The complex interplay of tumor-infiltrating cells in driving therapeutic resistance pathways.

Drug resistance remains a significant challenge in cancer treatment. Recently, the interactions among various cell types within the tumor microenvironment (TME) have deepened our understanding of the mechanisms behind treatment resistance. Therefore, this review aims to synthesize current research focusing on infiltrating cells and drug resistance suggesting that targeting the TME could be a viable strategy to combat this issue. Numerous factors, including inflammation, metabolism, senescence, hypoxia, and angiogenesis, contribute to drug resistance could be a viable strategy to combat this issue. Overexpression of STAT3 is commonly associated with drug-resistant cancer cells or stromal cells. Current research often generalizes the impact of stromal cells on resistance, lacking specificity and statistical robustness. Thus, future research should take notice of this issue and aim to provide high-quality evidence. Despite the existing limitations, targeting the TME to overcome therapy resistance hold promising and valuable potential.

Unraveling links between aging, circadian rhythm and cancer: Insights from evidence-based analysis.

Aging and circadian rhythms have been connected for decades, but their molecular interaction has remained unknown, especially for cancers. In this situation, we summarized the current research actuality and problems in this field using the bibliometric analysis. Publications in the PubMed and Web of Science databases were retrieved. Overall, there is a rising trend in the publication volume regarding aging and circadian rhythms in the field of cancer. Researchers from USA, Germany, Italy, China and England have greater studies than others. Top three publication institutions are University of California System, UDICE-French Research Universities and University of Texas System. Current research hotspots include oxidative stress, breast cancer, melatonin, cell cycle, calorie restriction, prostate cancer and NF-KB. In conclusion, results generated by bibliometric analysis indicate that many approaches involve in the complex interactions between aging and circadian rhythm in cancer. These established and emerging research directions guide our exploration of the regulatory mechanisms of aging and circadian rhythms in cancer and provide a reference for developing new research avenues.

Expert Consensus on the Application of Stem Cells in Psoriasis Research and Clinical Trials.

Psoriasis is an immune-mediated, chronic, relapsing, inflammatory, systemic disease induced by individual-environmental interactions, and is often lifelong because of the difficulty of treatment. In recent years, a variety of targeted therapies, including biologics, have improved the lesions and quality of life of most psoriasis patients, but they still do not address the problem of relapse and may be associated with decreased efficacy or adverse events such as infections over time. Therefore, there is an urgent need for breakthroughs in psoriasis treatment and in relapse-delaying and non-pharmacologic strategies, and stem cell therapy for psoriasis has emerged. In recent years, research on stem cell therapy for psoriasis has received a lot of attention, however, there is no reference standard as well as consensus in this field of research. Therefore, according to the latest consensus and guidelines, combined with relevant literature reports, clinical practice experience and the results of discussions with experts, this consensus specifies the types of stem cells commonly used in the treatment of psoriasis, the methods, dosages, and routes of stem cell therapy for psoriasis, as well as the clinical evaluations (efficacy and safety) of stem cell therapy for psoriasis. In addition, this consensus also provides normative standards for the processes of collection, preparation, preservation and quality control of stem cells and their related products, as well as recommendations for the management of stem cells during infusion for the treatment of psoriasis. This consensus provides the latest specific reference standards and practice guidelines for the field of stem cell therapy for psoriasis.

Relationship between clonal evolution and drug resistance in bladder cancer: A genomic research review.

Bladder cancer stands as a prevalent global malignancy, exhibiting notable sex-based variations in both incidence and prognosis. Despite substantial strides in therapeutic approaches, the formidable challenge of drug resistance persists. The genomic landscape of bladder cancer, characterized by intricate clonal heterogeneity, emerges as a pivotal determinant in fostering this resistance. Clonal evolution, encapsulating the dynamic transformations within subpopulations of tumor cells over time, is implicated in the emergence of drug-resistant traits. Within this review, we illuminate contemporary insights into the role of clonal evolution in bladder cancer, elucidating its influence as a driver in tumor initiation, disease progression, and the formidable obstacle of therapy resistance.

Interactions between oxidative stress and senescence in cancer: Mechanisms, therapeutic implications, and future perspectives.

BACKGROUND: Recently, numerous studies have reported the interaction between senescence and oxidative stress in cancer. However, there is a lack of a comprehensive understanding of the precise mechanisms involved. AIM: Therefore, our review aims to summarize the current findings and elucidate by presenting specific mechanisms that encompass functional pathways, target genes, and related aspects. METHODS: Pubmed and Web of Science databases were retrieved to search studies about the interaction between senescence and oxidative stress in cancer. Relevant publications in the reference list of enrolled studies were also checked. RESULTS: In carcinogenesis, oxidative stress-induced cellular senescence acts as a barrier against the transformation of stimulated cells into cancer cells. However, the senescence-associated secretory phenotype (SASP) is positively linked to tumorigenesis. In the cancer progression stage, targeting specific genes or pathways that promote oxidative stress-induced cellular senescence can suppress cancer progression. In terms of treatment, many current clinical therapies combine with novel drugs to overcome resistance and reduce side effects by attenuating oxidative stress-induced senescence. Notably, emerging drugs control cancer development by enhancing oxidative stress-induced senescence. These studies highlight the complacted effects of the interplay between oxidative stress and senescence at different cancer stages and among distinct cell populations. Future research should focus on characterizing the roles of distinct senescent cell types in various tumor stages and identifying the specific components of SASP. CONCLUDSION: We've summarized the mechanisms of senescence and oxidative stress in cancer and provided illustrative figures to guide future research in this area.

Application and progress of CRISPR/Cas9 gene editing in B-cell lymphoma: a narrative review.

Background and Objective: Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) gene editing and CRISPR/Cas9 screening libraries are hot topics, and have high application values in the diagnosis and treatment of genetic diseases, and the improvement of prognosis. The major treatment of B-cell lymphoma is chemotherapy combined with biological therapy. Due to the individual specificity and the emergence of drug resistance, the therapeutic efficacy varies. The objective of this article is to explore potential targets to enhance therapeutic effects, optimize treatment plans, and improve the prognosis of patients with B-cell lymphoma. Methods: We undertook a comprehensive, narrative review of the latest literature to define the current application and progress of CRISPR/Cas9 in B-cell lymphoma. Key Content and Findings: The concepts of CRISPR/Cas9, the mechanism of gene editing, and the procedures of CRISPR/Cas9 screening libraries are investigated for candidate genes. We mainly focus on application and progress of CRISPR/Cas9 in B-cell lymphoma and screen out some genes, signaling pathways, and cytokines, which may become potential targets for clinical treatment. Conclusions: CRISPR/Cas9 gene editing has great promise in the treatment of B-cell lymphoma. This article reviews some genes, signaling pathways, and cytokines related to the progression and prognosis of B-cell lymphoma to provide a strong theoretical basis.

Recent progresses in natural based therapeutic materials for Alzheimer's disease.

Alzheimer's disease is a neurological disorder that causes increased memory loss, mood swings, behavioral disorders, and disruptions in daily activities. Polymer scaffolds for the brain have been grown under laboratory, physiological, and pathological circumstances because of the limitations of conventional treatments for patients with central nervous system diseases. The blood-brain barrier prevents medications from entering the brain, challenging AD treatment. Numerous biomaterials such as biomolecules, polymers, inorganic metals, and metal oxide nanoparticles have been used to transport therapeutic medicines into the nervous system. Incorporating biocompatible materials that support neurogenesis through a combination of topographical, pharmacological, and mechanical stimuli has also shown promise for the transfer of cells to replenish dopaminergic neurons. Components made of naturally occurring biodegradable polymers are appropriate for the regeneration of nerve tissue. The ability of natural-based materials (biomaterials) has been shown to promote endogenous cell development after implantation. Also, strategic functionalization of polymeric nanocarriers could be employed for treating AD. In particular, nanoparticles could resolve Aß aggregation and thus help cure Alzheimer's disease. Drug moieties can be effectively directed to the brain by utilizing nano-based systems and diverse colloidal carriers, including hydrogels and biodegradable scaffolds. Notably, early investigations employing neural stem cells have yielded promising results, further emphasizing the potential advancements in this field. Few studies have fully leveraged the combination of cells with cutting-edge biomaterials. This study provides a comprehensive overview of prior research, highlighting the pivotal role of biomaterials as sophisticated drug carriers. It delves into various intelligent drug delivery systems, encompassing pH and thermo-triggered mechanisms, polymeric and lipid carriers, inorganic nanoparticles, and other vectors. The discussion synthesizes existing knowledge and underscores the transformative impact of these biomaterials in devising innovative strategies, augmenting current therapeutic methodologies, and shaping new paradigms in the realm of Alzheimer's disease treatment.

Prognostic model development and molecular subtypes identification in bladder urothelial cancer by oxidative stress signatures.

BACKGROUND: Mounting studies indicate that oxidative stress (OS) significantly contributes to tumor progression. Our study focused on bladder urothelial cancer (BLCA), an escalating malignancy worldwide that is growing rapidly. Our objective was to verify the predictive precision of genes associated with overall survival (OS) by constructing a model that forecasts outcomes for bladder cancer and evaluates the prognostic importance of these genetic markers. METHODS: Transcriptomic data were obtained from TCGA-BLCA and GSE31684, which are components of the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), respectively. To delineate distinct molecular subtypes, we employed the non-negative matrix factorization (NMF)method. The significance of OS-associated genes in predicting outcomes was assessed using lasso regression, multivariate Cox analysis, and univariate Cox regression analysis. For external validation, we employed the GSE31684 dataset. CIBERSORT was utilized to examine the tumor immune microenvironment (TIME). A nomogram was created and verified using calibration and receiver operating characteristic (ROC) curves, which are based on risk signatures. We examined variations in clinical characteristics and tumor mutational burden (TMB) among groups classified as high-risk and low-risk. To evaluate the potential of immunotherapy, the immune phenomenon score (IPS) was computed based on the risk score. In the end, the pRRophetic algorithm was employed to forecast the IC50 values of chemotherapy medications. RESULTS: In our research, we examined the expression of 275 genes associated with OS in 19 healthy and 414 cancerous tissues of the bladder obtained from the TCGA database. As a result, a new risk signature was created that includes 4 genes associated with OS (RBPMS, CRYAB, P4HB, and PDGFRA). We found two separate groups, C1 and C2, that showed notable variations in immune cells and stromal score. According to the Kaplan-Meier analysis, patients classified as high-risk experienced a considerably reduced overall survival in comparison to those categorized as low-risk (P<0.001). The predictive capability of the model was indicated by the area under the curve (AUC) of the receiver operating characteristic (ROC) curve surpassing 0.6. Our model showed consistent distribution of samples from both the GEO database and TCGA data. Both the univariate and multivariate Cox regression analyses validated the importance of the risk score in relation to overall survival (P < 0.001). According to our research, patients with a lower risk profile may experience greater advantages from using a CTLA4 inhibitor, whereas patients with a higher risk profile demonstrated a higher level of responsiveness to Paclitaxel and Cisplatin. In addition, methotrexate exhibited a more positive outcome in patients with low risk compared to those with high risk. CONCLUSIONS: Our research introduces a novel model associated with OS gene signature in bladder cancer, which uncovers unique survival results. This model can assist in tailoring personalized treatment approaches and enhancing patient therapeutic effect in the management of bladder cancer.

Interplay of oxidative stress, cellular communication and signaling pathways in cancer.

Cancer remains a significant global public health concern, with increasing incidence and mortality rates worldwide. Oxidative stress, characterized by the production of reactive oxygen species (ROS) within cells, plays a critical role in the development of cancer by affecting genomic stability and signaling pathways within the cellular microenvironment. Elevated levels of ROS disrupt cellular homeostasis and contribute to the loss of normal cellular functions, which are associated with the initiation and progression of various types of cancer. In this review, we have focused on elucidating the downstream signaling pathways that are influenced by oxidative stress and contribute to carcinogenesis. These pathways include p53, Keap1-NRF2, RB1, p21, APC, tumor suppressor genes, and cell type transitions. Dysregulation of these pathways can lead to uncontrolled cell growth, impaired DNA repair mechanisms, and evasion of cell death, all of which are hallmark features of cancer development. Therapeutic strategies aimed at targeting oxidative stress have emerged as a critical area of investigation for molecular biologists. The objective is to limit the response time of various types of cancer, including liver, breast, prostate, ovarian, and lung cancers. By modulating the redox balance and restoring cellular homeostasis, it may be possible to mitigate the damaging effects of oxidative stress and enhance the efficacy of cancer treatments. The development of targeted therapies and interventions that specifically address the impact of oxidative stress on cancer initiation and progression holds great promise in improving patient outcomes. These approaches may include antioxidant-based treatments, redox-modulating agents, and interventions that restore normal cellular function and signaling pathways affected by oxidative stress. In summary, understanding the role of oxidative stress in carcinogenesis and targeting this process through therapeutic interventions are of utmost importance in combating various types of cancer. Further research is needed to unravel the complex mechanisms underlying oxidative stress-related pathways and to develop effective strategies that can be translated into clinical applications for the management and treatment of cancer. Video Abstract.

Prediction of response to neoadjuvant chemo-immunotherapy in patients with esophageal squamous cell carcinoma by a rapid breath test.

BACKGROUND: Neoadjuvant chemo-immunotherapy combination has shown remarkable advances in the management of esophageal squamous cell carcinoma (ESCC). However, the identification of a reliable biomarker for predicting the response to this chemo-immunotherapy regimen remains elusive. While computed tomography (CT) is widely utilized for response evaluation, its inherent limitations in terms of accuracy are well recognized. Therefore, in this study, we present a novel technique to predict the response of ESCC patients before receiving chemo-immunotherapy by testing volatile organic compounds (VOCs) in exhaled breath. METHODS: This study employed a prospective-specimen-collection, retrospective-blinded-evaluation design. Patients' baseline breath samples were collected and analyzed using high-pressure photon ionization time-of-flight mass spectrometry (HPPI-TOFMS). Subsequently, patients were categorized as responders or non-responders based on the evaluation of therapeutic response using pathology (for patients who underwent surgery) or CT images (for patients who did not receive surgery). RESULTS: A total of 133 patients were included in this study, with 91 responders who achieved either a complete response (CR) or a partial response (PR), and 42 non-responders who had stable disease (SD) or progressive disease (PD). Among 83 participants who underwent both evaluations with CT and pathology, the paired t-test revealed significant differences between the two methods (p < 0.05). For the breath test prediction model using breath test data from all participants, the validation set demonstrated mean area under the curve (AUC) of 0.86 ± 0.06. For 83 patients with pathological reports, the breath test achieved mean AUC of 0.845 ± 0.123. CONCLUSIONS: Since CT has inherent weakness in hollow organ assessment and no other ideal biomarker has been found, our study provided a noninvasive, feasible, and inexpensive tool that could precisely predict ESCC patients' response to neoadjuvant chemo-immunotherapy combination using breath test based on HPPI-TOFMS.