[Exploration of cancer biological characteristics in people with different five movements and six climates constitution based on pan-cancer Bulk RNA-Seq].

According to the theory of five movements and six climates, the innate constitution plays a crucial role in determining the underlyingpa thological mechanisms of diseases later in life. Previous studies have demonstrated a close association between the constitution, as defined by the theory of five movements and six climates, and the development of various types of tumors. Furt hermore,the tumorsubtype determined by the constitution has prognostic implications. This highlights the potential of utilizing the fivemovements and six climates theory to guide the implementation of precision medicine strategies in thefield of oncology. However, no resear ch has yet been conducted to investigate the use of this theory in guiding the development of tumor molecular classification and precisi onmedicine strategies. The objective of this research is to uncover the biological characteristics of each constitution within a pancanc ercohort and identify potential anti-tumor drugs that are applicable to patients with different constitutional types. By doing so, we aimto c ontribute to the establishment of a precision medicine strategy for tumors derived from the original concepts of traditional Chi nesemedicine(TCM). In this study, we obtainedpan-cancer Bulk RNA-Seq data from UCSC Xena, GWAS cohort data from the UKBiobank, and cis-eQTLs data from eQ TLGen and GTEx V8. We employed machine learning methods to screen for hub genes associated with each constitution. Subsequently, we utilized informatics tools to explore the biological characteristics of each constitut iondefined by the theory of five movements and six bioclimates. Further, potential anti-tumor drugs suitable for patients with differen tconstitutional types were identified through mendelian randomization, molecular docking, and drug-like prediction techniques. Withinthe pan-cancer cohort, significant differences were observed among different constitutions in terms of progression-free interval, biological f unctions, immune cell abundance, tumor drug sensitivity, and immunotherapy response. These findings suggest that the five movements and six climates theory can guide tumor molecular classification and the development of precision medicine strategies. Moreover,the biological characteristics inherent to each constitution partially shed light on the scientific implications of Chinese medicinetheories, offering a fresh perspective towards clinical cancer treatment. Through molecular docking and drug-like prediction, several po tential anti-tumor drugs such as 17-beta-estradiol, serotonin, trans-resveratrol, and linoleic acid were identified. Overall, the util izationof multi-omics approaches pro vides a powerful tool to unravel the scientific foundations of TCM theories. The elucidation of themu lti-omics features associated witheach constitution in tumors serves as the basis for applying the five movements and six climates theoryto tumor molecular classification and the development of precision medicine strategies.

A crown ether embedded responsive π-gelator for transition from a one-component gel to a two-component gel.

A novel fluorescent π-gelator, incorporating a crown ether with host-guest recognition capability and a photoactive cyanostilbene unit, was designed. This unique structure enables the successful transition from a one-component gel to a two-component gel and exhibits gel-sol transition behaviors under heat, ions, and light stimuli.

Development of graphitic carbon nitride quantum dots-based oxygen self-sufficient platforms for enhanced corneal crosslinking.

Keratoconus, a disorder characterized by corneal thinning and weakening, results in vision loss. Corneal crosslinking (CXL) can halt the progression of keratoconus. The development of accelerated corneal crosslinking (A-CXL) protocols to shorten the treatment time has been hampered by the rapid depletion of stromal oxygen when higher UVA intensities are used, resulting in a reduced cross-linking effect. It is therefore imperative to develop better methods to increase the oxygen concentration within the corneal stroma during the A-CXL process. Photocatalytic oxygen-generating nanomaterials are promising candidates to solve the hypoxia problem during A-CXL. Biocompatible graphitic carbon nitride (g-C3N4) quantum dots (QDs)-based oxygen self-sufficient platforms including g-C3N4 QDs and riboflavin/g-C3N4 QDs composites (RF@g-C3N4 QDs) have been developed in this study. Both display excellent photocatalytic oxygen generation ability, high reactive oxygen species (ROS) yield, and excellent biosafety. More importantly, the A-CXL effect of the g-C3N4 QDs or RF@g-C3N4 QDs composite on male New Zealand white rabbits is better than that of the riboflavin 5'-phosphate sodium (RF) A-CXL protocol under the same conditions, indicating excellent strengthening of the cornea after A-CXL treatments. These lead us to suggest the potential application of g-C3N4 QDs in A-CXL for corneal ectasias and other corneal diseases.

Effective and mechanistic insights into shale gas wastewater reverse osmosis concentrate treatment using ozonation-biological activated carbon process.

Reverse osmosis (RO) plays a pivotal role in shale gas wastewater resource utilization. However, managing the reverse osmosis concentrate (ROC) characterized by high salinity and increased concentrations of organic matter is challenging. In this study, we aimed to elucidate the enhancement effects and mechanisms of pre-ozonation on organic matter removal efficacy in ROC using a biological activated carbon (BAC) system. Our findings revealed that during the stable operation phase, the ozonation (O3 and O3/granular activated carbon)-BAC system removes 43.6-72.2 % of dissolved organic carbon, achieving a 4-7 fold increase in efficiency compared with that in the BAC system alone. Through dynamic analysis of influent and effluent water quality, biofilm performance, and microbial community structure, succession, and function prediction, we elucidated the following primary enhancement mechanisms: 1) pre-ozonation significantly enhances the biodegradability of ROC by 4.5-6 times and diminishes the organic load on the BAC system; 2) pre-ozonation facilitates the selective enrichment of microbes capable of degrading organic compounds in the BAC system, thereby enhancing the biodegradation capacity and stability of the microbial community; and 3) pre-ozonation accelerates the regeneration rate of the granular activated carbon adsorption sites. Collectively, our findings provide valuable insights into treating ROC through pre-oxidation combined with biotreatment.

From structural design to delivery: mRNA therapeutics for cancer immunotherapy.

mRNA therapeutics have emerged as powerful tools for cancer immunotherapy in accordance with their superiority in expressing all sequence-known proteins in vivo. In particular, with a small dosage of delivered mRNA, antigen-presenting cells (APCs) can synthesize mutant neo-antigens and multi-antigens and present epitopes to T lymphocytes to elicit antitumor effects. In addition, expressing receptors like chimeric antigen receptor (CAR), T-cell receptor (TCR), CD134, and immune-modulating factors including cytokines, interferons, and antibodies in specific cells can enhance immunological response against tumors. With the maturation of in vitro transcription (IVT) technology, large-scale and pure mRNA encoding specific proteins can be synthesized quickly. However, the clinical translation of mRNA-based anticancer strategies is restricted by delivering mRNA into target organs or cells and the inadequate endosomal escape efficiency of mRNA. Recently, there have been some advances in mRNA-based cancer immunotherapy, which can be roughly classified as modifications of the mRNA structure and the development of delivery systems, especially the lipid nanoparticle platforms. In this review, the latest strategies for overcoming the limitations of mRNA-based cancer immunotherapies and the recent advances in delivering mRNA into specific organs and cells are summarized. Challenges and opportunities for clinical applications of mRNA-based cancer immunotherapy are also discussed.

RefAI: a GPT-powered retrieval-augmented generative tool for biomedical literature recommendation and summarization.

OBJECTIVES: Precise literature recommendation and summarization are crucial for biomedical professionals. While the latest iteration of generative pretrained transformer (GPT) incorporates 2 distinct modes-real-time search and pretrained model utilization-it encounters challenges in dealing with these tasks. Specifically, the real-time search can pinpoint some relevant articles but occasionally provides fabricated papers, whereas the pretrained model excels in generating well-structured summaries but struggles to cite specific sources. In response, this study introduces RefAI, an innovative retrieval-augmented generative tool designed to synergize the strengths of large language models (LLMs) while overcoming their limitations. MATERIALS AND METHODS: RefAI utilized PubMed for systematic literature retrieval, employed a novel multivariable algorithm for article recommendation, and leveraged GPT-4 turbo for summarization. Ten queries under 2 prevalent topics ("cancer immunotherapy and target therapy" and "LLMs in medicine") were chosen as use cases and 3 established counterparts (ChatGPT-4, ScholarAI, and Gemini) as our baselines. The evaluation was conducted by 10 domain experts through standard statistical analyses for performance comparison. RESULTS: The overall performance of RefAI surpassed that of the baselines across 5 evaluated dimensions-relevance and quality for literature recommendation, accuracy, comprehensiveness, and reference integration for summarization, with the majority exhibiting statistically significant improvements (P-values <.05). DISCUSSION: RefAI demonstrated substantial improvements in literature recommendation and summarization over existing tools, addressing issues like fabricated papers, metadata inaccuracies, restricted recommendations, and poor reference integration. CONCLUSION: By augmenting LLM with external resources and a novel ranking algorithm, RefAI is uniquely capable of recommending high-quality literature and generating well-structured summaries, holding the potential to meet the critical needs of biomedical professionals in navigating and synthesizing vast amounts of scientific literature.

Inhibition of DNMTs increases neoantigen-reactive T-cell toxicity against microsatellite-stable colorectal cancer in combination with radiotherapy.

The therapeutic efficacy of immunotherapy is limited in the majority of colorectal cancer patients due to the low mutational and neoantigen burdens in this immunogenically "cold" microsatellite stability-colorectal cancer (MSS-CRC) cohort. Here, we showed that DNA methyltransferase (DNMT) inhibition upregulated neoantigen-bearing gene expression in MSS-CRC, resulting in increased neoantigen presentation by MHC class I in tumor cells and leading to increased neoantigen-specific T-cell activation in combination with radiotherapy. The cytotoxicity of neoantigen-reactive T cells (NRTs) to DNMTi-treated cancer cells was highly cytotoxic, and these cells secreted high IFNγ levels targeting MSS-CRC cells after ex vivo expansion of NRTs with DNMTi-treated tumor antigens. Moreover, the therapeutic efficacy of NRTs further increased when NRTs were combined with radiotherapy in vivo. Administration of DNMTi-augmented NRTs and radiotherapy achieved an ∼50 % complete response and extended survival time in an immunocompetent MSS-CRC animal model. Moreover, remarkably, splenocytes from these mice exhibited neoantigen-specific T-cell responses, indicating that radiotherapy in combination with DNMTi-augmented NRTs prolonged and increased neoantigen-specific T-cell toxicity in MSS-CRC patients. In addition, these DNMTi-augmented NRTs markedly increase the therapeutic efficacy of cancer vaccines and immune checkpoint inhibitors (ICIs). These data suggest that a combination of radiotherapy and epi-immunotherapeutic agents improves the function of ex vivo-expanded neoantigen-reactive T cells and increases the tumor-specific cytotoxic effector population to enhance therapeutic efficacy in MSS-CRC.

Biointerface-Engineered Hybrid Nanovesicles for Targeted Reprogramming of Tumor Microenvironment.

The tumor microenvironment (TME) of typical tumor types such as triple-negative breast cancer is featured by hypoxia and immunosuppression with abundant tumor-associated macrophages (TAMs), which also emerge as potential therapeutic targets for antitumor therapy. M1-like macrophage-derived exosomes (M1-Exos) have emerged as a promising tumor therapeutic candidate for their tumor-targeting and macrophage-polarization capabilities. However, the limited drug-loading efficiency and stability of M1-Exos have hindered their effectiveness in antitumor applications. Here, a hybrid nanovesicle is developed by integrating M1-Exos with AS1411 aptamer-conjugated liposomes (AApt-Lips), termed M1E/AALs. The obtained M1E/AALs are loaded with perfluorotributylamine (PFTBA) and IR780, as P-I, to construct P-I@M1E/AALs for reprogramming TME by alleviating tumor hypoxia and engineering TAMs. P-I@M1E/AAL-mediated tumor therapy enhances the in situ generation of reactive oxygen species, repolarizes TAMs toward an antitumor phenotype, and promotes the infiltration of T lymphocytes. The synergistic antitumor therapy based on P-I@M1E/AALs significantly suppresses tumor growth and prolongs the survival of 4T1-tumor-bearing mice. By integrating multiple treatment modalities, P-I@M1E/AAL nanoplatform demonstrates a promising therapeutic approach for overcoming hypoxic and immunosuppressive TME by targeted TAM reprogramming and enhanced tumor photodynamic immunotherapy. This study highlights an innovative TAM-engineering hybrid nanovesicle platform for the treatment of tumors characterized by hypoxic and immunosuppressive TME.

Colorectal cancer-specific IFNß delivery overcomes dysfunctional dsRNA-mediated type I interferon signaling to increase the abscopal effect of radiotherapy.

BACKGROUND: Cancer-intrinsic type I interferon (IFN-I) production triggered by radiotherapy (RT) is mainly dependent on cytosolic double-stranded DNA (dsDNA)-mediated cGAS/STING signaling and increases cancer immunogenicity and enhances the antitumor immune response to increase therapeutic efficacy. However, cGAS/STING deficiency in colorectal cancer (CRC) may suppress the RT-induced antitumor immunity. Therefore, we aimed to evaluate the importance of the dsRNA-mediated antitumor immune response induced by RT in patients with CRC. METHODS: Cytosolic dsRNA level and its sensors were evaluated via cell-based assays (co-culture assay, confocal microscopy, pharmacological inhibition and immunofluorescent staining) and in vivo experiments. Biopsies and surgical tissues from patients with CRC who received preoperative chemoradiotherapy (neoCRT) were collected for multiplex cytokine assays, immunohistochemical analysis and SNP genotyping. We also generated a cancer-specific adenovirus-associated virus (AAV)-IFNß1 construct to evaluate its therapeutic efficacy in combination with RT, and the immune profiles were analyzed by flow cytometry and RNA-seq. RESULTS: Our studies revealed that RT stimulates the autonomous release of dsRNA from cancer cells to activate TLR3-mediated IFN-I signatures to facilitate antitumor immune responses. Patients harboring a dysfunctional TLR3 variant had reduced serum levels of IFN-I-related cytokines and intratumoral CD8+ immune cells and shorter disease-free survival following neoCRT treatment. The engineered cancer-targeted construct AAV-IFNß1 significantly improved the response to RT, leading to systematic eradication of distant tumors and prolonged survival in defective TLR3 preclinical models. CONCLUSION: Our results support that increasing cancer-intrinsic IFNß1 expression is an immunotherapeutic strategy that enhances the RT-induced antitumor immune response in locally patients with advanced CRC with dysfunctional TLR3.

Neoantigen-augmented iPSC cancer vaccine combined with radiotherapy promotes antitumor immunity in poorly immunogenic cancers.

Although irradiated induced-pluripotent stem cells (iPSCs) as a prophylactic cancer vaccine elicit an antitumor immune response, the therapeutic efficacy of iPSC-based cancer vaccines is not promising due to their insufficient antigenicity and the immunosuppressive tumor microenvironment. Here, we found that neoantigen-engineered iPSC cancer vaccines can trigger neoantigen-specific T cell responses to eradicate cancer cells and increase the therapeutic efficacy of RT in poorly immunogenic colorectal cancer (CRC) and triple-negative breast cancer (TNBC). We generated neoantigen-augmented iPSCs (NA-iPSCs) by engineering AAV2 vector carrying murine neoantigens and evaluated their therapeutic efficacy in combination with radiotherapy. After administration of NA-iPSC cancer vaccine and radiotherapy, we found that ~60% of tumor-bearing mice achieved a complete response in microsatellite-stable CRC model. Furthermore, splenocytes from mice treated with NA-iPSC plus RT produced high levels of IFNγ secretion in response to neoantigens and had a greater cytotoxicity to cancer cells, suggesting that the NA-iPSC vaccine combined with radiotherapy elicited a superior neoantigen-specific T-cell response to eradicate cancer cells. The superior therapeutic efficacy of NA-iPSCs engineered by mouse TNBC neoantigens was also observed in the syngeneic immunocompetent TNBC mouse model. We found that the risk of spontaneous lung and liver metastasis was dramatically decreased by NA-iPSCs plus RT in the TNBC animal model. Altogether, these results indicated that autologous iPSC cancer vaccines engineered by neoantigens can elicit a high neoantigen-specific T-cell response, promote tumor regression, and reduce the risk of distant metastasis in combination with local radiotherapy.

Clinical application of serum tumor abnormal protein in prostate cancer patients.

PURPOSE: To explore the clinical value of tumor abnormal protein (TAP) in the diagnosis and prognosis evaluation of prostate cancer. METHODS: This study enrolled a total of 265 patients who underwent prostate biopsy procedures from December 2017. TAP levels were assayed in their blood samples using a validated TAP testing kit. Comprehensive pathological assessments, including Gleason scores, TNM staging, and AJCC prognosis stages, were conducted on prostate cancer patients. Further analysis was carried out to examine the correlation between TAP expression levels and various clinical characteristics. RESULTS: A significantly elevated TAP concentration was discerned in prostate cancer patients relative to those with benign prostate hyperplasia. Moreover, a significantly elevated TAP expression was detected in prostate cancer patients with high Gleason score (≥ 8) and advanced stages (III and IV), as compared to those with Gleason scores of 6 and 7 and lower stages (I and II). When diagnosing prostate cancer in gray area of PSA, TAP demonstrated superior diagnostic capabilities over PSA alone, with higher diagnostic sensitivity, specificity and accuracy than fPSA/tPSA ratio. Additionally, post-surgical or hormonal treatment, there was a marked reduction in TAP expression level among prostate cancer patients. CONCLUSION: The assessment of TAP presents itself as a promising tool for early diagnosis and holds potential for sensitivity in monitoring treatment reponse in prostate cancer patients.

Analysis of Postoperative Urinary Incontinence and Influencing Factors of Transurethral Holmium Laser Enucleation of the Prostate.

INTRODUCTION: Aims of the study were to investigate the related factors of urinary incontinence after transurethral holmium laser enucleation of the prostate (HoLEP) and to provide guidance for clinical urinary control of HoLEP. METHODS: The clinical data of 548 patients who underwent HoLEP were retrospectively analyzed. The patients were followed up for the occurrence of urinary incontinence in the short term (2 weeks), medium term (3 months), and long term (6 months) after HoLEP. RESULTS: Among the 548 benign prostatic hyperplasia patients, 79 cases (14.42%) had urinary incontinence at 2 weeks, 19 cases (3.47%) at 3 months, and 2 cases (0.36%) at 6 months after surgery. Logistic regression analysis showed that age, prostate volume, diabetes mellitus, operation time, prostate tissue weight, and histological prostatitis were risk factors for recent urinary incontinence (p < 0.05). Age, diabetes, and operation time were risk factors for mid-term urinary incontinence (p < 0.05). The incidence of long-term urinary incontinence was low and no risk factor analysis was performed. CONCLUSIONS: For good urinary control after HoLEP, in addition to surgery-related factors such as surgical skills, proficiency, and precise anatomy, patients' risk factors should also be paid attention to in order to improve postoperative urinary control more effectively and reduce the incidence of urinary incontinence.

Robotic versus laparoscopic pelvic lateral lymph node dissection in locally advanced rectal cancer: a systemic review and meta-analysis.

BACKGROUND: There are few available studies that compare the feasibility, efficacy, and safety of robotic pelvic lateral lymph node dissection compared to laparoscopic pelvic lateral lymph node dissection (LPLND) in advanced rectal cancer. This meta-analysis aims to compare perioperative outcomes between robotic and LPLND. METHODS: We performed a systemic literature review of PubMed, Embase, and Web of Science databases. Perioperative parameters were extracted and pooled for analysis. This meta-analysis provided an analysis of heterogeneity and prediction intervals. RESULTS: Five studies were included: 567 patients divided between 266 robotic and 301 LPLND. Overall operation time was longer in the robotic group than laparoscopic group (difference in means = 67.11, 95% CI [30.80, 103.42], p < 0.001) but the difference in the pelvic lateral lymph dissection time was not statistically significant (difference in means = - 1.212, 95% CI [ - 11.594, 9.171], p = 0.819). There were fewer overall complications in the robotic than in the laparoscopic group (OR = 1.589, 95% CI [1.009, 2.503], p = 0.046), especially with respect to urinary retention (OR = 2.23, 95% CI [1.277, 3.894], p = 0.005). More pelvic lateral lymph nodes were harvested by robotic surgery than by laparoscopy (differences in means = - 1.992, 95% CI [ - 2.421, 1.563], p < 0.001). CONCLUSIONS: In this meta-analysis, robotic pelvic lateral lymph node dissection was associated with more pelvic lateral lymph nodes harvested and lower overall complications, especially urinary retention when compared to LPLND. Further studies are needed to reinforce these findings.

Activation of STING by the novel liposomal TLC388 enhances the therapeutic response to anti-PD-1 antibodies in combination with radiotherapy.

Current immune checkpoint inhibiters (ICIs) have contrasting clinical results in poorly immunogenic cancers such as microsatellite-stable colorectal cancer (MSS-CRC). Therefore, understanding and developing the combinational therapeutics for ICI-unresponsive cancers is critical. Here, we demonstrated that the novel topoisomerase I inhibitor TLC388 can reshape the tumor immune landscape, corroborating their antitumor effects combined with radiotherapy as well as immunotherapy. We found that TLC388 significantly triggered cytosolic single-stranded DNA (ssDNA) accumulation for STING activation, leading to type I interferons (IFN-Is) production for increased cancer immunogenicity to enhance antitumor immunity. TLC388-treated tumors were infiltrated by a vast number of dendritic cells, immune cells, and costimulatory molecules, contributing to the favorable antitumor immune response within the tumor microenvironment. The infiltration of cytotoxic T and NK cells were more profoundly existed within tumors in combination with radiotherapy and ICIs, leading to superior therapeutic efficacy in poorly immunogenic MSS-CRC. Taken together, these results showed that the novel topoisomerase I inhibitor TLC388 increased cancer immunogenicity by ssDNA/STING-mediated IFN-I production, enhancing antitumor immunity for better therapeutic efficacy in combination with radiotherapy and ICIs for poorly immunogenic cancer.

Evaluation of large language models in breast cancer clinical scenarios: a comparative analysis based on ChatGPT-3.5, ChatGPT-4.0, and Claude2.

BACKGROUND: Large language models (LLMs) have garnered significant attention in the AI domain owing to their exemplary context recognition and response capabilities. However, the potential of LLMs in specific clinical scenarios, particularly in breast cancer diagnosis, treatment, and care, has not been fully explored. This study aimed to compare the performances of three major LLMs in the clinical context of breast cancer. METHODS: In this study, clinical scenarios designed specifically for breast cancer were segmented into five pivotal domains (nine cases): assessment and diagnosis, treatment decision-making, postoperative care, psychosocial support, and prognosis and rehabilitation. The LLMs were used to generate feedback for various queries related to these domains. For each scenario, a panel of five breast cancer specialists, each with over a decade of experience, evaluated the feedback from LLMs. They assessed feedback concerning LLMs in terms of their quality, relevance, and applicability. RESULTS: There was a moderate level of agreement among the raters (Fleiss' kappa=0.345, P<0.05). Comparing the performance of different models regarding response length, GPT-4.0 and GPT-3.5 provided relatively longer feedback than Claude2. Furthermore, across the nine case analyses, GPT-4.0 significantly outperformed the other two models in average quality, relevance, and applicability. Within the five clinical areas, GPT-4.0 markedly surpassed GPT-3.5 in the quality of the other four areas and scored higher than Claude2 in tasks related to psychosocial support and treatment decision-making. CONCLUSION: This study revealed that in the realm of clinical applications for breast cancer, GPT-4.0 showcases not only superiority in terms of quality and relevance but also demonstrates exceptional capability in applicability, especially when compared to GPT-3.5. Relative to Claude2, GPT-4.0 holds advantages in specific domains. With the expanding use of LLMs in the clinical field, ongoing optimization and rigorous accuracy assessments are paramount.

The RNA sequencing results revealed the expression of different genes and signaling pathways during chemotherapy resistance in peripheral T-cell lymphoma.

BACKGROUND: Peripheral T-cell lymphoma (PTCL) is a subtype of non-Hodgkin's lymphoma that occurs primarily at extranodal sites and is commonly treated using chemotherapy and radiotherapy. PTCL is more malignant than other lymphoid tumors, resulting in a poor prognosis.The 5-year recurrence rate remains high, and there is a lack of standard treatment for patients with relapse-resistant disease. However, the molecular mechanisms underlying the resistance of peripheral T-cell lymphoma cells to chemotherapeutic drugs, as well as identifying strategies to overcome drug resistance remains unclear. In this study, we aimed to identify pivotal genes and signaling pathways associated with chemotherapy resistance in PTCL. METHODS: In this study, a total of 5 healthy controls and 7 clinical patients were enrolled; 4 patients were classified as chemotherapy sensitive, and 3 patients were classified as chemotherapy resistant. Peripheral blood samples were collected from each participant, and total RNA was extracted from the white blood cells. RNA sequencing was conducted on the Illumina HiSeq platform to obtain comprehensive gene expression profiles. Subsequently, the expression patterns of the DEGs associated with the most enriched signaling pathways, with a special focus on cancer-related genes, were validated using quantitative real-time polymerase chain reaction (qRT-PCR) in peripheral TCL patients. RESULTS: RNA sequencing (RNA-seq) analysis revealed 4063 differentially expressed genes (DEGs) in peripheral T-cell lymphoma specimens from patients with chemotherapy resistance, of which 1128 were upregulated and 2935 were downregulated. Subsequent quantitative gene expression analysis confirmed a differential expression pattern in all the libraries, with 9 downregulated genes and 10 upregulated genes validated through quantitative real-time PCR in 6 clinical specimens from patients with chemotherapy resistance. KEGG pathway analysis revealed significant alterations in several pathways, with 6 downregulated pathways and 9 upregulated pathways enriched in the DEGs. Notably, the TNF signaling pathway, which is extensively regulated, was among the pathways that exhibited significant changes. These findings suggest that DEGs and the TNF signaling pathway may play crucial roles in chemotherapy resistance in peripheral T-cell lymphoma. CONCLUSION: Our study revealed that the expression of specific genes, including TNFRSF1B, TRADD2, and MAP3K7, may play an important role in chemotherapy resistance in peripheral T-cell lymphoma. Moreover, we identified the downregulation of the TNF signaling pathway, a crucial pathway involved in cell survival, death, and differentiation, as a potential contributor to the development of chemotherapy resistance in peripheral T-cell lymphoma. These findings provide valuable insights into the molecular mechanisms underlying chemotherapy resistance and highlight potential targets for overcoming treatment resistance in this challenging disease.

Effect of autologous dendritic cell cytokine-induced killer on refractory metastatic colorectal cancer: a matched case-control comparative study.

Background: Patients with metastatic colorectal cancer (mCRC) who are refractory to two or more lines of systemic chemotherapy have limited therapeutic options. The aim of this study was to evaluate the effect of autologous dendritic cell cytokine-induced killer (DC-CIK) transfer on the survival of patients with mCRC who are refractory or intolerant to at least two lines of systemic chemotherapies. Methods: A matched case-control comparative study was conducted with patients who received DC-CIK immunotherapy in addition to standard chemotherapy (cases) and those with standard chemotherapy alone (controls). The primary objective was to compare the duration of oncologic survival, including overall survival (OS) and progression-free survival (PFS), between the two groups. Results: A total of 27 cases and 27 controls were included. The median OS in the DC-CIK case group was 18.73 ± 5.48 months, which was significantly longer than that in the control group (14.23 ± 1.90 months, p = 0.045). However, there was no significant difference in PFS between the two groups (p = 0.086). Subgroup analysis showed that in patients with liver or extra-regional lymph node metastasis, DC-CIK cases had longer OS than controls (17.0 vs. 11.87 months, p = 0.019; not match vs. 6.93 months, p = 0.002, respectively). In patients with Eastern Cooperative Oncology Group (ECOG) scale 0 or wild RAS/BRAF, DC-CIK cases showed a significant increase in OS duration compared to controls (28.03 vs. 14.53 months, p = 0.038; 18.73 vs. 11.87 months, p = 0.013, respectively). Conclusions: The addition of autologous DC-CIK to standard chemotherapy had a positive effect on OS of patients with refractory mCRC, especially those with liver or extra-regional lymph node metastasis, ECOG = 0, and wild RAS/BRAF status.

Macrophage-modulating nanomedicine for cancer immunotherapy.

Tumor-associated macrophages (TAMs) play crucial roles in the immunosuppressive solid tumor microenvironment (TME). Despite their tumor-promoting functions, TAMs can also be therapeutically modulated to exhibit tumor-killing properties, making them attractive targets for tumor immunotherapy. This review highlights the recent advances in nanomedicine-based strategies centered around macrophages for enhanced cancer immunotherapy. Emerging nanomedicine-based strategies to modulate TAMs in cancer treatment include repolarization of the TAM phenotype, inhibition of monocyte recruitment, depletion of TAMs, and blockage of immune checkpoints. These strategies have shown great promise in significantly improving the efficacy of cancer immunotherapy. Moreover, macrophage-inspired drug delivery systems have demonstrated significant promise in inducing immunotherapeutic effects and enhancing therapeutic efficacy by facilitating evasion from the reticuloendothelial system and promoting accumulation at the tumor site. Finally, we also discuss the challenges and propose future opportunities associated with macrophage-modulating nanomedicine to enhance cancer immunotherapy.