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This work focused on the analysis of various gene expression-based cancer subtype classification approaches. Correctly classifying cancer subtypes is critical for understanding cancer pathophysiology and effectively treating cancer patients by using gene expression data to categorize cancer subtypes. When dealing with limited samples and high-dimensional biological data, most classifiers may suffer from overfitting and lower precision. The goal of this research is to develop a machine learning (ML) system capable of classifying human cancer subtypes based on gene expression data in cancer cells. These issues can be solved using ML algorithms such as Transductive Support Vector Machines (TSVM), Boosting Cascade Deep Forest (BCD Forest), Enhanced Neural Network Classifier (ENNC), Deep Flexible Neural Forest (DFN Forest), Convolutional Neural Network (CNN), and Cascade Flexible Neural Forest (CFN Forest). In inferring the benefits and drawbacks of these strategies, such as DFN Forest and CFN Forest, the findings are 95%. [ABSTRACT FROM AUTHOR]

Background: Molecular pathways found to be important in pulmonary fibrosis are also involved in cancer pathogenesis, suggesting common pathways in the development of pulmonary fibrosis and lung cancer. Research question: Is pulmonary fibrosis from exposure to occupational carcinogens an independent risk factor for lung cancer? Study design and methods: A comprehensive search of PubMed, Embase, Web of Science and Cochrane databases with over 100 search terms regarding occupational hazards causing pulmonary fibrosis was conducted. After screening and extraction, quality of evidence and eligibility criteria for meta-analysis were assessed. Meta-analysis was performed using a random-effects model. Results: 52 studies were identified for systematic review. Meta-analysis of subgroups identified silicosis as a risk factor for lung cancer when investigating odds ratios for silicosis in autopsy studies (OR 1.47, 95% CI 1.13–1.90) and for lung cancer mortality in patients with silicosis (OR 3.21, 95% CI 2.67–3.87). Only considering studies with an adjustment for smoking as a confounder identified a significant increase in lung cancer risk (OR 1.58, 95% CI 1.34–1.87). However, due to a lack of studies including cumulative exposure, no adjustments could be included. In a qualitative review, no definitive conclusion could be reached for asbestosis and silicosis as independent risk factors for lung cancer, partly because the studies did not take cumulative exposure into account. Interpretation: This systematic review confirms the current knowledge regarding asbestosis and silicosis, indicating a higher risk of lung cancer in exposed individuals compared to exposed workers without fibrosis. These individuals should be monitored for lung cancer, especially when asbestosis or silicosis is present. [ABSTRACT FROM AUTHOR]

In the 21st century, melanoma and non-melanoma skin cancers have become an epidemic outbreak worldwide. Therefore, the exploration of all potential preventative and therapeutic measures based on either physical or bio-chemical mechanisms is essential via understanding precise pathophysiological pathways (Mitogen-activated protein kinase, Phosphatidylinositol 3-kinase Pathway, and Notch signaling pathway) and other aspects of such skin malignancies. Nano-gel, a three-dimensional polymeric cross-linked porous hydrogel having a diameter of 20–200 nm, possesses dual properties of both hydrogel and nanoparticle. The capacity of high drug entrapment efficiency with greater thermodynamic stability, remarkable solubilization potential, and swelling behavior of nano-gel becomes a promising candidate as a targeted drug delivery system in the treatment of skin cancer. Nano-gel can be either synthetically or architectonically modified for responding to either internal or external stimuli, including radiation, ultrasound, enzyme, magnetic, pH, temperature, and oxidation-reduction to achieve controlled release of pharmaceuticals and several bio-active molecules such as proteins, peptides, genes via amplifying drug aggregation in the active targeted tissue and reducing adverse pharmacological effects. Several drugs, such as anti-neoplastic biomolecules having short biological half-lives and prompt enzyme degradability capacity, must be appropriate for administration employing either chemically bridged or physically constructed nano-gel frameworks. The comprehensive review summarizes the advancement in the preparation and characterization methods of targeted nano-gel with enhanced pharmacological potential and preserved intracellular safety limits for the mitigation of skin malignancies with a special emphasize on skin cancer inducing pathophysiological pathways and prospective research opportunities for skin malignancy targeted nano-gels. [ABSTRACT FROM AUTHOR]

Abstract Aim In order to evaluate the role of MMP-14 in ovarian cancer, a systematic review was conducted. Methods In March 2020, a search in Pubmed was performed with MMP-14 and ovarian cancer as search terms. After exclusion of the references not on MMP-14 or ovarian cancer or not in English, the studies found were classified into two categories: basic research and clinicopathological research. Results In total, 94 references were found of which 33 were excluded. Two additional articles were found in the reference lists of the included studies. Based on the full texts, another 4 were excluded. Eventually, 59 studies were included in the review, 32 on basic research and 19 on clinicopathological research. 8 studies fell in both categories. The basic research studies show that MMP-14 plays an important role in ovarian cancer in the processes of proliferation, invasion, angiogenesis and metastasis. In clinocopathological research, MMP-14 expression is found in most tumours with characteristics of poor prognosis but this immunohistochemical MMP-14 determination does not seem to be an independent predictor of prognosis. Conclusions From this systematic review of the literature concerning MMP-14 in ovarian cancer it becomes clear that MMP-14 plays various important roles in the pathophysiology of ovarian cancer. The exact translation of these roles in the pathophysiology to the importance of MMP-14 in clinicopathological research in ovarian cancer and possible therapeutic role of anti-MMP-14 agents needs further elucidation.

Simple Summary: Breast and prostate cancers are serious public health issues that create considerable burden to both people and healthcare systems worldwide. Cancer is a heterogeneous disease influenced by numerous components, and its diverse intricate pathology challenges disease prevention, diagnosis, treatment, and survival. Although recent statistics suggest improvements in cancer diagnosis and treatment, many challenges remain before cancers are curable. This review presents relevant summarized information related to breast and prostate cancer. Cancer is a global issue, and it is expected to have a major impact on our continuing global health crisis. As populations age, we see an increased incidence in cancer rates, but considerable variation is observed in survival rates across different geographical regions and cancer types. Both breast and prostate cancer are leading causes of morbidity and mortality worldwide. Although cancer statistics indicate improvements in some areas of breast and prostate cancer prevention, diagnosis, and treatment, such statistics clearly convey the need for improvements in our understanding of the disease, risk factors, and interventions to improve life span and quality of life for all patients, and hopefully to effect a cure for people living in developed and developing countries. This concise review compiles the current information on statistics, pathophysiology, risk factors, and treatments associated with breast and prostate cancer. [ABSTRACT FROM AUTHOR]

Aim: In order to evaluate the role of MMP-14 in ovarian cancer, a systematic review was conducted. Methods: In March 2020, a search in Pubmed was performed with MMP-14 and ovarian cancer as search terms. After exclusion of the references not on MMP-14 or ovarian cancer or not in English, the studies found were classified into two categories: basic research and clinicopathological research. Results: In total, 94 references were found of which 33 were excluded. Two additional articles were found in the reference lists of the included studies. Based on the full texts, another 4 were excluded. Eventually, 59 studies were included in the review, 32 on basic research and 19 on clinicopathological research. 8 studies fell in both categories. The basic research studies show that MMP-14 plays an important role in ovarian cancer in the processes of proliferation, invasion, angiogenesis and metastasis. In clinocopathological research, MMP-14 expression is found in most tumours with characteristics of poor prognosis but this immunohistochemical MMP-14 determination does not seem to be an independent predictor of prognosis. Conclusions: From this systematic review of the literature concerning MMP-14 in ovarian cancer it becomes clear that MMP-14 plays various important roles in the pathophysiology of ovarian cancer. The exact translation of these roles in the pathophysiology to the importance of MMP-14 in clinicopathological research in ovarian cancer and possible therapeutic role of anti-MMP-14 agents needs further elucidation. [ABSTRACT FROM AUTHOR]

Background: Exosomes are extracellular nanometric vesicles used by cells to communicate with each other. They are responsible for many pathological conditions, including tumors by transferring regulatory biomolecules that impact target cell activity. Because of their high concentration in exosomes compared with parental cells and the rest of exosomal content, specificity to the cell of origin, and their well-organized sorting mechanism, microRNAs (miRNAs) are thought to be the most potent exosomes cargo and used by scientists to track exosomes and to detect cell activity changes and prognosis in cancer early. Purpose: In this review, the results of studies examining the role of exosomes in cancer pathophysiology and their clinical potential are discussed in detail. Summary of the Findings: Tumor-derived exosomes (TDEs) mediate the dynamic changes of cancer growth and invasion, including local microenvironment remodeling, distance metastasis, angiogenesis, and tumor-associated immunosuppression. They also contribute to hypoxia-induced tumor progression and cancer cell drug resistance. As a result of exosomes being present in all body fluids, it is possible to have early accessible and less-invasive diagnostic and prognostic measures by forming a table for each cancer type and its matched specific miRNAs. Under testing, available therapeutic uses of exosomes include interference of exosomes biogenesis, secretion, or uptake, and recruitment of exosomes as target-specific drug delivery vehicles, and immunostimulatory agents for both cancer patients and healthy population to avoid cancer development from the start. Conclusion: These data suggest that exosomes and exosomal microRNA are directly related to cancer progression mechanisms, and could be used in cancer early diagnosis, prognosis, and therapy. [ABSTRACT FROM AUTHOR]

It is well established that the role of the tumor microenvironment (TME) in cancer progression and therapeutic resistance is crucial, but many of the underlying mechanisms are still being elucidated. Even with better understanding of molecular oncology and identification of genomic drivers of these processes, there has been a relative lag in identifying and appreciating the cellular drivers of both invasion and resistance. Intercellular communication is a vital process that unifies and synchronizes the diverse components of the tumoral infrastructure. Elucidation of the role of extracellular vesicles (EVs) over the past decade has cast a brighter light on this field. And yet even with this advance, in addition to diffusible soluble factor-mediated paracrine and endocrine cell communication as well as EVs, additional niches of intratumoral communication are filled by other modes of intercellular transfer. Tunneling nanotubes (TNTs), tumor microtubes (TMs), and other similar intercellular channels are long filamentous actin-based cellular conduits (in most epithelial cancer cell types, ~15-500 µm in length; 50–1000+ nm in width). They extend and form direct connections between distant cells, serving as conduits for direct intercellular transfer of cell cargo, such as mitochondria, exosomes, and microRNAs; however, many of their functional roles in mediating tumor growth remain unknown. These conduits literally create a physical bridge to create a syncytial network of dispersed cells amidst the intercellular stroma-rich matrix. Emerging evidence suggests that they provide a cellular mechanism for induction and emergence of drug resistance and contribute to increased invasive and metastatic potential. They have been imaged in vitro and also in vivo and ex vivo in tumors from human patients as well as animal models, thus not only proving their existence in the TME, but opening further speculation about their exact role in the dynamic niche of tumor ecosystems. TNT cellular networks are upregulated between cancer and stromal cells under hypoxic and other conditions of physiologic and metabolic stress. Furthermore, they can connect malignant cells to benign cells, including vascular endothelial cells. The field of investigation of TNT-mediated tumor-stromal, and tumor-tumor, cell-cell communication is gaining momentum. The mixture of conditions in the microenvironment exemplified by hypoxia-induced ovarian cancer TNTs playing a crucial role in tumor growth, as just one example, is a potential avenue of investigation that will uncover their role in relation to other known factors, including EVs. If the role of cancer heterocellular signaling via TNTs in the TME is proven to be crucial, then disrupting formation and maintenance of TNTs represents a novel therapeutic approach for ovarian and other similarly invasive peritoneal cancers. [ABSTRACT FROM AUTHOR]

Les soins de support en oncologie permettent d'améliorer la prise en charge des symptômes d'inconfort. Dans ce cadre, l'efficacité des opioïdes est très recherchée dans le traitement des douleurs rebelles liées à une pathologie cancéreuse évoluée. Les propriétés antalgiques des opioïdes sont contrebalancées par des effets secondaires digestifs. L'objectif de cette étude est de décrire la prévalence et la gravité de la constipation induite par les opioïdes chez les patients cancéreux, et d'évaluer l'impact de dysfonctionnement intestinal induit par les opioïdes sur leur qualité de vie. Méthodes : il s'agit d'une étude transversale monocentrique auprès des patients souffrant de douleurs cancéreuses et qui sont sous traitement opioïde en utilisant deux questionnaires : KESS et PAC-QoL(pour patient assessment of constipation-quality of life). Résultats : 103 patients cancéreux ont été inclus dans cette étude, 75,7 % (n = 77) des patients souffraient de constipation selon le questionnaire KESS. Des symptômes de dysfonction intestinale, hors constipation, étaient présents chez 82,5 % des patients (n = 85) : ballonnements (70 %), perte d'appétit (60 %), flatulences (73,2 %), douleur lors de la défécation (45 %) et malaise épigastrique (23 %). Les résultats de la PAC-QoL démontraient que la qualité de vie globale était significativement dégradée chez les patients constipés (p < 0,0001) malgré un traitement laxatif. Conclusion : les patients cancéreux qui prennent des opioïdes pour la douleur sont très souvent constipés, en dépit de la prescription de laxatifs. Cela conduit à des altérations significatives de la qualité de vie. [ABSTRACT FROM AUTHOR]

Cancer stage at diagnosis is an important gap for Australian population based cancer registries. The study aims to understand the quality and completeness of three different collections of cancer staging data. The South Australian Cancer Registry data collection for breast and colorectal cancer (CRC) cases diagnosed in 2011, was linked to Registry Derived Stage (RDS) data, pathology plus hospital metastasis codes (pathology stage), and the South Australian Clinical Cancer Registry Stage (SACCR stage). The agreement between staging systems was examined using kappa statistics. Kaplan-Meier curves and Cox regression were used to examine the difference in survival by staging methods. Among 2,530 breast and CRC cases 98.8% were stageable (n = 2,500) according to histology. Among stageable cases, 84.6% had RDS, 51.2% had pathology stage and 29.5% had SACCR stage. The kappa statistic for RDS and pathology stage was 0.930 for breast cancer and 0.973 for CRC, and 0.574 for RDS and SACCR stage for breast cancer and 0.632 for CRC. The agreement between pathology stage and SACCR stage was 0.430 for breast cancer and 0.528 for CRC. The distribution of stage was similar across staging methods, although more stage four cancers by pathology stage, and survival patterns were similar but not the same. The agreement was high between different staging systems. Pathology stage had a higher than expected stage 4 proportion. This study highlights an opportunity to collect stage information in a cost-effective manner, while collecting data that usefully represent stage at diagnosis across the population, for population based epidemiological analyses. [ABSTRACT FROM AUTHOR]

Highlights from the article: However, most clinical trials testing systemic therapies in recent years have excluded patients with fibrolamellar, sarcomatoid and mixed tumors. They are the mainstay of the treatment of BCLC stage 0 and A tumors not suitable for resection, transplantation or ablation, and for BCLC stage B tumors that can be targeted superselectively, based on two randomized trials [[49]]. Regarding therapy, in the setting of early HCC, interventional radiology may offer valid therapeutic alternatives for patients with liver cirrhosis and early tumors not suitable for surgical approaches. 66 Bruix J, Qin S, Merle P, Granito A, Huang YH, Bodoky G. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial.

Abstract Objective As one broader class of non-coding RNAs (lncRNAs), non-coding antisense (AS) transcripts are functionally characterized to play pivotal roles in various pathophysiological processes, including tumor biology. Methods In this study, the exact biological functions and regulation mechanisms of GAS6-AS1 in gastric cancer (GC) was examined. Results The expression of GAS6-AS1 was markedly upregulated in GC tissues and is associated with advanced stage (III + IV) of GC patients. Gain-of-function and loss-of-function experiments showed that GAS6-AS1 promoted cell proliferation, migration, invasion ability in vitro and xenograft tumor growth in vivo by promoting entry into S-phase. The mechanistic investigations showed that GAS6-AS1 can control the expression of its cognate sense gene GAS6 at the transcriptional or translational levels by forming a RNA-RNA duplex, consequently inducing an increase of AXL level and driveling AXL signaling pathway activation. Conclusions Taken together, our studies indicate that GAS6-AS1 significantly driving the aggressive phenotype in GC through activating its cognate sense gene GAS6 , and provides a more complete understanding of GAS6-AS1 as a potential therapeutic target for GC. Highlights • GAS6-AS1 was markedly upregulated in gastric cancer (GC). • GAS6-AS1 promoted cell proliferation, migration, invasion ability in vitro and in vivo. • GAS6-AS1 can control GAS6 level by forming a RNA-RNA duplex in GC. • GAS6-AS1 may be as a potential GC biomarker. [ABSTRACT FROM AUTHOR]

Introduction: Our hospital is a tertiary medical center located in southern Taiwan, which is an endemic area for upper tract urothelial carcinoma (UTUC) cases. Using a large registry-based surgical database, we examined our cohort of patients with UTUC, and evaluated the treatment outcome and gender-specific differences in this population. Methods: A total of 506 patients with localized UTUC undergoing nephroureterectomy from 2004 to 2013 were enrolled. The patient, tumor, and treatment-related characteristics were prospectively recorded by the registry. Overall (OS) and cancer-specific (CSS) survival outcomes were evaluated as well. Gender differences as related to clinical and pathological factors were examined by chi-square testing. Univariate and multivariate Cox regression analyses were applied. Results: There were more female patients (57.9%) in this population. The median follow-up was 6.9 years for living patients. The actuarial 5-year OS and CSS rates were 69.4 and 84.9%, respectively. Being female, aged <70 years, and early T-stage were statistically significantly associated with better OS and CSS by multivariate analyses. The 5-year CSS rates for females vs. males were 89.6 and 78.5%, respectively (P < 0.005). A subgroup analysis suggested that better survival outcomes for females only existed in the stage 0a/0is/I (non-muscle-invasive), but not in the advanced stage. Conclusions: In an endemic area, females were more likely diagnosed with UTUC, but had significantly improved OS and CSS compared to their male counterparts, which were mostly driven by the non-muscle-invasive cases. Future research should focus on better understanding the epidemiologic risk-factor profile and pathophysiologic differences based on gender. [ABSTRACT FROM AUTHOR]

Thyroid hormones take major part in normal growth, development and metabolism. Over a century of research has supported a relationship between thyroid hormones and the pathophysiology of various cancer types. In vitro studies as well as research in animal models demonstrated an effect of the thyroid hormones T3 and T4 on cancer proliferation, apoptosis, invasiveness and angiogenesis. Thyroid hormones mediate their effects on the cancer cell through several non-genomic pathways including activation of the plasma membrane receptor integrin αvβ3. Furthermore, cancer development and progression are affected by dysregulation of local bioavailability of thyroid hormones. Case-control and population-based studies provide conflicting results regarding the association between thyroid hormones and cancer. However, a large body of evidence suggests that subclinical and clinical hyperthyroidism increase the risk of several solid malignancies while hypothyroidism may reduce aggressiveness or delay the onset of cancer. Additional support is provided from studies in which dysregulation of the thyroid hormone axis secondary to cancer treatment or thyroid hormone supplementation was shown to affect cancer outcomes. Recent preclinical and clinical studies in various cancer types have further shown promising outcomes following chemical reduction of thyroid hormones or inhibition or their binding to the integrin receptor. This review provides a comprehensive overview of the preclinical and clinical research conducted so far. [ABSTRACT FROM AUTHOR]

The purpose of the present study was to determine the prevalence of intestinal helminths and protozoa in colorectal cancer (CRC) patients and to evaluate the possible association between the prevalence and CRC pathogenesis. A total of 200 CRC patients and 200 residents of Tashkent, who had no complaints related to the gastrointestinal tract, were examined by triple coproscopy using a concentration method and estimations of protozoan infection intensity. Of the CRC patients tested, 144 were classified as T1-4N0M0 (without metastases) and 56 were classified as T1-4N1-2M0-1 (with metastases). Parasitological examination was performed during CRC diagnosis before and after surgery and chemotherapy. A significantly higher prevalence of Blastocystis sp., Chilomastix mesnili, Jodamoeba butschlii, and Endolimax nana was found in CRC patients than in the control population (p < 0.0001), amounting to 80, 20, 22.5, and 11.5%, respectively. The high prevalence of Blastocystis sp., as well as the patterns of infection intensity, was stable at all stages of examination. The ratio of the number of CRC patients with and without Blastocystis sp. in the T1-4N0M0 and T1-4N1-2M0-1 groups amounted to 3.3 and 7.0, respectively. The ratios for C. mesnili, E. coli, J. butschlii, and E. nana in both groups were 0.2 and 0.2, 0.07 and 0.07, 0.3 and 0.16, and 0.18 and 0.01, respectively. The prevalence of helminths and Giardia lamblia in CRC patients and the control population was not significantly different. Taken together, these data indicate a possible role for Blastocystis sp. in CRC pathogenesis. Diagnosis, treatment, and further observation of patients with Blastocystis sp. are necessary at all stages of CRC, including during diagnosis and before and after surgery and chemotherapy. [ABSTRACT FROM AUTHOR]

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Cancer is a multifaceted disorder frequently linked to the dysregulation of several biological processes. The SLPI is a multifunctional protein involved in the modulation of immunological response and the inhibition of protease activities. SLPI acts as an inhibitor of proteases, exerts antibacterial properties, and suppresses the transcription of proinflammatory genes through the nuclear factor-kappa B (NF-κB) pathway. The role of this protein as a regulatory agent has been implicated in various types of cancer. Recent research has revealed that SLPI upregulation in cancer cells enhances the metastatic capacity of epithelial malignancies, indicating the deleterious effects of this protein. Furthermore, SLPI interacts intricately with other cancer-promoting factors, including matrix metalloproteinase-2 (MMP-2), MMP-9, the NF-κB and Akt pathways, and the p53-upregulated modulator of apoptosis (PUMA). This review provides an overview of the role of SLPI in cancer pathophysiology, emphasizing its expression in cancer cells and tissues, its potential as a prognostic biomarker, and its therapeutic promise as a target in cancer treatment. The mechanisms of SLPI action in cancer, including its anti-inflammatory effects, regulation of cell proliferation and angiogenesis, and modulation of the tumor microenvironment, have been investigated. The clinical implications of SLPI in cancer have been discussed, including its potential as a diagnostic and prognostic biomarker, its role in chemoresistance, and its therapeutic potential in several types of cancer, such as hepatocellular carcinoma (HCC), colorectal cancer (CRC), pancreatic cancer, head and neck squamous cell carcinoma (HNSCC), ovarian cancer (OvCa), prostate cancer (PC), gastric cancer (GC), breast cancer, and other cancers. In addition, we emphasized the significance of SLPI in cancer, which offers fresh perspectives on potential targets for cancer therapy. [ABSTRACT FROM AUTHOR]

Intercellular communication is vital to the ecosystem of cancer cell organization and invasion. Identification of key cellular cargo and their varied modes of transport are important considerations in understanding the basic mechanisms of cancer cell growth. Gap junctions, exosomes, and apoptotic bodies play key roles as physical modalities in mediating intercellular transport. Tunneling nanotubes (TNTs)—narrow actin-based cytoplasmic extensions—are unique structures that facilitate direct, long distance cell-to-cell transport of cargo, including microRNAs, mitochondria, and a variety of other sub cellular components. The transport of cargo via TNTs occurs between malignant and stromal cells and can lead to changes in gene regulation that propagate the cancer phenotype. More notably, the transfer of these varied molecules almost invariably plays a critical role in the communication between cancer cells themselves in an effort to resist death by chemotherapy and promote the growth and metastases of the primary oncogenic cell. The more traditional definition of “Systems Biology” is the computational and mathematical modeling of complex biological systems. The concept, however, is now used more widely in biology for a variety of contexts, including interdisciplinary fields of study that focus on complex interactions within biological systems and how these interactions give rise to the function and behavior of such systems. In fact, it is imperative to understand and reconstruct components in their native context rather than examining them separately. The long-term objective of evaluating cancer ecosystems in their proper context is to better diagnose, classify, and more accurately predict the outcome of cancer treatment. Communication is essential for the advancement and evolution of the tumor ecosystem. This interplay results in cancer progression. As key mediators of intercellular communication within the tumor ecosystem, TNTs are the central topic of this article.

Background: Studies have indicated a variation in colon cancer pathology with increased age. More findings have also suggested differences in genetics, biology, and demography in terms of ethnicity. Large-scale studies closely examining tumor location shift with aging and ethnicity are scarce. Objective: We compared the tumor location shift with aging and the difference in survival based on tumor location by age group among the African-American, White, and Asian/Pacific Islander patients with colorectal cancer. Materials and methods: We collected 270,390 cases from the Surveillance, Epidemiology, and End Results database between 2004 and 2014. Ethnicity distribution between younger (age <70 years) and older (age ≥70 years) patients was analyzed using univariate and multivariate logistic regression. The Kaplan–Meier method was used to compare the tumor location survival difference in the African-American, White, and Asian/Pacific Islander patients. Results: Larger tumors, female sex, M0, advanced N stage, no treatment, moderate to poor differentiation, total number of lymph nodes evaluated >12, and right-sided colon cancer were more common in patients aged ≥70 years. More adverse prognosis was found in younger patients compared to older patients. Tumor location frequency differed based on age; the most pronounced differences were found in White patients. The right-sided colon cancer survival inferiority was present only in White patients. Conclusion: Our findings support the premise of etiological and carcinogenic differences based on tumor location and between younger and older patients. [ABSTRACT FROM AUTHOR]

Background: Aberrant AKT activation is prevalent across human cancer lineages, providing an important therapeutic target. AKT comprises three isoforms that mediate critical non-redundant, even opposing functions in cancer pathophysiology. Therefore, targeting specific AKT isoforms in particular cancers may be more effective than pan-AKT inhibition while avoiding disadvantages of pan-AKT inhibition. Currently, AKT isoform-specific expression and activation in cancer are not clearly characterized.Methods: We systematically characterized AKT isoform-specific expression and activation in 211 cancer cell lines derived from different lineages and genetic backgrounds using a reverse-phase protein array platform.Results: We found that phosphorylation, but not expression, of AKT1 and AKT2 was coordinated in most but not all cells. Different cancer lineages displayed differential AKT1 and AKT2 expression and phosphorylation. A PIK3CA hotspot mutation H1047R but not E545K was associated with selective activation of AKT2 but not AKT1.Conclusions: Our study identified and validated AKT isoform-specific expression and phosphorylation in certain cell lines and demonstrated that genetic changes can affect AKT isoform-specific activation. These results provide a more precise understanding of AKT isoform-specific signaling and, in addition, facilitate AKT isoform targeting for personalized cancer therapies. [ABSTRACT FROM AUTHOR]

Background: The immune system has been implicated in the pathophysiology of cutaneous squamous cell carcinoma (cSCC) as evidenced by the substantially increased risk of cSCC in immunosuppressed individuals. Associations between cSCC risk and single nucleotide polymorphisms (SNPs) in the HLA region have been identified by genome-wide association studies (GWAS). The translation of the associated HLA SNPs to structural amino acids changes in HLA molecules has not been previously elucidated.Methods: Using data from a GWAS that included 7238 cSCC cases and 56,961 controls of non-Hispanic white ancestry, we imputed classical alleles and corresponding amino acid changes in HLA genes. Logistic regression models were used to examine associations between cSCC risk and genotyped or imputed SNPs, classical HLA alleles, and amino acid changes.Results: Among the genotyped SNPs, cSCC risk was associated with rs28535317 (OR = 1.20, p = 9.88 × 10− 11) corresponding to an amino-acid change from phenylalanine to leucine at codon 26 of HLA-DRB1 (OR = 1.17, p = 2.48 × 10− 10). An additional independent association was observed for a threonine to isoleucine change at codon 107 of HLA-DQA1 (OR = 1.14, p = 2.34 × 10− 9). Among the classical HLA alleles, cSCC was associated with DRB1*01 (OR = 1.18, p = 5.86 × 10− 10). Conditional analyses revealed additional independent cSCC associations with DQA1*05:01 and DQA1*05:05. Extended haplotype analysis was used to complement the imputed haplotypes, which identified three extended haplotypes in the HLA-DR and HLA-DQ regions.Conclusions: Associations with specific HLA-DR and -DQ alleles are likely to explain previously observed GWAS signals in the HLA region associated with cSCC risk. [ABSTRACT FROM AUTHOR]

Head and neck cancer presents primarily as head and neck squamous cell carcinoma (HNSCC), a debilitating malignancy fraught with high morbidity, poor survival rates, and limited treatment options. Mounting evidence indicates that the Wnt/β-catenin signaling pathway plays important roles in the pathobiology of HNSCC. Wnt/β-catenin signaling affects multiple cellular processes that endow cancer cells with the ability to maintain and expand immature stem-like phenotypes, proliferate, extend survival, and acquire aggressive characteristics by adopting mesenchymal traits. A central component of canonical Wnt signaling is β-catenin, which balances its role as a structural component of E-cadherin junctions with its function as a transcriptional coactivator of numerous target genes. Recent genomic characterization of head and neck cancer revealed that while β-catenin is not frequently mutated in HNSCC, its activity is unchecked by more common mutations in genes encoding upstream regulators of β-catenin, NOTCH1, FAT1, and AJUBA. Wnt/β-catenin signaling affects a wide range epigenetic and transcriptional activities, mediated by the interaction of β-catenin with different transcription factors and transcriptional coactivators and corepressors. Furthermore, Wnt/β-catenin functions in a network with many signaling and metabolic pathways that modulate its activity. In addition to its effects on tumor epithelia, β-catenin activity regulates the tumor microenvironment by regulating extracellular matrix remodeling, fibrotic processes, and immune response. These multifunctional oncogenic effects of β-catenin make it an attractive bona fide target for HNSCC therapy. [ABSTRACT FROM AUTHOR]

Recent evidence suggests that dysregulation of iron regulatory factors may play essential roles in cancer pathophysiology. Six-transmembrane epithelial antigen of prostate 3 (STEAP3) is a metalloreductase, which is vital for cellular iron uptake and homeostasis. However, the clinical significance and function of STEAP3 in the development of human gliomas remain unclear. Through analysis of publicly available databases, we found that STEAP3 was highly expressed in malignant gliomas, especially in the mesenchymal glioma molecular subtype and isocitrate dehydrogenase 1/2 (IDH1/2) wild-type gliomas. Expression levels of STEAP3 in gliomas correlated inversely with patient overall survival (OS) and served as an independent prognostic marker by multivariate Cox regression analysis. In functional assays performed with RNA knockdown, loss of STEAP3 attenuated aggressive phenotypes in glioma cells, including cell proliferation, invasion, and sphere formation in vitro and tumor growth in vivo. Finally, STEAP3 drives these activities by inducing mesenchymal transition, promoting transferrin receptor (TfR) expression, and activating STAT3-FoxM1 axis signaling. Taken together, these results indicate that STEAP3 functions as an oncogenic mediator in glioma progression and is thus a potential therapeutic target for the treatment of the disease. [ABSTRACT FROM AUTHOR]

Iodide (I-) metabolism is crucial for the synthesis of thyroid hormones (THs) in the thyroid and the subsequent action of these hormones in the organism. I- is principally transported by the sodium iodide symporter (NIS) and by the anion exchanger PENDRIN, and recent studies have demonstrated the direct participation of new transporters including anoctamin 1 (ANO1), cystic fibrosis transmembrane conductance regulator (CFTR) and sodium multivitamin transporter (SMVT). Several of these transporters have been found expressed in various tissues, implicating them in I- recycling. New research supports the exciting idea that I- participates as a protective antioxidant and can be oxidized to hypoiodite, a potent oxidant involved in the host defense against microorganisms. This was possibly the original role of I- in biological systems, before the appearance of TH in evolution. I- per se participates in its own regulation, and new evidence indicates that it may be antineoplastic, anti-proliferative and cytotoxic in human cancer. Alterations in the expression of I- transporters are associated with tumor development in a cancer-type-dependent manner and, accordingly, NIS, CFTR and ANO1 have been proposed as tumor markers. Radioactive iodide has been the mainstay adjuvant treatment for thyroid cancer for the last seven decades by virtue of its active transport by NIS. The rapid advancement of techniques that detect radioisotopes, in particular I-, has made NIS a preferred target-specific theranostic agent. [ABSTRACT FROM AUTHOR]

Background: A recent animal study showed that parathyroid hormone-related peptide (PTHrP) is associated with cancer cachexia by promoting adipose tissue browning, and we previously demonstrated that PTHrP predicts weight loss (WL) in patients with cancer. In this study, we investigated whether prediction of WL by PTHrP is influenced by clinical factors such as serum albumin, corrected calcium levels, cancer stage, and performance status (PS). Methods: A cohort of 219 patients with cancer whose PTHrP level was measured was enrolled and followed for body weight (BW) changes. Subjects were divided into two groups by serum albumin (cutoff value, 3.7 g/dL), corrected calcium (cutoff value, 10.5 mg/dL), cancer stage (stage 1 to 3 or 4), or PS (Eastern Cooperative Oncology Group 0 to 1 or 2 to 4), respectively. Clinically significant WL was defined as either percent of BW change (% BW) <-5% or % BW <-2% plus body mass index (BMI) <20 kg/m2. Results: After a median follow-up of 327 days, 74 patients (33.8%) experienced clinically significant WL. A positive PTHrP level was associated with a 2-fold increased risk of WL after adjusting for age, baseline BMI, serum albumin, corrected calcium level, cancer stage, and PS. The effect of PTHrP on WL remained significant in patients with low serum albumin, stage 4 cancer, and good PS. Regardless of calcium level, the effect of PTHrP on WL was maintained, although there was an additive effect of higher calcium and PTHrP levels. Conclusion: Early recognition of patients with advanced cancer who are PTHrP positive with hypercalcemia or hypoalbuminemia is needed for their clinical management. [ABSTRACT FROM AUTHOR]

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Copyright of Nereis is the property of Universidad Catolica de Valencia, San Vicente Martir and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Cancer development is a multifactorial process resulting from the aberrant activation of multiple signaling pathways. It has become increasingly clear that the coordination of the signaling events leading to cancer formation and progression is under the control of macromolecular transduction complexes organized by scaffolding proteins. A-kinase anchoring proteins (AKAPs) constitute a family of scaffolding proteins involved in the spatio-temporal activation of pathways controlling cancer cell proliferation, cell survival, and invasion. Mutations or altered expression of AKAP coding genes results in unregulated signaling associated with oncogenesis, cancer maintenance, and metastasis. This review will focus on recent advances illustrating the role of AKAPs in cancer pathophysiology as well as on their potential as therapeutic targets. [ABSTRACT FROM AUTHOR]

Background The purpose of this study was to analyze the correlation between the pathology and clinical presentations in patients with adenoid cystic carcinoma (ACC) of the external auditory canal. Methods Twenty-nine patients with ACC of the external auditory canal who underwent surgery were retrospectively reviewed. Results Fifty percent of patients with solid pattern disease had recurrences, followed by those with cribriform (33%) and tubular (0%) pattern. Perineural invasion was common (55%), and occurred most frequently in the solid subtype (67%). The rate of otalgia was less in patients with perineural invasion (31% vs 46%). Most tumors (59%) involved the parotid gland, but it was not seen on preoperative MRI (35%). Conclusion The solid subtype presents the worst prognosis, and is prone to perineural invasion. Despite frequently occurring in ACC of the external auditory canal, perineural invasion may not be associated with otalgia. In ACC of the external auditory canal, high rates of occult parotid involvement support adjunctive superficial parotidectomy. [ABSTRACT FROM AUTHOR]

Aims Heat shock proteins ( HSPs) are a group of molecules induced by a variety of environmental and pathophysiological stresses, including cancer. HSPs are implicated in the regulation of apoptosis and immunity in neoplasm. Transcription factor heat shock factor 1 ( HSF1) acts as the master regulator to control HSP expression, and is therefore involved in tumorigenesis. The purpose of this study was to evaluate the expression and clinicopathological relevance of HSPs and HSF1 in clear cell renal cell carcinoma (cc RCC). Methods and results The expression of HSP27, HSP60, HSP70, HSP90 and HSF1 was assessed in 428 cases of cc RCC using immunohistochemistry. High expression of HSP60 and HSP70 was correlated positively with grade and stage. High expression of HSF1 was correlated positively with stage. Univariate and multivariate analyses demonstrated that 216 patients (52%) with tumour expressing three or four markers in a panel of HSP60, HSP70, HSP90 and HSF1 had a significantly heightened risk for cancer-specific mortality than tumours expressing fewer than three markers ( P < 0.0001; concordance index, 0.81). Conclusions Immunohistochemical examination of HSPs and HSF1 provides useful prognostic information that may contribute to the design of therapeutic strategies for patients with cc RCC. [ABSTRACT FROM AUTHOR]

Background The origin of chronic subdural hematomas (CSDH) and the pathophysiology of its enlargement remain unknown. The chemical fluid composition of CSDH, the contribution of cerebrospinal fluid (CSF) to its enlargement, and the relationship to its appearance on computed tomography (CT) also are not entirely clear. Methods In this prospective study, 58 samples in 41 patients treated surgically for CSDH were analyzed. CSDHs were evaluated for the presence of CSF via β-2 transferrin and substances related to cell breakdown and hemolysis. These were compared with normal value of those substances in the serum and the CT appearances of the CSDH. Results In this study, 24% of the samples contained β-2 transferrin, which was statistically significant. Total protein, lactate dehydrogenase, total bilirubin, and red blood cells also were statistically different when compared with their normal serum concentration, indicating an active process of rebleeding and hemolysis rather than plasma ultrafiltration; however, their concentrations did not correlate with specific CT scan appearance. The absence of CSF in CSDH in 76% of cases did not support the theory that most CSDHs originate from subdural hygromas. The presence of hemolysis and cell breakdown, byproducts supports the hypothesis that the primary enlargement of CSDH develops through neomembrane and neovascular formation, rebleeding, and inhibition of the blood coagulation process. Our study did not test for serum transudation as a component of the enlargement of CSDH. Conclusions Our study confirms that the origin and enlargement of CSDH is multifactorial, but the contribution of individual factors and condition under which it occurs still remains unclear. CT scan findings do not correlate with the chemical composition or the presence of CSF in the CSDH. [ABSTRACT FROM AUTHOR]

Cancer is a cause of high deaths worldwide and also a huge burden for the health system. Cancer cells have unique properties such as a high rate of proliferation, self-renewal, metastasis, and treatment resistance, therefore, the development of novel diagnoses of cancers is a tedious task. Exosomes are secreted by virtually all cell types and have the ability to carry a multitude of biomolecules crucial for intercellular communication, hence, contributing a crucial part in the onset and spread of cancer. These exosomal components can be utilized in the development of markers for diagnostic and prognostic purposes for various cancers. This review emphasized primarily the following topics: exosomes structure and functions, isolation and characterization strategies of exosomes, the role of exosomal contents in cancer with a focus in particular on noncoding RNA and protein, exosomes, and the cancer microenvironment interactions, cancer stem cells, and tumor diagnosis and prognosis based on exosomes. [ABSTRACT FROM AUTHOR]

As an important endogenous gaseous signaling molecule, hydrogen sulfide (H2S) exerts various effects in the body. A variety of pathological changes, such as cancer, glycometabolic disorders, and diabetes, are associated with altered endogenous levels of H2S, especially decreased. Therefore, the supplement of H2S is of great significance for the treatment of diseases containing the above pathological changes. At present, many efforts have been made to increase the in vivo levels of H2S by administration of gaseous H2S, simple inorganic sulfide salts, sophisticated synthetic slow-releasing controllable H2S donors or materials, and using H2S stimulating agents. In this article, we reviewed the recent development of H2S releasing/stimulating reagents and their potential applications in two common pathological processes including cancer and glycometabolic disorders. [ABSTRACT FROM AUTHOR]

It is known that apoptotic cells can have diverse effects on the tumor microenvironment. Emerging evidence indicates that, despite its renowned role in tumor suppression, apoptosis may also promote oncogenic evolution or posttherapeutic relapse through multiple mechanisms. These include immunomodulatory, anti-inflammatory, and trophic environmental responses to apoptosis, which drive tumor progression. Our group has introduced the term "onco-regenerative niche (ORN)" to describe a conceptual network of conserved cell death-driven tissue repair and regeneration mechanisms that are hijacked in cancer. We propose that, among the key elements of the ORN are extracellular vesicles (EVs), notably those derived from apoptotic tumor cells. EVs are membrane-delimited subcellular particles, which contain multiple classes of bioactive molecules including markers of the cell from which they are derived. EVs are implicated in an increasing number of physiological and pathological contexts as mediators of local and systemic intercellular communication and detection of specific EVs may be useful in monitoring disease progression. Here, we discuss the mechanisms by which EVs produced by apoptotic tumor cells--both constitutively and as a consequence of therapy-- may mediate host responsiveness to cell death in cancer. We also consider how the monitoring of such EVs and their cargoes may in the future help to improve cancer diagnosis, staging, and therapeutic efficacy. [ABSTRACT FROM AUTHOR]

Myoepithelioma is a rare salivary gland neoplasm. They most commonly affect the major and minor salivary glands with the parotid gland being the most common, approximately 40%. Only 1% of all salivary gland neoplasms are myoepitheliomas. Myoepithelioma is usually a benign tumor arising from neoplastic myoepithelial or basket cells which are found between the basement membrane and the basal plasma membrane of acinar cells. They also contain multiple cellular elements. We present a case of a 73-year-old female with myoepithelioma of the parotid gland, an extremely rare neoplasm. There have been approximately 42 cases reported through 1985 and fewer than 100 cases through 1993. We will discuss the clinical presentation, pathophysiology, diagnosis, and treatment of such neoplasms. [ABSTRACT FROM AUTHOR]

Although chronic inflammation and immune disorders are of great importance to the pathogenesis of both dementia and cancer, the pathophysiological mechanisms are not clearly understood. In recent years, growing epidemiological evidence and meta-analysis data suggest an inverse association between Alzheimer’s disease (AD), which is the most common form of dementia, and cancer. It has been revealed that some common genes and biological processes play opposite roles in AD and cancer; however, the biological immune mechanism for the inverse association is not clearly defined. An unsupervised matrix decomposition two-stage bioinformatics procedure was adopted to investigate the opposite behaviors of the immune response in AD and breast cancer (BC) and to discover the underlying transcriptional regulatory mechanisms. Fast independent component analysis (FastICA) was applied to extract significant genes from AD and BC microarray gene expression data. Based on the extracted data, the shared transcription factors (TFs) from AD and BC were captured. Second, the network component analysis (NCA) algorithm in this study was presented to quantitatively deduce the TF activities and regulatory influences because quantitative dynamic regulatory information for TFs is not available via microarray techniques. Based on the NCA results and reconstructed transcriptional regulatory networks, inverse regulatory processes and some known innate immune responses were described in detail. Many of the shared TFs and their regulatory processes were found to be closely related to the adaptive immune response from dramatically different directions and to play crucial roles in both AD and BC pathogenesis. From the above findings, the opposing cellular behaviors demonstrate an invaluable opportunity to gain insights into the pathogenesis of these two types of diseases and to aid in developing new treatments. [ABSTRACT FROM AUTHOR]

It is often helpful to classify biomarker values into groups of different risk levels to facilitate evaluation of a biological, physiological, or pathological state. Stratification of patients into two risk groups is commonly seen, but there is always need for more than two groups for fine assessment. So far, there are no standard methods or tools to help decide how many cutoff points are optimal. In this study, we developed a comprehensive package that included methods to determine both the optimal number and locations of cutoff points for both survival data and dichotomized outcome. We illustrated workflow of this package with data from 797 patients with cervical cancer. By analyzing several risk factors of cervical cancer such as tumor size, body mass index (BMI), number of lymph nodes involved and depth of stromal invasion, in relation to survival and clinical outcome such as lymph nodal metastasis and lymphovascular invasion, we demonstrated that the best choice for BMI and stromal invasion was two cutoff points and one for the others. This study provided a useful tool to facilitate medical decisions and the analyses on cervical cancer may also be of interest to gynecologists. The package can be freely downloaded. [ABSTRACT FROM AUTHOR]

Pericytes are a heterogeneous population of cells located in the blood vessel wall. They were first identified in the 19th century by Rouget, however their biological role and potential for drug targeting have taken time to be recognised. Isolation of pericytes from several different tissues has allowed a better phenotypic and functional characterization. These findings revealed a tissue-specific, multi-functional group of cells with multilineage potential. Given this emerging evidence, pericytes have acquired specific roles in pathobiological events in vascular diseases. In this review article, we will provide a compelling overview of the main diseases in which pericytes are involved, from well-established mechanisms to the latest findings. Pericyte involvement in diabetes and cancer will be discussed extensively. In the last part of the article we will review therapeutic approaches for these diseases in light of the recently acquired knowledge. To unravel pericyte-related vascular pathobiological events is pivotal not only for more tailored treatments of disease but also to establish pericytes as a therapeutic tool. [ABSTRACT FROM AUTHOR]

Autotaxin, an ecto-lysophospholipase D encoded by the human ENNP2 gene, is expressed in multiple tissues, and participates in numerous critical physiologic and pathologic processes including inflammation, pain, obesity, embryo development, and cancer via the generation of the bioactive lipid lysophosphatidate. Overwhelming evidences indicate that the autotaxin/lysophosphatidate signaling axis serves key roles in the numerous processes central to tumorigenesis and progression, including proliferation, survival, migration, invasion, metastasis, cancer stem cell, tumor microenvironment, and treatment resistance by interacting with a series of at least six G-protein-coupled receptors (LPAR1--6). This review provides an overview of the autotaxin/lysophosphatidate axis and collates current knowledge regarding its specific role in pancreatic cancer. With a deeper understanding of the critical role of the autotaxin/lysophosphatidate axis in pancreatic cancer, targeting autotaxin or lysophosphatidate receptor may be a potential and promising strategy for cancer therapy. [ABSTRACT FROM AUTHOR]

DNA replicates in a timely manner with each cell division. Multiple proteins and factors are involved in the initiation of DNA replication including a dynamic interaction between Cdc10-dependent transcript (Cdt1) and Geminin (GMNN). A conformational change between GMNN-Cdt1 heterotrimer and heterohexamer complex is responsible for licensing or inhibition of the DNA replication. This molecular switch ensures a faithful DNA replication during each S phase of cell cycle. GMNN inhibits Cdt1-mediated minichromosome maintenance helicases (MCM) loading onto the chromatin-bound origin recognition complex (ORC) which results in the inhibition of pre-replication complex assembly. GMNN modulates DNA replication by direct binding to Cdt1, and thereby alters its stability and activity. GMNN is involved in various stages of development such as pre-implantation, germ layer formation, cell commitment and specification, maintenance of genome integrity at mid blastula transition, epithelial to mesenchymal transition during gastrulation, neural development, organogenesis and axis patterning. GMNN interacts with different proteins resulting in enhanced hematopoietic stem cell activity thereby activating the development-associated genes' transcription. GMNN expression is also associated with cancer pathophysiology and development. In this review we discussed the structure and function of GMNN in detail. Inhibitors of GMNN and their role in DNA replication, repair, cell cycle and apoptosis are reviewed. Further, we also discussed the role of GMNN in virus infected host cells. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM) is one of the most lethal brain tumors with an inadequately understood pathophysiology. Biomarkers that guide accurate diagnosis and treatment decisions would greatly support precision medicine for GBM. Previous studies of GBM have focused on signaling pathways such as epidermal growth factor receptor (EGFR), platelet-derived growth factor receptors (PDGFRs), notch, wnt, and others, identified with single omics technology platforms (genomics, transcriptomics, or proteomics), but not with their integrated use. In this context, we report here a multi-omics pathway view, expanded through integration of the expression data at transcriptomic and proteomic levels, followed by selection of a functionally related group of proteins such as kinases deregulated in GBM. By using this strategy, we observed a highly significant enrichment of the gonadotropin-releasing hormone (GnRH) signaling pathway that was not deciphered with single omics datasets. The curation of the GnRH pathway with extensive literature analysis brought about a comprehensive annotation of the pathway, which included several additional pathway members that were not previously annotated. A targeted search resulted in identification of additional nonkinase members of the pathway in the GBM multi-omics datasets. We found evidence of GnRH receptor expression in GBM and other cancers. We offer here an updated generic pathway map of GnRH signaling, show its enrichment in the context of GBM, and discuss its plausible cross-connectivity with EGFR, wnt, calcium, and focal adhesion kinase signaling pathways that were earlier shown to be the top deregulated pathways in GBM. In conclusion, this study demonstrates the promise of multi-omics research and analyses to better understand complex cancers and suggests continued efforts and research in this direction in the field of integrative biology. [ABSTRACT FROM AUTHOR]

Iron is a tightly regulated micronutrient with no physiologic means of elimination and is necessary for cell division in normal tissue. Recent evidence suggests that dysregulation of iron regulatory proteins may play a role in cancer pathophysiology. We use public data from The Cancer Genome Atlas (TCGA) to study the association between survival and expression levels of 61 genes coding for iron regulatory proteins in patients with World Health Organization Grade II-III gliomas. Using a feature selection algorithm we identified a novel, optimized subset of eight iron regulatory genes (STEAP3, HFE, TMPRSS6, SFXN1, TFRC, UROS, SLC11A2, and STEAP4) whose differential expression defines two phenotypic groups with median survival differences of 52.3 months for patients with grade II gliomas (25.9 vs. 78.2 months, p< 10−3), 43.5 months for patients with grade III gliomas (43.9 vs. 87.4 months, p = 0.025), and 54.0 months when considering both grade II and III gliomas (79.9 vs. 25.9 months, p < 10−5). [ABSTRACT FROM AUTHOR]

Accurate pathologic diagnosis and reporting in malignant pleural mesothelioma are essential for clinical care, and cancer registration. Practical guidelines for pathologists are provided in publications and textbooks but it is unclear how these recommendations are applied in routine practice. We investigated the characteristics of pathology reports, and the extent to which they meet guideline standards. We reviewed 819 pathology reports relating to a first diagnosis of malignant pleural mesothelioma. Data sources were a regional section of the Italian network of the Mesothelioma Registry (2001–2014) and a pathology archive (1990–2000). We evaluated tumor characteristics, the diagnosis field including terminology and immunohistochemistry (IHC) workup, and report completeness (the proportion of items recorded). We investigated also two IHC panels identified by the most used markers in current practical guidelines, one best suited for epithelioid mesotheliomas (combinations of at least 2 positive and at least 2 negative mesothelioma markers) and the other best suited for sarcomatoid mesotheliomas (positive mesothelioma markers plus cytokeratins). Reports (753 histology, 66 cytology, IHC-confirmed 86%) were 74% complete and always narrative. Missing data were related to clinical history (76%), tumor laterality (61%), specimen size (38%), and histological subtype (23%). The proportion of cases with IHC was higher for epithelioid (90%) than sarcomatoid mesothelioma (87%). Compliance to IHC recommendations was higher for epithelioid (59%) than sarcomatoid mesothelioma (11%). The mean number of stains was significantly higher for sarcomatoid than epithelioid mesothelioma (p < 0.000; Kruskal-Wallis test). Our findings show that although guidelines are designed to improve actual reporting practices, there is ample room for improvement in their application to standardize the diagnosis of mesothelioma. Synoptic pathology reporting needs to be implemented to better utilize pathology information. [ABSTRACT FROM AUTHOR]

Survivin is an anti-apoptotic protein belonging to the inhibitor of apoptosis protein (IAP) family. It is involved in the regulation of important physiological and pathological processes in cells and functions to inhibit cell apoptosis and promote cell proliferation. Normally and terminally differentiated tissues are nearly negative for survivin. In contrast, survivin is highly expressed in most human tumor tissues, including hepatocellular carcinoma (HCC). The abnormal overexpression of survivin is closely related to the malignant biological behaviors of tumors. During the development and progression of HCC, the high level of survivin expression promotes cancer cell proliferation, inhibits cancer cell apoptosis, induces tumor stromal angiogenesis, reduces the sensitivity of cancer cells to radiotherapy and chemotherapy, and ultimately affects the prognosis of patients with HCC. Survivin expression is regulated by a large number of factors. The latest discovery indicated that the transcription factor octamer-binding transcription factor 4 (OCT4) enhances the expression of survivin though cyclin D1 (CCND1), which, in part, accounts for tumor cell proliferation, recurrence and metastasis. Survivin plays key roles in HCC, which renders it an ideal target for the treatment of HCC. The present article reviews the research progress on the relationship between survivin and HCC and on the HCC treatment strategies targeting survivin. [ABSTRACT FROM AUTHOR]

The epigenetic mechanism that incorporates DNA methylation alterations, histone modifications, and non-coding RNA expression has been identified as a major characteristic in distinguishing physiological and pathological settings of cancers including hepatocellular carcinoma (HCC), the third leading cause of mortality related cancer. The advance in methylation modification of chromatin elements (for both genomic DNA and histone tails) and the emerging roles of long noncoding RNA (lncRNA) have given us a better understanding of molecular mechanisms underlying HCC. Recently, methods like genome-wide lncRNA profiling and histone hallmark detection were reported to discover mass tumor-associated lncRNAs epigenetically deregulated by differential chromosome modification, mainly by genomic DNA and histone methylation. Therefore, aberrant methylation modification of certain particular lncRNA genes could be crucial events correlating with unfavorable outcomes in HCC. In addition, amount of lncRNAs could act as a manipulator for DNA methylation or a scaffold for histone modification to affect key signaling pathways in hepatocarcinogenesis. This suggests that methylation modification of chromatin elements may have functional crosstalk with lncRNA. Here, we aim to outline the emerging role of the methylation and lncRNA, and their crosstalk of molecular mechanism. [ABSTRACT FROM AUTHOR]

Background: Activating transcription factor 2 (ATF2) is a basic helix-loop-helix transcription factor, which has been shown to participate in the pathobiology of numerous cancers. However, the role of ATF2 in renal cell carcinoma (RCC) remains unclear. Methods: ATF2 knockdown and overexpression studies were performed in RCC cells to evaluate changes in cell viability, cell cycle, apoptosis, migration and invasion. Xenograft models were used to examine the tumorigenic and metastatic capability of RCC cells upon ATF2 suppression. The expression of ATF2 in human RCC samples was determined using immunohistochemistry on a tissue microarray. Results: ATF2 knockdown in RCC cells reduced their proliferative and metastatic potentials, whereas ATF2 overexpression enhanced these properties. Mechanistic studies revealed that the transcription of CyclinB1, CyclinD1, Snail and Vimentin was directly regulated by ATF2 in RCC cells. Moreover, ATF2 was shown to be highly expressed in RCC tissues, especially in tumors with metastases. High expression of ATF2 correlated with aggressive clinico-pathological characteristics and predicted poor prognosis of RCC patients. Conclusions: ATF2 exerts an oncogenic role in RCC and could serve as an important prognostic biomarker. [ABSTRACT FROM AUTHOR]

Objectives DNA methyltransferases (DNMTs) are an important part of the methylation pathway that is highly correlated with the pathophysiology of cancers. Several studies have reported overexpression of DNMTs in human lung cancer, but none have compared the expression pattern to pathological features. In this study, we clarified the association of DNMT3a expression pattern with pathological features and prognosis of lung adenocarcinoma. Materials and methods 135 cases of surgically resected lung adenocarcinoma specimens were used for DNMT3a immunohistochemistry (IHC). IHC score was determined by counting the number of positive nuclei. The ROC curve was drawn to determine the best cut-off point of the score; this was set at 57.5. Western blot also implemented and confirmed the specificity of the antibody. Correlations between expression pattern and clinicopathological features and prognosis were analyzed using chi-squared method and Cox proportional hazards model respectively. Result Seventy-nine of the 135 cases (58.5%) showed strong positive reactivity to anti-DNMT3a. In terms of histological subtypes, among invasive lung adenocarcinomas 41 out of 53 lepidic adenocarcinomas (77%) were strongly positive, while among the other histological subtypes only 23 out of 66 cases (34.8%) showed a positive reaction. Among non-invasive lung adenocarcinomas 15 out of 16 cases (93.8%) were strongly positive. The level of DNMT3a expression was associated with patient outcome, and patients with weak expression of DNMT3a had a poorer outcome than those with strong expression. Multivariate analysis also indicated that DNMT3a is an independent prognostic marker in lung adenocarcinoma. Conclusion Our results indicate that DNMT3a expression in lung adenocarcinoma is associated with the histologically non-invasive type and lepidic subtype, and a favorable prognosis. We also showed that DNMT3a expression is an independent prognostic marker in lung adenocarcinoma. Since lack of DNMT3a is thought to facilitate tumor progression, DNMT3a might be clinically applicable as an indicator of favorable prognosis. [ABSTRACT FROM AUTHOR]

Since basement membranes represent a critical barrier during breast cancer progression, timely imaging of these signposts is essential for early diagnosis of breast cancer. A label-free method using multiphoton microscopy (MPM) based on two-photon excited fluorescence signals and second harmonic generation signals for analyzing the morphology of basement membrane in normal and cancerous breast tissues is likely to enable a better understanding of the pathophysiology of breast cancer and facilitate improved clinical management and treatment of this disease. The aim of this study was to determine whether MPM has the potential for label-free assessment of the morphology of basement membrane in normal and cancerous breast tissues. A total of 60 tissue section samples (comprising 30 fresh breast cancer specimens and 30 normal breast tissues) were first imaged (fresh, unfixed and unstained) with MPM and are then processed for routine hematoxylin and eosin (H&E) histopathology. Comparisons were made between MPM imaging and gold standard sections for each specimen stained with H&E. Simply by visualizing morphological features appearing on multiphoton images, cancerous lesions may be readily identified by the loss of basement membrane and tumor cells characterized by irregular size and shape, enlarged nuclei and increased nuclear-cytoplasmic ratio. These results suggest that MPM has potential as a label-free method of imaging the morphology of basement membranes and cell features to effectively distinguish between normal and cancerous breast tissues. [ABSTRACT FROM AUTHOR]

Background: Females 80 years and older comprise 22% of the total U.S. survivor population, yet the impact of cancer on the physical well-being of women is this age group has not been well characterized.Methods: We compared women, 80 years of age and older in the Women's Health Initiative extension 2, who did (n = 2,270) and did not (n = 20,272) have an adjudicated history of cancer during Women's Health Initiative enrollment; analyses focused on women >2-years postcancer diagnosis. The physical functioning subscale of the RAND-36 was the primary outcome. Demographic, health-status, and psychosocial covariates were drawn from Women's Health Initiative assessments. Analysis of covariance was used to examine the effect of cancer history on physical function, with and without adjustment for covariates.Results: In adjusted models, women with a history of cancer reported significantly lower mean physical functioning (56.6, standard error [SE] 0.4) than those without a cancer history (58.0, SE 0.1), p = .002. In these models, younger current age, lower body mass index, increased physical activity, higher self-rated health, increased reported happiness, and the absence of noncancer comorbid conditions were all associated with higher physical functioning in both women with and without a history of cancer.Conclusions: Women older than 80 years of age with a cancer history have only a moderately lower level of physical function than comparably aged women without a cancer history. Factors associated with higher levels of physical functioning were similar in both groups. [ABSTRACT FROM AUTHOR]