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Objective: This article aims to analyze the current status and research hotspots of literature related to perioperative management of patients with Lung Cancer and provide reference for future research directions. Methods: This study conducted a bibliometric analysis of research literature related to perioperative management of Lung Cancer published between 2004 and 2024, retrieved from the Web of Science database. R software and VOSviewer were used for analyzing keyword clusters and research themes, revealing trends and frontiers in this field. Results: A total of 4,942 studies on perioperative management of lung cancer were included. In recent years, research in this area has shown a global upward trend, with particular focus on surgical risk assessment, complication prevention, and postoperative management. Perioperative biomarkers before and after surgery have emerged as a central focus due to their impact on diagnosis and treatment. The application of novel therapies, such as targeted drugs and immunotherapy, in perioperative management is also becoming a significant research hotspot. Additionally, China has been a leading contributor to research output in this field, demonstrating strong performance in international collaborations. Conclusion: Perioperative management is a critical factor influencing the prognosis of Resectable lung cancer patients. Through a systematic analysis of the current status and research hotspots in perioperative management of lung cancer, this study provides valuable references for future clinical practice and research, particularly regarding the integration of novel therapies to optimize patient outcomes. [ABSTRACT FROM AUTHOR]

AbstractMore than 80% of newly diagnosed chronic lymphocytic leukemia (CLL) patients present with asymptomatic, early-stage CLL. Of these, only 30–50% progress to advanced stage with reduced survival, while the rest may never require treatment. According to the 2018 International Workshop on CLL (iwCLL) guidelines, patients who do not meet the criteria for treatment initiation should only be treated within the context of clinical trials, as data demonstrating an overall survival benefit in early-stage CLL are still awaited. Risk stratification through continually advancing prognostic models can assist in identifying high-risk patients for early, risk-adapted treatment within clinical trials. Currently, new targeted therapies with high efficacy and lower toxicity are available in early intervention trials. This review (1) explores the development of prognostic models for identifying high-risk patients, (2) examines the design of early intervention trial, (3) summarizes the outcomes of early intervention trials, particularly in the context of targeted therapies, and (4) highlights ongoing clinical trials involving targeted treatments. [ABSTRACT FROM AUTHOR]

Fibroblast growth factors (FGFs) and their receptors regulate numerous cellular processes, such as metabolism and signal transduction, but can also drive tumorigenesis. Specifically, in lung cancer, the overexpression of FGFs, as well as the amplification, mutation and fusion of FGFR genes, are closely linked to the initiation, progression and resistance of the disease, suggesting that targeting FGF/FGFR is an attractive therapeutic strategy for lung cancer treatment. Nintedanib, a multitarget tyrosine kinase inhibitor (TKI) used in combination with docetaxel, has shown some success as a second-line therapy for lung cancer. However, clinical trials evaluating other FGFR inhibitors have yielded mixed results, indicating substantial complexity in targeting aberrant FGF/FGFR signaling. In this review, we describe the aberrations in FGF/FGFR signaling in lung cancer and summarize the clinical efficacy of FGFR inhibitors, such as multitarget TKIs, selective FGFR-TKIs and biological agents. We also discuss various challenges associated with FGFR targeting in lung cancer, including precision patient selection, toxicity and resistance. Finally, we provide perspectives on future directions, namely, developing novel FGFR-targeting drugs, such as FGFR degraders and more specific FGFR-TKIs, adopting combination therapy and targeting FGFs. [ABSTRACT FROM AUTHOR]

High-risk acute myeloid leukemia has been associated with a poor outcome. Hematopoietic stem cell transplantation (HSCT) represents the only curative option for eligible patients. Relapse after HSCT is a dramatic event with poor chances of survival. With the aim of reducing the rate of post-HSCT relapse, maintenance treatment has been investigated in this setting. Results from clinical trials suggest an advantage in the use of a maintenance strategy; however, standardized guidelines are not yet available due to the lack of prospective clinical trials. In this review, we have reported the most important strategies adopted as post-HSCT maintenance, highlighting their efficacy, but the current research also opens questions. [ABSTRACT FROM AUTHOR]

Targeted drug delivery has emerged as a transformative approach in the treatment of periorbital skin malignancies, offering the potential for enhanced efficacy and reduced side effects compared to traditional therapies. This review provides a comprehensive overview of targeted therapies in the context of periorbital malignancies, including basal cell carcinoma, squamous cell carcinoma, sebaceous gland carcinoma, and Merkel cell carcinoma. It explores the mechanisms of action for various targeted therapies, such as monoclonal antibodies, small molecule inhibitors, and immunotherapies, and their applications in treating these malignancies. Additionally, this review addresses the management of ocular and periocular side effects associated with these therapies, emphasizing the importance of a multidisciplinary approach to minimize impact and ensure patient adherence. By integrating current findings and discussing emerging trends, this review aims to highlight the advancements in targeted drug delivery and its potential to improve treatment outcomes and quality of life for patients with periorbital skin malignancies. [ABSTRACT FROM AUTHOR]

Opinion Statement: Hepatocellular carcinoma (HCC) is a common type of tumor worldwide. The development of systemic treatment of advanced HCC has remained stagnant for a considerable period. During the last years, a series of new treatment regimens based on the combination of immunotherapeutic drugs and targeted drugs have been gradually developed, increased the objective response rate (ORR), overall survival (OS), and progression free survival (PFS) of HCC patients. Among the different combination therapy groups, atezolizumab plus bevacizumab and sintilimab plus IBI-305 seem to have unique advantages, while head-to-head comparisons are still needed. A comprehensive understanding of the developments, the ongoing clinical trials and the mechanisms of combination of immunotherapy and targeted therapy might lead to the development of new combination strategies and solving current challenges such as the molecular biomarkers, the clinical administration order of drugs and the second-line treatments after combination therapy. [ABSTRACT FROM AUTHOR]

Abstract Fibroblast growth factors (FGFs) and their receptors regulate numerous cellular processes, such as metabolism and signal transduction, but can also drive tumorigenesis. Specifically, in lung cancer, the overexpression of FGFs, as well as the amplification, mutation and fusion of FGFR genes, are closely linked to the initiation, progression and resistance of the disease, suggesting that targeting FGF/FGFR is an attractive therapeutic strategy for lung cancer treatment. Nintedanib, a multitarget tyrosine kinase inhibitor (TKI) used in combination with docetaxel, has shown some success as a second-line therapy for lung cancer. However, clinical trials evaluating other FGFR inhibitors have yielded mixed results, indicating substantial complexity in targeting aberrant FGF/FGFR signaling. In this review, we describe the aberrations in FGF/FGFR signaling in lung cancer and summarize the clinical efficacy of FGFR inhibitors, such as multitarget TKIs, selective FGFR-TKIs and biological agents. We also discuss various challenges associated with FGFR targeting in lung cancer, including precision patient selection, toxicity and resistance. Finally, we provide perspectives on future directions, namely, developing novel FGFR-targeting drugs, such as FGFR degraders and more specific FGFR-TKIs, adopting combination therapy and targeting FGFs.

High-risk acute myeloid leukemia has been associated with a poor outcome. Hematopoietic stem cell transplantation (HSCT) represents the only curative option for eligible patients. Relapse after HSCT is a dramatic event with poor chances of survival. With the aim of reducing the rate of post-HSCT relapse, maintenance treatment has been investigated in this setting. Results from clinical trials suggest an advantage in the use of a maintenance strategy; however, standardized guidelines are not yet available due to the lack of prospective clinical trials. In this review, we have reported the most important strategies adopted as post-HSCT maintenance, highlighting their efficacy, but the current research also opens questions.

Abstract Objective The study purpose was to explore the causal association between pyruvate metabolism and breast cancer (BC), as well as the molecular role of key metabolic genes, by using bioinformatics and Mendelian randomization (MR) analysis. Methods We retrieved and examined diverse datasets from the GEO database to ascertain differentially acting genes (DAGs) in BC via differential expression analysis. Following this, we performed functional and pathway enrichment analyses to ascertain noteworthy molecular functions and metabolic pathways in BC. Employing MR analysis, we established a causal association between pyruvate metabolism and the susceptibility to BC. Additionally, utilizing the DGIdb database, we identified potential targeted medications that act on genes implicated in the pyruvate metabolic pathway and formulated a competing endogenous RNA (ceRNA) regulatory network in BC. Results We collected the datasets GSE54002, GSE70947, and GSE22820, and identified a total of 1127 DEGs between the BC and NC groups. GO and KEGG enrichment analysis showed that the molecular functions of these DEGs mainly included mitotic nuclear division, extracellular matrix, signaling receptor activator activity, etc. Metabolic pathways were mainly concentrated in PI3K−Akt signaling pathway, Cytokine−cytokine receptor binding and Pyruvate, Tyrosine, Propanoate and Phenylalanine metabolism, etc. In addition, MR analysis demonstrated a causal relationship between pyruvate metabolism and BC risk. Finally, we constructed a regulatory network between pathway genes (ADH1B, ACSS2, ACACB, ADH1A, ALDH2, and ADH1C) and targeted drugs, as well as a ceRNA (lncRNA-miRNA-mRNA) regulatory network for BC, further revealing their interactions. Conclusions Our research revealed a causal association between pyruvate metabolism and BC risk, found that ADH1B, ACSS2, ACACB, ADH1A, ALDH2, and ADH1C takes place an important part in the development of BC in the molecular mechanisms related to pyruvate metabolism, and identified some potential targeted small molecule drugs.

With the development of nanomedicine, nanomaterials have been widely used, offering specific drug delivery to target sites, minimal side effects, and significant therapeutic effects. The kidneys have filtration and reabsorption functions, with various potential target cell types and a complex structural environment, making the strategies for kidney function protection and recovery after injury complex. This also lays the foundation for the application of nanomedicine in kidney diseases. Currently, evidence in preclinical and clinical settings supports the feasibility of targeted therapy for kidney diseases using drug delivery based on nanomaterials. The prerequisite for nanomedicine in treating kidney diseases is the use of carriers with good biocompatibility, including nanoparticles, hydrogels, liposomes, micelles, dendrimer polymers, adenoviruses, lysozymes, and elastin-like polypeptides. These carriers have precise renal uptake, longer half-life, and targeted organ distribution, protecting and improving the efficacy of the drugs they carry. Additionally, attention should also be paid to the toxicity and solubility of the carriers. While the carriers mentioned above have been used in preclinical studies for targeted therapy of kidney diseases both in vivo and in vitro, extensive clinical trials are still needed to ensure the short-term and long-term effects of nano drugs in the human body. This review will discuss the advantages and limitations of nanoscale drug carrier materials in treating kidney diseases, provide a more comprehensive catalog of nanocarrier materials, and offer prospects for their drug-loading efficacy and clinical applications.

"Metaflammation," proposed by Hotamisligil in 2006, refers to a chronic low-grade inflammation triggered by metabolic factors such as excessive nutrition and energy, persisting at subacute levels over an extended period. Immune cells infiltrate the inflammatory site, leading to enhanced expression or activity of various inflammatory molecules and subsequent inflammatory damage. Recent research on metabolic-related fatty liver disease has revealed that modern metaflammation plays a pivotal role in the pathogenesis of NAFLD. The associated inflammatory pathways offer promising prospects for the development of targeted drugs. This article provides an updated review on the advancements in metaflammation within NAFLD. [ABSTRACT FROM AUTHOR]

The development and use of HER2-targeted drugs has improved the prognosis of HER2-positive cancer patients. However, in addition to improved survival rates, treatment-induced adverse events and nontumor-related deaths have increased. We sought to assess the incidence of cardiovascular adverse events when HER2-targeted drugs are combined with other drugs. We systematically searched the literature on the cardiotoxicity of anti-HER2 drugs in electronic databases, including PubMed, Web of Science, Cochrane Library, OVID and CNKI, from their inception to April 2022. The Cochrane Collaboration's tool for assessing risk of bias and the Jadad scale were used to evaluate the risk of bias and quality of the studies, respectively. For each included trial, we calculated the incidence of cardiovascular adverse effects (CAEs) and 95% confidence intervals (95% CIs) and performed a meta-analysis using a random effects model (REM). The meta-analysis was performed using R 4.2.1. We included 41 randomized clinical trials (RCTs) in the meta-analysis, consisting of 56 groups and 31,934 patients. The meta-analysis revealed the following: (1) The incidence of cardiotoxicity in groups given monoclonal antibody treatment was 14% for single therapy (95% CI: 2–34%) and 10%, 11%, and 12% for adjuvant therapy combined with combined therapy (95% CI: 6–13%), chemotherapy (95% CI: 8–13%) and endocrine therapy (95% CI: 7–18%), respectively. However, in the groups treated with the antibody‒drug conjugates (ADCs), the percentage of patients treated with the combination therapy was 1% (95% CI: 0–2%) and 5% (95% CI: 4–7%), respectively, with a significant difference (P < 0.01). The heterogeneity among the included studies was significant (I2 = 94%, p < 0.01). (2) When monoclonal antibodies were combined with chemotherapy, the incidence of cardiotoxicity under anthracycline-containing therapy (10.3%) was significantly greater than that under nonanthracycline-containing therapy (8.8%). (3) Significant differences were found between subgroups, except for the endocrine group versus some others, although this difference might result from the different inclusion criteria of the original trials. (1) When anti-HER2 drugs are administered in combination with anthracycline-containing chemotherapy, the incidence of cardiotoxicity is greater than with other drugs. (2) Safety benefits can be achieved by replacing traditional monoclonal antibodies with ADCs. The comprehensive use of these drugs necessitates collaboration between oncologists and cardiologists. [ABSTRACT FROM AUTHOR]

The advent of targeted drug therapy has greatly changed the treatment landscape of advanced non-small cell lung cancer(NSCLC), but the cardioxic side effects of targeted drug anti-cancer therapy seriously affect the prognosis of NSCLC, and it has become the second leading cause of death in cancer patients. Therefore, early identification of the cardiotoxic side effects of targeted drugs is crucial for the prevention and treatment of cardiovascular diseases. The cardiotoxic side effects that may be caused by novel targeted drugs epidermal growth factor receptor inhibitors, including thromboembolic events, heart failure, cardiomyopathy, arrhythmia and hypertension, are discussed, and the mechanisms of their respective adverse cardiovascular reactions are summarized, to provide useful recommendations for cardiacmanagement of patients with advanced lung cancer to maximize treatment outcomes for lung cancer survivors. Clinicians need to balance the risk-benefit ratio between targeted therapy for malignant tumors and drug-induced cardiotoxicity, and evaluate and monitor TKIs-induced cardiotoxicity through electrocardiogram, cardiac imaging, biomarkers, etc., so as to remove the susceptibility risk factors as soon as possible and provide a reference for the clinical use of such drugs in the treatment of malignant tumors. [ABSTRACT FROM AUTHOR]

Objective: The study purpose was to explore the causal association between pyruvate metabolism and breast cancer (BC), as well as the molecular role of key metabolic genes, by using bioinformatics and Mendelian randomization (MR) analysis. Methods: We retrieved and examined diverse datasets from the GEO database to ascertain differentially acting genes (DAGs) in BC via differential expression analysis. Following this, we performed functional and pathway enrichment analyses to ascertain noteworthy molecular functions and metabolic pathways in BC. Employing MR analysis, we established a causal association between pyruvate metabolism and the susceptibility to BC. Additionally, utilizing the DGIdb database, we identified potential targeted medications that act on genes implicated in the pyruvate metabolic pathway and formulated a competing endogenous RNA (ceRNA) regulatory network in BC. Results: We collected the datasets GSE54002, GSE70947, and GSE22820, and identified a total of 1127 DEGs between the BC and NC groups. GO and KEGG enrichment analysis showed that the molecular functions of these DEGs mainly included mitotic nuclear division, extracellular matrix, signaling receptor activator activity, etc. Metabolic pathways were mainly concentrated in PI3K−Akt signaling pathway, Cytokine−cytokine receptor binding and Pyruvate, Tyrosine, Propanoate and Phenylalanine metabolism, etc. In addition, MR analysis demonstrated a causal relationship between pyruvate metabolism and BC risk. Finally, we constructed a regulatory network between pathway genes (ADH1B, ACSS2, ACACB, ADH1A, ALDH2, and ADH1C) and targeted drugs, as well as a ceRNA (lncRNA-miRNA-mRNA) regulatory network for BC, further revealing their interactions. Conclusions: Our research revealed a causal association between pyruvate metabolism and BC risk, found that ADH1B, ACSS2, ACACB, ADH1A, ALDH2, and ADH1C takes place an important part in the development of BC in the molecular mechanisms related to pyruvate metabolism, and identified some potential targeted small molecule drugs. [ABSTRACT FROM AUTHOR]

ObjectiveThis article aims to analyze the current status and research hotspots of literature related to perioperative management of patients with Lung Cancer and provide reference for future research directions.MethodsThis study conducted a bibliometric analysis of research literature related to perioperative management of Lung Cancer published between 2004 and 2024, retrieved from the Web of Science database. R software and VOSviewer were used for analyzing keyword clusters and research themes, revealing trends and frontiers in this field.ResultsA total of 4,942 studies on perioperative management of lung cancer were included. In recent years, research in this area has shown a global upward trend, with particular focus on surgical risk assessment, complication prevention, and postoperative management. Perioperative biomarkers before and after surgery have emerged as a central focus due to their impact on diagnosis and treatment. The application of novel therapies, such as targeted drugs and immunotherapy, in perioperative management is also becoming a significant research hotspot. Additionally, China has been a leading contributor to research output in this field, demonstrating strong performance in international collaborations.ConclusionPerioperative management is a critical factor influencing the prognosis of Resectable lung cancer patients. Through a systematic analysis of the current status and research hotspots in perioperative management of lung cancer, this study provides valuable references for future clinical practice and research, particularly regarding the integration of novel therapies to optimize patient outcomes.

The editorial "Novelties in acute myeloid leukemia: from biology to clinical applications" discusses recent advances in understanding acute myeloid leukemia (AML) biology and treatment. Topics covered include new prognostic biomarkers, therapeutic strategies such as CAR-T cells and targeted drugs, and the impact of mutations like RAS on cell metabolism. The research highlights the importance of personalized treatment approaches and the ongoing need for novel therapies for AML patients. [Extracted from the article]

Sjögren's syndrome (SS) is a prevalent systemic autoimmune disease, primarily affecting exocrine glands, characterized by lymphocyte and plasma cell infiltration. Patients typically exhibit dry mouth and eyes, with potential involvement of the digestive tract, lungs, and kidneys. In China, SS prevalence ranges from 0.29% to 0.77%, rising to 3.00%-4.00% among the elderly. In Europe, the prevalence is approximately 0.23%. The pathogenesis of SS involves interactions of multiple cells and cytokines, including salivary gland epithelial cells, T-cells, B-cells, dendritic cells, interferon (IFN), interleukin (IL), tumour necrosis factor (TNF) and inflammasomes. Currently, glandular therapy for SS is primarily localised, while treatment for systemic involvement is mainly borrowed from other autoimmune diseases, with no approved targeted drugs yet. Among the targeted therapeutic agents for SS, rituximab, a B-cell targeted therapy, is the most studied and has shown improved salivary efficacy in SS patients with cryoglobulin vasculitis. BAFF inhibitors, CD40 targeting agents, and mesenchymal stem cells have also demonstrated cartain therapeutic effects. For most systemic involvement, glucocorticoids (GCs) are the first-line treatment, while immunosuppressants and biologics serve as second-line options for GCs-tolerant or resistant patients. Although many potential therapeutic targets have been identified, few drugs have been clinically translated. Currently, there is a need to develop relatively safe and effective treatment regimens with minimal adverse effects through comprehensive patient assessment and multidisciplinary collaboration. Future SS drug research will focus on targeted therapies, adverse effects reduction, and multi-drug combinations.

Ferroptosis is a distinct mode of cell death, distinguishing itself from typical apoptosis by its reliance on the accumulation of iron ions and lipid peroxides. Cells manifest an imbalance between oxidative stress and antioxidant equilibrium during certain pathological contexts, such as tumours, resulting in oxidative stress. Notably, recent investigations propose that heightened intracellular reactive oxygen species (ROS) due to oxidative stress can heighten cellular susceptibility to ferroptosis inducers or expedite the onset of ferroptosis. Consequently, comprehending role of ROS in the initiation of ferroptosis has significance in elucidating disorders related to oxidative stress. Moreover, an exhaustive exploration into the mechanism and control of ferroptosis might offer novel targets for addressing specific tumour types. Within this context, our review delves into recent fundamental pathways and the molecular foundation of ferroptosis. Four classical ferroptotic molecular pathways are well characterized, namely, glutathione peroxidase 4‐centred molecular pathway, nuclear factor erythroid 2‐related factor 2 molecular pathway, mitochondrial molecular pathway, and mTOR‐dependent autophagy pathway. Furthermore, we seek to elucidate the regulatory contributions enacted by ROS. Additionally, we provide an overview of targeted medications targeting four molecular pathways implicated in ferroptosis and their potential clinical applications. Here, we review the role of ROS and oxidative stress in ferroptosis, and we discuss opportunities to use ferroptosis as a new strategy for cancer therapy and point out the current challenges persisting within the domain of ROS‐regulated anticancer drug research and development. [ABSTRACT FROM AUTHOR]

The current review aims to uphold all the attributes of protein-based nanostructures and their applications in therapeutics. Nanostructures have successfully revolutionized the era of novel drug delivery systems. Owing to the paramount advantages of nanoscale preparations, they have gained importance exponentially in recent years. Among the varied range of nanostructures, protein-based nanostructures have acquired a predominant orientation. Being a natural biomolecule, proteins have zero levels of toxicity, biodegradability, and biocompatibility. The present scenario states that the fourth generation of nanomedicines is being formulated which implements biomolecule nano-vectors that can exhibit the virtues of target specificity, multifunctionality, and stimuli-responsiveness. By virtue of possessing these attributes, apart from being able to partake in complex supramolecular assemblage, proteins have proven to be the best approach in the development of nanoscale structures. The review studies the supremacy of various protein-based nanoparticles over other nanostructures, their mode of preparation, efficacious delivery of a plethora of drugs, and their implementation in the field of nanomedicines along with various characterization techniques. As our insightfulness of protein-based nanoparticles expands, they grip boundless potential for revolutionizing drug delivery and renovating the treatment scenario for a widespread range of disorders. [ABSTRACT FROM AUTHOR]

Objective To analyze the current status of drug compliance and influencing factors of oral anti-tumor targeted drugs in elderly patients with colon cancer after discharge. Methods A total of 110 elderly patients with colon cancer admitted to the First Affiliated Hospital of Harbin Medical University from February 2022 to February 2023 were selected.All patients received oral anti-tumor targeted drug therapy after discharge.Morisky medication compliance questionnaire was used to assess medication compliance, and then the factors affecting medication compliance were statistically analyzed. Results A total of 34 patients had good compliance(good compliance group) and 76 patients had poor compliance (poor compliance group).Univariate analysis showed that the proportion of lack of social support, adverse reactions to oral targeted drug therapy, adverse psychological reactions, poor economic conditions, and lack of knowledge of oral targeted drug therapy in the poor compliance group was significantly higher than that in the good compliance group, and the differences were statistically significant(P

Abstract While strategies such as chemotherapy and immunotherapy have become the first-line standard therapies for patients with advanced or metastatic cancer, acquired resistance is still inevitable in most cases. The introduction of antibody‒drug conjugates (ADCs) provides a novel alternative. ADCs are a new class of anticancer drugs comprising the coupling of antitumor mAbs with cytotoxic drugs. Compared with chemotherapeutic drugs, ADCs have the advantages of good tolerance, accurate target recognition, and small effects on noncancerous cells. ADCs occupy an increasingly important position in the therapeutic field. Currently, there are 13 Food and Drug Administration (FDA)‒approved ADCs and more than 100 ADC drugs at different stages of clinical trials. This review briefly describes the efficacy and safety of FDA-approved ADCs, and discusses the related problems and challenges to provide a reference for clinical work.

Targeted drug delivery has emerged as a transformative approach in the treatment of periorbital skin malignancies, offering the potential for enhanced efficacy and reduced side effects compared to traditional therapies. This review provides a comprehensive overview of targeted therapies in the context of periorbital malignancies, including basal cell carcinoma, squamous cell carcinoma, sebaceous gland carcinoma, and Merkel cell carcinoma. It explores the mechanisms of action for various targeted therapies, such as monoclonal antibodies, small molecule inhibitors, and immunotherapies, and their applications in treating these malignancies. Additionally, this review addresses the management of ocular and periocular side effects associated with these therapies, emphasizing the importance of a multidisciplinary approach to minimize impact and ensure patient adherence. By integrating current findings and discussing emerging trends, this review aims to highlight the advancements in targeted drug delivery and its potential to improve treatment outcomes and quality of life for patients with periorbital skin malignancies.

Introduction: The objective of this study was to estimate the safety profile of pulmonary hypertension-specific therapies using placebo-controlled and active comparator trials. Material and methods: The search corpus comprised Medline, Scopus, Embase and Clinical Trials databases. A systematic review and meta-analysis was performed to assess the relative risk of severe events and discontinuations as well as of adverse drug reactions (ADRs) classified into 26 categories and 21 subcategories defined by the Medical Dictionary for Regulatory Activities (MedRA). Results: Pulmonary hypertension-specific therapies had the greatest effect on such events as flushing and headache as well as jaw pain, limb pain and myalgia or gastrointestinal disorders. The relative risk for ADRs in patients receiving monotherapy (vs. placebo/supportive therapies) and combined regimens (vs. monotherapy) was significantly increased. The risk of cessation for the combined regimen was slightly higher (Qinter-group, p = 0.0778). Such ADRs as blood and lymphatic system disorders with the anemia subgroup, gastrointestinal disorders with diarrhea and nausea subgroups, respiratory and thoracic diseases or nervous system disorders with headache tended to occur more often in combination regimens as compared to monotherapy. Conclusions: About half of the main categories and subcategories of adverse reactions according to MedRA were associated with a relatively high frequency and hazard ratio. Their risk can be increased when combination regimens are used, especially. [ABSTRACT FROM AUTHOR]

Background: In the two European Union (EU)-funded projects, PCM4EU (Personalized Cancer Medicine for all EU citizens) and PRIME-ROSE (Precision Cancer Medicine Repurposing System Using Pragmatic Clinical Trials), we aim to facilitate implementation of precision cancer medicine (PCM) in Europe by leveraging the experience from ongoing national initiatives that have already been particularly successful. Patients and methods: PCM4EU and PRIME-ROSE gather 17 and 24 partners, respectively, from 19 European countries. The projects are based on a network of Drug Rediscovery Protocol (DRUP)-like clinical trials that are currently ongoing or soon to start in 11 different countries, and with more trials expected to be established soon. The main aims of both the projects are to improve implementation pathways from molecular diagnostics to treatment, and reimbursement of diagnostics and tumour-tailored therapies to provide examples of best practices for PCM in Europe. Results: PCM4EU and PRIME-ROSE were launched in January and July 2023, respectively. Educational materials, including a podcast series, are already available from the PCM4EU website (http://www.pcm4eu.eu). The first reports, including an overview of requirements for the reimbursement systems in participating countries and a guide on patient involvement, are expected to be published in 2024. Conclusion: European collaboration can facilitate the implementation of PCM and thereby provide affordable and equitable access to precision diagnostics and matched therapies for more patients.

Abstract Background In the last decade, Ibrutinib has become the standard of care in the treatment of several lymphoproliferative diseases such as chronic lymphocytic leukemia (CLL) and several non-Hodgkin lymphoma. Beyond Bruton tyrosine kinase inhibition, Ibrutinib shows broad immunomodulatory effects that may promote the occurrence of infectious complications, including opportunistic infections. The infectious burden has been shown to vary by disease status, neutropenia, and prior therapy but data focusing on severe infections requiring intensive care unit (ICU) admission remain scarce. We sought to investigate features and outcomes of severe infections in a multicenter cohort of 69 patients receiving ibrutinib admitted to 10 French intensive care units (ICU) from 1 January 2015 to 31 December 2020. Results Median time from ibrutinib initiation was 6.6 [3–18] months. Invasive fungal infections (IFI) accounted for 19% (n = 13/69) of severe infections, including 9 (69%; n = 9/13) invasive aspergillosis, 3 (23%; n = 3/13) Pneumocystis pneumonia, and 1 (8%; n = 1/13) cryptococcosis. Most common organ injury was acute respiratory failure (ARF) (71%; n = 49/69) and 41% (n = 28/69) of patients required mechanical ventilation. Twenty (29%; n = 20/69) patients died in the ICU while day-90 mortality reached 55% (n = 35/64). In comparison with survivors, decedents displayed more severe organ dysfunctions (SOFA 7 [5–11] vs. 4 [3–7], p = 0.004) and were more likely to undergo mechanical ventilation (68% vs. 31%, p = 0.010). Sixty-three ibrutinib-treated patients were matched based on age and underlying malignancy with 63 controls receiving conventional chemotherapy from an historic cohort. Despite a higher median number of prior chemotherapy lines (2 [1–2] vs. 0 [0–2]; p

Abstract Background This meta-analysis was conducted to evaluate the efficacy of the treat-repair-treat (TRT) strategy in the treatment of severe pulmonary arterial hypertension with congenital heart disease (PAH-CHD). Methods PubMed, EMBASE, Cochrane and Web of Science online databases were searched by two independent investigators for studies that used the TRT strategy for PAH-CHD, and the retrieved studies were reviewed by a third investigator. The main outcomes were pulmonary artery pressure (PAP), pulmonary vascular resistance (PVR), 6-minute walk distance (6MWD), and transcutaneous oxygen saturation (SpO2). The changes were compared between follow-up and baseline. Stata version 14.0 was used for data analysis. A random-effects model was selected for meta-analysis. Subgroup analysis and meta-regression were used to find the source of heterogeneity. Results A total of 335 patients from 9 single-arm studies were included. Meta-analysis showed significant reductions in PAP and PVR and improvements in 6MWD and SpO2 (PAP: SMD -2.73 95% CI -2.97, − 2.50 p =

Abstract Objective The impact of inflammatory response on tumor development and therapeutic response is of significant importance in clear cell renal cell carcinoma (ccRCC). The customization of specialized prognostication approaches and the exploration of supplementary treatment options hold critical clinical implications in relation to the inflammatory response. Methods In the present study, unsupervised clustering was implemented on TCGA-KIRC tumors using transcriptome profiles of inflammatory response genes, which was then validated in two ccRCC datasets (E-MATB-1980 and ICGC) and two immunotherapy datasets (IMvigor210 and Liu et al.) via SubMap and NTP algorithms. Combining co-expression and LASSO analyses, inflammatory response-based scoring system was defined, which was evaluated in pan-cancer. Results Three reproducible inflammatory response subtypes (named IR1, IR2 and IR3) were determined and independently verified, each exhibiting distinct molecular, clinical, and immunological characteristics. Among these subtypes, IR2 had the best OS outcomes, followed by IR3 and IR1. In terms of anti-angiogenic agents, sunitinib may be appropriate for IR1 patients, while axitinib and pazopanib may be suitable for IR2 patients, and sorafenib for IR3 patients. Additionally, IR1 patients might benefit from anti-CTLA4 therapy. A scoring system called IRscore was defined for individual ccRCC patients. Patients with high IRscore presented a lower response rate to anti-PD-L1 therapy and worse prognostic outcomes. Pan-cancer analysis demonstrated the immunological features and prognostic relevance of the IRscore. Conclusion Altogether, characterization of inflammatory response subtypes and IRscore provides a roadmap for patient risk stratification and personalized treatment decisions, not only in ccRCC, but also in pan-cancer.

Small-cell lung cancer (SCLC) has a poor prognosis and can be diagnosed with systemic metastases. Nevertheless, the molecular mechanisms underlying the development of SCLC are unclear, requiring further investigation. The current research aims to identify relevant biomarkers and available drugs to treat SCLC. The bioinformatics analysis comprised three Gene Expression Omnibus datasets (including GSE2149507, GSE6044, and GSE30219). Using the limma R package, we discovered differentially expressed genes (DEGs) in the current work. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were made by adopting the DAVID website. The DEG protein–protein interaction network was built based on the Search Tool for the Retrieval of Interacting Genes/Proteins website and visualized using the CytoHubba plugin in Cytoscape, aiming to screen the top ten hub genes. Quantitative real-time polymerase chain reaction was adopted for verifying the level of the top ten hub genes. Finally, the potential drugs were screened and identified using the QuartataWeb database. Totally 195 upregulated and 167 downregulated DEGs were determined. The ten hub genes were NCAPG, BUB1B, TOP2A, CCNA2, NUSAP1, UBE2C, AURKB, RRM2, CDK1, and KIF11. Ten FDA-approved drugs were screened. Finally, two genes and related drugs screened could be the prospective drug targets for SCLC treatment.

Objective: to summarize scientific information about the basic principles of modern drug therapy for patients with chronic myeloid leukemia (CML) considering their individual characteristics.Material and methods. The basis of the study included modern scientific articles and clinical guidelines on CML diagnosis and treatment (2021), State Register of Medicines (SRM) of the Russian Federation, instructions for the use of medicines. The following methods were used: structural analysis, analytical method, content analysis, retrospective analysis, systematic approach, situational-logical and graphical methods of analysis.Results. The analysis made it possible to summarize scientific information about the basic principles of drug therapy for patients suffering from CML. It was revealed that the problem of CML therapy today is relevant, since every year there is an increase in the incidence of this nosology. Currently, the most significant is the prescription of tyrosine kinase inhibitors (TKIs), since they have pronounced effects and are well tolerated by patients. Therapy for CML in TKIs prescription consists of several lines. Imatinib is the first line therapy because it has better safety profile. There are combinations with imatinib; for example, it is used together with interferon alfa, which allows, in some cases, to increase the response to treatment. The following drugs are used in the second line: nilotinib, dasatinib, bosutinib, ponatinib. If TKI therapy is ineffective, it is possible to prescribe standard chemotherapy, interferon therapy, or bone marrow transplantation in the absence of contraindications. Studies are underway on the possibility of using and including in clinical guidelines such drugs as arsenic trioxide, decitabine, omacetaxime, inhibitors of farnesyl transferases, granulocyte-macrophage factors, antitumor vaccines. The analysis of SRM identified 27 trade names for TKIs, the share of domestic drugs was 60%. There were no Russian analogues for bosutinib and ponatinib in SRM, which are recommended for use in case of ineffective TKI therapy of previous lines.Conclusion. The study of drug provision for CML patients is an urgent task for pharmaceutical practice and for the healthcare system as a whole. Currently, the acute issues are the individual approach to the treatment of each CML patient considering concomitant diseases, and the search for new, more effective drugs that can increase the life expectancy and quality of life of patients suffering from this disease.

Gastrointestinal stromal tumors (GIST) are most common mesenchymal tumors in gastrointestinal tract which originate from interstitial cells of Cajal and characterized by the mutations in the KIT or PDGFRA tyrosine kinase receptors. Thus, the common therapeutic approach for GIST therapy (including metastatic, recurrent and non-resectable forms) is based on inhibiton of activities of receptor tyrosine kinases indicated above by corresponding receptor tyrosine kinase inhibitors, including first-line therapeutic agent imatinib mesylate – Gleevec. Despite of high efficacy of IM-based therapy, most of GIST patients acquire resistance to this receptor tyrosine kinase inhibitor, which in turn requires second-, third- and fourth-line therapies. The review also describes the common molecular and genetic variants of GIST and the mechanisms of primary and secondary GIST resistance to the targeted-based therapies. In addition, the role of immune microenvironment in GIST and its relationship with tumor’s mutational burden are discussed in detail, thereby illustrating the immunotherapy as one of the attractive future directions for GIST therapy. Lastly, the manuscript provides the information about the ongoing clinical trials of GIST immunotherapy.

Background: Lumbar disc degeneration (LDD) is an important pathological basis for the development of degenerative diseases of the lumbar spine. Most clinical patients have low back pain as their main symptom. The deterioration of the biomechanical environment is an important cause of LDD. Although there is a large amount of basic research on LDD, there are fewer reports that correlate biomechanical mechanisms with basic research. Our research aims to identify 304 key genes involved in LDD due to biomechanical deterioration, using a bioinformatics approach. We focus on SMAD3, CAV1, SMAD7, TGFB1 as hub genes, and screen for 30 potential target drugs, offering novel insights into LDD pathology and treatment options. Methods: The Gene Cards, GenCLip3, OMIM and Drugbank databases were explored to obtain genes associated with biomechanics and LDD, followed by making veen plots to obtain both co-expressed genes. GO enrichment analysis and KEGG pathway analysis of the co-expressed genes were obtained using the DAVID online platform and visualised via a free online website. Protein interaction networks (PPI) were obtained through the STRING platform and visualised through Cytoscape 3.9.0. These genes were predicted for downstream interaction networks using the STITCH platform. Then, the GSE56081 dataset was used to validate the key genes. RT-PCR was used to detect mRNA expression of core genes in the degenerated nucleus pulposus (NP) samples and western bolt was used for protein expression. Lastly, the obtained hub genes were searched in the drug database (DGIdb) to find relevant drug candidates. Results: From the perspective of biomechanics-induced LDD, we obtained a total of 304 genes, the GO functional enrichment and KEGG pathway enrichment analysis showed that the functions of these genes are mostly related to inflammation and apoptosis. The PPI network was constructed and four Hub genes were obtained through the plug-in of Cytoscape software, namely SMAD3, CAV1, SMAD7 and TGFB1. The analysis of key genes revealed that biomechanical involvement in LDD may be related to the TGF-β signaling pathway. Validation of the GSE56081 dataset revealed that SMAD3 and TGFB1 were highly expressed in degenerating NP samples. RT-PCR results showed that the mRNA expression of SMAD3 and TGFB1 was significantly increased in the severe degeneration group; Western blot results also showed that the protein expression of TGFB1 and P-SMAD3 was significantly increased. In addition, we identified 30 potential drugs. Conclusion: This study presented a new approach to investigate the correlation between biomechanical mechanisms and LDD. The deterioration of the biomechanical environment may cause LDD through the TGF-β signaling pathway. TGFB1 and SMAD3 are important core targets. The important genes, pathways and drugs obtained in this study provided a new basis and direction for the study, diagnosis and treatment of LDD.

Background: In the last decade, Ibrutinib has become the standard of care in the treatment of several lymphoproliferative diseases such as chronic lymphocytic leukemia (CLL) and several non-Hodgkin lymphoma. Beyond Bruton tyrosine kinase inhibition, Ibrutinib shows broad immunomodulatory effects that may promote the occurrence of infectious complications, including opportunistic infections. The infectious burden has been shown to vary by disease status, neutropenia, and prior therapy but data focusing on severe infections requiring intensive care unit (ICU) admission remain scarce. We sought to investigate features and outcomes of severe infections in a multicenter cohort of 69 patients receiving ibrutinib admitted to 10 French intensive care units (ICU) from 1 January 2015 to 31 December 2020. Results: Median time from ibrutinib initiation was 6.6 [3–18] months. Invasive fungal infections (IFI) accounted for 19% (n = 13/69) of severe infections, including 9 (69%; n = 9/13) invasive aspergillosis, 3 (23%; n = 3/13) Pneumocystis pneumonia, and 1 (8%; n = 1/13) cryptococcosis. Most common organ injury was acute respiratory failure (ARF) (71%; n = 49/69) and 41% (n = 28/69) of patients required mechanical ventilation. Twenty (29%; n = 20/69) patients died in the ICU while day-90 mortality reached 55% (n = 35/64). In comparison with survivors, decedents displayed more severe organ dysfunctions (SOFA 7 [5–11] vs. 4 [3–7], p = 0.004) and were more likely to undergo mechanical ventilation (68% vs. 31%, p = 0.010). Sixty-three ibrutinib-treated patients were matched based on age and underlying malignancy with 63 controls receiving conventional chemotherapy from an historic cohort. Despite a higher median number of prior chemotherapy lines (2 [1–2] vs. 0 [0–2]; p < 0.001) and higher rates of fungal [21% vs. 8%, p = 0.001] and viral [17% vs. 5%, p = 0.027] infections in patients receiving ibrutinib, ICU (27% vs. 38%, p = 0.254) and day-90 mortality (52% vs. 48%, p = 0.785) were similar between the two groups. Conclusion: In ibrutinib-treated patients, severe infections requiring ICU admission were associated with a dismal prognosis, mostly impacted by initial organ failures. Opportunistic agents should be systematically screened by ICU clinicians in this immunocompromised population. [ABSTRACT FROM AUTHOR]

In the era of targeted therapy, there has been increasing concern about the development of oncology drugs based on the "more is better" paradigm, developed decades ago for chemotherapy. Recently, the US Food and Drug Administration (FDA) initiated Project Optimus to reform the dose optimization and dose selection paradigm in oncology drug development. To accommodate this paradigm shifting, we propose a dose‐ranging approach to optimizing dose (DROID) for oncology trials with targeted drugs. DROID leverages the well‐established dose‐ranging study framework, which has been routinely used to develop non‐oncology drugs for decades, and bridges it with established oncology dose‐finding designs to optimize the dose of oncology drugs. DROID consists of two seamlessly connected stages. In the first stage, patients are sequentially enrolled and adaptively assigned to investigational doses to establish the therapeutic dose range (TDR), defined as the range of doses with acceptable toxicity and efficacy profiles, and the recommended phase 2 dose set (RP2S). In the second stage, patients are randomized to the doses in RP2S to assess the dose–response relationship and identify the optimal dose. The simulation study shows that DROID substantially outperforms the conventional approach, providing a new paradigm to efficiently optimize the dose of targeted oncology drugs. DROID aligns with the approach of a randomized, parallel dose‐response trial design recommended by the FDA in the Guidance on Optimizing the Dosage of Human Prescription Drugs and Biological Products for the Treatment of Oncologic Diseases. [ABSTRACT FROM AUTHOR]

Tumorigenesis and tumor development are closely related to the abnormal regulation of ubiquitination. Neural precursor cell expressed developmentally downregulated 4-like (NEDD4L), an E3 ubiquitin ligase critical to the ubiquitination process, plays key roles in the regulation of cancer stem cells, as well as tumor cell functions, including cell proliferation, apoptosis, cell cycle regulation, migration, invasion, epithelial--mesenchymal transition (EMT), and tumor drug resistance, by controlling subsequent protein degradation through ubiquitination. NEDD4L primarily functions as a tumor suppressor in several tumors but also plays an oncogenic role in certain tumors. In this review, we comprehensively summarize the relevant signaling pathways of NEDD4L in tumors, the regulatory mechanisms of its upstream regulatory molecules and downstream substrates, and the resulting functional alterations. Overall, therapeutic strategies targeting NEDD4L to treat cancer may be feasible. [ABSTRACT FROM AUTHOR]

Background: This meta-analysis was conducted to evaluate the efficacy of the treat-repair-treat (TRT) strategy in the treatment of severe pulmonary arterial hypertension with congenital heart disease (PAH-CHD). Methods: PubMed, EMBASE, Cochrane and Web of Science online databases were searched by two independent investigators for studies that used the TRT strategy for PAH-CHD, and the retrieved studies were reviewed by a third investigator. The main outcomes were pulmonary artery pressure (PAP), pulmonary vascular resistance (PVR), 6-minute walk distance (6MWD), and transcutaneous oxygen saturation (SpO2). The changes were compared between follow-up and baseline. Stata version 14.0 was used for data analysis. A random-effects model was selected for meta-analysis. Subgroup analysis and meta-regression were used to find the source of heterogeneity. Results: A total of 335 patients from 9 single-arm studies were included. Meta-analysis showed significant reductions in PAP and PVR and improvements in 6MWD and SpO2 (PAP: SMD -2.73 95% CI -2.97, − 2.50 p = < 0.001; PVR: SMD -1.27 95% CI -1.53, − 1.02 p = < 0.001; 6MWD: SMD 1.88 95% CI 1.49, 2.27 p = < 0.001; SpO2: SMD 3.72 95% CI 3.13, 4.32 p = < 0.001). Subgroup analysis showed that younger patients had better efficacy, and the change in SpO2 was an indication for patient selection. The combined mortality rate was 5% at follow-up. Conclusions: In this meta-analysis, we demonstrated that the TRT strategy may have positive effects on haemodynamics and cardiac function in patients with severe PAH-CHD at short-term follow-up. Our analysis suggests that changes in age and SpO2 may be related to patient prognosis. Trial registration: The protocol was registered on the PROSPERO website with the registration number CRD42022366552. The relevant registration information can be obtained from the website https://www.crd.york.ac.uk/prospero/#searchadvanced. [ABSTRACT FROM AUTHOR]

PARP was an enzyme found in the nucleus of eukaryotic cells that played a crucial role in repairing damaged DNA. Recently, PARP inhibitors have demonstrated great potential in cancer treatment. Thus, the FDA has approved several smallmolecule PARP inhibitors for cancer maintenance therapy. The combination of PARP inhibitors and radiotherapy relies on synthetic lethality, taking advantage of the flaws in DNA repair pathways to target cancer cells specifically. Studies conducted prior to clinical trials have suggested that the combination of PARP inhibitors and radiotherapy can enhance the sensitivity of cancer cells to radiation, intensify DNA damage, and trigger cell death. Combining radiotherapy with PARP inhibitors in clinical trials has enhanced the response rate and progression-free survival of diverse cancer patients. The theoretical foundation of PARP inhibitors combined with radiotherapy is explained in detail in this article, and the latest advances in preclinical and clinical research on these inhibitors for tumor radiotherapy are summarized. The problems in the current field are recognized in our research and potential therapeutic applications for tumors are suggested. Nevertheless, certain obstacles need to be tackled when implementing PARP inhibitors and radiotherapies in clinical settings. Factors to consider when using the combination therapy are the most suitable schedule and amount of medication, identifying advantageous candidates, and the probable adverse effects linked with the combination. The combination of radiotherapy and PARP inhibitors can greatly enhance the effectiveness of cancer treatment. [ABSTRACT FROM AUTHOR]

Background: The association between acquired ADAMTS13-deficient thrombotic thrombocytopenic purpura (aTTP) and systemic lupus erythematosus (SLE) has been studied; however, the underlying molecular causes remain poorly understood. This research aimed to employ bioinformatics approaches to elucidate potential molecular mechanisms contributing to the pathogenesis of SLE and aTTP. Material and methods: The Gene Expression Omnibus (GEO) database yielded GSE121239 and GSE36418 to get mutual different expression genes (DEGs). Subsequently, DEGs were subjected to process Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Then, the DEGs were used for protein–protein interaction (PPI) analysis and screened for hub genes and drugs by the DGIDB drug database. Results: A total of 87 DEGs between the SLE and TTP datasets were identified. In the GO and KEGG analyses, DEGs were mainly enriched in the "regulation of transcription by RNA polymerase II" and "signaling pathways regulating pluripotency of stem cells." After a PPI analysis, three hub genes (BMPR2, SMAD5, and ATF2) were identified. Finally, two drugs targeted to ATF2 were predicted by the DGIDB drug database. Conclusions: Three core genes were linked to the molecular pathogenesis of SLE and aTTP, and two drugs may be viable treatments for both diseases. [ABSTRACT FROM AUTHOR]

Objective: Systemic lupus erythematosus (SLE) patients are at risk during the COVID‐19 pandemic, yet the underlying molecular mechanisms remain incompletely understood. This study sought to analyze the potential molecular connections between COVID‐19 and SLE, employing a bioinformatics approach to identify effective drugs for both conditions. Methods: The data sets GSE100163 and GSE183071 were utilized to determine share differentially expressed genes (DEGs). These DEGs were later analyzed by various bioinformatic methods, including functional enrichment, protein–protein interaction (PPI) network analysis, regulatory network construction, and gene–drug interaction construction. Results: A total of 50 common DEGs were found between COVID‐19 and SLE. Gene ontology (GO) functional annotation revealed that "immune response," "innate immune response," "plasma membrane," and "protein binding" were most enriched in. Additionally, the pathways that were enriched include "Th1 and Th2 cell differentiation." The study identified 48 genes/nodes enriched with 292 edges in the PPI network, of which the top 10 hub genes were CD4, IL7R, CD3E, CD5, CD247, KLRB1, CD40LG, CD7, CR2, and GZMK. Furthermore, the study found 48 transcription factors and 8 microRNAs regulating these hub genes. Finally, four drugs namely ibalizumab (targeted to CD4), blinatumomab (targeted to CD3E), muromonab‐CD3 (targeted to CD3E), and catumaxomab (targeted to CD3E) were found in gene–drug interaction. Conclusion: Four possible drugs that targeted two specific genes, which may be beneficial for COVID‐19 patients with SLE. [ABSTRACT FROM AUTHOR]

Objective: The impact of inflammatory response on tumor development and therapeutic response is of significant importance in clear cell renal cell carcinoma (ccRCC). The customization of specialized prognostication approaches and the exploration of supplementary treatment options hold critical clinical implications in relation to the inflammatory response. Methods: In the present study, unsupervised clustering was implemented on TCGA-KIRC tumors using transcriptome profiles of inflammatory response genes, which was then validated in two ccRCC datasets (E-MATB-1980 and ICGC) and two immunotherapy datasets (IMvigor210 and Liu et al.) via SubMap and NTP algorithms. Combining co-expression and LASSO analyses, inflammatory response-based scoring system was defined, which was evaluated in pan-cancer. Results: Three reproducible inflammatory response subtypes (named IR1, IR2 and IR3) were determined and independently verified, each exhibiting distinct molecular, clinical, and immunological characteristics. Among these subtypes, IR2 had the best OS outcomes, followed by IR3 and IR1. In terms of anti-angiogenic agents, sunitinib may be appropriate for IR1 patients, while axitinib and pazopanib may be suitable for IR2 patients, and sorafenib for IR3 patients. Additionally, IR1 patients might benefit from anti-CTLA4 therapy. A scoring system called IRscore was defined for individual ccRCC patients. Patients with high IRscore presented a lower response rate to anti-PD-L1 therapy and worse prognostic outcomes. Pan-cancer analysis demonstrated the immunological features and prognostic relevance of the IRscore. Conclusion: Altogether, characterization of inflammatory response subtypes and IRscore provides a roadmap for patient risk stratification and personalized treatment decisions, not only in ccRCC, but also in pan-cancer. [ABSTRACT FROM AUTHOR]

Background: The optimal local treatment for HCC with tumor diameter = 5 cmis not well established. This research evaluated the effectiveness of external beam radiation therapy (EBRT) versus transcatheter arterial chemoembolization (TACE) for HCC with tumor diameter = 5 cm. Methods: A total of 1210 HCC patients were enrolled in this study, including 302 and 908 patients that received EBRT and TACE, respectively. Propensity score matching (PSM) was used to identify patient pairs with similar baseline characteristics. Overall survival (OS) was the primary study endpoint. Results: We identified 428 patients using 1:1 PSM for survival comparison. Compared with the TACE group, the EBRT group had a significantly longer median OS (mOS) before (14.9 vs. 12.3 months, p = 0.0085) and after (16.8 vs. 11.4 months, p = 0.0026) matching. In the subgroup analysis, compared with the TACE group, the EBRT group had a significantly longer mOS for HCC with tumor diameters of 5-7 cm (34.1 vs. 14.3 months, p = 0.04) and 7-10 cm (34.4 vs. 10 months, p = 0.00065), whereas for HCC with tumor diameters = 10 cm, no significant difference in mOS was observed (11.2 vs. 11.2 months, p = 0.83). In addition, the multivariable Cox analysis showed that Child-A, alkaline phosphatase < 125 U/L, and EBRT were independent prognostic indicators for longer survival. Conclusion: EBRT is more effective than TACE as the primary local treatment for HCC with tumor diameter = 5 cm, especially for HCC with tumor diameter of 5-10 cm. [ABSTRACT FROM AUTHOR]

ObjectiveTo assess the efficacy and safety of camrelizumab plus different targeted drugs in adjuvant therapy after hepatocellular carcinoma (HCC) surgery.Patients and methodsThis retrospective cohort study included HCC patients who, after undergoing failed postoperative adjuvant lenvatinib therapy, received intravenous camrelizumab 200 mg every 3 weeks (C group, n = 97), camrelizumab plus oral apatinib 250 mg daily (C+A group, n = 125), camrelizumab plus oral lenvatinib 12 mg daily (for bodyweight ≥60 kg)/lenvatinib 8 mg daily (for bodyweight

Abstract Objective Systemic lupus erythematosus (SLE) patients are at risk during the COVID‐19 pandemic, yet the underlying molecular mechanisms remain incompletely understood. This study sought to analyze the potential molecular connections between COVID‐19 and SLE, employing a bioinformatics approach to identify effective drugs for both conditions. Methods The data sets GSE100163 and GSE183071 were utilized to determine share differentially expressed genes (DEGs). These DEGs were later analyzed by various bioinformatic methods, including functional enrichment, protein–protein interaction (PPI) network analysis, regulatory network construction, and gene–drug interaction construction. Results A total of 50 common DEGs were found between COVID‐19 and SLE. Gene ontology (GO) functional annotation revealed that “immune response,” “innate immune response,” “plasma membrane,” and “protein binding” were most enriched in. Additionally, the pathways that were enriched include “Th1 and Th2 cell differentiation.” The study identified 48 genes/nodes enriched with 292 edges in the PPI network, of which the top 10 hub genes were CD4, IL7R, CD3E, CD5, CD247, KLRB1, CD40LG, CD7, CR2, and GZMK. Furthermore, the study found 48 transcription factors and 8 microRNAs regulating these hub genes. Finally, four drugs namely ibalizumab (targeted to CD4), blinatumomab (targeted to CD3E), muromonab‐CD3 (targeted to CD3E), and catumaxomab (targeted to CD3E) were found in gene–drug interaction. Conclusion Four possible drugs that targeted two specific genes, which may be beneficial for COVID‐19 patients with SLE.

Pituitary adenoma (PA) is the third most common central nervous system tumor originating from the anterior pituitary, but its pathogenesis remains unclear. The Wnt signaling pathway is a conserved pathway involved in cell proliferation, Self-renewal of stem cells, and cell differentiation. It is related to the occurrence of various tumors, including PA. This article reviews the latest developments in Wnt pathway inhibitors and pathway-targeted drugs. It discusses the possibility of combining Wnt pathway inhibitors with immunotherapy to provide a theoretical basis for the combined treatment of PA. [ABSTRACT FROM AUTHOR]

Introduction: Tumor immunotherapy targeting PD-L1 has emerged as one of the powerful tools for tumor therapy. Numerous studies indicate that tumor-targeted drugs critically have an influence on the interaction between the immune system and tumors by changing the expression of PD-L1, which is beneficial for immunotherapy. Our study provided novel evidence for improving the drug regimen in tumor targeted therapy and immunotherapy. Methods: The expression of PD-L1 on SKBR3, MDA-MB-231, MCF7, 4T1, MC38 and B16 cells was evaluated by flow cytometry after treatment with six preclinical targeted drugs (ARN-509, AZD3514, Galeterone, Neratinib, MLN8237 and LGK974). AURKA was knockdowned by using the specific siRNA or CRISPRCas9 technology. In the 4T1-breast tumor and colorectal cancer xenograft tumor models, we determined the number of infiltrated CD3+ and CD8+ T cells in tumor tissues by IHC. Results: We found that AURKA inhibitor MLN8237 promoted the expression of PD-L1 in a time- and concentration-dependent manner while exerted its antitumor effect. Knockdown of AURKA could induce the upregulation of PD-L1 on SKBR3 cells.MLN8237-induced PD-L1 upregulationwas mainly associated with the phosphorylation of STAT3. In the 4T1-breast tumor xenograft model, the infiltrated CD3+ and CD8+ T cells decreased after treatment with MLN8237. When treated with MLN8237 in combination with anti-PD-L1 antibody, the volumes of tumor were significantly reduced and accompanied by increasing the infiltration of CD3+ and CD8+ T cells in colorectal cancer xenograft tumor model. Discussion: Our data demonstrated that MLN8237 improved the effect of immunology-related therapy on tumor cells by interacting with anti-PD-L1 antibody, which contributed to producing creative sparks for exploring the possible solutions to overcoming drug resistance to tumor targeted therapy. [ABSTRACT FROM AUTHOR]

Objective: To summarize the situation of antineoplastic agents-induced interstitial lung diseases (ILD), provide reference for strengthening clinical management of druginduced interstitial lung diseases (DILD). Methods: We retrospectively investigated the medical records of 12 patients with antineoplastic agents-induced ILD in a hospital between January and December 2020. Data collected included patients’ characteristic (gender, age, ECOG PS score, smoking history, primary tumor, concurrent diseases or complications.) and treatment conditions (DILD-causing drugs, clinical symptoms, chest CT, DILD treatment drugs, onset cycle, onset time, severity of DILD, DILD course and prognosis.). Results: The median age of 12 DILD cases was 68%, 66.67% of the patients were male, lung cancer accounted for 58.33% (7/12). DILD was induced by cytotoxicity drugs, targeted drugs and immune checkpoint inhibitors (ICIs), of which ICIs accounted for 66.67% (8/12). Scattered patchy, cord-like, grid-like or flocculent shadows were observed on chest CT, mainly under the pleura of lungs. Once DILD occurs, the suspected antineoplastic agents were stopped and glucocorticoid was given, among which 83.33% (10/12) patients were treated with antibiotics. Finally, 16.67% (2/12) were cured, 33.33% (4/12) were improved, 16.67% (2/12) were not cured and 33.33% (4/12) were dead. Conclusion: Antineoplastic agents-induced ILD is mostly found in elderly male lung cancer patients with smoking history. The clinical symptoms of DILD are diverse and lack of specificity. ICIs-ILD has the characteristic of high incidence and poor prognosis compared with other antineoplastic agents. Comprehensive evaluation before medication, regular review, early and adequate glucocorticoid shock therapy after onset can improve the prognosis of DILD patients. [ABSTRACT FROM AUTHOR]

Background: In patients with hepatocellular carcinoma (HCC), the tumor microenvironment (TME) is resistant to immunotherapy because of its specificity. It is meaningful to explore the role of macrophage, which is one of the most abundant immune cells in the TME, in cellular communication and its effect on the prognosis and immunotherapy of HCC. Methods: Dimensionality reduction and clustering of the single-cell RNA-seq data from the GSE149614 dataset were carried out to identify the cellular composition of HCC. CellChat was used to analyze the communication between different cells. The specifically highly expressed genes of macrophages were extracted for univariate Cox regression analysis to obtain prognostic genes for HCC cluster analysis, and the risk system of macrophage-specifically highly expressed genes was developed by random forest analysis and multivariate Cox regression analysis. Prognosis, TME infiltration, potential responses to immunotherapy, and antineoplastic drugs were compared among molecular subtypes and between risk groups. Results: We found that HCC included nine identifiable cell types, of which macrophages had the highest communication intensity with each of the other eight cell types. Of the 179 specifically highly expressed genes of macrophage, 56 were significantly correlated with the prognosis of HCC, which classified HCC into three subtypes, which were reproducible and produced different survival outcomes, TME infiltration, and immunotherapy responses among the subtypes. In the integration of four macrophage-specifically highly expressed genes for the development of a risk system, the risk score was significantly involved in higher immune cell infiltration, poor prognosis, immunotherapy response rate, and sensitivity of six drugs. Conclusion: In this study, through single-cell RNA-seq data, we identified nine cell types, among which macrophage had the highest communication intensity with the rest of the cell types. Based on specifically highly expressed genes of macrophage, we successfully divided HCC patients into three clusters with distinct prognosis, TME, and therapeutic response. Additionally, a risk system was constructed, which provided a potential reference index for the prognostic target and preclinical individualized treatment of HCC. [ABSTRACT FROM AUTHOR]