Search

Cancer is the most challenging global health crisis. In the recent times, studies on extracellular vesicles (EVs) are adding a new chapter to cancer research and reports on EVs explores cancer in a new dimension. Exosomes are a group of subpopulations of EVs. It originates from the endosomes and carries biologically active molecules to the neighboring cells which in turn transforms the recipient cell activity. In general, it plays a role in cellular communication. The correlation between exosomes and cancer is fascinating. Tumor-derived exosomes (TEXs) play a dynamic role in cancer progression and are associated with uncontrolled cell growth, angiogenesis, immune suppression, and metastasis. Its molecular cargo is an excellent source of cancer biomarkers. Several advanced molecular profiling approaches assist in exploring the TEXs in depth. This paves the way for a strong foundation for identifying and detecting more specific and efficient biomarkers. TEXs are also gaining importance in scientific society for its role in cancer therapy and several clinical trials based on TEXs is a proof of its significance. In this review, we have highlighted the role of TEXs in mediating immune cell reprogramming, cancer development, metastasis, EMT, organ-specific metastasis, and its clinical significance in cancer theranostics. TEXs profiling is an effective method to understand the complications associated with cancer leading to good health and well-being of the individual and society as a whole. [ABSTRACT FROM AUTHOR]

Regardless of the significant progress made in surgical techniques and adjuvant therapies, brain tumors are a major contributor to cancer-related morbidity and mortality in both pediatric and adult populations. Gliomas represent a significant proportion of cerebral neoplasms, exhibiting diverse levels of malignancy. The etiology and mechanisms of resistance of this malignancy are inadequately comprehended, and the optimization of patient diagnosis and prognosis is a challenge due to the diversity of the disease and the restricted availability of therapeutic options. Metabolomics refers to the comprehensive analysis of endogenous and exogenous small molecules, both in a targeted and untargeted manner, that enables the characterization of an individual's phenotype and offers valuable insights into cellular activity, particularly in the context of cancer biology, including brain tumor biology. Metabolomics has garnered attention in current years due to its potential to facilitate comprehension of the dynamic spatiotemporal regulatory network of enzymes and metabolites that enables cancer cells to adapt to their environment and foster the development of tumors. Metabolic changes are widely acknowledged as a significant characteristic for tracking the advancement of diseases, treatment efficacy, and identifying novel molecular targets for successful medical management. Metabolomics has emerged as an exciting area for personalized medicine and drug discovery, utilizing advanced analytical techniques such as nuclear magnetic resonance spectroscopy (MRS) and mass spectrometry (MS) to achieve high-throughput analysis. This review examines and highlights the latest developments in MRS, MS, and other technologies in studying human brain tumor metabolomics. [ABSTRACT FROM AUTHOR]

Cancer and related diseases are the second leading cause of death worldwide. The human papillomavirus (HPV) is an infectious agent that can be spread mainly through sexual contact and has been linked to several malignancies in both sexes. HPV is linked to almost all cases of cervical cancer. It is also linked to many head and neck cancer (HNC) cases, especially oropharyngeal cancer. Also, some HPV-related cancers, like vaginal, vulvar, penile, and anal cancers, are related to the anogenital area. Over the past few decades, testing for and preventing cervical cancer has improved, but anogenital cancers are still harder to confirm. HPV16 and HPV18 have been extensively researched due to their significant carcinogenic potential. The products of two early viral genes, E6 and E7, have been identified as playing crucial roles in cellular transformation, as emphasized by biological investigations. The complete characterization of numerous mechanisms employed by E6 and E7 in undermining the regulation of essential cellular processes has significantly contributed to our comprehension of HPV-induced cancer progression. This review focuses on the various types of cancers caused by HPV infection and also sheds light on the signaling cascades involved in the same. [ABSTRACT FROM AUTHOR]

Breast cancer is the most common type of cancer and the second most common cause of death. Influential and widely accepted breast cancer prevention strategies are still elusive. Aspirin and other nonsteroidal anti-inflammatory drugs, such as ibuprofen, are frequently recommended to treat fever, pain, and inflammation. Studies have shown that these medications also have anticancer effects. A key target of tumor-targeted therapy has been discovered in recent years, and it is the PI3K/AKT/mTOR signalling pathway. In order for tumour cells to proliferate, develop, migrate, and survive, the PI3K/AKT/mTOR signalling system is essential. So, using in silico analysis, we chose to determine whether the NSAID Diclofenac and other phytochemicals have anticancer properties and also act as PI3K/AKT/mTOR inhibitors. We conducted docking analyses for the drugs diclofenac, piperine, naringin, eugenol, d-limonene, cinnamaldehyde, and curcumin versus the FDA-approved AKT/PI3K and mTOR inhibitors alpelisib, rapamycin, and afuresertib. Both bioactivity and ADMET profiling were done for these drugs. We concluded from our in silico analysis that diclofenac, d-limonene, and piperine do not contradict any of Lipinski's rules and can be effective AKT/PI3K/mTOR inhibitors. [ABSTRACT FROM AUTHOR]

Infection with viruses, bacteria, and parasites are thought to be the underlying cause of about 8–17% of the world's cancer burden, i.e., approximately one in every five malignancies globally is caused by an infectious pathogen. Oncogenesis is thought to be aided by eleven major pathogens. It is crucial to identify microorganisms that potentially act as human carcinogens and to understand how exposure to such pathogens occur as well as the following carcinogenic pathways they induce. Gaining knowledge in this field will give important suggestions for effective pathogen-driven cancer care, control, and, ultimately, prevention. This review will mainly focus on the major onco-pathogens and the types of cancer caused by them. It will also discuss the major pathways which, when altered, lead to the progression of these cancers. [ABSTRACT FROM AUTHOR]

Byline: Aayush. Poddar, Ritchlynn. Aranha, Madhav. Royam, Kodiveri. Gothandam, Ramesh. Nachimuthu, Rama. Jayaraj BACKGROUND: Head and neck cancer (HNC) is a heterogeneous tumor at various anatomic sites and one of [...]

Dual drug delivery has become the choice of interest nowadays due to its increased therapeutic efficacy in targeting the tumor site precisely. As quoted in recent literature, it has been known to treat several cancers with an acute course of action. Even so, its use is restricted due to the drug's low pharmacological activity, which leads to poor bioavailability and increases first-pass metabolism. To overcome these issues, a drug delivery system using nanomaterials which would not only encapsulate the drugs of interest but also carry them to the target site of action is needed. Given all these attributes, we have formulated dual drug-loaded nanoliposomes with cisplatin (cis-diamminedichloroplatinum(II) (CDDP)), an effective anti-cancer drug, and diallyl disulfide (DADS), an organosulfur compound derived from garlic. The CDDP and DADS-loaded nanoliposomes (Lipo-CDDP/DADS) exhibited better physical characteristics such as size, zeta potential, polydispersity index, spherical shape, optimal stability, and satisfactory encapsulation percentage. The in vitro anti-cancer activity against MDA-MB-231 and A549 cell lines revealed that Lipo-CDDP/DADS showed significant efficacy against the cancer cell lines, depicted through cell nucleus staining. We conclude that Lipo-CDDP/DADS hold exceptional pharmacological properties with better anti-cancer activity and would serve as a promising formulation to treat various cancers. [ABSTRACT FROM AUTHOR]

Background: Chemoresistance is a significant barrier to combating head and neck cancer, and decoding this resistance can widen the therapeutic application of such chemotherapeutic drugs. This systematic review and meta-analysis explores the influence of microRNA (miRNA) expressions on chemoresistance in head and neck cancers (HNC). The objective is to evaluate the theragnostic effects of microRNA expressions on chemoresistance in HNC patients and investigate the utility of miRNAs as biomarkers and avenues for new therapeutic targets. Methods: We performed a comprehensive bibliographic search that included the SCOPUS, PubMed, and Science Direct bibliographic databases. These searches conformed to a predefined set of search strategies. Following the PRISMA guidelines, inclusion and exclusion criteria were framed upon completing the literature search. The data items extracted were tabulated and collated in MS Excel. This spreadsheet was used to determine the effect size estimation for the theragnostic effects of miRNA expressions on chemoresistance in HNC, the hazard ratio (HR), and 95% confidence intervals (95% CI). The comprehensive meta-analysis was performed using the random effects model. Heterogeneity among the data collected was assessed using the Q test, Tau2, I2, and Z measures. Publication bias of the included studies was checked using the Egger's bias indicator test, Orwin and classic fail-safe N test, Begg and Mazumdar rank collection test, and Duval and Tweedie's trim and fill methods. Results: After collating the data from 23 studies, dysregulation of 34 miRNAs was observed in 2189 people. These data were gathered from 23 studies. Out of the 34 miRNAs considered, 22 were up-regulated, while 12 were down-regulated. The TaqMan transcription kits were the most used miRNA profiling platform, and miR-200c was seen to have a mixed dysregulation. We measured the overall pooled effect estimate of HR to be 1.516 for the various analyzed miRNA at a 95% confidence interval of 1.303–1.765, with a significant p-value. The null hypothesis test's Z value was 5.377, and the p-value was correspondingly noted to be less than 0.0001. This outcome indicates that the risk of death is determined to be higher in up-regulated groups than in down-regulated groups. Among the 34 miRNAs that were investigated, seven miRNAs were associated with an improved prognosis, especially with the overexpression of these seven miRNAs (miR15b-5p, miR-548b, miR-519d, miR-1278, miR-145, miR-200c, Hsa- miR139-3p). Discussion: The findings reveal that intricate relationships between miRNAs' expression and chemotherapeutic resistance in HNC are more likely to exist and can be potential therapeutic targets. This review suggests the involvement of specific miRNAs as predictors of chemoresistance and sensitivity in HNC. The examination of the current study results illustrates the significance of miRNA expression as a theragnostic biomarker in medical oncology. [ABSTRACT FROM AUTHOR]

Background: The most often diagnosed malignancy in women worldwide is cancer of the cervix. It is also the most prevalent kind of gynecological cancer in women. This cancer originates in the opening of the cervix and spreads through sexual contact. Even though human papillomavirus (HPV) may not cause cancer immediately, it does develop over time as a result of the virus's lengthy persistence to cause dysplastic changes overtime, particularly in high-risk kinds. The primary objective of this research is to see if miRNAs are dysregulated as a result of treatment resistance in cervical cancer (CC). The aim is to see if these microRNAs may be utilized as biomarkers for detecting chemoresistance in CC, particularly for clinical applications. Methods: The recommended protocol for comprehensive study and meta-analysis (PRISMA-P) standards will be utilized for the analysis and data interpretation. The bibliographic databases will be methodically searched using a combination of search keywords. Based on established inclusion and exclusion criteria, the acquired findings will be reviewed, and data retrieved from the selected scientific papers for systematic review. We will then construct a forest from the pooled Hazard ratio (HR) and 95% C.I. values, data obtained using the random-effects model. Discussion: The focus of this study is to identify the function of miRNAs as a chemoresistance regulator and determine if they have the potential scope to be considered as biomarkers for cervical cancer. Through this systematic review and meta-analysis, the goal is to collect, compare, and analyze the data pertaining to the role of miRNAs in cervical cancer, thereby, enabling us to understand the role they play in chemosensitivity. [ABSTRACT FROM AUTHOR]

miRNAs biomarkers are emerging as an essential part of clinical oncology. Their oncogenic and tumour suppressor properties playing a role in malignancy has generated interest in their potential for use in disease prognosis. While several studies on miRNA have been carried out across the globe, evaluating the clinical implications of miRNAs in cancer diagnosis and prognosis research has currently not been attempted. A study delineating the area of miRNA research, including the topics presently being focused on, the seminal papers in this field, and the direction of research interest, does not exist. This study aims to conduct a large-scale, global data analysis and bibliometric profiling analysis of studies to evaluate the research output of clinical implications of miRNAs in cancer diagnosis and prognosis listed in the SCOPUS database. A systematic search strategy was followed to identify and extract all relevant studies, subsequently analysed to generate a bibliometric map. SPSS software (version 27) was used to calculate bibliometric indicators or parameters for analysis, such as year and country of affiliation with leading authors, journals, and institutions. It is also used to analyse annual research outputs, including total citations and the number of times it has been cited with productive nations and H-index. The number of global research articles retrieved for miRNA-Cancer research over the study period 2003 to 2019 was 18,636. Between 2012 and 2019, the growth rate of global publications is six times (n = 15,959; 90.71 percent articles) that of 2003 to 2011. (2704; 9.29 per cent articles). China published the most publications in the field of miRNA in cancer (n = 7782; 41%), while the United States had the most citations (n = 327,538; 48%) during the time span. Of these journals, Oncotarget has the highest percentage of article publications. The journal Cancer Research had the most citations (n = 41,876), with 6.20 per cent (n = 41,876). This study revealed a wide variety of journals in which miRNA-Cancer research are published; these bibliometric parameters exhibit crucial clinical information on performance assessment of research productivity and quality of research output. Therefore, this study provides a helpful reference for clinical oncologists, cancer scientists, policy decision-makers and clinical data researchers. [ABSTRACT FROM AUTHOR]

Zingiber officinale (ZO) and Terminalia chebula (TC) are plants used for the treatment of diverse illnesses in traditional medicine. The present study investigates the preventive effect of Zingiber officinale–Terminalia chebula extract (ZOTC) against DMBA-induced breast cancer in a rat model. Bioactive compounds from ZO (6-gingerol, 6-shogaol) and TC (gallic acid, ellagic acid, corilagin, chebulinic acid, and chebulagic acid) were detected using high-performance liquid chromatography. Mammary carcinogenesis was induced in rats with a single subcutaneous injection of 7,12-Dimethylbenz[a]anthracene (DMBA). Oral administration of ZOTC ameliorated the antioxidant status in mammary tissues, serum lipid levels, and serum cytokines. Histological analysis of the mammary tissue (normal and tumor) was carried out to obtain pathological alterations due to ZOTC treatment. The effect of ZOTC on the mechanistic target of rapamycin (mTOR) gene and accumulation of corresponding gene product was also investigated. mTOR plays a central role in cell metabolism and proliferation in normal and cancer cells. Transcriptional and immunohistochemical analysis showed the downregulation of mTOR expression in the mammary tissues of ZOTC-treated rats. In conclusion, the results obtained suggest that ZOTC can suppress tumor progression in DMBA-induced breast cancer rats via inhibition of the mTOR pathway. [ABSTRACT FROM AUTHOR]

Abstract Background Globally, alcohol-related injuries cause millions of deaths and huge economic loss each year . The incidence of facial (jawbone) fractures in the Northern Territory of Australia is second only to Greenland, due to a strong involvement of alcohol in its aetiology, and high levels of alcohol consumption. The highest incidences of alcohol-related trauma in the Territory are observed amongst patients in the Maxillofacial Surgery Unit of the Royal Darwin Hospital. Accordingly, this project aims to introduce screening and brief interventions into this unit, with the aims of changing health service provider practice, improving access to care, and improving patient outcomes. Methods Establishment of Project Governance: The project governance team includes a project manager, project leader, an Indigenous Reference Group (IRG) and an Expert Reference Group (ERG). Development of a best practice pathway: PACT project researchers collaborate with clinical staff to develop a best practice pathway suited to the setting of the surgical unit. The pathway provides clear guidelines for screening, assessment, intervention and referral. Implementation: The developed pathway is introduced to the unit through staff training workshops and associate resources and adapted in response to staff feedback. Evaluation: File audits, post workshop questionnaires and semi-structured interviews are administered. Discussion This project allows direct transfer of research findings into clinical practice and can inform future hospital-based injury prevention strategies.

Background: Oral squamous cell carcinoma (OSCC) is a malignant oral cavity neoplasm that affects many people, especially in developing countries. Despite several advances that have been made in diagnosis and treatment, the morbidity and mortality rates due to OSCC remain high. Accumulating evidence indicates that aberrant activation of cellular signaling pathways, such as the Notch, Wnt and Hedgehog pathways, occurs during the development and metastasis of OSCC. In this review, we have articulated the roles of the Notch, Wnt and Hedgehog signaling pathways in OSCC and their crosstalk during tumor development and progression. We have also examined possible interactions and associations between these pathways and treatment regimens that could be employed to effectively tackle OSCC and/or prevent its recurrence. Conclusions: Activation of the Notch signaling pathway upregulates the expression of several genes, including c-Myc, β-catenin, NF-κB and Shh. Associations between the Notch signaling pathway and other pathways have been shown to enhance OSCC tumor aggressiveness. Crosstalk between these pathways supports the maintenance of cancer stem cells (CSCs) and regulates OSCC cell motility. Thus, application of compounds that block these pathways may be a valid strategy to treat OSCC. Such compounds have already been employed in other types of cancer and could be repurposed for OSCC. [ABSTRACT FROM AUTHOR]

Abstract Background The incidence of mandibular fractures in the Northern Territory of Australia is very high, especially among Indigenous people. Alcohol intoxication is implicated in the majority of facial injuries, and substance use is therefore an important target for secondary prevention. The current study tests the efficacy of a brief therapy, Motivational Care Planning, in improving wellbeing and substance misuse in youth and adults hospitalised with alcohol-related facial trauma. Methods and design The study is a randomised controlled trial with 6 months of follow-up, to examine the effectiveness of a brief and culturally adapted intervention in improving outcomes for trauma patients with at-risk drinking admitted to the Royal Darwin Hospital maxillofacial surgery unit. Potential participants are identified using AUDIT-C questionnaire. Eligible participants are randomised to either Motivational Care Planning (MCP) or Treatment as Usual (TAU). The outcome measures will include quantity and frequency of alcohol and other substance use by Timeline Followback. The recruitment target is 154 participants, which with 20% dropout, is hoped to provide 124 people receiving treatment and follow-up. Discussion This project introduces screening and brief interventions for high-risk drinkers admitted to the hospital with facial trauma. It introduces a practical approach to integrating brief interventions in the hospital setting, and has potential to demonstrate significant benefits for at-risk drinkers with facial trauma. Trial Registration The trial has been registered in Australian New Zealand Clinical Trials Registry (ANZCTR) and Trial Registration: ACTRN12611000135910.

Background: An edible tuber named Amorphophallus commutatus var. wayanadensis (ACW) is used by the local ethnic communities of Wayanad, India, for hemorrhoids while the health benefits remain unexplored to the scientific community. Objectives: Hence, our study was performed to screen the anti-inflammatory and analgesic activities of ACW. Materials and Methods: Screening for the in vitro anti-inflammatory potential on isolated peritoneal macrophages was performed using nitrite assay, nitroblue tetrazolium assay, tumor necrosis factor (TNF)-α production, and cyclooxygenase (COX) enzyme activity. Carrageenan- and formalin-induced paw edema assays were performed to determine anti-inflammatory potential, while tail immersion assays and acetic acid-induced writhing assays were carried out to explore antinociceptive activity in animal models. Results: Bio-molecular mechanistic investigation to evaluate the in-vitro anti-inflammatory activity confirmed the suppressive effect of MEAC on TNF-α, nitric oxide and COX-2 on lipopolysaccharide stimulated peritoneal macrophages, which benchmarked ACW as a potent medicinal plant against inflammation. Further, the efficacy of methanolic extract of A. commutatus var. wayanadensis (MEAC) as an anti-inflammatory agent in murine anti-inflammatory models was demonstrated by formalin- and carrageenan-induced paw edema assays. Administration of MEAC significantly increased the tail flicking latency in mice and also showed prominent reduction in the number of writhes induced by acetic acid, which establishes the real time application of ACW as an analgesic agent. Conclusion: The vital information regarding in vitro and in vivo action of MEAC provided scientific evidence for its traditional usage for hemorrhoids. Thus, this herbal medicine of ethnic tribes can be translated toward modern medicine for health maintenance and disease prevention. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is prevalent cancer among women and a major cause of death worldwide due to various genetic and environmental factors. Citrus sinensis is widely taken fruit juice in most countries that are believed to reduce breast cancer risk. However, the mechanism through which it acts remains unclear. Our objective was to explore the mechanism through which Citrus sinensis acts as a cytotoxic agent. Materials and Methods: FT-IR and GC-MS analyses of lyophilzed orange juice (LOJ) were performed to find phytocompounds that were subjected to in silico docking analysis against phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway. The proteins that showed the low free energy of binding was taken for gene expression analysis. RT-PCR analysis was carried out to observe PI3K/AKT/mTOR genes inhibition in LOJ treated cells. Cytotoxicity, apoptosis, caspase 9 activity were performed against the human breast cancer cell line (MCF-7). Results: The docking analysis against PI3K/AKT/mTOR with LOJ compounds showed the best interactions. Further down-regulation of PI3K/AKT and moderate up-regulation of mTOR was confirmed using gene expression analysis. LOJ showed concentration-dependent cytotoxicity, apoptosis, decreased mitochondrial membrane stability and caspase 9 against the MCF-7 cell line. Conclusion: This study concludes that LOJ can induce apoptosis in MCF-7 cells via PI3K and AKT inhibition. [ABSTRACT FROM AUTHOR]

Purpose: T-cell acute lymphoblastic leukemia (T-ALL) affects lymphoid cells. Previous studies have reported that miRNAs play a significant role in T-ALL prognosis and have the potential to function as biomarkers in T-ALL. Therefore, this systematic review and meta-analysis study was designed to evaluate the overall prognostic impact of miRNAs in T-ALL patients. Methods: Eligible studies published between Jan 2010 and April 2018 were retrieved from online bibliographic databases based on multiple keywords to generate search strings. Meta-analysis was performed using the outcome measure, Hazard Ratio (HR). A survival analysis of all studies was conducted and a subsequent forest plot was generated to evaluate the pooled effect size, across all T-ALL patients. Subgroup analysis was conducted based on demographic characteristics and commonly represented miRNAs among the included studies. Results: A total of 17 studies were included for systematic review, among which 16 studies were eligible for meta-analysis, which, in total discussed 32 different miRNAs. The mean effect size of HR value was 0.929 (CI 0.878– 0984), which indicates a decrease in risk of death by 7.1%. The analysis was based on the random effects model with the heterogeneity measure index (I 2) being 84.92%. The pooled effect size (HR) of upregulated and downregulated miRNA expressions on survival outcome in the T-ALL patient was 0.787 (CI 0.732– 0.845) and 1.225 (CI 1.110– 1.344) respectively. The subgroup analysis was performed based on demographic characteristics (age, gender, lactate dehydrogenase, WBC count) and expression of miR221 and miR46a. Conclusion: Our systematic review and meta-analysis findings suggest that the overall miRNA expression is potentially associated with a decreased likelihood of death in T-ALL patients. Although our findings are inconclusive, the results point toward miRNA expression allowing for prognostic evaluation of T-ALL patients. [ABSTRACT FROM AUTHOR]

Background: We performed a systematic review and meta-analysis to identify and underline multiple microRNAs (miRNAs) as biomarkers of disease prognosis in stage II colorectal cancer (CRC) patients. Methods and analysis: This systematic review and meta-analysis study was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The required articles were collected from online bibliographic databases from January 2011 to November 2019 with multiple permutation keywords. Quantitative data synthesis was based on a meta-analysis with pooled data to observe and analyse the outcome measures and effect estimates by using the random effect model. The subgroup analysis was performed from demographic characteristics and the available data. Results: Eighteen articles were included in this study, 16 of which were incorporated for meta-analysis to examine the stage II CRC prognosis with up- and downregulated miRNA expressions. The pooled hazard ratio (HR) for death in stage II CRC patients was 1.90 (95% confidence interval 1.63–2.211), with a significant p value. A subgroup analysis based on up- or downregulated miRNA expression individually and any deregulated miRNA was also associated with a worse prognosis. The subgroup analysis included parameters such as age, gender, stage II and III combined patients' survival and the repetitive miRNAs (miR21, miR215, miR143-5p, miR106a and miR145) individually. Conclusion: MicroRNAs play a significant role in determining prognosis in stage II CRC patients, with upregulation of miR21, miR215, miR143-5p and miR106a, in particular, portending a worse prognosis. These miRNAs could be considered for further evaluation as biomarkers of prognosis and to guide the decision to administer adjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

Background: Forkhead box C1 (FOXC1), a member of the Forkhead box (Fox) transcription factor family, plays an essential role in lymphatic vessel formation, angiogenesis and metastasis. Observational studies examining the relationship between the protein biomarker FOXC1 and breast cancer prognosis have reported conflicting findings. This systematic review and meta-analysis evaluates the prognostic value of the FOXC1 expression in association with patient survival in breast cancer and other types of cancers in order to identify the overall prognostic effectiveness of FOXC1. Methods: This study followed the guidelines established in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We conducted a broad search on the online bibliographic databases EMBASE, PubMed, Science Direct and Scopus, limiting search to publications from 2010 to 2018. The prognostic value was demonstrated by a random effects model meta-analysis using the hazard ratio (HR) with 95% confidence interval (CI) for overall survival (OS) in various cancer patients. The heterogeneity was measured by the I2 statistic. Publication bias and quality assessment for the selected articles was performed. Subgroup analysis was conducted based on the data available from the selected articles. Results: A total of 16 studies met the predefined selection criteria established for our systematic review and meta-analysis, with multiple studies using diverse methodologies and reported on differing clinical outcomes, falling under a common banner of FOXC1 expression and survival in cancer. Overall, we observed a statistically non-significant association between FOXC1 protein expression and patients survival (HR: 1.186 and 95% CI 1.122–1.255, p = 0.000, I2 = 88.83%). Conclusion: In summary, FOXC1 protein expression indicated poor survival outcome in various carcinomas, especially in patients with breast cancer, suggesting it as a possible biomarker for the prognosis in multiple carcinomas. Further clinical evaluation and large-scale cohort studies are required to accurately identify its possible clinical utility. [ABSTRACT FROM AUTHOR]

Highlights • The immunogenicity and efficacy of Fasciola DNA vaccines have been comprehensively summarised in a systematic review and meta-analysis. • Moderate protective efficacy was observed for Cysteine Protease and Phosphoglycerate Kinase. • Meta-analysis revealed that DNA vaccines with cysteine protease or phosphoglycerate kinase as the antigen. • DNA vaccines lead to overall heightened protective efficacy across all included studies. Abstract The immunogenicity and efficacy of Fasciola DNA vaccines have not yet been comprehensively summarised in the form of a systematic review and meta-analysis. Though multiple vaccine studies with respect to Fasciola vaccines exist, the variance in the experimental parameters has made comparison difficult. We conducted a bibliographic database search in Scopus, PubMed, Science Direct, Cochrane Library, EMBASE and Web of Science databases, limited to publications from 1998 to 2017. The key words: Liver fluke, Fasciola hepatica , Fasciola gigantica , DNA vaccination, and immunogenicity were used in combination to form search strings. A total of 4760 studies were identified after initial screening, of which 14 qualified for systematic review and 7 for meta-analysis. The mean Odds Ratio (OR) for all studies was 0.565 (95% confidence interval (CI) of 0.293 to 1.087), which means the percentage of protection in terms of decreased fluke burden in animals vaccinated with DNA vaccines was 43.5%. A moderate protective efficacy was observed for cysteine protease and phosphoglycerate kinase vaccine antigen candidates (pooled OR and 95% CI, [0.542; 0.179–1.721] and [0.616; 0.219–1.735], respectively). Vaccine effectiveness was observed in individual studies and cohorts; however, the overall pooled efficacy for all vaccine candidates was found to be non-significant. Despite multiple individual studies showing promising results for various DNA vaccine candidates against fascioliasis, the pooled studies showed the non-significant effect of the vaccine formulations against fluke burden, and displayed minimal protective efficacy against Fasciola infection. Though promising results are observed in isolated studies, further animal trials with standardised experimental parameters are required to develop new vaccine candidates effective against Fasciola. [ABSTRACT FROM AUTHOR]

Background: Nasopharyngeal cancer (NPC), despite being one of the most malignant head and neck carcinomas (HNC), lacks comprehensive prognostic biomarkers that predict patient survival. Therefore, this systematic review and meta-analysis is aimed to evaluate the potential prognostic value of miRNAs as prognostic biomarkers in NPC. Methods: PRISMA guidelines were used to conduct this systematic review and meta-analysis study. Permutations of multiple “search key-words” were used for the search strategy, which was limited to articles published between January 2012 and March 2018. The retrieved articles were meticulously searched with multi-level screening by two reviewers and confirmed by other reviewers. Meta-analysis was performed using Hazard Ratios (HR) and associated 95% Confidence Interval (CI) of survival obtained from previously published studies. Publication bias was assessed by Egger’s bias indicator test and funnel plot symmetry. Results: A total of 5069 patients across 21 studies were considered eligible for inclusion in the systematic review, with 65 miRNAs being evaluated in the subsequent meta-analysis. Most articles included in this study originated from China and one study from North Africa. The forest plot was generated using cumulated survival data, resulting in a pooled HR value of 1.196 (95% CI: 0.893–1.601) indicating that the upregulated miRNAs increased the likelihood of death of NPC patients by 19%. Conclusion: To our knowledge, this is the first meta-analysis that examines the prognostic effectiveness of miRNAs as biomarkers in NPC patients. We noted that the combined effect estimate of HR across multiple studies indicated that increased miRNA expression in NPC potentially leads to poor overall survival. However, further large-scale prospective studies on the clinical significance of the miRNAs, with sizable cohorts are necessary in order to obtain conclusive results. [ABSTRACT FROM AUTHOR]

Background: Findings from observational clinical studies examining the relationship between biomarker expression and theranosis in colorectal cancer (CRC) have been conflicting.Objective: We conducted this systematic review and meta-analysis to summarise the existing evidence to demonstrate the involvement of microRNAs (miRNAs) in chemoresistance and sensitivity in CRC through drug genetic pathways.Methods: Using PRISMA guidelines, we systematically searched PubMed and Science Direct for relevant studies that took place between 2012 and 2017. A random-effects model of meta-analysis was applied to evaluate the pooled effect size of hazard ratios (HRs) across the included studies. Cochran's Q test and the I2 statistic were used to detect heterogeneity. A funnel plot was used to assess potential publication bias.Results: Of the 4700 studies found, 39 studies comprising 2822 patients with CRC met the inclusion criteria. The included studies used one or a combination of 14 chemotherapy drugs, including 5-fluorouracil and oxaliplatin. Of the 60 miRNAs, 28 were associated with chemosensitivity, 20 with chemoresistance, and one with differential expression and radiosensitivity; ten miRNAs were not associated with any impact on chemotherapy. The results outline the importance of 34 drug-regulatory pathways of chemoresistance and sensitivity in CRC. The mean effect size was 0.689 (95% confidence interval 0.428-1.110), indicating that the expression of miRNAs decreased the likelihood of death by about 32%.Conclusion: Studies have consistently shown that multiple miRNAs could act as clinical predictors of chemoresistance and sensitivity. An inclusion of supplementary miRNA estimation in CRC routine practice needs to be considered to evaluate the efficacy of chemotherapy after confirming our findings with large-scale prospective cohort studies.PROSPERO registration number: CRD42017082196. [ABSTRACT FROM AUTHOR]

Background: Melanoma is the most aggressive and deadly form of skin cancer. The molecular variability involving microRNA (miRNA) expression plays a significant role in melanogenesis, which leads to poor prognostic effects in melanoma. Since there is a scarcity of comprehensive data on the prognostic role of miRNAs in melanoma patients, this study focuses on filling this knowledge gap through a systematic review and meta-analysis.Methods: The included studies were extracted from several bibliographic databases between 2012 and 2018 using multiple keywords according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The hazard ratios (HRs) and 95% confidence intervals (CIs) for different survival endpoints were compared to the high and low expression levels of miRNAs. The mean effect size of HR values was estimated using a random-effects model of meta-analysis. Inverted funnel plot symmetry was used to assess publication bias. Subgroup analysis was carried out individually for multiple miRNAs across different studies.Results: A total of 24 studies across eight countries were included, of which 16 studies were eligible for meta-analysis. Twenty-five miRNA expression levels were studied from 2669 melanoma patients to estimate the association between the prognostic role of miRNAs and survival outcome in these 16 studies. The overall pooled effect size (HR) for up- and downregulated miRNAs was 1.043 (95% CI 0.921-1.181; p = 0.506), indicating that the miRNA expression increased the likelihood of death in melanoma patients by 4.3%. Subgroup analysis for miRNA10b, miRNA16 and miRNA21 showed a poor prognosis. The quality assessment revealed that 16 studies were good quality and eight studies were of fair quality.Conclusion: This is one of the first pooled meta-analysis studies on the role of miRNAs in the prognosis of melanoma. Our findings are inconclusive but suggest that miRNA expression could predict poor survival in melanoma patients. Therefore, miRNA expression could act as promising prognostic marker for melanoma. [ABSTRACT FROM AUTHOR]

Objectives Treatment failure and poor 5-year survival in mucosal head and neck squamous cell carcinoma (HNSCC) has remained unchanged for decades mainly due to advanced stage of presentation and high rates of recurrence. Incomplete surgical removal of the tumour, attributed to lack of reliable methods to delineate the surgical margins, is a major cause of disease recurrence. The predictability of recurrence using immunohistochemistry (IHC) to delineate surgical margins (PRISM) in mucosal HNSCC study aims to redefine margin status by identifying the true extent of the tumour at the molecular level by performing IHC with molecular markers, eukaryotic initiation factor, eIF4Eand tumour suppressor gene, p53, on the surgical margins and test the use of Lugol's iodine and fluorescence visualisation prior to the wide local excision. This article describes the study protocol at its pre-results stage. Methods and analysis PRISM-HNSCC is a bilateral observational research being conducted in Darwin, Australia and Vellore, India. Individuals diagnosed with HNSCC will undergo the routine wide local excision of the tumour followed by histopathological assessment. Tumours with clear surgical margins that satisfy the exclusion criteria will be selected for further staining of the margins with eIF4E and p53 antibodies. Results of IHC staining will be correlated with recurrences in an attempt to predict the risk of disease recurrence. Patients in Darwin will undergo intraoperative staining of the lesion with Lugol's iodine and fluorescence visualisation to delineate the excision margins while patients in Vellore will not undertake these tests. The outcomes will be analysed. Ethics and dissemination The PRISM-HNSCC study was approved by the institutional ethics committees in Darwin (Human Research Ethics Committee 13-2036) and Vellore (Institutional Review Board Min. no. 8967). Outcomes will be disseminated through publications in academic journals and presentations at educational meetings and conferences. It will be presented as dissertation at the Charles Darwin University. We will communicate the study results to both participating sites. Participating sites will communicate results with patients who have indicated an interest in knowing the results. [ABSTRACT FROM AUTHOR]

Molecular markers can be used to identify residual cancer at the surgical margins of head and neck squamous cell carcinoma (HNSCC) and assist in evaluating the complete resection of the tumour. The purpose of the present study was to investigate the expression levels of prognostic molecular markers at the histological tumour free surgical margins. In the present clinical retrospective study, 24/48 patients were selected with negative surgical margins for further analysis with immunohistochemical staining. Contingency tables and Fisher's exact tests were used to investigate the association between the expression levels of p53 and eukaryotic translation imitation factor 4E (eIF4E) with the clinical outcomes for patients with HNSCC. The expression levels of p53 and eIF4E were 54.2 and 87.5%, respectively, in the surgical margins of patients with HNSCC. A total of 3/7 patients with recurrent cancer (42.8%) were identified with p53-positive margins, and 6 (85.7%) patients exhibited recurrence with eIF4e-positive margins. No statistically significant differences were identified for the recurrence risk between the overexpression of p53 and eIF4E in the surgical margins (P=0.88 and P=0.99, respectively). The eIF4E marker appears to be a more marked prognosticator compared with p53, as overexpression of eIF4E was identified in the margins of 6/7 patients with local recurrence. [ABSTRACT FROM AUTHOR]

The per capita alcohol consumption of the Northern Territory, Australia, is second highest in the world, estimated 15.1 liters of pure alcohol per year. Alcohol abuse is a major public health concern among Aboriginal and Torres Strait Islander people in Australia. The Aboriginal and Torres Strait Islanders in the Northern Territory consume approximately 16.9 liters of pure alcohol per year. This descriptive review is based on current published and grey literature in the context of high risk alcohol use, with a special focus on the epidemiological, etiological, and social factors, to predict alcohol misuse among the Australian Aboriginal and Torres Strait Islanders in Northern Territory. The methodology involved a descriptive search on PubMed, Northern Territory government reports, health databases, and Web sites with an emphasis on the etiology and epidemiology of high-risk alcohol consumption among the Australian Aboriginal and Torres Strait Islanders of the Northern Territory. This review has its own limitations because it does not rely on systematic review methodologies. However, it presents real data on the motives for binge drinking and alcohol-related violent assaults of this vulnerable population. Alcohol abuse and alcohol-related harms are considerably high among the rural and remote communities where additional research is needed. High-risk alcohol misuse within Australian Aboriginal and Torres Strait Islanders communities often leads to a series of physical and social consequences. This review highlights the need for culturally appropriate intervention approaches focusing on alcohol misuse among the Aboriginal and Torres Strait Islanders population of the Northern Territory. [ABSTRACT FROM AUTHOR]

3 Jayaraj R, Kumarasamy C. Comment on "Increased risk of second cancers at sites associated with HPV after a prior HPV-associated malignancy, a systematic review and meta-analysis ". 2 Jayaraj R, Kumarasamy C, Madhav MR, Shetty S. Clinical validation of the salivary HPV DNA assessment and its link to the locoregional disease burden in advanced HPV associated oropharyngeal cancer. Recently Malagón et al have published an article in the I International Journal of Cancer i pertaining to a systematic review and meta-analysis study of progression rates to precancer and cancer for human papillomavirus (HPV)-positive, cytology normal women.1 Our study conducted a thorough and well-defined analysis of prospective observational studies and randomized controlled trials, which measured the risk of progressing to histologically ascertain precancerous lesions and cancer for women who are positive for HPV DNA. [Extracted from the article]

The article discusses about the study methods used in analysis of various diseases in dentistry.

High risk drinking is linked with high rates of physical harm. The reported incidence of alcohol - related trauma among Aboriginal and Torres Strait Islander people in the Northern Territory is the highest in the world. Facial fractures are common among young Aboriginal and Torres Strait Islanders. They are often linked with misuse of alcohol in the Northern Territory and are frequently secondary to assault. This review focuses on alcohol-related trauma in the Territory and draws attention to an urgent need for preventative health approach to address this critical issue. [ABSTRACT FROM AUTHOR]

Background: Liver fluke can infect cattle and sheep, and is also emerging as a human pathogen in developing countries. Cathepsin B (Cat B2) is a major cysteine protease secreted by the juvenile flukes. To enhance the immune responses of Cat B2, the cDNA sequence was fused with four different DNA vaccine vectors. The induced cellular and antibody responses were compared in vaccinated mice. Methods: The following recombinant DNA vaccine constructs were constructed: empty vector VR1012 as negative control, cytoplasmic construct pVR1012 Cat B2, secretory construct pVR1020 Cat B2, chemokine-fused construct pMCP3 Cat B2 and lymph node targeting construct pCTLA-4 Cat B2. Plasmids were constructed using standard procedures, and positive constructs screened and selected using restriction digestion analysis followed by sequence analysis. The constructs were then tested in Cos-7 cells for in vitro expression, which was analysed using immunoblotting. Subsequently, female BALB/c mice were immunised with DNA constructs as vaccines. Elicited antibody responses were measured using ELISA. The ratio between IgG1 and IgG2a antibody responses was estimated among different vaccine groups. IgG antibody avidity assay was performed and the relative avidity index was calculated. The induced cytokine production from splenocytes of vaccinated animals was estimated using ELISPOT. Results: DNA vaccine constructs carrying Cat B2 were expressed in Cos-7 cell lines and encoded protein was recognised using western blotting using rat anti- cathepsin B antibody. DNA vaccines elicited high Cat B2- specific IgG, IgG1, IgE and also modest IgG2a antibody responses. Cat B2 specific IL-4 T cell responses were also observed in Cat B2 vaccinated mice. The comparison of immunogenic potential in each of these constructs was demonstrated as enhanced antibody responses on the lymph-node targeting vector pCTLA-4 Cat B2, the high antibody avidity of chemo-attractant pMCP3 Cat B2 and stronger T cellular responses of non-secretory DNA vaccine pVR1012 Cat B2 in vaccinated animals. Conclusion: This study showed that the targeting DNA vaccine strategies enhanced specific immune responses to juvenile fluke Cat B2. The results of our current study have demonstrated that a gene-based vaccine as an immunotherapeutic approach to combat Fasciola infection may be feasible. [ABSTRACT FROM AUTHOR]

Abstract: Scabies infestations are difficult to diagnose clinically and current serologic tests have less than 50% accuracy. To develop more reliable diagnosis of scabies, specific IgE antibodies to a major scabies antigen recombinant Sar s 14.3 (rSar s 14.3) were measured in 140 plasma samples from scabies-infested and control subject groups using dissociation-enhanced lanthanide fluorescent immunoassays (DELFIA). Levels of rSar s 14.3-specific IgE were quantified, and cross-reactivity with its house dust mite homologue, Der p 14, was assessed. The rSar s 14.3 DELFIA showed excellent diagnostic capability, with 100% sensitivity and 93.75% specificity for distinguishing subjects with current scabies infestation from control, uninfested subjects. Recombinant Der p 14 preparation was ineffective at inhibiting IgE binding to rSar s 14.3. This study shows that quantification of levels of IgE antibody to rSar s 14.3 is a highly sensitive method for diagnosis of scabies infestation in clinical practice. [Copyright &y& Elsevier]

Introduction: Melanoma is a global disease that is predominant in Western countries. However, reliable data resources and comprehensive studies on the theragnostic efficiency of miRNAs in melanoma are scarce. Hence, a decisive study or comprehensive review is required to collate the evidence for profiling miRNAs as a theragnostic marker. This protocol details a comprehensive systematic review and meta-analysis on the impact of miRNAs on chemoresistance and their association with theragnosis in melanoma. Methods and analysis: The articles will be retrieved from online bibliographic databases, including Cochrane Review, EMBASE, MEDLINE, PubMed, Scopus, Science Direct, and Web of Science, with different permutations of 'keywords'. To obtain full-text papers of relevant research, a stated search method will be used, along with selection criteria. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis for Protocols 2015 (PRISMA-P) standards were used to create this study protocol. The hazard ratio (HR) with a 95% confidence interval will be analyzed using Comprehensive Meta-Analysis (CMA) software 3.0. (CI). The pooled effect size will be calculated using a random or fixed-effects meta-analysis model. Cochran's Q test and the I2 statistic will be used to determine heterogeneity. Egger's bias indicator test, Orwin's and the classic fail-safe N tests, the Begg and Mazumdar rank collection test, and Duval and Tweedie's trim and fill calculation will all be used to determine publication bias. The overall standard deviation will be evaluated using Z-statistics. Subgroup analyses will be performed according to the melanoma participants' clinicopathological and biological characteristics and methodological factors if sufficient studies and retrieved data are identified and available. The source of heterogeneity will be assessed using a meta-regression analysis. A pairwise matrix could be developed using either a pairwise correlation or expression associations of miRNA with patients' survival for the same studies. [ABSTRACT FROM AUTHOR]

Background: The microRNAs (miRNAs) are small noncoding single-stranded RNAs typically 19–25 nucleotides long and regulated by cellular and epigenetic factors. These miRNAs plays important part in several pathways necessary for cancer development, an altered miRNA expression can be oncogenic or tumor-suppressive. Recent experimental results on miRNA have illuminated a different perspective of the molecular pathogenesis of head and neck cancers. Regulation of miRNA can have a detrimental effect on the efficacy of chemotherapeutic drugs in both neoadjuvant and adjuvant settings. This miRNA-induced chemoresistance can influence the prognosis and survival rate. The focus of the study is on how regulations of various miRNA levels contribute to chemoresistance in head and neck cancer (HNC). Recent findings suggest that up or down-regulation of miRNAs may lead to resistance towards various chemotherapeutic drugs, which may influence the prognosis. Methods: Studies on miRNA-specific chemoresistance in HNC were collected through literary (bibliographic) databases, including SCOPUS, PubMed, Nature, Elsevier, etc., and were systematically reviewed following PRISMA-P guidelines (Preferred Reporting Items for Systematic Review and Meta-analysis Protocol). We evaluated various miRNAs, their up and downregulation, the effect of altered regulation on the patient's prognosis, resistant cell lines, etc. The data evaluated will be represented in the form of a review and meta-analysis. Discussion: This meta-analysis aims to explore the miRNA-induced chemoresistance in HNC and thus to aid further researches on this topic. PROSPERO registration: CRD42018104657. [ABSTRACT FROM AUTHOR]