in
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Current ovarian cancer screening guidelines in high-risk women vary according to different organizations. Risk reducing surgery remains the gold standard for definitive treatment in BRCA mutation carriers, but research advancements have created more short-term options for patients to consider. The decisions involved in how a woman manages her BRCA mutation status can cause a great deal of stress and worry due to the imperfect therapy options. The goal of this review was to critically analyze the screening recommendations and alternative options for high-risk ovarian cancer patients and evaluate how these discrepancies and choices affect a woman’s management decisions. Full article
Open AccessReview Cancer Stem Cells, Bone and Tumor Microenvironment: Key Players in Bone Metastases
Received: 5 December 2017 / Revised: 12 February 2018 / Accepted: 17 February 2018 / Published: 20 February 2018
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Abstract
Tumor mass is constituted by a heterogeneous group of cells, among which a key role is played by the cancer stem cells (CSCs), possessing high regenerative properties. CSCs directly metastasize to bone, since bone microenvironment represents a fertile environment that protects CSCs against
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Tumor mass is constituted by a heterogeneous group of cells, among which a key role is played by the cancer stem cells (CSCs), possessing high regenerative properties. CSCs directly metastasize to bone, since bone microenvironment represents a fertile environment that protects CSCs against the immune system, and maintains their properties and plasticity. CSCs can migrate from the primary tumor to the bone marrow (BM), due to their capacity to perform the epithelial-to-mesenchymal transition. Once in BM, they can also perform the mesenchymal-to-epithelial transition, allowing them to proliferate and initiate bone lesions. Another factor explaining the osteotropism of CSCs is their ability to recognize chemokine gradients toward BM, through the CXCL12–CXCR4 axis, also known to be involved in tumor metastasis to other organs. Moreover, the expression of CXCR4 is associated with the maintenance of CSCs’ stemness, and CXCL12 expression by osteoblasts attracts CSCs to the BM niches. CSCs localize in the pre-metastatic niches, which are anatomically distinct regions within the tumor microenvironment and govern the metastatic progression. According to the stimuli received in the niches, CSCs can remain dormant for long time or outgrow from dormancy and create bone lesions. This review resumes different aspects of the CSCs’ bone metastastic process and discusses available treatments to target CSCs. Full article
(This article belongs to the Special Issue Targeting Bone Metastasis in Cancer)
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Open AccessFeature PaperArticle Towards a Clinical Decision Support System for External Beam Radiation Oncology Prostate Cancer Patients: Proton vs. Photon Radiotherapy? A Radiobiological Study of Robustness and Stability
Received: 27 November 2017 / Revised: 19 January 2018 / Accepted: 14 February 2018 / Published: 18 February 2018
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Abstract
We present a methodology which can be utilized to select proton or photon radiotherapy in prostate cancer patients. Four state-of-the-art competing treatment modalities were compared (by way of an in silico trial) for a cohort of 25 prostate cancer patients, with and without
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We present a methodology which can be utilized to select proton or photon radiotherapy in prostate cancer patients. Four state-of-the-art competing treatment modalities were compared (by way of an in silico trial) for a cohort of 25 prostate cancer patients, with and without correction strategies for prostate displacements. Metrics measured from clinical image guidance systems were used. Three correction strategies were investigated; no-correction, extended-no-action-limit, and online-correction. Clinical efficacy was estimated via radiobiological models incorporating robustness (how probable a given treatment plan was delivered) and stability (the consistency between the probable best and worst delivered treatments at the 95% confidence limit). The results obtained at the cohort level enabled the determination of a threshold for likely clinical benefit at the individual level. Depending on the imaging system and correction strategy; 24%, 32% and 44% of patients were identified as suitable candidates for proton therapy. For the constraints of this study: Intensity-modulated proton therapy with online-correction was on average the most effective modality. Irrespective of the imaging system, each treatment modality is similar in terms of robustness, with and without the correction strategies. Conversely, there is substantial variation in stability between the treatment modalities, which is greatly reduced by correction strategies. This study provides a ‘proof-of-concept’ methodology to enable the prospective identification of individual patients that will most likely (above a certain threshold) benefit from proton therapy. Full article
(This article belongs to the Special Issue Proton and Carbon Ion Therapy)
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Open AccessReview Advanced EUS Guided Tissue Acquisition Methods for Pancreatic Cancer
Received: 8 December 2017 / Revised: 9 February 2018 / Accepted: 11 February 2018 / Published: 17 February 2018
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Abstract
Pancreas cancer is a lethal cancer as the majority patients are diagnosed at an advanced incurable stage. Despite improvements in diagnostic modalities and management strategies, including surgery and chemotherapies, the outcome of pancreas cancer remains poor. Endoscopic ultrasound (EUS) is an important imaging
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Pancreas cancer is a lethal cancer as the majority patients are diagnosed at an advanced incurable stage. Despite improvements in diagnostic modalities and management strategies, including surgery and chemotherapies, the outcome of pancreas cancer remains poor. Endoscopic ultrasound (EUS) is an important imaging tool for pancreas cancer. For decades, resected pancreas cancer and other cancer specimens have been used to identify tissue biomarkers or genomics for precision therapy; however, only 20% of patients undergo surgery, and thus, this framework is not useful for unresectable pancreas cancer. With advancements in needle technologies, tumor specimens can be obtained at the time of tissue diagnosis. Tumor tissue can be used for development of personalized cancer treatment, such as performing whole exome sequencing and global genomic profiling of pancreas cancer, development of tissue biomarkers, and targeted mutational assays for precise chemotherapy treatment. In this review, we discuss the recent advances in tissue acquisition of pancreas cancer. Full article
(This article belongs to the Special Issue Latest Development in Pancreatic Cancer)
Open AccessArticle A Phase I/II Study Targeting Angiogenesis Using Bevacizumab Combined with Chemotherapy and a Histone Deacetylase Inhibitor (Valproic Acid) in Advanced Sarcomas
Received: 1 January 2018 / Revised: 13 February 2018 / Accepted: 14 February 2018 / Published: 17 February 2018
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Abstract
Epigenetic events and genetic alterations under the control of the tumor microenvironment potentially mediate tumor induced angiogenesis involved in soft tissue sarcoma (STS) metastasis. Addition of antiangiogenic agent, such as bevacizumab, to standard chemotherapy in treatment of sarcoma has been studied in clinical
[...] Read more.
Epigenetic events and genetic alterations under the control of the tumor microenvironment potentially mediate tumor induced angiogenesis involved in soft tissue sarcoma (STS) metastasis. Addition of antiangiogenic agent, such as bevacizumab, to standard chemotherapy in treatment of sarcoma has been studied in clinical trials, but most of the findings have not supported its use. We hypothesized the existence of an epigenetically mediated “angiogenic switch”, and the tumor microenvironment, prevents bevacizumab from truly blocking angiogenesis. The addition of valproic acid (VPA), a weak histone deacetylase inhibitor, and bevacizumab, a monoclonal antibody against vascular endothelial growth factor, together with the cytotoxic effects of gemcitabine and docetaxel, may enhance responses and alter chemoresistance. This was designed as a phase I/II trial with primary endpoints including safety of the treatment combination and tumor response. Unresectable or metastatic sarcoma patients >18 years of age, irrespective of number of prior treatments, received VPA 40 mg/kg orally for 5 days prior to day 1, bevacizumab at 15 mg/kg IV on day 1, gemcitabine 900 mg/m2 (day 1, day 8), and docetaxel 75 mg/m2 (day 8). Cycles were of 28 day duration. Bevacizumab and VPA were continued as maintenance after 6 cycles, until disease progression. A standard 3 + 3 phase I dose de-escalation design was utilized to evaluate safety. Gain of function p53 gene mutation testing was performed on available archival tissue specimens. A total of 46 patients (30 female, 16 male) with median age of 60 (range 24–81) years were enrolled; 34 (73.9%) patients received prior chemotherapy, 14 (30%) of which received prior gemcitabine and docetaxel. Patients received a median of 5.5 cycles (range 0–24 of treatment (min 0, one patient died prior to completing the first cycle; max: 24, one patient received 6 cycles and 18 maintenance cycles before progressing). Seventeen patients underwent dose reduction, of which VPA was reduced in 6 patients. Forty-one patients were evaluable for response. There was a confirmed complete response in 1 (epithelioid sarcoma), and a partial response (PR) in 6 (1 carcinosarcoma, 2 extrauterine leiomyosarcoma (LMS), 2 undifferentiated pleomorphic sarcoma, and 1 uterine LMS) patients. Stable disease (SD) was seen in 21 patients for at least 2 months. One subject with prior gemcitabine and docetaxel had PR, and 7 had SD. Median progression-free survival (PFS) was 5.7 months (95% CI: 2.1–8.0), and overall survival (OS) was 12.9 months (95% CI: 8.3–14.5). Three patients died due to tumor progression while on the study. The combination of VPA, bevacizumab, gemcitabine, and docetaxel appears to be moderately safe and well tolerated. Given that there are very limited options for patients with relapsed refractory STS, this drug combination may be an important therapy to consider. This combination treatment deserves further investigation in epithelioid and carcinosarcoma subtypes. Full article
(This article belongs to the Special Issue Epigenetic Influence on Cancer Metastasis and/or Treatment Resistance)
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Open AccessEditorial The Epithelial-to-Mesenchymal Transition in Cancer
Received: 11 February 2018 / Revised: 13 February 2018 / Accepted: 13 February 2018 / Published: 16 February 2018
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Abstract
The epithelial-to-mesenchymal transition (EMT) occurs during normal embryonic development, tissue regeneration, organ fibrosis, and wound healing.[...] Full article
(This article belongs to the Special Issue The Epithelial-to-Mesenchymal Transition (EMT) in Cancer)
Open AccessReview Next Generation Immunotherapy for Pancreatic Cancer: DNA Vaccination is Seeking New Combo Partners
Received: 15 January 2018 / Revised: 7 February 2018 / Accepted: 14 February 2018 / Published: 16 February 2018
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Abstract
Pancreatic Ductal Adenocarcinoma (PDA) is an almost incurable radio- and chemo-resistant tumor, and its microenvironment is characterized by a strong desmoplastic reaction associated with a significant infiltration of T regulatory lymphocytes and myeloid-derived suppressor cells (Tregs, MDSC). Investigating immunological targets has identified a
[...] Read more.
Pancreatic Ductal Adenocarcinoma (PDA) is an almost incurable radio- and chemo-resistant tumor, and its microenvironment is characterized by a strong desmoplastic reaction associated with a significant infiltration of T regulatory lymphocytes and myeloid-derived suppressor cells (Tregs, MDSC). Investigating immunological targets has identified a number of metabolic and cytoskeletal related molecules, which are typically recognized by circulating antibodies. Among these molecules we have investigated alpha-enolase (ENO1), a glycolytic enzyme that also acts a plasminogen receptor. ENO1 is also recognized by T cells in PDA patients, so we developed a DNA vaccine that targets ENO1. This efficiently induces many immunological processes (antibody formation and complement-dependent cytotoxicity (CDC)-mediated tumor killing, infiltration of effector T cells, reduction of infiltration of myeloid and Treg suppressor cells), which significantly increase the survival of genetically engineered mice that spontaneously develop pancreatic cancer. Although promising, the ENO1 DNA vaccine does not completely eradicate the tumor, which, after an initial growth inhibition, returns to proliferate again, especially when Tregs and MDSC ensue in the tumor mass. This led us to develop possible strategies for combinatorial treatments aimed to broaden and sustain the antitumor immune response elicited by DNA vaccination. Based on the data we have obtained in recent years, this review will discuss the biological bases of possible combinatorial treatments (chemotherapy, PI3K inhibitors, tumor-associated macrophages, ENO1 inhibitors) that could be effective in amplifying the response induced by the immune vaccination in PDA. Full article
(This article belongs to the Special Issue Latest Development in Pancreatic Cancer)
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Open AccessReview Alleviating Pancreatic Cancer-Associated Pain Using Endoscopic Ultrasound-Guided Neurolysis
Received: 14 January 2018 / Revised: 9 February 2018 / Accepted: 12 February 2018 / Published: 15 February 2018
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Abstract
The most common symptom in patients with advanced pancreatic cancer is abdominal pain. This has traditionally been treated with nonsteroidal anti-inflammatory drugs and opioid analgesics. However, these treatments result in inadequate pain control or drug-related adverse effects in some patients. An alternative pain-relief
[...] Read more.
The most common symptom in patients with advanced pancreatic cancer is abdominal pain. This has traditionally been treated with nonsteroidal anti-inflammatory drugs and opioid analgesics. However, these treatments result in inadequate pain control or drug-related adverse effects in some patients. An alternative pain-relief modality is celiac plexus neurolysis, in which the celiac plexus is chemically ablated. This procedure was performed percutaneously or intraoperatively until 1996, when endoscopic ultrasound (EUS)-guided celiac plexus neurolysis was first described. In this transgastric anterior approach, a neurolytic agent is injected around the celiac trunk under EUS guidance. The procedure gained popularity as a minimally invasive approach and is currently widely used to treat pancreatic cancer-associated pain. We focus on two relatively new techniques of EUS-guided neurolysis: EUS-guided celiac ganglia neurolysis and EUS-guided broad plexus neurolysis, which have been developed to improve efficacy. Although the techniques are safe and effective in general, some serious adverse events including ischemic and infectious complications have been reported as the procedure has gained widespread popularity. We summarize reported clinical outcomes of EUS-guided neurolysis in pancreatic cancer (from the PubMed and Embase databases) with a goal of providing information useful in developing strategies for pancreatic cancer-associated pain alleviation. Full article
(This article belongs to the Special Issue Latest Development in Pancreatic Cancer)
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Open AccessReview Beyond Brooding on Oncometabolic Havoc in IDH-Mutant Gliomas and AML: Current and Future Therapeutic Strategies
Received: 30 December 2017 / Revised: 3 February 2018 / Accepted: 6 February 2018 / Published: 11 February 2018
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Abstract
Isocitrate dehydrogenases 1 and 2 (IDH1,2), the key Krebs cycle enzymes that generate NADPH reducing equivalents, undergo heterozygous mutations in >70% of low- to mid-grade gliomas and ~20% of acute myeloid leukemias (AMLs) and gain an unusual new activity of reducing the α-ketoglutarate
[...] Read more.
Isocitrate dehydrogenases 1 and 2 (IDH1,2), the key Krebs cycle enzymes that generate NADPH reducing equivalents, undergo heterozygous mutations in >70% of low- to mid-grade gliomas and ~20% of acute myeloid leukemias (AMLs) and gain an unusual new activity of reducing the α-ketoglutarate (α-KG) to D-2 hydroxyglutarate (D-2HG) in a NADPH-consuming reaction. The oncometabolite D-2HG, which accumulates >35 mM, is widely accepted to drive a progressive oncogenesis besides exacerbating the already increased oxidative stress in these cancers. More importantly, D-2HG competes with α-KG and inhibits a large number of α-KG-dependent dioxygenases such as TET (Ten-eleven translocation), JmjC domain-containing KDMs (histone lysine demethylases), and the ALKBH DNA repair proteins that ultimately lead to hypermethylation of the CpG islands in the genome. The resulting CpG Island Methylator Phenotype (CIMP) accounts for major gene expression changes including the silencing of the MGMT (O6-methylguanine DNA methyltransferase) repair protein in gliomas. Glioma patients with IDH1 mutations also show better therapeutic responses and longer survival, the reasons for which are yet unclear. There has been a great surge in drug discovery for curtailing the mutant IDH activities, and arresting tumor proliferation; however, given the unique and chronic metabolic effects of D-2HG, the promise of these compounds for glioma treatment is uncertain. This comprehensive review discusses the biology, current drug design and opportunities for improved therapies through exploitable synthetic lethality pathways, and an intriguing oncometabolite-inspired strategy for primary glioblastoma. Full article
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Open AccessReview Early Diagnosis to Improve the Poor Prognosis of Pancreatic Cancer
Received: 1 January 2018 / Revised: 25 January 2018 / Accepted: 2 February 2018 / Published: 11 February 2018
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Abstract
Pancreatic cancer (PC) has a poor prognosis due to delayed diagnosis. Early diagnosis is the most important factor for improving prognosis. For early diagnosis of PC, patients with clinical manifestations suggestive of PC and high risk for developing PC need to be selected
[...] Read more.
Pancreatic cancer (PC) has a poor prognosis due to delayed diagnosis. Early diagnosis is the most important factor for improving prognosis. For early diagnosis of PC, patients with clinical manifestations suggestive of PC and high risk for developing PC need to be selected for examinations for PC. Signs suggestive of PC (e.g., symptoms, diabetes mellitus, acute pancreatitis, or abnormal results of blood examinations) should not be missed, and the details of risks for PC (e.g., familial history of PC, intraductal mucin producing neoplasm, chronic pancreatitis, hereditary pancreatitis, or life habit) should be understood. Multidetector computed tomography (MDCT) and magnetic resonance imaging (MRI) can be performed for diagnosing PC, but the diagnostic ability of these examinations for PC is limited. Endoscopic diagnostic procedures, such as endoscopic ultrasonography, including fine-needle aspiration, and endoscopic retrograde pancreatocholangiography, including Serial Pancreatic-juice Aspiration Cytologic Examination (SPACE), could be recommended for a detailed examination to diagnose pancreatic carcinoma earlier. Full article
(This article belongs to the Special Issue Latest Development in Pancreatic Cancer)
Open AccessFeature PaperReview Bioapplications of Cell-SELEX-Generated Aptamers in Cancer Diagnostics, Therapeutics, Theranostics and Biomarker Discovery: A Comprehensive Review
Received: 17 December 2017 / Revised: 24 January 2018 / Accepted: 25 January 2018 / Published: 9 February 2018
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Abstract
Currently, functional single-stranded oligonucleotide probes, termed aptamers, generated by an iterative technology, Systematic Evolution of Ligands by Exponential Enrichment (SELEX), are utilized to selectively target molecules or cells with high affinity. Aptamers hold considerable promise as multifunctional molecules or conjugates for challenging nanotechnologies
[...] Read more.
Currently, functional single-stranded oligonucleotide probes, termed aptamers, generated by an iterative technology, Systematic Evolution of Ligands by Exponential Enrichment (SELEX), are utilized to selectively target molecules or cells with high affinity. Aptamers hold considerable promise as multifunctional molecules or conjugates for challenging nanotechnologies or bioapplications now and in the future. In this review, we first describe recent endeavors to select aptamers towards live cancer cells via cell-SELEX. We then introduce several characteristic applications of selected aptamers, especially in imaging, drug delivery and therapy. In part, these advances have been made possible via synthesis of aptamer-based nanomaterials, which, by their sizes, shapes, and physicochemical properties, allow such aptamer-nanomaterial complexes to function as signal reporters or drug carriers. We also describe how these aptamer-based molecular tools contribute to cancer biomarker discovery through high-affinity recognition of membrane protein receptors. Full article
(This article belongs to the Special Issue Aptamers: Promising Tools for Cancer Diagnosis and Therapy)
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Open AccessFeature PaperReview Liver Transplantation for Alcoholic Liver Disease and Hepatocellular Carcinoma
Received: 18 December 2017 / Revised: 1 February 2018 / Accepted: 7 February 2018 / Published: 9 February 2018
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Abstract
Hepatocellular carcinoma is one of the main important causes of cancer-related death and its mortality is increasingly worldwide. In Europe, alcohol abuse accounts for approximately half of all liver cancer cases and it will become the leading cause of hepatocellular carcinoma in the
[...] Read more.
Hepatocellular carcinoma is one of the main important causes of cancer-related death and its mortality is increasingly worldwide. In Europe, alcohol abuse accounts for approximately half of all liver cancer cases and it will become the leading cause of hepatocellular carcinoma in the next future with the sharp decline of chronic viral hepatitis. The pathophysiology of alcohol-induced carcinogenesis involves acetaldehyde catabolism, oxidative stress and chronic liver inflammation. Genetic background plays also a significant role and specific patterns of gene mutations in alcohol-related hepatocellular carcinoma have been characterized. Survival is higher in patients who undergo specific surveillance programmes than in patients who do not. However, patients with alcohol cirrhosis present a significantly greater risk of liver decompensation than those with cirrhosis due to other aetiologies. Furthermore, the adherence to screening program can be suboptimal. Liver transplant for patients with Milan-in hepatocellular carcinoma represents the best possible treatment in case of tumour recurrence/progression despite loco-regional or surgical treatments. Long-term result after liver transplantation for alcohol related liver disease is good. However, cardiovascular disease and de novo malignancies can significantly hamper patients’ survival and should be carefully considered by transplant team. In this review, we have focused on the evolution of alcohol-related hepatocellular carcinoma epidemiology and risk factors as well as on liver transplantation in alcoholic patients with and without hepatocellular carcinoma. Full article
(This article belongs to the Special Issue Alcohol and Cancer)
Open AccessReview Linking Extracellular Matrix Agrin to the Hippo Pathway in Liver Cancer and Beyond
Received: 4 January 2018 / Revised: 5 February 2018 / Accepted: 5 February 2018 / Published: 6 February 2018
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Abstract
In addition to the structural and scaffolding role, the extracellular matrix (ECM) is emerging as a hub for biomechanical signal transduction that is frequently relayed to intracellular sensors to regulate diverse cellular processes. At a macroscopic scale, matrix rigidity confers long-ranging effects contributing
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In addition to the structural and scaffolding role, the extracellular matrix (ECM) is emerging as a hub for biomechanical signal transduction that is frequently relayed to intracellular sensors to regulate diverse cellular processes. At a macroscopic scale, matrix rigidity confers long-ranging effects contributing towards tissue fibrosis and cancer. The transcriptional co-activators YAP/TAZ, better known as the converging effectors of the Hippo pathway, are widely recognized for their new role as nuclear mechanosensors during organ homeostasis and cancer. Still, how YAP/TAZ senses these “stiffness cues” from the ECM remains enigmatic. Here, we highlight the recent perspectives on the role of agrin in mechanosignaling from the ECM via antagonizing the Hippo pathway to activate YAP/TAZ in the contexts of cancer, neuromuscular junctions, and cardiac regeneration. Full article
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Open AccessReview Integrin Inhibitors in Prostate Cancer
Received: 21 November 2017 / Revised: 12 January 2018 / Accepted: 19 January 2018 / Published: 6 February 2018
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Abstract
Prostate cancer (PCa) is the most frequently diagnosed cancer and the third highest cause of cancer-related deaths in men in the U.S. The development of chemotherapeutic agents that can bind PCa tumor cells with high specificity is critical in order to increase treatment
[...] Read more.
Prostate cancer (PCa) is the most frequently diagnosed cancer and the third highest cause of cancer-related deaths in men in the U.S. The development of chemotherapeutic agents that can bind PCa tumor cells with high specificity is critical in order to increase treatment effectiveness. Integrin receptors and their corresponding ligands have different expression patterns in PCa cells. They have been identified as promising targets to inhibit pathways involved in PCa progression. Currently, several compounds have proven to target specific integrins and their subunits in PCa cells. In this article, we review the role of integrins inhibitors in PCa and their potential as therapeutic targets for PCa treatments. We have discussed the following: natural compounds, monoclonal antibodies, statins, campothecins analog, aptamers, d-aminoacid, and snake venom. Recent studies have shown that their mechanisms of action result in decrease cell migration, cell invasion, cell proliferation, and metastasis of PCa cells. Full article
(This article belongs to the Special Issue Integrins in Cancer)
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