Era Of Medicine Research Articles

Nanogel: A versatile drug delivery system for the treatment of various diseases and their future perspective.

Nanogel (NG) drug delivery systems have emerged as promising tools for targeted and controlled drug release, revolutionizing treatment approaches across various diseases.Their unique physicochemical properties, such as nano size, high surface area,biocompatibility, stability, and tunable drug release, make themideal carriers for a wide range of therapeutic agents. Nanogels (NGs), characterized by their 3D network of crosslinked polymers, offer unique edges like high drug loading capacity, controlled release, and targeted delivery. Additionally, the diverse applications of NGs in medical therapeutics highlight their versatility and potential impact on improving patient outcomes. Their application spans cancer treatment, infectious diseases, and chronic conditions, allowing for precise drug delivery to specific tissues or cells, minimizing side effects, and enhancing therapeutic efficacy. Despite their potential, challenges such as scalability, manufacturing reproducibility, and regulatory hurdles must be addressed. Achieving clinical translation requires overcoming these obstacles to ensure therapeutic payloads' safe and efficient delivery. Strategies such as surface modification and incorporating stimuli-responsive elements enhanced NG performance and addressed specific therapeutic challenges. Advances in nanotechnology, biomaterials, and targeted drug design offer opportunities to improve the performance of NGs and address current limitations. Tailoring NGs for exploring combination therapies and integrating diagnostics for real-time monitoring represent promising avenues for future research. In conclusion, NG drug delivery systems have demonstrated tremendous potential in diverse disease applications. Overcoming challenges and leveraging emerging technologies will pave the way for their widespread clinical implementation, ushering in a new era of precision medicine and improved patient care.

Patient safety and healthcare quality of U.S. laboratory developed tests (LDTs) in the AI/ML era of precision medicine.

This policy brief summarizes current U.S. regulatory considerations for ensuring patient safety and health care quality of genetic/genomic test information for precision medicine in the era of artificial intelligence/machine learning (AI/ML). The critical role of innovative and efficient laboratory developed tests (LDTs) in providing accurate diagnostic genetic/genomic information for U.S. patient- and family-centered healthcare decision-making is significant. However, many LDTs are not fully vetted for sufficient analytic and clinical validity via current FDA and CMS regulatory oversight pathways. The U.S. Centers for Disease Control and Prevention's Policy Analytical Framework Tool was used to identify the issue, perform a high-level policy analysis, and develop overview recommendations for a bipartisan healthcare policy reform strategy acceptable to diverse precision and systems medicine stakeholders.

Oncogenic Enhancers in Leukemia.

Although the study of leukemogenesis has traditionally focused on protein-coding genes, the role of enhancer dysregulation is becoming increasingly recognized. The advent of high-throughput sequencing, together with a better understanding of enhancer biology, has revealed how various genetic and epigenetic lesions produce oncogenic enhancers that drive transformation. These aberrations include translocations that lead to enhancer hijacking, point mutations that modulate enhancer activity, and copy number alterations that modify enhancer dosage. In this review, we describe these mechanisms in the context of leukemia and discuss potential therapeutic avenues to target these regulatory elements. Significance: Large-scale sequencing projects have uncovered recurrent gene mutations in leukemia, but the picture remains incomplete: some patients harbor no such aberrations, whereas others carry only a few that are insufficient to bring about transformation on their own. One of the missing pieces is enhancer dysfunction, which only recently has emerged as a critical driver of leukemogenesis. Knowledge of the various mechanisms of enhancer dysregulation is thus key for a complete understanding of leukemia and its causes, as well as the development of targeted therapies in the era of precision medicine.

Is Tunisia ready for precision medicine? Challenges of medical genomics within a LMIC healthcare system.

As one of the key tools on the precision medicine workbench, high-throughput genetic testing has enormous promise for improving healthcare outcomes. Tunisia has made tremendous progress in acquiring and implementing the technology in the clinical context. However, current utilization does not ensure the whole range of benefits that high-throughput genomic testing provides which impedes the country's ability to move forward into the new era of precision medicine. This issue is primarily related to the current state of Tunisia's healthcare ecosystem and the sociological attributes of its population, creating numerous challenges that must be addressed. In the current review, we aimed to identify and highlight these challenges that may be prevalent in other low and middle-income countries. Essentially, they fall into three main categories that include the socio-economic landscape in Tunisia, which prevents citizens from engaging in precision medicine activities; the current settings of the healthcare system that lack or miss key components for the successful implementation of precision medicine practices; and the inability of the current infrastructure and resources to handle the various challenges related to genomic data and metadata. We also propose five pillar solutions as a framework for addressing all of these challenges, which could strengthen Tunisia's capability for effective precision medicine implementation in today's clinical environment.

Correlation between tooth decay and insulin resistance in normal weight males prompts a role for myo-inositol as a regenerative factor in dentistry and oral surgery: a feasibility study.

In an era of precision and stratified medicine, homogeneity in population-based cohorts, stringent causative entry, and pattern analysis of datasets are key elements to investigate medical treatments. Adhering to these principles, we collected in vivo and in vitro data pointing to an insulin-sensitizing/insulin-mimetic effect of myo-inositol (MYO) relevant to cell regeneration in dentistry and oral surgery. Confirmation of this possibility was obtained by in silico analysis of the relation between in vivo and in vitro results (the so-called bed-to-benchside reverse translational approach). Fourteen subjects over the 266 screened were young adult, normal weight, euglycemic, sedentary males having normal appetite, free diet, with a regular three-times-a-day eating schedule, standard dental hygiene, and negligible malocclusion/enamel defects. Occlusal caries were detected by fluorescence videoscanning, whereas body composition and energy balance were estimated with plicometry, predictive equations, and handgrip. Statistically significant correlations (Pearson r coefficient) were found between the number of occlusal caries and anthropometric indexes predicting insulin resistance (IR) in relation to the abdominal/visceral fat mass, fat-free mass, muscular strength, and energy expenditure adjusted to the fat and muscle stores. This indicated a role for IR in affecting dentin reparative processes. Consistently, in vitro administration of MYO to HUVEC and Swiss NIH3T3 cells in concentrations corresponding to those administered in vivo to reduce IR resulted in statistically significant cell replication (ANOVA/Turkey tests), suggesting that MYO has the potential to counteract inhibitory effects of IR on dental vascular and stromal cells turnover. Finally, in in silico experiments, quantitative evaluation (WOE and information value) of a bioinformatic Clinical Outcome Pathway confirmed that in vitro trophic effects of MYO could be transferred in vivo with high predictability, providing robust credence of its efficacy for oral health. Our reverse bed-to-benchside data indicate that MYO might antagonize the detrimental effects of IR on tooth decay. This provides feasibility for clinical studies on MYO as a regenerative factor in dentistry and oral surgery, including dysmetabolic/aging conditions, bone reconstruction in oral destructive/necrotic disorders, dental implants, and for empowering the efficacy of a number of tissue engineering methodologies in dentistry and oral surgery.

Remote organ cancer adversely alters renal function and induces kidney injury, inflammation, and fibrosis.

Approximately 30% of cancer patients experience kidney complications, which hinder optimal cancer management, imposing a burden on patients' quality of life and the healthcare system. The etiology of kidney complications in cancer patients is often attributed to nephrotoxic oncological therapies. However, the direct impact of cancer on kidney health is underestimated, as most nephrotoxic oncological therapies have been studied in animal models that do not have cancer. Our previous study demonstrated that advanced lung cancer adversely alters kidney physiology and function, and exacerbates chemotherapy-induced nephrotoxicity, indicating lung cancer-kidney crosstalk. This study examines whether this phenomenon is specific to the employed cancer model. Female and male mice of various strains were injected with different cell lines representing human and mouse lung cancer, breast cancer, and melanoma, and their kidney tissues were analyzed for toxicity and fibrosis. The impact of cancer on the kidney varied by cancer type. Breast cancer and specific subtypes of lung cancer, including KRAS- and EGFR-mutant cancer, pathologically altered kidney physiology and function in a manner dependent on the metastatic potential of the cell line. This was independent of mouse strain, sex, and cancer cell line origin. Moreover, tumor DNA was not detected in the renal tissue, excluding metastases to the kidney as a causative factor for the observed pathological alterations. Lewis lung carcinoma and B16 melanoma did not cause nephrotoxicity, regardless of the tumor size. Our results confirm cancer-kidney crosstalk in specific cancer types and highlight gaps in understanding the risk of renal complications in cancer patients. In the era of precision medicine, further research is essential to identify at-risk oncology populations, enabling early detection and management of renal complications.

Traditional care and alternative therapies for pregnant women: a comparative review

Traditional care and alternative therapies are gradually becoming prevalent in the era of pharmaceutical medicine. Pregnant women are now using more of the traditional therapies because of the increasing acceptance, notably after the COVID-19 outbreak, to handle pregnancy issues such as morning sickness, anxiety, and pain naturally and holistically. The article includes some of the most popular traditional and alternative treatments, which include yoga, ayurveda, herbal treatment, acupressure, reflexology, massage therapy, moxibustion plus music and dance therapy, as well as aromatherapy, hypnotherapy homeopathy, and reiki. Patients will require knowledge of what each one of them has to benefit them when they use them during pregnancy since not all could be safe or even helpful while expecting a baby. A well-known fact in the literature today is an increasing reliance on traditional treatments, which is considered risk-free compared to conventional medicine, enhancing physical and psychological well-being. The paper is a basic guide to pregnancy management that may involve using traditional and alternative medicines, which have been proved by research. If these care and therapies are accompanied by good medical advice on issues concerning the wellness of the unborn child and its mother in general, will help to ease their pregnancy journey.

Advances, recognition, and interpretation of molecular heterogeneity among conventional and subtype histology of urothelial carcinoma (UC): a survey among urologic pathologists and comprehensive review of the literature.

Urothelial carcinoma (UC) demonstrates significant molecular and histologic heterogeneity. The WHO 2022 classification has hinted at adding molecular signatures to the morphologic diagnosis. As morphology and associated molecular repertoire may potentially translate to choices of and response to therapy and relapse rate, broader acceptability of recognizing these key features among uropathologists is needed. This prompted an international survey to ascertain the practice patterns in classical/subtype UC among uropathologists across the globe. A survey instrument was shared among 98 uropathologists using SurveyMonkey software. Anonymized respondent data were analysed. The response rate was 85%. A majority were in concordance with the profiles of luminal (93%) and basal (82%) types. Opinion on the FGFR3 testing platform was variable. While 95% concurred that TERT promoter mutation is the key driver in UC, 72% had the opinion that APOBEC mutagenesis is the main signature in muscle invasive bladder cancer (MIBC). Uropathologists have divergent opinions on MIBC and ERCC2 mutations. Among the participants, 94% would quantify aggressive micropapillary and sarcomatoid histology, while 88% would reevaluate another transurethral resection of the bladder tumour specimen in nonmuscle invasive tumour with micropapillary, small cell, or sarcomatoid histology. A leading number agreed to specific molecular signatures of micropapillary (93%), plasmacytoid (97%), and small cell (86%) subtypes. Ninety-six percent of participants agreed that a small-cell component portends a more aggressive course and should be treated with neoadjuvant chemotherapy and 63% would perform HER2/neu testing only on oncologist's request in advanced tumours. Ninety percent agreed that microsatellite instability testing, although not a standard protocol, should be considered in young patients with upper tract UC. Eighty-six percent agreed that UC with high tumour mutational burden would be a better candidate for immunotherapy. In the era of precision medicine, enhanced understanding of molecular heterogeneity of UC will contribute to better therapeutic options, novel biomarker discovery, innovative management protocols, and outcomes. Our survey provides a broad perspective of pathologists' perceptions and experience regarding incorporation of histomolecular approaches to "personalize" therapy. Due to variable clinical adoption, there is a need for additional data using uniform study criteria. This will drive generation of best practice guidelines in this area for widespread and consistent clinical utility.

Immunohistochemistry Markers in Ovarian and Fallopian Tube Neoplasms: a Comprehensive Review.

Immunohistochemistry (IHC) has emerged as a crucial tool in diagnosing and managing ovarian cancer, offering invaluable insights into tumor biology and guiding therapeutic decisions. The intricate histopathological landscape of ovarian cancer presents challenges in accurate diagnosis and classification. IHC offers a complementary approach, aiding in the characterization of tumor subtypes, prognostication, and prediction of treatment response. By targeting specific biomarkers, IHC enables the identification of diverse histological features and molecular alterations associated with ovarian malignancies. The integration of IHC into routine diagnostic workflows enhances diagnostic accuracy, aids in the subclassification of ovarian tumors, and facilitates personalized treatment strategies. Emphasis is placed on the judicious selection of antibody panels tailored to specific clinical scenarios, ensuring optimal utilization of resources and minimizing diagnostic pitfalls. Overall, this review underscores the pivotal role of IHC in refining the diagnosis, prognostication, and management of ovarian cancer, highlighting its significance in the era of precision medicine. By leveraging the molecular insights provided by IHC, clinicians and pathologists can optimize patient care and improve outcomes in ovarian cancer management.

Population Screening for Hereditary Haemochromatosis-Should It Be Carried Out, and If So, How?

The Human Genome Project, completed in 2003, heralded a new era in precision medicine. Somewhat tempering the excitement of the elucidation of the human genome is the emerging recognition that there are fewer single gene disorders than first anticipated, with most diseases predicted to be polygenic or at least gene-environment modified. Hereditary haemochromatosis (HH) is an inherited iron overload disorder, for which the vast majority of affected individuals (>90%) have homozygosity for a single pathogenic variant in the HFE gene, resulting in p.Cys282Tyr. Further, there is significant benefit to an individual in identifying the genetic risk of HH, since the condition evolves over decades, and the opportunity to intervene and prevent disease is both simple and highly effective through regular venesection. Add to that the immediate benefit to society of an increased pool of ready blood donors (blood obtained from HH venesections can generally be used for donation), and the case for population screening to identify those genetically at risk for HH becomes more cogent. Concerns about genetic discrimination, creating a cohort of "worried well", antipathy to acting on medical advice to undertake preventive venesection or simply not understanding the genetic risk of the condition adequately have all been allayed by a number of investigations. So why then has HH population genetic screening not been routinely implemented anywhere in the world? The answer is complex, but in this article we explore the pros and cons of screening for HH and the different views regarding whether it should be phenotypic (screening for iron overload by serum ferritin and/or transferrin saturation) or genotypic (testing for HFE p.Cys282Tyr). We argue that now is the time to give this poster child for population genetic screening the due consideration required to benefit the millions of individuals at risk of HFE-related iron overload.

Functional genomics reveals an off-target dependency of drug synergy in gastric cancer therapy

BackgroundIntegrating molecular-targeted agents into combination chemotherapy is transformative for enhancing treatment outcomes in cancer. However, realizing the full potential of this approach requires a clear comprehension of the genetic dependencies underlying drug synergy. While the interactions between conventional chemotherapeutics are well-explored, the interplay of molecular-targeted agents with conventional chemotherapeutics remains a frontier in cancer treatment. Hence, we leveraged a powerful functional genomics approach to decode genomic dependencies that drive synergy in molecular-targeted agent/chemotherapeutic combinations in gastric adenocarcinoma, addressing a critical need in gastric cancer therapy.MethodsWe screened pharmacological interactions between fifteen molecular-targeted agent/conventional chemotherapeutic pairs in gastric adenocarcinoma cells, and examined the genome-scale genetic dependencies of synergy integrating genome-wide CRISPR screening with the shRNA-based signature assay. We validated the synergy in cell death using fluorescence-based and lysis-dependent inference of cell death kinetics assay, and validated the genetic dependencies by single-gene knockout experiments.ResultsOur combination screen identified SN-38/erlotinib as the drug pair with the strongest synergism. Functional genomics assays unveiled a genetic dependency signature of SN-38/erlotinib identical to SN-38. Remarkably, the enhanced cell death with improved kinetics induced by SN-38/erlotinib was attributed to erlotinib’s off-target effect, inhibiting ABCG2, rather than its on-target effect on EGFR.ConclusionIn the era of precision medicine, where emphasis on primary drug targets prevails, our research challenges this paradigm by showcasing a robust synergy underpinned by an off-target dependency. Further dissection of the intricate genetic dependencies that underlie synergy can pave the way to developing more effective combination strategies in gastric cancer therapy.

Endotyping Chronic Respiratory Diseases: T2 Inflammation in the United Airways Model.

Over the past 15 years, the paradigm of viewing the upper and lower airways as a unified system has progressively shifted the approach to chronic respiratory diseases (CRDs). As the global prevalence of CRDs continues to increase, it becomes evident that acknowledging the presence of airway pathology as an integrated entity could profoundly impact healthcare resource allocation and guide the implementation of pharmacological and rehabilitation strategies. In the era of precision medicine, endotyping has emerged as another novel approach to CRDs, whereby pathologies are categorized into distinct subtypes based on specific molecular mechanisms. This has contributed to the growing acknowledgment of a group of conditions that, in both the upper and lower airways, share a common type 2 (T2) inflammatory signature. These diverse pathologies, ranging from allergic rhinitis to severe asthma, frequently coexist and share diagnostic and prognostic biomarkers, as well as therapeutic strategies targeting common molecular pathways. Thus, T2 inflammation may serve as a unifying endotypic trait for the upper and lower airways, reinforcing the practical significance of the united airways model. This review aims to summarize the literature on the role of T2 inflammation in major CRDs, emphasizing the value of common biomarkers and integrated treatment strategies targeting shared molecular mechanisms.

Towards genomic medicine: a tailored next-generation sequencing panel for hydroxyurea pharmacogenomics in Tanzania

BackgroundPharmacogenomics of hydroxyurea is an important aspect in the management of sickle cell disease (SCD), especially in the era of genomic medicine. Genetic variations in loci associated with HbF induction and drug metabolism are prime targets for hydroxyurea (HU) pharmacogenomics, as these can significantly impact the therapeutic efficacy and safety of HU in SCD patients.MethodsThis study involved designing of a custom panel targeting BCL11A, ARG2, HBB, HBG1, WAC, HBG2, HAO2, MYB, SAR1A, KLF10, CYP2C9, CYP2E1 and NOS1 as potential HU pharmacogenomics targets. These genes were selected based on their known roles in HbF induction and HU metabolism. The panel was designed using the Illumina Design Studio (Illumina, San Diego, CA, USA) and achieved a total coverage of 96% of all genomic targets over a span of 51.6 kilobases (kb). This custom panel was then sequenced using the Illumina MiSeq platform to ensure high coverage and accuracy.ResultsWe are reporting a successfully designed Illumina (MiSeq) HU pharmacogenomics custom panel encompassing 51.6 kilobases. The designed panel achieved greater than 1000x amplicon coverage which is sufficient for genomic analysis.ConclusionsThis study provides a valuable tool for research in HU pharmacogenomics, especially in Africa where SCD is highly prevalent, and personalized medicine approaches are crucial for improving patient outcomes. The custom-designed Illumina (MiSeq) panel, with its extensive coverage and high sequencing depth, provides a robust platform for studying genetic variations associated with HU response. This panel can contribute to the development of tailored therapeutic strategies, ultimately enhancing the management of SCD through more effective and safer use of hydroxyurea.

Local therapy in glioma: An evolving paradigm from history to horizons (Review).

Despite the implementation of multimodal treatments after surgery, glioblastoma (GBM) remains an incurable disease, posing a significant challenge in neuro-oncology. In this clinical setting, local therapy (LT), a developing paradigm, has received significant interest over time due to its potential to overcome the drawbacks of conventional therapy options for GBM. The present review aimed to trace the historical development, highlight contemporary advances and provide insights into the future horizons of LT in GBM management. In compliance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols criteria, a systematic review of the literature on the role of LT in GBM management was conducted. A total of 2,467 potentially relevant articles were found and, after removal of duplicates, 2,007 studies were screened by title and abstract (Cohen's κ coefficient=0.92). Overall, it emerged that 15, 10 and 6 clinical studies explored the clinical efficiency of intraoperative local treatment modalities, local radiotherapy and local immunotherapy, respectively. GBM recurrences occur within 2 cm of the radiation field in 80% of cases, emphasizing the significant influence of local factors on recurrence. This highlights the urgent requirement for LT strategies. In total, three primary reasons have thus led to the development of numerous LT solutions in recent decades: i) Intratumoral implants allow the blood-brain barrier to be bypassed, resulting in limited systemic toxicity; ii) LT facilitates bridging therapy between surgery and standard treatments; and iii) given the complexity of GBM, targeting multiple components of the tumor microenvironment through ligands specific to various elements could have a synergistic effect in treatments. Considering the spatial and temporal heterogeneity of GBM, the disease prognosis could be significantly improved by a combination of therapeutic strategies in the era of precision medicine.

Regulatory Considerations for Genome-Edited T-cell Therapies.

Methods to engineer the genomes of human cells for therapeutic intervention continue to advance at a remarkable pace. Chimeric antigen receptor-engineered T lymphocytes have pioneered the way for these therapies, initially beginning with insertions of chimeric antigen receptor transgenes into T-cell genomes using classical gene therapy vectors. The broad use of clustered regularly interspaced short palindromic repeats (CRISPR)-based technologies to edit endogenous genes has now opened the door to a new era of precision medicine. To add complexity, many engineered cellular therapies under development integrate gene therapy with genome editing to introduce novel biological functions and enhance therapeutic efficacy. Here, we review the current state of scientific, translational, and regulatory oversight of gene-edited cell products.

The synergy of artificial intelligence and personalized medicine for the enhanced diagnosis, treatment, and prevention of disease.

The completion of the Human Genome Project in 2003 marked the beginning of a transformative era in medicine. This milestone laid the foundation for personalized medicine, an innovative approach that customizes healthcare treatments. Central to the advancement of personalized medicine is the understanding of genetic variations and their impact on drug responses. The integration of artificial intelligence (AI) into drug response trials has been pivotal in this domain. These technologies excel in handling large-scale genomic datasets and patient histories, significantly improving diagnostic accuracy, disease prediction and drug discovery. They are particularly effective in addressing complex diseases such as cancer and genetic disorders. Furthermore, the advent of wearable technology, when combined with AI, propels personalized medicine forward by offering real-time health monitoring, which is crucial for early disease detection and management. The integration of AI into personalized medicine represents a significant advancement in healthcare, promising more accurate diagnoses, effective treatment plans and innovative drug discoveries. As technology continues to evolve, the role of AI in enhancing personalized medicine and transforming the healthcare landscape is expected to grow exponentially. This synergy between AI and healthcare holds great promise for the future, potentially revolutionizing the way healthcare is delivered and experienced.

Decoding the Prognostic Significance and Therapeutic Implications of Inflammation-Based Scores in Hepatocellular Carcinoma: A Comprehensive Review.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer, posing a significant global health challenge with an increasing incidence. In recent years, multiple staging systems and scores have been proposed, emphasising the necessity for the development of precise prognostic tools. The well-documented etiological relationship between chronic inflammation and carcinogenesis has prompted researchers to explore novel prognostic markers associated with the inflammatory status of HCC patients. This review summarises the current data about inflammation-based scores in the context of HCC. We discuss established scores like the Glasgow Prognostic Score (GPS), modified GPS (mGPS) and the neutrophil-to-lymphocyte ratio (NLR) and others not as extensively studied, examining their utility in predicting survival outcomes and treatment response in HCC patients. Furthermore, we explore emerging scores, including the prognostic nutritional index (PNI) and other lymphocyte-based scores, assessing their potential in refining risk stratification and guiding therapeutic decisions in the era of precision medicine. As research progresses and these scores undergo further refinement and integration into the evolving landscape of HCC management, they carry significant potential for improving patient outcomes.

Cutting-edge Approach of Carbon Nanostructures: Targeted Drug Delivery to Central Nervous System.

Drug delivery through the blood-brain barrier (BBB) is one of the key challenges in the modern era of medicine due to the highly semipermeable characteristics of BBB that restrict the entry of various drugs into the central nervous system (CNS) for the management of brain disorders. Drugs can be easily incorporated into carbon nanocarriers that can cross the bloodbrain barrier. Numerous nanocarriers have been developed, including polymeric nanoparticles, carbon nanoparticles, lipid-based nanoparticles, etc. Among these, carbon nanostructures could be superior due to their easier BBB penetration and strong biocompatibility. Several CDs (Carbon dots) and CD-ligand conjugates have explored effectively penetrating the BBB, which enables significant progress in using CD-based drug delivery systems (DDS) to manage CNS diseases. Despite the drug delivery applications, they might also be used as a central nervous system (CNS) drug; few of the carbon nanostructures show profound neurodegenerative activity. Further, their impact on neuronal growth and anti- amyloid action is quite interesting. The present study covers diverse carbon nanostructures for brain-targeted drug delivery, exploring a variety of CNS activities. Moreover, it emphasizes recent patents on carbon nanostructures for CNS disorders.

Biobanks as an Indispensable Tool in the "Era" of Precision Medicine: Key Role in the Management of Complex Diseases, Such as Melanoma.

In recent years, medicine has undergone profound changes, strongly entering a new phase defined as the "era of precision medicine". In this context, patient clinical management involves various scientific approaches that allow for a comprehensive pathology evaluation: from preventive processes (where applicable) to genetic and diagnostic studies. In this scenario, biobanks play an important role and, over the years, have gained increasing prestige, moving from small deposits to large collections of samples of various natures. Disease-oriented biobanks are rapidly developing as they provide useful information for the management of complex diseases, such as melanoma. Indeed, melanoma, given its highly heterogeneous characteristics, is one of the oncologic diseases with the greatest clinical and therapeutic management complexity. So, the possibility of extrapolating tissue, genetic and imaging data from dedicated biobanks could result in more selective study approaches. In this review, we specifically analyze the several biobank types to evaluate their role in technology development, patient monitoring and research of new biomarkers, especially in the melanoma context.

Insight into the Role of the miR-584 Family in Human Cancers.

Among the non-coding RNAs, the aberrant expression of microRNAs (miRNAs) is well described in the oncology field. It is clear that the altered expression of miRNAs is crucial for a variety of processes such as proliferation, apoptosis, motility, angiogenesis and metastasis insurgence. Considering these aspects, RNA-based therapies and the use of miRNAs as non-invasive biomarkers for early diagnosis are underlined as promising opportunities against cancer death. In the era of precision medicine, significant progress in next-generation sequencing (NGS) techniques has broadened knowledge regarding the miRNAs expression profile in cancer tissues and in the blood of cancer patients. In this scenario, pre-clinical and clinical studies suggested that the members of the miR-584 family, i.e., miR-584-5p and -3p, are prominent players in cancer development and progression. Under some conditions, these miRNAs are under-expressed in cancer tissues acting as tumor suppressors, while in other conditions, they are overexpressed, acting as oncogenes increasing the aggressive behavior of cancer cells. The aim of this review is to provide a comprehensive and up-to-date overview on the expression, upstream genes, molecular targets and signaling pathways influenced by the miR-584 family (i.e., miR-584-3p and -5p) in various human solid and hematological cancers. To achieve this goal, 64 articles on this topic are discussed. Among these articles, 55 are focused on miR-584-5p, and it is outlined how this miRNA could be used in future applications as a potential new therapeutic strategy and diagnostic tool.