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For glioblastoma patients, the efficacy-targeted therapy is limited to date. Most of the molecular therapies previously studied are lacking efficacy in this population. More trials are needed to study the actual actionability of biomarkers in (recurrent) glioblastoma. This study aimed to assess the current clinical trial landscape to assess the role of molecular biomarkers in trials on recurrent glioblastoma treatment. The database ClinicalTrials.gov was used to identify not yet completed clinical trials on recurrent glioblastoma in adults. Recruiting studies were assessed to investigate the role of molecular criteria, which were retrieved as detailed as possible. Primary outcome was molecular criteria used as selection criteria for study participation. Next to this, details on moment and method of testing, and targets and drugs studied, were collected. In 76% (181/237) of the included studies, molecular criteria were not included in the study design. Of the remaining 56 studies, at least one specific genomic alteration as selection criterium for study participation was required in 33 (59%) studies. Alterations in EGFR, CDKN2A/B or C, CDK4/6, and RB were most frequently investigated, as were the corresponding drugs abemaciclib and ribociclib. Of the immunotherapies, CAR-T therapies were the most frequently studied therapies. Previously, genomics studies have revealed the presence of potentially actionable alterations in glioblastoma. Our study shows that the potential efficacy of targeted treatment is currently not translated into genome-driven trials in patients with recurrent glioblastoma. An intensification of genome-driven trials might help in providing evidence for (in)efficacy of targeted treatments. [ABSTRACT FROM AUTHOR]

Background: The administration of omega-3 polyunsaturated fatty acid supplements is recommended as an adjuvant therapy for adults diagnosed with major depressive disorder. The evaluation of replicated data in combination treatment with omega-3 has been extensively conducted in adults over the past decade. However, the generalizability of these findings to pediatric groups is still uncertain. The objectives of this evaluation were twofold: (1) to evaluate the effectiveness of omega-3 and associated combination therapies in reducing the severity of depressive symptoms, and (2) to include remission rates (i.e., reduction of more than 50% in depression symptoms) as a measure of therapeutic efficacy. Methods: We conducted a literature search on PubMed/EMBASE from inception to October 2023. Data analyses were conducted using Stata (version 17.0). Results: We identified a total of 3168 articles. After eligibility screening of identified studies, nine studies (n = 561 participants) were included in our analysis herein. Pairwise comparisons revealed no significant improvement in depression symptoms for any intervention versus placebo. However, a clustered ranking plot identified omega-3 plus inositol as the most effective treatment for pediatric depression (77.3% efficacy). Omega-3 paired with psychoeducational psychotherapy significantly lowered the remission rate compared to placebo (standardized mean difference = 0.44, 95% confidence interval: 0.00–0.87, p = 0.048), resulting in a 91.5% remission rate, making it the most effective treatment in the study. Conclusions: Taken together, this network meta-analysis presents compelling evidence supporting the antidepressant effects of omega-3 in pediatric groups with depression. Future research should aim to investigate omega-3 as monotherapy for young individuals with depression, as well as investigate the efficacy of omega-3 in comparison to psychosocial interventions for affected individuals. [ABSTRACT FROM AUTHOR]

Abstract Background Catenin (Cadherin-Associated Protein), Beta 1 (CTNNB1) genomic alterations are rare in prostate cancer (PCa). Gain-of-function mutations lead to overexpression of β-catenin, with consequent hyperactivation of the Wnt/β-catenin signaling pathway, implicated in PCa progression and treatment resistance. To date, successful targeted treatment options for Wnt/β-catenin - driven PCa are lacking. Methods We report a rare histologic transformation of a CTNNB1 (β-catenin) mutated metastatic castration resistant prostate cancer (mCRPC), clinically characterized by highly aggressive disease course. We histologically and molecularly characterized the liver metastatic tumor samples, as well as successfully generated patient-derived organoids (PDOs) and patient-derived xenograft (PDX) from a liver metastasis. We used the generated cell models for further molecular characterization and drug response assays. Results Immunohistochemistry of liver metastatic biopsies and PDX tumor showed lack of expression of typical PCa (e.g., AR, PSA, PSAP, ERG) or neuroendocrine markers (synaptophysin), compatible with double-negative CRPC, but was positive for nuclear β-catenin expression, keratin 7 and 34βE12. ERG rearrangement was confirmed by fluorescent in situ hybridization (FISH). Drug response assays confirmed, in line with the clinical disease course, lack of sensitivity to common drugs used in mCRPC (e.g., enzalutamide, docetaxel). The casein kinase 1 (CK1) inhibitor IC261 and the tankyrase 1/2 inhibitor G700-LK showed modest activity. Moreover, despite harbouring a CTNNB1 mutation, PDOs were largely insensitive to SMARCA2/4- targeting PROTAC degraders and inhibitor. Conclusions The reported CTNNB1-mutated mCRPC case highlights the potential challenges of double-negative CRPC diagnosis and underlines the relevance of further translational research to enable successful targeted treatment of rare molecular subtypes of mCRPC.

Highlights To summarize the mechanisms and pathophysiological features of ALI after burn. To classify the targets for the treatment of ALI. Describe the types of nanomedicines used to treat ALI. These findings suggest the prospects and outlook for nanomaterial-targeted therapy for ALI.

Lung cancer has surpassed other types of cancer to become the primary cause of cancer-related deaths. Surgery stands as the foremost clinical treatment strategy available for tackling this condition, but it receives a low efficiency for most patients. In recent years, some adjuvant therapies are employed to improve the lung cancer treatment efficiency, such as chemotherapy, targeted therapy and immunotherapy. However, these strategies have not significantly increased overall survival of patients. Additionally, the random distribution of drugs will induce severe side effects. Nanomedicines have got great attentions to boost drug effect and reduce adverse reactions, including liposome-based nanoparticles, polymeric nanoparticles, inorganic nanoparticles, and exosomes. Importantly, nanomedicines contribute to improving drug bioavailability, stability and residency in target regions. Benefiting from the physiological characteristics of lung, the inhaled pulmonary delivery strategy in combination with nanomedicine will provide a non-invasive and effective strategy for treating lung cancer. Furthermore, the use of targeting ligands enables precise delivery of loaded drugs to lung cancer cells. Inhaled nanomedicine exhibits unique distribution and sustained release behaviors in the alveoli, amplifying the therapeutic effect and reducing side effects. This review aims to discuss various inhaled methods of delivering nanomedicine to treat lung cancer and also summarizes the clearance mechanism of nanomedicine in the lung. Overall, this review focuses on the application of different inhalable nanomedicines, which may inspire the development of more effective treatments against lung cancer.

The placenta plays a crucial role in maintaining normal pregnancy. The failure of spiral artery remodeling (SAR) is a key factor leading to placental ischemia and poor perfusion which is strongly associated with obstetric diseases, including preeclampsia (PE) and fetal growth restriction (FGR). Existing interventions for PE and FGR are limited and termination of pregnancy is inevitable when the maternal or fetus condition deteriorates. Considering the safety of the mother and fetus, treatments that may penetrate the placental barrier and harm the fetus are not accepted. Developing targeted treatment strategies for these conditions is urgent and necessary. With the proven efficacy of targeted therapy in treating conditions such as endometrial cancer and trophoblastic tumors, research on placental dysfunction continues to deepen. This article reviews the studies on placenta-targeted treatment and drug delivery strategies, summarizes the characteristics proposes corresponding improvement measures in targeted treatment, provides solutions for existing problems, and makes suggestions for future studies. [ABSTRACT FROM AUTHOR]

Simple Summary: Isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) are essential metabolic enzymes involved in the tricarboxylic acid (TCA) cycle. Several mutations in IDH genes have recently been described in many solid tumors, including glioma, cholangiocarcinoma, and chondrosarcoma. These mutations lead to neomorphic enzymatic activity affecting cancer pathogenesis. This review aims to summarize the diagnostic and prognostic role of IDH mutations and to provide an overview of the actual IDH inhibitor-based therapies used in various solid malignancies, outlining the findings of the most recent clinical trials and searching for future perspectives. The isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) enzymes are involved in key metabolic processes in human cells, regulating differentiation, proliferation, and oxidative damage response. IDH mutations have been associated with tumor development and progression in various solid tumors such as glioma, cholangiocarcinoma, chondrosarcoma, and other tumor types and have become crucial markers in molecular classification and prognostic assessment. The intratumoral and serum levels of D-2-hydroxyglutarate (D-2-HG) could serve as diagnostic biomarkers for identifying IDH mutant (IDHmut) tumors. As a result, an increasing number of clinical trials are evaluating targeted treatments for IDH1/IDH2 mutations. Recent studies have shown that the focus of these new therapeutic strategies is not only the neomorphic activity of the IDHmut enzymes but also the epigenetic shift induced by IDH mutations and the potential role of combination treatments. Here, we provide an overview of the current knowledge about IDH mutations in solid tumors, with a particular focus on available IDH-targeted treatments and emerging results from clinical trials aiming to explore IDHmut tumor-specific features and to identify the clinical benefit of IDH-targeted therapies and their combination strategies. An insight into future perspectives and the emerging roles of circulating biomarkers and radiomic features is also included. [ABSTRACT FROM AUTHOR]

• Nanoparticles (NPs) are versatile agents to treat all phases of ischemic stroke. • Thrombolysis and neuroprotection can be tackled with nanotechnologies. • Many NPs have promising preclinical results, but only few reach the clinical stage. • Robust and scalable production methods are needed to produce NPs for clinical use. • Efficacy and biosafety tests must be standardized to improve nanosystem assessment. Stroke is responsible for 11% of all deaths worldwide, the majority of which are caused by ischemic strokes, thus making the need to urgently find safe and effective therapies. Today, these can be cured either by mechanical thrombectomy when the thrombus is accessible, or by intravenous injection of fibrinolytics. However, the latter present several limitations, such as potential severe side effects, few eligible patients and low rate of partial and full recovery. To design safer and more effective treatments, nanomedicine appeared in this medical field a few decades ago. This review will explain why nanoparticle-based therapies and imaging techniques are relevant for ischemic stroke management. Then, it will present the different nanoparticle types that have been recently developed to treat this pathology. It will also study the various targeting strategies used to bring nanoparticles to the stroke site, thereby limiting side effects and improving the therapeutic efficacy. Finally, this review will present the few clinical studies testing nanomedicine on stroke and discuss potential causes for their scarcity. [ABSTRACT FROM AUTHOR]

Summary: The treatment landscape of acute myeloid leukaemia (AML) is evolving rapidly. Venetoclax in combination with intensive chemotherapy or doublets or triplets with targeted or immune therapies is the focus of numerous ongoing trials. The development of mutation‐targeted therapies has greatly enhanced the treatment armamentarium, with FLT3 inhibitors and isocitrate dehydrogenase inhibitors improving outcomes in frontline and relapsed/refractory (RR) AML, and menin inhibitors showing efficacy in RR NPM1mut and KMT2A‐rearranged AML. With so many new drugs approved, the number of potential combinatorial approaches to leverage the maximal benefit of these agents has increased dramatically, while at the same time introducing clinical challenges, such as key preclinical and clinical data supporting the development of combinatorial therapy, how to optimally combine or sequence these novel agents, how to optimise dose and duration to maintain safety while enhancing efficacy, the optimal duration of therapy and the role of measurable residual disease in decision‐making in both intensive and low‐intensity therapy settings. In this review, we will outline the evidence leading to the approval of key agents in AML, their on‐label current approvals and how they may be optimally combined in a safe and deliverable fashion to further improve outcomes in AML. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a complex and heterogeneous skin disease for which achieving complete clinical clearance for most patients has proven challenging through single cytokine inhibition. Current studies integrate biomarkers and evaluate their role in AD, aiming to advance our understanding of the diverse molecular profiles implicated. Although traditionally characterized as a T H 2-driven disease, extensive research has recently revealed the involvement of T H 1, T H 17, and T H 22 immune pathways as well as the interplay of pivotal immune molecules, such as OX40, OX40 ligand (OX40L), thymic stromal lymphopoietin, and IL-33. This review explores the mechanistic effects of treatments for AD, focusing on mAbs and Janus kinase inhibitors. It describes how these treatments modulate immune pathways and examines their impact on key inflammatory and barrier biomarkers. [ABSTRACT FROM AUTHOR]

Unfortunately, ovarian cancer is still diagnosed most often only in an advanced stage and is also the most lethal gynecological cancer. Another problem is the fact that treated patients have a high risk of disease recurrence. Moreover, ovarian cancer is very diverse in terms of molecular, histological features and mutations. Many patients may also develop platinum resistance, resulting in poor response to subsequent lines of treatment. To improve the prognosis of patients with ovarian cancer, it is expected to make better existing and implement new, promising treatment methods. Targeted therapies seem very promising. Currently, bevacizumab - a VEGF inhibitor and therapy with olaparib - a polyADP-ribose polymerase inhibitor are approved. Other methods worth considering in the future include: folate receptor a, immune checkpoints or other immunotherapy methods. To improve the treatment of ovarian cancer, it is also important to ameliorate the determination of molecular features to describe and understand which group of patients will benefit most from a given treatment method. This is important because a larger group of patients treated for ovarian cancer can have a greater chance of surviving longer without recurrence. [ABSTRACT FROM AUTHOR]

Background: Catenin (Cadherin-Associated Protein), Beta 1 (CTNNB1) genomic alterations are rare in prostate cancer (PCa). Gain-of-function mutations lead to overexpression of β-catenin, with consequent hyperactivation of the Wnt/β-catenin signaling pathway, implicated in PCa progression and treatment resistance. To date, successful targeted treatment options for Wnt/β-catenin - driven PCa are lacking. Methods: We report a rare histologic transformation of a CTNNB1 (β-catenin) mutated metastatic castration resistant prostate cancer (mCRPC), clinically characterized by highly aggressive disease course. We histologically and molecularly characterized the liver metastatic tumor samples, as well as successfully generated patient-derived organoids (PDOs) and patient-derived xenograft (PDX) from a liver metastasis. We used the generated cell models for further molecular characterization and drug response assays. Results: Immunohistochemistry of liver metastatic biopsies and PDX tumor showed lack of expression of typical PCa (e.g., AR, PSA, PSAP, ERG) or neuroendocrine markers (synaptophysin), compatible with double-negative CRPC, but was positive for nuclear β-catenin expression, keratin 7 and 34βE12. ERG rearrangement was confirmed by fluorescent in situ hybridization (FISH). Drug response assays confirmed, in line with the clinical disease course, lack of sensitivity to common drugs used in mCRPC (e.g., enzalutamide, docetaxel). The casein kinase 1 (CK1) inhibitor IC261 and the tankyrase 1/2 inhibitor G700-LK showed modest activity. Moreover, despite harbouring a CTNNB1 mutation, PDOs were largely insensitive to SMARCA2/4- targeting PROTAC degraders and inhibitor. Conclusions: The reported CTNNB1-mutated mCRPC case highlights the potential challenges of double-negative CRPC diagnosis and underlines the relevance of further translational research to enable successful targeted treatment of rare molecular subtypes of mCRPC. [ABSTRACT FROM AUTHOR]

Highlights: To summarize the mechanisms and pathophysiological features of ALI after burn. To classify the targets for the treatment of ALI. Describe the types of nanomedicines used to treat ALI. These findings suggest the prospects and outlook for nanomaterial-targeted therapy for ALI. Acute lung injury (ALI) is a common complication in patients with severe burns and has a complex pathogenesis and high morbidity and mortality rates. A variety of drugs have been identified in the clinic for the treatment of ALI, but they have toxic side effects caused by easy degradation in the body and distribution throughout the body. In recent years, as the understanding of the mechanism underlying ALI has improved, scholars have developed a variety of new nanomaterials that can be safely and effectively targeted for the treatment of ALI. Most of these methods involve nanomaterials such as lipids, organic polymers, peptides, extracellular vesicles or cell membranes, inorganic nanoparticles and other nanomaterials, which are targeted to reach lung tissues to perform their functions through active targeting or passive targeting, a process that involves a variety of cells or organelles. In this review, first, the mechanisms and pathophysiological features of ALI occurrence after burn injury are reviewed, potential therapeutic targets for ALI are summarized, existing nanomaterials for the targeted treatment of ALI are classified, and possible problems and challenges of nanomaterials in the targeted treatment of ALI are discussed to provide a reference for the development of nanomaterials for the targeted treatment of ALI. [ABSTRACT FROM AUTHOR]

Copyright of Dermatologie Pro Praxi is the property of SOLEN sro 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.)

PurposeEndometrial cancer (EMCA) is the most common gynecologic malignancy, and new diagnoses are increasing in the United States. Black patients are more likely to present with advanced stage, be diagnosed with high-risk uterine serous carcinoma (USC) and die of their cancer.MethodsPatients with endometrial adenocarcinoma who received tumor FoundationOne CDx testing at our institution between January 2017 and August 2022 were identified. Genomic alterations, demographic and clinical characteristics were collected. Descriptive statistics and Fisher’s exact test were used to analyze data.ResultsA total of 289 patients (29.4% Black and 52.6% White) with advanced or recurrent endometrial adenocarcinoma underwent FoundationOne CDx testing. USC comprised 26.3% (76 of 289) of tested tumors. Of USC tumors, 33 of 76 (44%) were of Black race. USC occurred more frequently in Black patients (33 of 85 [38.8%] Black patients compared to 30 of 152 [19.7%] White patients, p

Glaucoma presents a significant global health concern and affects millions of individuals worldwide and predicted a high increase in prevalence of about 111 million by 2040. The current standard treatment involves hypotensive eye drops; however, challenges such as patient adherence and limited drug bioavailability hinder the treatment effectiveness. Nanopharmaceuticals or nanomedicines offer promising solutions to overcome these obstacles. In this manuscript, we summarized the current limitations of conventional antiglaucoma treatment, role of nanomedicine in glaucoma treatment, rational design, factors effecting the performance of nanomedicine and different types of nanocarriers in designing of nanomedicine along with their applications in glaucoma treatment from recent literature. Current clinical challenges that hinder real-time application of antiglaucoma nanomedicine are highlighted. Lastly, future directions are identified for improving the therapeutic potential and translation of antiglaucoma nanomedicine into clinic.

Simple Summary: Cholangiocarcinoma is a rare cancer with a dismal prognosis. The rate of recurrence after treatment of localized disease is high. In this review, we discuss the evidence regarding the use of radiation to improve outcomes in unresectable cholangiocarcinoma. We also discuss studies that have incorporated radiation before and after surgery. The review also briefly highlights recent developments in systemic therapy, especially targeted treatments and immunotherapy. Cholangiocarcinoma (CCA) is a rare cancer of bile ducts. It is associated with a poor prognosis. The incidence of CCA is rising worldwide. Anatomical subgroups have been used to classify patients for treatment and prognosis. There is a growing understanding of clinically important distinctions based on underlying genetic differences that lead to different treatment options and outcomes. Its management is further complicated by a heterogeneous population and relative rarity, which limits the conduct of large trials to guide management. Surgery has been the primary method of therapy for localized disease; however, recurrence and death remain high with or without surgery. Therefore, there have been concerted efforts to investigate new treatment options, such as the use of neoadjuvant treatments to optimize surgical outcomes, targeted therapy, leveraging a new understanding of immunobiology and stereotactic radiation. In this narrative review, we address the evidence to improve suboptimal outcomes in unresectable CCA with radiation, as well as the role of radiation in neoadjuvant and postoperative treatment. We also briefly discuss the recent developments in systemic treatment with targeted therapies and immune checkpoint inhibitors. [ABSTRACT FROM AUTHOR]

Copyright of Die Ophthalmologie is the property of Springer Nature 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.)

Clusterin (CLU) protein is involved in various pathophysiological processes including carcinogenesis and tumor progression. In recent years, the role of the secretory isoform has been demonstrated in tumor cells, where it inhibits apoptosis and favors the acquisition of resistance to conventional treatments used to treat cancer. To determine the possible therapeutic potential of inhibiting this protein, numerous studies have been carried out in this field. In this article, we present the existing knowledge to date on the inhibition of this protein in different types of cancer and analyze the importance it could have in the development of new therapies targeted against this disease. [ABSTRACT FROM AUTHOR]

New targeted treatments are urgently needed to improve triple-negative breast cancer (TNBC) patient survival. Previously, we identified the cell surface protein A Disintegrin And Metalloprotease 8 (ADAM8) as a driver of TNBC tumor growth and spread via its metalloproteinase and disintegrin (MP and DI) domains. In proof-of-concept studies, we demonstrated that a monoclonal antibody (mAb) that simultaneously inhibits both domains represents a promising therapeutic approach. Here, we screened a hybridoma library using a multistep selection strategy, including flow cytometry for Ab binding to native conformation protein and in vitro cell-based functional assays to isolate a novel panel of highly specific human ADAM8 dual MP and DI inhibitory mAbs, called ADPs. The screening of four top candidates for in vivo anti-cancer activity in an orthotopic MDA-MB-231 TNBC model of ADAM8-driven primary growth identified two lead mAbs, ADP2 and ADP13. Flow cytometry, hydrogen/deuterium exchange–mass spectrometry (HDX-MS) and alanine (ALA) scanning mutagenesis revealed that dual MP and DI inhibition was mediated via binding to the DI. Further testing in mice showed ADP2 and ADP13 reduce aggressive TNBC characteristics, including locoregional regrowth and metastasis, and improve survival, demonstrating strong therapeutic potential. The continued development of these mAbs into an ADAM8-targeted therapy could revolutionize TNBC treatment. [ABSTRACT FROM AUTHOR]

Adverse drug effects, commonly referred to as adverse drug reactions (ADRs), represent undesirable and unintended responses to medications or pharmaceutical products when used at recommended doses for therapeutic purposes. These effects can range from mild, tolerable symptoms to severe, life-threatening conditions and can manifest in various ways, affecting different organ systems within the human body. ADE analysis plays a pivotal role in prioritizing patient safety. By meticulously examining the relationship between drug administration and patient responses, healthcare providers can tailor medications to individual profiles, minimizing risks of adverse reactions. This ensures a patient-centric approach to treatment, where prescriptions are finely tuned to maximize efficacy while minimizing potential harm. This research aims to address this challenge by developing a machine learning system utilizing the Naive Bayes and XGBoost algorithms to enhance the categorization of drugs with adverse effects, ultimately contributing to improved patient safety and healthcare decision-making. In our approach, we made a system that detects ADR to effectively combine and collate patient medical history and drug information to detect if a patient would suffer adverse effects or reaction after taking the medication in its correct expert prescribed dose. The XGBoost algorithm gave a 75% accuracy score while Naive Bayes algorithm gave a score of 99%. [ABSTRACT FROM AUTHOR]

Aim: To explore the incorporation of novel agents in the first-line setting for acute myeloid leukemia patients. Materials & methods: Observational study based on data from a multi-country cross-sectional retrospective web-based survey sent to 518 physicians in Europe between 2020 and 2021. Information from 2040 patients was analyzed. Results: 604 patients (29.6%) received novel agents in both intensive and non-intensive setting. Comorbidities were not a barrier for the use of novel agents. The presence of tumor mutations was observed to be an important element for treatment decision. Conclusion: There is a progressive incorporation of novel agents for newly diagnosed acute myeloid leukemia patients. We now have new treatments for patients suffering from a type of blood cancer called acute myeloid leukemia (acronym AML). They are available as the first choice of therapy. In this study we explored how these new treatments are included in daily patient care. We reviewed the data of 2040 patients in Europe, obtained from an online survey sent to physicians in two waves (between 2020 and 2021). The use of these new AML treatments was more frequent in patients who presented some specific gene alterations (changes in their DNA sequence) and were in worse health due to other diseases and old age. Most of the new treatments were administered together with other milder chemotherapies. The results of this study help us understand how new AML treatments are being used. Observational study with 2040 AML patients showed incorporation of novel therapies into 1st line in combination with hypomethylating agents. Presence of tumor mutations observed to be an important element for treatment decision. [ABSTRACT FROM AUTHOR]

Background: The chloride intracellular channels (CLICs) family includes six ion channels (CLIC1-CLIC6) expressed on the cellular level and secreted into interstitial fluid and blood. They are involved in the physiological functioning of multiple systems as well as the pathogenetic processes of cancer. CLICs play essential roles in the tumor microenvironment. The current systematic review aimed at identifying and summarizing the research of CLICs in oncology on clinical material to assess CLICs' potential as novel biomarkers and personalized therapy targets. Materials and methods: The authors systematically searched the PubMed database for original articles concerning CLIC research on clinical material of all types of cancer -- fluids and tissues. Results: Fifty-three articles investigating in summary 3944 clinical samples were qualified for the current review. Studied material included 3438 tumor samples (87%), 437 blood samples (11%), and 69 interstitial fluid samples (2%). Studies investigated 21 cancer types, mostly hepatocellular carcinoma, colorectal, ovarian, and gastric cancer. Importantly, CLIC1, CLIC2, CLIC3, CLIC4, and CLIC5 were differently expressed in cancerous tissues and patients' blood compared to healthy controls. Moreover, CLICs were found to be involved in several cancer-associated signaling pathways, such as PI3K/AKT, MAPK/ERK, and MAPK/p38. Conclusion: CLIC family members may be candidates for potential novel cancer biomarkers due to the contrast in their expression between cancerous and healthy tissues and secretion to the interstitial fluid and blood. CLICs are investigated as potential therapeutic targets because of their involvement in cancer pathogenesis and tumor microenvironment. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) of the temporomandibular joint (TMJ) occurs spontaneously in humans and various animal species, including horses. In humans, obtaining tissue samples is challenging and clinical symptoms appear late in the disease progression. Therefore, genetically modified, induced, and naturally occurring animal models play a crucial role in understanding the pathogenesis and evaluating potential therapeutic interventions for TMJ OA. Among the naturally occurring models, the equine TMJ OA model is characterized by slow, age-related progression, a wide range of clinical examinations, and imaging modalities that can be performed on horses, as well as easy tissue and synovial fluid collection. The morphological and functional similarities of TMJ structures in both species make the equine model of TMJ OA an excellent opportunity to track disease progression and response to treatment. However, much work remains to be carried out to determine the utility of human TMJ OA biomarkers in horses. Among the main TMJ OA biomarkers, IL-1, IL-6, TGF-β, TNF-α, and PGE2 have been recently investigated in the equine model. However, the majority of biomarkers for cartilage degradation, chondrocyte hypertrophy, angiogenesis, and TMJ overload—as well as any of the main signaling pathways—have not been studied so far. Therefore, it would be advisable to focus further research on equine specimens, considering both mediators and signaling. [ABSTRACT FROM AUTHOR]

Background and purpose: The Precision Oncology Platform (POP) trial represents the effort of the Portuguese Oncology Institute of Porto (IPO Porto) for joining other leading European institutions in both ‘Personalised Cancer Medicine for all EU citizens’ (PCM4EU), and ‘PRecisIon Cancer MEdicine RepurpOsing SystEm Using Pragmatic Clinical Trials’ (PRIME-ROSE) consortia, enabling the development of the Portuguese version of the Drug Rediscovery Protocol (DRUP)-like Clinical Trial (DLCT), based on the experience of the DRUP trial developed in The Netherlands. Patients/material and methods: The POP trial is a phase II, pragmatic multicentric, non-randomised, open-label study, designed entirely like the other DLCTs. Its primary objective is to describe anti-tumour activity of targeted anticancer drugs in patients with advanced malignancies harbouring actionable molecular alterations. The primary endpoint is disease control rate (DCR). Secondary endpoints encompass treatment-related grade ≥3 adverse events, objective response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Exploratory objectives will assess biomarkers, resource use and costs, and patient-reported outcome measures (PROMs). Interpretation: The POP trial will offer access to innovative treatments for patients without further therapeutic options and provide evidence on efficacy and safety of molecularly-guided treatments. Methodologically, it represents a pioneer approach in Portugal, including a pay-for-performance model embedded in the clinical trial. The POP trial represents a unique opportunity to integrate clinical research within cancer care, pursuing an evidence-based precision oncology strategy, and facilitating its rational and cost-effective implementation into the Portuguese healthcare system.

Unfortunately, ovarian cancer is still diagnosed most often only in an advanced stage and is also the most lethal gynecological cancer. Another problem is the fact that treated patients have a high risk of disease recurrence. Moreover, ovarian cancer is very diverse in terms of molecular, histological features and mutations. Many patients may also develop platinum resistance, resulting in poor response to subsequent lines of treatment. To improve the prognosis of patients with ovarian cancer, it is expected to make better existing and implement new, promising treatment methods. Targeted therapies seem very promising. Currently, bevacizumab - a VEGF inhibitor and therapy with olaparib - a polyADP-ribose polymerase inhibitor are approved. Other methods worth considering in the future include: folate receptor α, immune checkpoints or other immunotherapy methods. To improve the treatment of ovarian cancer, it is also important to ameliorate the determination of molecular features to describe and understand which group of patients will benefit most from a given treatment method. This is important because a larger group of patients treated for ovarian cancer can have a greater chance of surviving longer without recurrence.

Recent studies have shown that cross reacting material (CRM197), a nontoxic variant of diphtheria toxin, may play an important role in treating cancers with poor prognoses. Doxorubicin-hydrochloride (DOX) is an antineoplastic prescription medicine for the treatment of certain types of cancer. Considering that CRM197 is a known carrier in targeted delivery, CRM197-DOX complexes might be a step towards targeted therapy and reduced overall toxicity. Aim. This study aims to explore the potential to inhibit the growth of tumour cells. To achieve that goal, we evaluated the usage of CRM197-DOX complexes in squamous carcinoma cell line A431 and compared it with the effect on other immortalised cell lines. The methods used in this research include derivation and purification of recombinant CRM197 through immobilized-metal affinity chromatography and electrophoresis in a denaturing polyacrylamide gel. DOX-loaded CRM197 complexes were formed by the addition of a 5 μM solution of doxorubicin to 0.5 μg of protein with further dialysis in PBS. The cell viability assay was conducted using free CRM197 at different concentrations, DOX, CRM197 with DOX, as well as DOX-loaded CRM197. DOX-loaded CRM197 along with CRM197 with the addition of DOX showed significant differences in cell viability compared to control wells. CRM197- Results. DOX complexes have an evident inhibitory effect on epidermoid carcinoma cell growth and can be used as treatment against epithelial tumours, with CRM197 as a promising carrier for targeted drug delivery. Conclusions. CRM197-DOX complexes show evident inhibition of epidermoid carcinoma cell growth and can be used as treatment against epithelial tumours, especially those overexpressing the proHB-EGF and its receptors, EGFR1 and EGFR4, with CRM197 as a promising carrier for targeted drug delivery.

Rheumatoid arthritis （RA） is a systemic autoimmune disease characterized by chronic and erosive polyarthritis. The core pathological changes involve persistent synovial inflammation and angioproliferation，leading to the destruction of joint cartilage and bone. The etiology and pathogenesis of RA remain unclear and complex. Despite decades of accumulated evidence and experience in the treatment of RA，there are currently no definitive methods to reverse RA joint tissue damage. Nanoparticle drug delivery platforms，as systems based on nanomaterials for drug delivery，are designed to improve drug distribution，enhance therapeutic effects，and reduce drug-related toxic side effects. This review focuses on the pathogenesis of synovitis in RA and explores the application and potential of macrophage-targeted nanoparticle drug delivery platforms in the prevention and treatment of RA.

Introduction. Meningioma is one of the most common central nervous system tumors, accounting for 39.7 % of all primary brain tumors. The tumor originates from arachnoid meningothelial cells and is characterized by a wide range of histological types classified into 15 subtypes. The histological classification of meningiomas allows us to predict meningioma behavior and the risk of disease recurrence, as well as to define treatment strategies. However, clinical outcomes in histological subgroups of patients are often inconsistent with the histological grade of malignancy. Thus, a more reliable method is needed both to determine the histological subtype of the tumor and to predict the clinical course of the disease with the potential for targeted treatment.The purpose of the study was to summarize the available data on the effect of results of the genomic and proteomic tumor analysis on carcinogenesis with the relationship between the mutational changes and noninvasive diagnosis, treatment and the course of the disease.Material and Methods. Literature search was carried out in the PubMed, Elibrary system, publications were included mainly from 2010 to 2023. with the identification of articles by the keyword “genetic analysis of meningiomas” and synonyms. 550 articles were found, of which 55 were used to write a literature review.Conclusion. The study of the molecular genetic profile of meningiomas will improve the classification and establish a correlation with MRI data, the course of the disease and prognosis.

Reports of Ascaridia galli in laying hens in Europe have increased since the ban on conventional battery cages in 2012. As this parasite is transmitted directly via the faecal-oral route by parasite eggs containing a larva, it is reasonable to assume that the escalating problem is related to the increased exposure now occurring in modern welfare-friendly cage-free housing systems. On many farms, A. galli reappears in subsequent flocks, even though the birds have no access to the outdoors, biosecurity is high and empty houses are cleaned and disinfected during downtime. Since the egg production cycle lasts only ≈80 weeks and recombinant antigen production for helminth vaccines has not yet been solved, the development of a vaccine seems to be an unrealistic option. Therefore, disrupting the life cycle of the parasite by other means, including the strategic use of dewormers, appears to be the key to controlling infection. Of concern is that only one class of anthelmintics is licenced for poultry in Europe and that are usually administered indiscriminately through the birds' drinking water and often too late when the parasite is already established. If current calendar-based parasite control strategies are not changed, there is a risk that resistance to anthelmintics may develop, as has already been demonstrated with nematodes in livestock. We insist that treatments can be more effective and the risk of developing drug resistance can be mitigated if we invest in a better understanding of A. galli responses to more prudent and judicious use of anthelmintics. This review identifies knowledge gaps and highlights aspects of sustainable parasite control that require further research to support commercial egg producers.

Colorectal cancer (CRC) is a devastating disease that ranks third in diagnosis and as the second leading cause of cancer-related deaths. The early detection of CRC has been shown to be the most effective strategy to improve treatment outcomes and patient survival. Therefore, current lines of research focus on the development of reliable diagnostic tools. Targeted therapies, in combination with standard chemotherapy and immune checkpoint inhibitors, have emerged as promising treatment protocols in CRC. However, their effectiveness is linked to the molecular characteristics of each patient. The importance of discovering biomarkers that help predict response to therapies and assess prognosis is evident as they allow for a fundamental step towards personalized care and successful treatments. Among the ongoing efforts to identify them, mass spectrometry-based translational proteomics presents itself as a unique opportunity as it enables the discovery and application of protein biomarkers that may revolutionize the early detection and treatment of CRC. Our objective is to show the most recent studies focused on the identification of CRC-related protein markers, as well as to provide an updated view of advances in the field of proteomics and cancer. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic and erosive polyarthritis. The core pathological changes involve persistent synovial inflammation and angioproliferation, leading to the destruction of joint cartilage and bone. The etiology and pathogenesis of RA remain unclear and complex. Despite decades of accumulated evidence and experience in the treatment of RA, there are currently no definitive methods to reverse RA joint tissue damage. Nanoparticle drug delivery platforms, as systems based on nanomaterials for drug delivery, are designed to improve drug distribution, enhance therapeutic effects, and reduce drug-related toxic side effects. This review focuses on the pathogenesis of synovitis in RA and explores the application and potential of macrophage-targeted nanoparticle drug delivery platforms in the prevention and treatment of RA. [ABSTRACT FROM AUTHOR]

Reports of Ascaridia galli in laying hens in Europe have increased since the ban on conventional battery cages in 2012. As this parasite is transmitted directly via the faecal-oral route by parasite eggs containing a larva, it is reasonable to assume that the escalating problem is related to the increased exposure now occurring in modern welfare-friendly cage-free housing systems. On many farms, A. galli reappears in subsequent flocks, even though the birds have no access to the outdoors, biosecurity is high and empty houses are cleaned and disinfected during downtime. Since the egg production cycle lasts only ≈80 weeks and recombinant antigen production for helminth vaccines has not yet been solved, the development of a vaccine seems to be an unrealistic option. Therefore, disrupting the life cycle of the parasite by other means, including the strategic use of dewormers, appears to be the key to controlling infection. Of concern is that only one class of anthelmintics is licenced for poultry in Europe and that are usually administered indiscriminately through the birds' drinking water and often too late when the parasite is already established. If current calendar-based parasite control strategies are not changed, there is a risk that resistance to anthelmintics may develop, as has already been demonstrated with nematodes in livestock. We insist that treatments can be more effective and the risk of developing drug resistance can be mitigated if we invest in a better understanding of A. galli responses to more prudent and judicious use of anthelmintics. This review identifies knowledge gaps and highlights aspects of sustainable parasite control that require further research to support commercial egg producers. [Display omitted] • Research efforts to optimise the control of Ascaridia galli in laying hens are needed. • The use of a TT approach based on a combination of diagnostic tools is a viable control option. • Investigating the extent to which A. galli is resistant to BZ drugs should be a priority. • Advances in diagnostic parasitology offer the potential to fill knowledge gaps. • When and how to sample the flocks should not be ignored. [ABSTRACT FROM AUTHOR]

Background: The roles of many long noncoding RNAs (lncRNAs) in breast cancer (BC) are unclear, and the medications that affect them have attracted less attention. Objectives: This study aimed to identify lncRNAs that have the highest association with poor prognosis in BC. Moreover, the relationship between the expression of identified lncRNA and conventional chemotherapy agents was investigated. Methods: The cancer genome atlas data were used to identify lncRNA with the most significant impact on BC survival. The relation of identified lncRNA levels with different subtypes of BC and mutation was assessed. PharmacoGX data and the GEO database were used to evaluate the association of identified lncRNA levels with drug sensitivity and find appropriate medications to reduce its expression, respectively. To assess the effect of the identified drugonthe level of lncRNA expression, MCF7, andMDA-MB-468cell lines were used, and the expression level of target genes was assessed by quantitative reverse transcription polymerase chain reaction. Results: The expression level of lncRNA MIR4435-2HG was most associated with the poor survival of BC patients, and its expression level can be related to TP53 mutation and estrogen and progesterone receptors. Increased expression of MIR4435-2HG was observed in cancer samples, and MIR4435-2HG level was correlated with metastasis pathway genes. Drug sensitivity to epirubicin, irinotecan, andlestaurtinib correlated with MIR4435-2HG levels. Furthermore, GEO data showed that the expression level of MIR4435-2HG could decrease under estrogen receptor (ER) activity. Finally, in vitro, results showed that MIR4435-2HG expression declined in response to estradiol as an ER-activating ligand in the MCF7 cell line. Conclusions: The expression of MIR4435-2HG can be a powerful biomarker for poor prognosis in BC. The data also suggested that this lncRNA may play an oncogenic role in metastatic pathways, and ER activity could regulate its expression. [ABSTRACT FROM AUTHOR]

Background: In recent years, breast cancer has become the most common cancer in the world, increasing women's health risks. Approximately 60% of breast cancers are categorized as human epidermal growth factor receptor 2 (HER2)-low tumors. Recently, antibody-drug conjugates have been found to have positive anticancer efficacy in patients with HER2-low breast cancer, but more studies are required to comprehend their clinical and molecular characteristics. Methods: In this study, we retrospectively analyzed the data of 165 early breast cancer patients with pT1-2N1M0 who had undergone the RecurIndex testing. To better understand HER2-low tumors, we investigated the RecurIndex genomic profiles, clinicopathologic features, and survival outcomes of breast cancers according to HER2 status. Results: First, there were significantly more hormone receptor (HR)-positive tumors, luminal-type tumors, and low Ki67 levels in the HER2-low than in the HER2-zero. Second, RI-LR (P =.0294) and RI-DR (P =.001) scores for HER2-low and HER2-zero were statistically significant. Third, within HER2-negative disease, HR-positive/HER2-low tumors showed highest ESR1, NFATC2IP, PTI1, ERBB2, and OBSL1 expressions. Fourth, results of the survival analysis showed that lower expression of HER2 was associated with improved relapse-free survival for HR-positive tumors, but not for HR-negative tumors. Conclusions: The present study highlights the unique features of HER2-low tumors in terms of their clinical characteristics as well as their gene expression profiles. HR status may influence the prognosis of patients with HER2-low expression, and patients with HR-positive/HER2-low expression may have a favorable outcome. In this study, the data of patients with early stage breast cancer who had undergone RecurIndex testing was analyzed. To better understand HER2-low tumors, genomic profiles, clinicopathologic features, and survival outcomes of breast cancers according to HER2 status were investigated. [ABSTRACT FROM AUTHOR]

Tumoral heterogeneity has been associated with treatment resistance and failure in patients with cancer. Tumoral heterogeneity can be either intertumoral (static variation of cancer cells) or intratumoral (spatial and temporal variation of cancer cells). Nonsmall-cell lung cancer (NSCLC) is considered a model disease for the study of tumoral heterogeneity, given the emerging evidence about the clinical implications of genetic variations among NSCLC subtypes. This review provides an overview of the etiology, detection, and management methods of intratumoral heterogeneity in NSCLC and discusses their clinical implications.

Aim. To explore the potential to inhibit the growth of tumour cells which express EGF receptors, in this study, we evaluated the usage of CRM197-DOX complexes in squamous carcinoma cell line A431 and compared it with the effect on other immortalised cell lines such as 3T3 fibroblasts and kidney epithelial Vero cells. Methods. Cell lines. All cell lines were cultivated in a humidified 37 °C incubator with 5% CO2, using Dulbecco’s Modified Eagle Medium (DMEM) supplemented with 10% heat-inactivated fetal bovine serum (FBS) and antibiotics. Protein extraction and purification. For recombinant CRM197 and HB-EGF protein expression, E.coli, containing pET28(a)-CRM197 and pET32(a)-HB-EGF plasmids respectively, were grown in the lysogeny broth with the edition of an antibiotic (Kanamycin or Ampicillin) for ~2 h at 37 °C. Later, each culture was induced with IPTG and was further grown for ~3 h at 30 °C. Both cultures were centrifuged, pellets resuspended in separate tubes with the buffer containing 6 M urea and lysed by ultrasound homogenisation. Homogenized cell mass was centrifuged and the supernatants containing CRM197 and HB-EGF were retained and used for the purification of respective proteins. PolyHis labelled CRM197 and HB-EGF were purified by Ni2+-NTA affinity chromatography and eluate fractions were dialysed in phosphate-buffered saline (PBS) [4]. Aliquots of proteins with sodium dodecyl sulfate (SDS) loading buffer were used for 10% SDS-PAGE. The gel was stained with Coomassie Brilliant Blue G-250. The expression of CRM197 and HB-EGF was confirmed by comparing bands appearing on the gel at ~58 kDa and ~10 kDa respectively. Complex loading. 5 μM of doxorubicin was dissolved in 1 ml of 20 mM Tris-HCl buffer. The DOX solution was added to the 0.5 μg of protein. Then, the heterogenous solution was mixed for 12 h at 4 °C with further dialysis in PBS (for loaded CRM197-DOX). MTT assay. Cells were cultivated in 96-well flat-bottomed plates in DMEM supplemented with 10% FBS and antibiotics for 24 h, then washed twice with PBS, and a fresh FBS-free culture medium was added. Control substances were added at the following concentrations: DOX — 5 μM, HB-EGF — 0.5 μg/ml, CRM197 — 0.5 μg/ml and 1 μg/ml, CRM197 + DOX — 0.5 μg/ml of protein and 5 μM of DOX, CRM197-DOX (loaded) — 0.5 μg/ml (according to protein). After incubation for 48 h in a humidified 37 °C incubator with 5% CO2, the optical density of the samples was measured using a multi-well spectrophotometer at 570 nm [5]. Statistics. Shapiro-Wilk test, one-way ANOVA and the Tukey–Kramer procedure were performed using Statistics Kingdom and showed significant effects for pairwise comparisons of control to test groups (P < 0.05). Results and Discussion. Analytic expression with further running SDS-PAGE (Fig. 1) indicated that CRM197 is extracted in an insoluble form; purified and eluated CRM197 (~0.1 mg/ml) in the fraction C was later used in the experiment (Fig. 2). In the A431 cell line (Fig. 3, A), treatment with CRM197 inhibited cell growth by 11% (0.5 μg/ ml) and 25% (1 μg/ml). CRM197 + DOX showed results similar to those of CRM197 at 1 μg/ml concentration and of 5 μM DOX. CRM197-DOX loaded complex inhibited cell growth by 17%. It is worth noting that the excess of unbound DOX was removed by dialysis, therefore the main cytostatic effect is caused by the loaded CRM197-DOX, adding to the hypothesis that these complexes may further be used for targeted treatment of tumour cells. The 3T3 cell line (Fig. 3, B) showed little to no reaction to CRM197 treatment but was excessively responding to treatment with doxorubicin-hydrochloride. CRM197 + DOX and the loaded CRM197- DOX showed results of 43% and 19% respectively. The Vero cell line (Fig. 3, C) reacted to CRM197 at 0.5 μg/ml with a growth inhibition by 26%, and both 1 μg/ml concentration and CRM197 + DOX showed a result of ~37%. The loaded complex showed efficiency of 31%. All CRM197 treatments were significantly more effective than DOX. Conclusions. CRM197-DOX complexes show evident inhibition of epidermoid carcinoma cell growth and can be used as treatment against epithelial tumours, especially those overexpressing the proHB-EGF and its receptors, EGFR1 and EGFR4, with CRM197 as a promising carrier for targeted drug delivery. Since DOX-loaded CRM197 complex shows lesser cytotoxicity than free DOX, we concluded that a certain amount of the antibiotic is lost in the process of loading, but DOX-loaded CRM197 complex still inhibits cell proliferation more strongly than free CRM197. However, there is still a need for more efficient loading techniques and to fill the gap of DOX to CRM197 loading process mechanisms. [ABSTRACT FROM AUTHOR]

Chronic consequences of mild traumatic brain injury (mTBI) are heterogeneous, but may be treatable with targeted medical and rehabilitation interventions. A biological signature for the likelihood of response to therapy (i.e., ?predictive? biomarkers) would empower personalized medicine post-mTBI. The purpose of this study was to correlate pre-intervention blood biomarker levels and the likelihood of response to targeted interventions for patients with chronic issues attributable to mTBI. Patients with chronic symptoms and/or disorders secondary to mTBI >3 months previous (104 days to 15 years; n?=?74) were enrolled. Participants completed pre-intervention assessments of symptom burden, comprehensive clinical evaluation, and blood-based biomarker measurements. Multi-domain targeted interventions for specific symptoms and impairments across a 6-month treatment period were prescribed. Participants completed a follow-up testing after the treatment period. An all-possible model's backward logistic regression was built to identify predictors of improvement in relation to blood biomarker levels before intervention. The minimum clinically important difference (MCID) of the change score (post-intervention subtracted from pre-intervention) for the Post-Concussion Symptom Scale (PCSS) to identify treatment responders from non-responders was the primary outcome. The MCID for total PCSS score was 10. The model to predict change in PCSS score over the 6-month intervention was significant (R2?=?0.09; p?=?0.01) and identified ubiquitin C-terminal hydrolase L1 (odds ratio [OR]?=?2.53; 95% confidence interval [CI], 1.18?5.46; p?=?0.02) and hyperphosphorylated tau (p-tau; OR?=?0.70; 95% CI, 0.51?0.96; p?=?0.03) as significant predictors of symptom improvement beyond the PCSS MCID. In this cohort of chronic TBI subjects, blood biomarkers before rehabilitation intervention predicted the likelihood of response to targeted therapy for chronic disorders post-TBI.

The management of wounds is a critical aspect of healthcare as it affects patients' quality of life and puts a financial burden on the healthcare industry. The development of smart bandages has shown great potential in wound monitoring and targeted treatment. This review paper gives information on the latest updates in smart bandage technology that can monitor various biomarkers such as temperature, moisture, oxygen, blood flow, external pressure, pH, and infection status in real time. Additionally, this review discusses targeted treatment by integrating drug delivery systems that can release drugs on-demand based on the wound condition. Furthermore, this paper gives a summary of information on the current improvements in smart bandages, including their design, fabrication, and clinical applications. This paper also discussed the current challenges and future opportunities with smart bandages and their potential to transform the field of wound care. With the ability to noninvasively diagnose wound parameters, reduce pain, and accelerate wound healing, smart bandages are expected to play a significant role in future wound care.

In recent decades, an escalating incidence of tumors has been observed, necessitating more precise and less side-effect-prone therapies. Micro/nanorobots have been successfully engineered to address this challenge. These minute intelligent machines are capable of navigating to, and even infiltrating, tumor cells or tissues under external control. This enables targeted drug delivery and precise tumor therapy. To elucidate this sophisticated technology to a general audience, this paper adopts a personification style. Utilizing an engaging "battle narrative between micro/nanorobots and tumor cells", we briefly outline the design, fabrication, propulsion mechanisms, and therapeutic principles for a wider readership. [ABSTRACT FROM AUTHOR]

Drug resistance is a bottleneck in cancer treatment. Commonly, a molecular treatment for cancer leads to the emergence of drug resistance in the long term. Thus, some drugs, despite their initial excellent response, are withdrawn from the market. Lung cancer is one of the most mutated cancers, leading to dozens of targeted therapeutics available against it. Here, we have developed a mechanistic mathematical model describing sensitization to nine groups of targeted therapeutics and the emergence of intrinsic drug resistance. As we focus only on intrinsic drug resistance, we perform the computer simulations of the model only until clinical diagnosis. We have utilized, for model calibration, the whole-exome sequencing data combined with clinical information from over 1000 non-small-cell lung cancer patients. Next, the model has been applied to find an answer to the following questions: When does intrinsic drug resistance emerge? And how long does it take for early-stage lung cancer to grow to an advanced stage? The results show that drug resistance is inevitable at diagnosis but not always detectable and that the time interval between early and advanced-stage tumors depends on the selection advantage of cancer cells. [ABSTRACT FROM AUTHOR]

Relatlimab is a human anti-lymphocyte activation gene 3 protein antibody approved for the treatment of metastatic or unresectable melanoma in combination with nivolumab, an existing programmed cell death protein 1 inhibitor. In this article, we review the clinical literature on the efficacy and therapeutic use of the immune checkpoint inhibitor relatlimab in combination with nivolumab for metastatic melanoma. We provide an overview of the mechanism of action, clinical efficacy, and safety profile of relatlimab-nivolumab through a review of recent publications on this emerging therapeutic combination. Ongoing clinical trials studying the use of relatlimab and associated areas of active investigation are also highlighted. This review strives to inform practicing dermatologists on the use of relatlimab-nivolumab as an approved first-line dual checkpoint inhibitor for metastatic melanoma in appropriate clinical cases. [ABSTRACT FROM AUTHOR]

Colorectal cancer is the third most diagnosed cancer, behind only breast and lung cancer. In terms of overall mortality, it ranks second due to, among other factors, problems with screening programs, which means that one of the factors that directly impacts survival and treatment success is early detection of the disease. Clusterin (CLU) is a molecular chaperone that has been linked to tumorigenesis, cancer progression and resistance to anticancer treatments, which has made it a promising drug target. However, it is still necessary to continue this line of research and to adjust the situations in which its use is more favorable. The aim of this paper is to review the current genetic knowledge on the role of CLU in tumorigenesis and cancer progression in general, and discuss its possible use as a therapeutic target in colorectal cancer. [ABSTRACT FROM AUTHOR]