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OBJECTIVE: The metabolic characteristics of liver cancer drive considerable hurdles to immune cells function and cancer immunotherapy. However, how metabolic reprograming in the tumour microenvironment impairs the antitumour immune response remains unclear. DESIGN: Human samples and multiple murine models were employed to evaluate the correlation between GPR109A and liver cancer progression. GPR109A knockout mice, immune cells depletion and primary cell coculture models were used to determine the regulation of GPR109A on tumour microenvironment and identify the underlying mechanism responsible for the formation of intratumour GPR109A+myeloid cells. RESULTS: We demonstrate that glutamine shortage in liver cancer tumour microenvironment drives an immunosuppressive GPR109A+myeloid cells infiltration, leading to the evasion of immune surveillance. Blockade of GPR109A decreases G-MDSCs and M2-like TAMs abundance to trigger the antitumour responses of CD8+ T cells and further improves the immunotherapy efficacy against liver cancer. Mechanistically, tumour cells and tumour-infiltrated myeloid cells compete for glutamine uptake via the transporter SLC1A5 to control antitumour immunity, which disrupts the endoplasmic reticulum (ER) homoeostasis and induces unfolded protein response of myeloid cells to promote GPR109A expression through IRE1α/XBP1 pathway. The restriction of glutamine uptake in liver cancer cells, as well as the blockade of IRE1α/XBP1 signalling or glutamine supplementation, can eliminate the immunosuppressive effects of GPR109A+ myeloid cells and slow down tumour progression. CONCLUSION: Our findings identify the immunometabolic crosstalk between liver cancer cells and myeloid cells facilitates tumour progression via a glutamine metabolism/ER stress/GPR109A axis, suggesting that GPR109A can be exploited as an immunometabolic checkpoint and putative target for cancer treatment.
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Ten undocumented carbazole derivatives (2-11) along with the reported analogue (1) were isolated from the mangrove-derived Streptomyces sp. OUCMDZ-5511, cultured with NaBr-supplemented liquid medium. Compounds 1-7 are brominated carbazoles, and 8, 10, and 11 feature an additional thiazole or 2,3-dihydro-1,4-oxathiine rings, respectively. Their structures were identified through spectroscopic techniques, computational chemistry, and X-ray crystallography. Notably, compounds 6 and 8 effectively inhibited immune cell migration, indicating anti-inflammatory activity in vivo, potentially via Myd88/Nf-κB pathways, as suggested for compound 6.
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Carbazóis , Streptomyces , Streptomyces/química , Carbazóis/química , Carbazóis/farmacologia , Carbazóis/isolamento & purificação , Estrutura Molecular , Cristalografia por Raios X , Bromo/química , Enxofre/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Biologia Marinha , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , AnimaisRESUMO
Objective: The objective of the study is to evaluate the safety and efficacy of three different treatment methods for pediatric ulnar and radial double fractures. Methods: 120 children with ulnar and radial double fractures were included in the study. According to the different treatment plans, children were divided into three groups: manual reduction, splint external fixation, double elastic intramedullary fixation, and double plate fixation. Surgical indicators, radiological results, clinical efficacy, and complications were evaluated and compared among the groups. Results: The average hospital stay and operation time were significantly longer in the double plate internal fixation group compared to the other two groups. The double elastic intramedullary nailing group showed a higher fracture healing rate at 3 months compared to the other groups. There were no significant differences in clinical efficacy among the three groups. Complications were observed in all groups but did not show significant statistical differences. Conclusion: Double elastic intramedullary nailing fixation demonstrated favorable outcomes in terms of surgical indicators and fracture healing rates for pediatric ulnar and radial double fractures.
Objetivo: Evaluar la seguridad y eficacia de tres métodos de tratamiento diferentes para las fracturas dobles cubital y radial pediátricas. Métodos: Se incluyeron en el estudio 120 niños con fracturas dobles de cúbito y radio. Según los diferentes planes de tratamiento, los niños se dividieron en tres grupos: reducción manual, fijación externa con férula, fijación intramedular doble elástica y fijación con doble placa. Se evaluaron y compararon entre los grupos indicadores quirúrgicos, resultados radiológicos, eficacia clínica y complicaciones. Resultados: La estancia hospitalaria promedio y el tiempo de operación fueron significativamente más prolongados en el grupo de fijación interna con doble placa en comparación con los otros dos grupos. El grupo de clavo intramedular elástico doble mostró una mayor tasa de curación de la fractura a los 3 meses en comparación con los otros grupos. No hubo diferencias significativas en la eficacia clínica entre los tres grupos. Se observaron complicaciones en todos los grupos pero no mostraron diferencias estadísticas significativas. Conclusión: La fijación con clavo intramedular elástico doble demostró resultados favorables en términos de indicadores quirúrgicos y tasas de curación de fracturas pediátricas dobles cubital y radial.
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BACKGROUND: To evaluate the cost-effectiveness of Tislelizumab vs Sorafenib as the first-line treatment of unresectable hepatocellular carcinoma (HCC) from the perspective of the Chinese health service system. METHODS: A lifetime partitioned survival model (PSM) was developed to cost-effectively analyze Tislelizumab vs Sorafenib as the first-line treatment of unresectable HCC. The clinical and safety data were derived from a recently randomized clinical trial (RATIONALE-301). Utilities were collected from the published literature. Costs were obtained from an open-access database (http://www.yaozh.com) and previous studies. The model cycle was 21 days, according to the RATIONALE-301 study, and the simulation period was patients' lifetime. Long-term direct medical costs and quality-adjusted life-years (QALYs) were determined. The incremental cost-effectiveness ratio (ICER) was used as the evaluation index. one-way sensitivity analysis (OSWA) and probabilistic sensitivity analysis (PSA) were used to analyze the uncertainty of parameters and to adjust and verify the stability of the baseline results. RESULTS: The Tislelizumab group generated a cost of $39,746.34 and brought health benefits to 2.146 QALYs, while the cost and utility of the Sorafenib group were $26750.95 and 1.578 QALYs, respectively. The Tislelizumab group increased QALYs by 0.568, the incremental cost was $12995.39, and the ICER was $22869.64/QALY, lower than the willingness to pay threshold (WTP). OSWA results showed that the utility of progressed disease (PD), cost of Camrelizumab, and cost of Tislelizumab were the main factors affecting the ICER. PSA results showed that, within 1000 times the Monte Carlo simulation, the cost of the Tislelizumab group was lower than three times the per capita gross domestic product (GDP) of China ($37653/QALY). The cost-effectiveness acceptability curves (CEAC) revealed that when WTP was no less than $12251.00, the Tislelizumab group was the dominant scheme, and the economic advantage grew with an increasing WTP. When WTP ≥ $19000.00, the Tislelizumab group became the absolute economic advantage. CONCLUSION: Under the current economic conditions in China, the Tislelizumab therapeutic scheme is more cost-effective than the Sorafenib therapeutic scheme for treating patients with unresectable HCC.
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Anticorpos Monoclonais Humanizados , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Sorafenibe/uso terapêutico , Análise de Custo-Efetividade , Neoplasias Hepáticas/tratamento farmacológicoRESUMO
Background: The occurrence and development of Hepatic fibrosis (HF) are closely related to the gut microbial composition and alterations in host metabolism. Qijia Rougan decoction (QJ) is a traditional Chinese medicine compound utilized clinically for the treatment of HF with remarkable clinical efficacy. However, its effect on the gut microbiota and metabolite alterations is unknown. Therefore, our objective was to examine the impact of QJ on the gut microbiota and metabolism in Carbon tetrachloride (CCl4)-induced HF. Methods: 40% CCl4 was used to induce HF, followed by QJ administration for 6 weeks. Serum biochemical analyses, histopathology, immunohistochemistry, RT-PCR, 16S rRNA gene sequencing, and non-targeted metabolomics techniques were employed in this study to investigate the interventional effects of QJ on a CCl4-induced HF model in rats. Results: This study demonstrated that QJ could effectively ameliorate CCl4-induced hepatic inflammation and fibrosis. Moreover, QJ upregulated the expression of intestinal tight junction proteins (TJPs) and notably altered the abundance of some gut microbes, for example, 10 genera closely associated with HF-related indicators and TJPs. In addition, metabolomics found 37 key metabolites responded to QJ treatment and strongly associated with HF-related indices and TJPs. Furthermore, a tight relation between 10 genera and 37 metabolites was found post correlation analysis. Among them, Turicibacter, Faecalibaculum, Prevotellaceae UCG 001, and unclassified Peptococcaceae may serve as the core gut microbes of QJ that inhibit HF. Conclusion: These results suggest that QJ ameliorates hepatic inflammation and fibrosis, which may be achieved by improving intestinal tight junctions and modulating gut microbiota composition as well as modulating host metabolism.
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BACKGROUND AND OBJECTIVES: Increasing longevity and advances in treatment have increased the cancer burden in the elderly, resulting in complex follow-up care needs; however, in China, little is known about the follow-up care preferences of these patients. This study quantified older cancer patients' preferences for follow-up care and examined the trade-offs they are willing to make to accept an alternative follow-up model. METHODS: A discrete choice experiment was conducted among inpatients aged over 60 years with breast, prostate, or colorectal cancer, at two large tertiary hospitals in Nantong, China. Preference weights for follow-up care were estimated using mixed logit analysis. Subgroup analysis and latent class analysis were used to explore preference heterogeneity. RESULTS: Complete results were obtained from 422 patients (144 with breast cancer, 133 with prostate cancer, 145 with colorectal cancer), with a mean age of 70.81 years. Older cancer patients stated a preference for follow-up by specialists over primary healthcare (PHC) providers ( ß = -1.18, 95% confidence interval -1.40 to -0.97). The provider of follow-up care services was the most valued attribute among patients with breast cancer (relative importance [RI] 37.17%), while remote contact services were prioritized by patients with prostate (RI 43.50%) and colorectal cancer (RI 33.01%). The uptake rate of an alternative care model integrating PHC increased compared with the baseline setting when patients were provided with preferred services (continuity of care, individualized care plans, and remote contact services). CONCLUSION: To encourage older cancer patients to use PHC-integrated follow-up care, alternative follow-up care models need to be based on patients' preferences before introducing them as a routine option.
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Comportamento de Escolha , Preferência do Paciente , Atenção Primária à Saúde , Humanos , Masculino , Idoso , Feminino , China , Atenção Primária à Saúde/organização & administração , Pessoa de Meia-Idade , Neoplasias/terapia , Neoplasias/psicologia , Neoplasias da Próstata/terapia , Neoplasias da Próstata/psicologia , Idoso de 80 Anos ou mais , Neoplasias da Mama/terapia , Neoplasias da Mama/psicologia , Neoplasias Colorretais/terapia , Neoplasias Colorretais/psicologia , Assistência ao Convalescente/organização & administraçãoRESUMO
Our understanding of the DNA damage responses of human cells to radiation has increased remarkably over the recent years although some notable signaling events remain to be discovered. Here we provide a brief account of the key molecular events of the responses to reflect the current understanding of the key underlying mechanisms involved.
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OBJECTIVE: Both microbubble ultrasound contrast agents and acoustic phase change droplets (APCD) have been explored in hepatocellular carcinoma (HCC). This work aimed to evaluate changes to the HCC microenvironment following either microbubble or APCD destruction in a syngeneic pre-clinical model. METHODS: Mouse RIL-175 HCC tumors were grown in the right flank of 64 immunocompetent mice. Pre-treatment, photoacoustic volumetric tumor oxygenation, and power Doppler measurements were obtained using a Vevo 3100 system (VisualSonics, Toronto, Canada). The experimental groups received a 0.1 mL bolus injection of either Definity ultrasound contrast agent (Lantheus Medical Imaging) or APCD fabricated by condensing Definity. Following injection, ultrasound destruction was performed using flash-replenishment sequences on a Sequoia with a 10L4 probe (Siemens) for the duration of enhancement. Tumor oxygenation and power Doppler measurements were then repeated immediately post-ultrasound treatment. Twenty-four hours post-treatment, animals were euthanized, and tumors were harvested and stained for CD31, Cleaved Caspase 3 and CD45. RESULTS: Imaging biomarkers demonstrated a significant reduction in percent vascularity following either microbubble or APCD destruction in the tumor microenvironment ( p < 0.022) but no significant changes in tumor oxygenation (p = 0.12). Similarly, immunohistochemistry data demonstrated a significant decrease in CD31 expression (p < 0.042) and an increase in apoptosis (p < 0.014) in tumors treated with destroyed microbubbles or APCD relative to controls. Finally, a significant increase in CD45 expression was observed in tumors treated with APCD (p = 0.046), indicating an increase in tumor immune response. CONCLUSION: Ultrasound-triggered destruction of both microbubbles and APCD reduces vascularity, increases apoptosis, and may also increase immune response in this HCC model.
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Carcinoma Hepatocelular , Meios de Contraste , Neoplasias Hepáticas , Microbolhas , Microambiente Tumoral , Animais , Camundongos , Carcinoma Hepatocelular/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Modelos Animais de Doenças , FluorocarbonosRESUMO
BACKGROUND: The liver is the most common organ injured in blunt abdominal trauma and makes up roughly 5% of all trauma admissions. Current treatments are invasive and resource-intensive, which may delay care. We aim to develop and validate a contrast-enhanced ultrasound (CEUS)guided noninvasive tool to treat liver lacerations at the bedside. METHODS: Two 1.8 MHz high-intensity focused ultrasound (HIFU) elements were coupled to a C1-6 diagnostic ultrasound probe and a Logiq E10 scanner (GE HealthCare) utilizing a custom enclosure for co-registered imaging and ablation. A phantom was created from polyacrylamide gel combined with thermochromic ink whose color changes above biological ablative temperatures (60 °C). The HIFU wave was focused approximately 0.5 cm below the surface utilizing a 50% duty cycle generating 11.9 MPa for 20, 30, 40, 50, and 60s. Experiments were repeated on ex vivo chicken livers in a water bath. Finally, the livers of 4 live swine underwent up to 6 CEUS-guided treatments using parameters optimized from in vitro work. RESULTS: Treatment of the phantom between 20-60s, produced ablation sizes from 0.016 to 0.4 cm 3 . The relationship between time and size was exponential (R 2 = 0.992). Ablation areas were also well visualized on with ultrasound imaging. The ex vivo liver ablation size at 20s was 0.37 cm 3 , at 30s was 0.66 cm 3 , and at 100 s was 5.0 cm 3 . For the in-vivo swine experiments, the average ablation area measured 2.0x0.75 cm with a maximum of 3.5x1.5 cm. CEUS was utilized with the contrast agent Definity (Lantheus) for identification of lacerations as well as immediate post operative evaluation of therapy. CONCLUSION: These experiments demonstrate the feasibility of CEUS guided transdermal HIFU ablation and the time-dependent size of ablation. This work warrants future investigations into using ultrasound to detect active bleeding and HIFU to coagulate grade III and IV liver laceration. STUDY TYPE: Therapeutic/care management.
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Aim: The aim of this meta-analysis was to investigate the relationship between the baseline systemic immune inflammatory index (SII) and prognosis in patients with NSCLC. Materials & methods: The relation between pretreatment SII and overall survival, disease-free survival, cancer-specific survival, progression-free survival and recurrence-free survival in NSCLC patients was analyzed combined with hazard ratio and 95% CI. Results: The results showed that high SII was significantly correlated with overall survival and progression-free survival of NSCLC patients, but not with disease-free survival, cancer-specific survival and recurrence-free survival. Conclusion: The study suggests that a higher SII has association with worse prognosis in NSCLC patients. PROSPERO registration number: CRD42022336270.
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Background and Objective: Erectile dysfunction (ED) is a common condition in men, and many patients refractory to conservative treatment may undergo penile prostheses (PPs) placement. The primary concern following PP implantation is device infection. Although antibiotic and hydrophilic coatings have reduced the incidence of inflatable PP (IPP) infections, there remains room for improvement. Optimization of PP outcomes requires a practical in vivo model to better understand mechanisms of infection and to test new infection control strategies. We aimed to describe a new rabbit model which contains a functional IPP and review previously reported animal PP models. Methods: An IPP was placed into rabbit flanks and cycled for functionality testing. Rabbits were evaluated for signs of pain and distress over 14 days. Separately, narrative review methodology was utilized to search the PubMed and Scopus databases for all publications through March 21, 2023, which studied PP within an in vivo setting. Three independent reviewers ultimately selected 12 papers from 1992-2021 for inclusion. Key Content and Findings: Several animal studies highlighted the initial functionality or feasibility of devices for ED before their introduction in the clinical setting. There are several subsequent studies aimed at optimizing the type of antibiotic use or coating material using segments of PP material in an in vivo setting. However, the literature lacks a contemporary animal model containing a functional IPP. Our novel rabbit model offers a safe, practical way to implant a functioning IPP and investigate new perioperative infection prevention and treatment strategies before trials in the clinical setting. Conclusions: Animal models have played a key role in testing medical devices, including PPs, prior to their clinical introduction. Our review uncovered no modern animal studies involving placement of a functional PP. A new animal model can facilitate study of evolving microorganism profiles, novel methods to enhance antibiotic delivery, and proposed treatment options.
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Pancreatic adenocarcinoma (PAAD) remains challenging to diagnose and treat clinically due to its difficult early diagnosis, low surgical resection rate, and high risk of postoperative recurrence and metastasis. SMAD4 is a classical mutated gene in pancreatic cancer and is lost in up to 60%-90 % of PAAD patients, and its mutation often predicts a poor prognosis and treatment resistance. In this study, based on the expression profile data in The Cancer Genome Atlas database, we identified a ceRNA network composed of 2 lncRNAs, 1 miRNA, and 4 mRNAs through differential expression analysis and survival prognosis analysis. Among them, high expression of KLK10/LIPH/PARD6B/SLC52A3 influenced the prognosis and overall survival of PAAD patients. We confirmed the high expression of these target genes in pancreatic tissue of pancreatic-specific SMAD4-deficient mice. In addition, immune infiltration analysis showed that the high expression of these target genes affects the tumor immune environment and contributes to the progression of PAAD. Abnormal overexpression of these target genes may be caused by hypermethylation. In conclusion, we found that KLK10/LIPH/PARD6B/SLC52A3 is a potential prognostic marker for PAAD based on a competing endogenous RNA-mediated mechanism and revealed the potential pathogenic mechanism by which deficient expression of SMAD4 promotes pancreatic cancer progression, which provides a new pathway and theoretical basis for targeted therapy or improved prognosis of pancreatic cancer. These data will help reveal potential therapeutic targets for pancreatic cancer and improve the prognosis of pancreatic cancer patients.
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ABSTRACT: The objective of the study was to use a deep learning model to differentiate between benign and malignant sentinel lymph nodes (SLNs) in patients with breast cancer compared to radiologists' assessments.Seventy-nine women with breast cancer were enrolled and underwent lymphosonography and contrast-enhanced ultrasound (CEUS) examination after subcutaneous injection of ultrasound contrast agent around their tumor to identify SLNs. Google AutoML was used to develop image classification model. Grayscale and CEUS images acquired during the ultrasound examination were uploaded with a data distribution of 80% for training/20% for testing. The performance metric used was area under precision/recall curve (AuPRC). In addition, 3 radiologists assessed SLNs as normal or abnormal based on a clinical established classification. Two-hundred seventeen SLNs were divided in 2 for model development; model 1 included all SLNs and model 2 had an equal number of benign and malignant SLNs. Validation results model 1 AuPRC 0.84 (grayscale)/0.91 (CEUS) and model 2 AuPRC 0.91 (grayscale)/0.87 (CEUS). The comparison between artificial intelligence (AI) and readers' showed statistical significant differences between all models and ultrasound modes; model 1 grayscale AI versus readers, P = 0.047, and model 1 CEUS AI versus readers, P < 0.001. Model 2 r grayscale AI versus readers, P = 0.032, and model 2 CEUS AI versus readers, P = 0.041.The interreader agreement overall result showed κ values of 0.20 for grayscale and 0.17 for CEUS.In conclusion, AutoML showed improved diagnostic performance in balance volume datasets. Radiologist performance was not influenced by the dataset's distribution.
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Neoplasias da Mama , Aprendizado Profundo , Linfonodo Sentinela , Humanos , Feminino , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Linfonodo Sentinela/diagnóstico por imagem , Pessoa de Meia-Idade , Idoso , Adulto , Radiologistas/estatística & dados numéricos , Ultrassonografia Mamária/métodos , Meios de Contraste , Metástase Linfática/diagnóstico por imagem , Ultrassonografia/métodos , Biópsia de Linfonodo Sentinela/métodos , Mama/diagnóstico por imagem , Reprodutibilidade dos TestesRESUMO
RATIONALE AND OBJECTIVE: Hepatocellular carcinoma (HCC) locoregional treatment response is commonly evaluated using the Modified Response Evaluation Criteria in Solid Tumors and the American College of Radiology (ACR) Liver Reporting and Data System (LI-RADS) Treatment Response Assessment (TRA) for MRI/CT. This study aims to evaluate the diagnostic performance of the new ACR contrast-enhanced ultrasound (CEUS) Nonradiation TRA LI-RADS v2024 in HCC treated with transarterial chemoembolization (TACE). MATERIALS AND METHODS: This retrospective observational study included 87 patients treated with TACE from a previously reported cohort. At 15- and 30-days post-treatment, 68 and 72 HCC lesions were evaluated. Three blinded radiologists with different levels of CEUS experience interpreted the images independently. According to CEUS Nonradiation TRA LI-RADSv2024, both intralesional and perilesional tumor viability were evaluated and final TRA categories were as follows: TR-Nonviable, TR-Equivocal, and TR-Viable. The reference standard used was a composite of histology and imaging. RESULTS: 140 HCC lesions were analyzed. At 15 days post-treatment, the sensitivity (SN), specificity (SP), positive predictive value (PPV), negative predictive value (NPV), and accuracy of TR-Viable classification ranged from 72.5-94.3%, 72.2-86.4%, 86.8-91.4%, 65.6-86.7%, 76.9-86.8%, respectively. At 30 days post-treatment, the SN, PPV, and NPV of TR-Viable classification decreased, ranging from 65.9-84.2%, 85.7-90.6%, and 59.5-73.9%, respectively, while the SP increased, ranging from 80.0-88.0%. Kappa values ranged from 0.557-0.730, indicating moderate to substantial agreement. CONCLUSION: CEUS Nonradiation TRA LI-RADS is a reliable tool for the detection of viable tumors in lesions treated with TACE and demonstrates reproducibility across readers.
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Synthetic lethality is a phenomenon wherein the simultaneous deficiency of two or more genes results in cell death, while the deficiency of any individual gene does not lead to cell death. In recent years, synthetic lethality has emerged as a significant topic in the field of targeted cancer therapy, with certain drugs based on this concept exhibiting promising outcomes in clinical trials. Nevertheless, the presence of tumor heterogeneity and the intricate DNA repair mechanisms pose challenges to the effective implementation of synthetic lethality. This review aims to explore the concepts, development, and ethical quandaries surrounding synthetic lethality. Additionally, it will provide an in-depth analysis of the clinical application and underlying mechanism of synthetic lethality.
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Neoplasias , Mutações Sintéticas Letais , Morte Celular , Reparo do DNA , Neoplasias/tratamento farmacológico , Neoplasias/genéticaRESUMO
Esophageal squamous cell carcinoma (ESCC) is a deadly malignancy with notable metabolic reprogramming, yet the pivotal metabolic feature driving ESCC progression remains elusive. Here, we show that methionine cycle exhibits robust activation in ESCC and is reversely associated with patient survival. ESCC cells readily harness exogenous methionine to generate S-adenosyl-methionine (SAM), thus promoting cell proliferation. Mechanistically, methionine augments METTL3-mediated RNA m6A methylation through SAM and revises gene expression. Integrative omics analysis highlights the potent influence of methionine/SAM on NR4A2 expression in a tumor-specific manner, mediated by the IGF2BP2-dependent stabilization of methylated NR4A2 mRNA. We demonstrate that NR4A2 facilitates ESCC growth and negatively impacts patient survival. We further identify celecoxib as an effective inhibitor of NR4A2, offering promise as a new anti-ESCC agent. In summary, our findings underscore the active methionine cycle as a critical metabolic characteristic in ESCC, and pinpoint NR4A2 as a novel methionine-responsive oncogene, thereby presenting a compelling target potentially superior to methionine restriction.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Metionina , Membro 2 do Grupo A da Subfamília 4 de Receptores Nucleares , Animais , Humanos , Camundongos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/metabolismo , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/genética , Regulação Neoplásica da Expressão Gênica , Metionina/metabolismo , Camundongos Nus , Membro 2 do Grupo A da Subfamília 4 de Receptores Nucleares/metabolismo , Membro 2 do Grupo A da Subfamília 4 de Receptores Nucleares/genética , OncogenesRESUMO
BACKGROUND: Pancreatic cancer, referred to as the "monarch of malignancies," is a neoplastic growth mostly arising from the epithelial cells of the pancreatic duct and acinar cells. This particular neoplasm has a highly unfavorable prognosis due to its marked malignancy, inconspicuous initial manifestation, challenging early detection, rapid advancement, and limited survival duration. Cellular immunotherapy is the ex vivo culture and expansion of immune effector cells, granting them the capacity to selectively target malignant cells using specialized techniques. Subsequently, these modified cells are reintroduced into the patient's organism with the purpose of eradicating tumor cells and providing therapeutic intervention for cancer. PRESENT SITUATION: Presently, the primary cellular therapeutic modalities employed in the treatment of pancreatic cancer encompass CAR T-cell therapy, TCR T-cell therapy, NK-cell therapy, and CAR NK-cell therapy. AIM OF REVIEW: This review provides a concise overview of the mechanisms and primary targets associated with various cell therapies. Additionally, we will explore the prospective outlook of cell therapy in the context of treating pancreatic cancer.