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1.
Nucleic Acids Res ; 2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-33751124

RESUMO

CRISPR-mediated gene activation (CRISPRa) is a promising therapeutic gene editing strategy without inducing DNA double-strand breaks (DSBs). However, in vivo implementation of these CRISPRa systems remains a challenge. Here, we report a compact and robust miniCas9 activator (termed miniCAFE) for in vivo activation of endogenous target genes. The system relies on recruitment of an engineered minimal nuclease-null Cas9 from Campylobacter jejuni and potent transcriptional activators to a target locus by a single guide RNA. It enables robust gene activation in human cells even with a single DNA copy and is able to promote lifespan of Caenorhabditis elegans through activation of longevity-regulating genes. As proof-of-concept, delivered within an all-in-one adeno-associated virus (AAV), miniCAFE can activate Fgf21 expression in the liver and regulate energy metabolism in adult mice. Thus, miniCAFE holds great therapeutic potential against human diseases.

2.
Autophagy ; : 1-2, 2021 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-33779488

RESUMO

ENDOG (endonuclease G), a mitochondrial endonuclease, is known to participate in apoptosis and paternal mitochondria elimination. However, the role and underlying mechanism of ENDOG in regulating macroautophagy remain unclear. We recently reported that ENDOG released from mitochondria promotes autophagy during starvation, which we demonstrated is evolutionarily conserved across species by performing experiments in human cell lines, mice, Drosophila, and C. elegans. This study demonstrates that ENDOG can be phosphorylated by GSK3B, which enhances the interaction between ENDOG with YWHAG and leads to the release of TSC2 and PIK3C3 from YWHAG, followed by MTOR pathway suppression and autophagy initiation. Additionally, the endonuclease activity of ENDOG is essential for activating the DNA damage response and thus inducing autophagy. Consequently, this study uncovered an exciting new role for ENDOG as a crucial regulator of autophagy.

3.
Cancer Res ; 2021 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-33685992

RESUMO

Oncogenic activation of the fibroblast growth factor receptor (FGFR) pathway is frequent in lung and other cancers. However, due to drug resistance, pharmacological blockage of aberrant FGFR signaling has provided little clinical benefit in patients with FGFR-amplified tumors. The determining factors for the limited efficacy of FGFR-targeted therapy remain incompletely understood. In this study, we performed kinome-wide CRISPR/Cas9 loss-of-function screens in FGFR1-amplified lung cancer cells treated with an FGFR inhibitor. These screens identified PLK1 as a potent synthetic lethal target that mediates a resistance mechanism by overriding DNA damage and cell cycle arrest upon FGFR1 inhibition. Genetic and pharmacological antagonism of PLK1 in combination with FGFR inhibitor therapy synergized to enhance anti-proliferative effects and drove cancer cell death in vitro and in vivo through activation of the γH2AX-CHK-E2F1 axis. These findings suggest a previously unappreciated role for PLK1 in modulating FGFR1 inhibitor sensitivity and demonstrate a synergistic drug combination for treating FGFR1-amplified lung cancer.

4.
Eur J Surg Oncol ; 2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-33632591

RESUMO

OBJECTIVES: The effects of ligating the pulmonary vein first or pulmonary artery first during lobectomy on the long-term survival of patients with non-small cell lung cancer (NSCLC) remain controversial. We conducted the first systematic review and meta-analysis to determine the association between different sequences of vessel ligation during lobectomy and the prognosis of patients with NSCLC. METHODS: Literature retrieval was performed by systematically searching Embase, PubMed and Web of Science to identify relevant articles published from the inception of each database to November 2020. The overall survival (OS) and disease-free survival (DFS) of patients treated with vein-first ligation versus those treated with artery-first ligation during lobectomy were analyzed. A standard fixed-effect model test (Mantel-Haenszel method) was used to calculate pooled hazard ratios (HRs) and 95% confidence intervals (CIs). Heterogeneity was assessed using the Q-test and I2-test. Sensitivity analysis was performed to further examine the stability of pooled HRs. RESULTS: Five studies with a total of 1109 patients receiving lobectomy, including one randomized controlled trial and four retrospective studies, were included in this meta-analysis. The results showed that patients with vein-first ligation had a significantly better OS (HR 1.25, 95% CI 1.03-1.50; P = 0.02) and DFS (HR 1.54, 95% CI 1.16-2.04; P = 0.003) than those with artery-first ligation during lobectomy. Significant heterogeneity and publication bias were not observed during analysis. CONCLUSION: Our meta-analysis indicates that vein-first ligation may improve the prognosis of NSCLC patients receiving lobectomy. Therefore, vein-first ligation is recommended during lobectomy for patients with non-small cell lung cancer whenever possible.

5.
Medicine (Baltimore) ; 100(5): e23693, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33592828

RESUMO

ABSTRACT: This study aims to analyze the relationship between clinicopathological characteristics and survival in young patients (≤35 years old) with resected breast cancer.A total of 173 cases were included in this study. The clinicopathological factors potentially associated with prognosis were evaluated. Furthermore, we categorized patients into different groups to evaluate the prognosis according to hormone receptor status or important risk factors.Younger age (≤30 years) was an independent predictor for poor disease-free survival (DFS) and overall survival (OS). Besides, PR negative status, tumor grade, and advanced lymph nodes postsurgery were independent prognostic factors of DFS, while PR negative status and advanced lymph nodes postsurgery were independent prognostic factors of OS. For hormone receptor-positive patients, people with ER+ or PR+ and HER2-/+ showed poorer prognosis than the other 2 levels. Risk factor grouping based on the ER, PR, HER2, Ki-67 status, tumor grade, and lymph nodes postsurgery showed that patients in highest score group received the poorest prognosis. Grading system based on the hormone status or the risk factor grouping may offer a useful approach to assess which subgroups of young breast cancer present poorer prognosis.


Assuntos
Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Adulto , Fatores Etários , Biomarcadores Tumorais , Neoplasias da Mama/cirurgia , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Antígeno Ki-67/metabolismo , Metástase Linfática , Gradação de Tumores , Prognóstico , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/metabolismo
6.
J Cell Mol Med ; 25(6): 2872-2884, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33528895

RESUMO

The Xuanwei area of Yunnan Province, China, is one of the regions suffering from the highest occurrence and mortality rate of lung cancer in the world. Local residents tend to use bituminous coal as domestic fuel, which causes serious indoor air pollution and is established as the main carcinogen. After the local government carried out furnace and stove reform work, lung cancer rate including incidence and mortality among residents remains high. We herein wonder if there are specific mechanisms at protein level for the development of non-small-cell lung cancer (NSCLC) in this area. We investigated the changes of protein profiling in tumour of the patients from Xuanwei area. Tandem mass tag (TMT) was employed to screen the differential proteins between carcinoma and para-carcinoma tissues. We identified a total of 422 differentially expressed proteins, among which 162 proteins were significantly up-regulated and 260 were downregulated compared to para-carcinoma tissues. Many of the differentially expressed proteins were related to extracellular matrix (ECM)-receptor interaction, focal adhesion, PI3K/AKT pathway and ferroptosis. Further experiments on the two differential proteins, thioredoxin 2 (TXN2) and haptoglobin (HP), showed that the change of their expressions could make the lung cancer cell lines more resistant to erastin or RSL-induced ferroptosis in vitro, and promote the growth of tumour in nude mice. In conclusion, this study revealed that aberrant regulation of ferroptosis may involve in the development of lung cancer in Xuanwei area.

7.
Thorac Cancer ; 12(6): 993-994, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33569901

RESUMO

A 53-year-old man was admitted to our hospital with a history of a right lung nodule which had gradually increased in size. Wedge resection of the right middle lobe using video-assisted thoracoscopic surgery (VATS) was performed and revealed a yellowish, soft, well circumscribed nodule. Histological analysis confirmed the diagnosis of an uncommon lipolymph node. The patient recovered well from surgery, and there has been no recurrence in the lung for over one-year of follow-up. To the best of our knowledge, this is the first report of a lipolymph node in the lung.

8.
Sci Adv ; 7(1)2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33523838

RESUMO

Environmental stress can induce survival advantages that are passed down to multiple generations, representing an evolutionarily advantageous adaptation at the species level. Using the nematode worm Caenorhabditis elegans as a model, we found that heat shock experienced in either parent could increase the longevity of themselves and up to the fifth generation of descendants. Mechanistic analyses revealed that transcription factor DAF-16/FOXO, heat shock factor HSF-1, and nuclear receptor DAF-12/FXR functioned transgenerationally to implement the hormetic stress response. Histone H3K9me3 methyltransferases SET-25 and SET-32 and DNA N6-methyl methyltransferase DAMT-1 participated in transmitting high-temperature memory across generations. H3K9me3 and N6-methyladenine could mark heat stress response genes and promote their transcription in progeny to extend life span. We dissected the mechanisms responsible for implementing and transmitting environmental memories in descendants from heat-shocked parents and demonstrated that hormetic stress caused survival benefits could be transmitted to multiple generations through H3K9me3 and N6-mA modifications.

9.
J Hematol Oncol ; 14(1): 18, 2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33461583

RESUMO

Accurate interpretation of BRCA1/2 variants is critical for risk assessment and precise treatment of breast cancer (BC). Hence, the establishment of an ethnicity-based BRCA1/2 variant database of the Chinese population is of paramount importance. In this study, panel-based sequencing served to detect BRCA1/2 variants in a Chinese multicenter cohort of 21,216 BC patients and 6434 healthy controls. Overall, the percentage of subjects carrying pathogenic variants was 5.5% (1174/21,216) in BC patients and 1.1% (71/6434) in healthy controls. We identified 13 pathogenic variants as high-frequency variants that had a frequency of > 0.45‰ in BC patients (≥ 10 in 21,216 patients), none of which has been reported in Caucasians. Pathogenic BRCA1/2 variants correlated with younger onset age, higher frequencies of bilateral and triple-negative BC (TNBC), invasive carcinomas, high histological grades, and family history of BC and other cancers. Furthermore, the percentage of the subjects carrying VUS was 9.8% (2071/21,216) in BC patients and 6.9% (446/6434) in healthy controls. Based on our cohort study, we unambiguously reclassified 7 out of the 858 VUS resulting in lower VUS ratio in patients (from 9.8 to 7.9%) as well as in healthy control (from 6.9 to 5.3%). We also re-analyzed the 100 variants in 13 exons (2-5 and 15-23) of the BRCA1 genes using a functional assay (saturation genome editing; SGE). 55 of the 59 VUS had distinct status in the SGE study: 24 (43.6%) were pathogenic, and 31 (56.4%) were benign. Strong ethnicity-specific occurrences of pathogenic BRCA1/2 variants were identified in the Chinese population. Hence, the findings provide rationale and sequencing information for the implementation of BRCA1/2 variants tailored to the Chinese population into clinical risk assessment.

10.
Nat Commun ; 12(1): 476, 2021 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-33473107

RESUMO

Endonuclease G (ENDOG), a mitochondrial nuclease, is known to participate in many cellular processes, including apoptosis and paternal mitochondrial elimination, while its role in autophagy remains unclear. Here, we report that ENDOG released from mitochondria promotes autophagy during starvation, which we find to be evolutionally conserved across species by performing experiments in human cell lines, mice, Drosophila and C. elegans. Under starvation, Glycogen synthase kinase 3 beta-mediated phosphorylation of ENDOG at Thr-128 and Ser-288 enhances its interaction with 14-3-3γ, which leads to the release of Tuberin (TSC2) and Phosphatidylinositol 3-kinase catalytic subunit type 3 (Vps34) from 14-3-3γ, followed by mTOR pathway suppression and autophagy initiation. Alternatively, ENDOG activates DNA damage response and triggers autophagy through its endonuclease activity. Our results demonstrate that ENDOG is a crucial regulator of autophagy, manifested by phosphorylation-mediated interaction with 14-3-3γ, and its endonuclease activity-mediated DNA damage response.


Assuntos
Autofagia/fisiologia , Dano ao DNA/fisiologia , Endodesoxirribonucleases/genética , Endodesoxirribonucleases/metabolismo , Transdução de Sinais/fisiologia , Serina-Treonina Quinases TOR/metabolismo , Proteínas 14-3-3/metabolismo , Animais , Apoptose , Caenorhabditis elegans , Linhagem Celular , Classe III de Fosfatidilinositol 3-Quinases/metabolismo , Drosophila , Técnicas de Inativação de Genes , Células Hep G2 , Humanos , Fígado/metabolismo , Fígado/patologia , Camundongos , Camundongos Knockout , Mitocôndrias/metabolismo , Fosforilação , Transcriptoma , Proteína 2 do Complexo Esclerose Tuberosa/metabolismo
13.
Gene ; 766: 145134, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-32898605

RESUMO

BACKGROUND: Artesunate (ART) has been used extensively as anti-malarial drugs worldwide. Besides, it has also been reported to have anti-cancer activities. This study was aimed to explore the anti-cancer activity of ART in combination with cisplatin (CIS) on A549 cells. METHODS: Cells were cultured with different concentrations of ART and/or CIS for 24, 48, or 72 h to test the anti-proliferative effects by CCK-8 assay. Colony formation assay and EdU staining were also performed. TUNEL staining was used to illustrate the morphologic changes. Cell cycle and apoptosis were determined by flow cytometry assay, and Western blot analysis was conducted to detect the expression of apoptosis- and proliferation-related proteins. Caspase activities were determined by colorimetric assay kit. Moreover, the synergistic effect of ART with CIS in A549 cell xenograft model was also determined. RESULTS: ART significantly inhibited cell proliferation in dose- and time-dependent manners. Collectively, the combination treatment remarkably decreased colony formation rates and increased the rates of TUNEL-positive cells compared with mono-treatment. Mechanistically, the combination treatment influenced the expression of Bcl-2, Bax, p-P53, Caspase-3/7, Caspase-9, CyclinB1, P34, P21, and synergistically regulated the activity of P38/JNK/ERK1/2 MAPK pathway. In mice A549 xenograft tumors, the combination strategy significantly increased the anti-cancer efficacy of ART and CIS alone, consistent with the in vitro observations. CONCLUSIONS: ART exhibited significant anti-tumor effect on A549 cells and this efficiency could be enhanced by combination with CIS.


Assuntos
Antineoplásicos/farmacologia , Artesunato/farmacologia , Cisplatino/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Células A549 , Animais , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sinergismo Farmacológico , Feminino , Humanos , Neoplasias Pulmonares/metabolismo , Camundongos , Camundongos Nus , Inibidores de Proteínas Quinases/farmacologia
14.
Food Chem ; 339: 128114, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33152890

RESUMO

Lipids are hydrophobic metabolites implicated in tea flavor quality. Understanding their transformations during tea manufacture is of particular interest. To date, the detailed lipid composition and variations during green tea manufacture are largely unknown. Herein, we performed a comprehensive characterization of the dynamic changes of lipids during green tea manufacture, by applying nontargeted lipidomics using ultrahigh performance liquid chromatography-quadrupole-Orbitrap mass spectrometry (UHPLC-Q-Exactive/MS) combined with chemometric tools. Totally, 283 lipid species were detected, covering 20 subclasses. Significant lipidomic variations were observed during green tea manufacture, especially in the fixation stage, mainly associated with chlorophyll decomposition, phosphatidic acids (PAs) reduction and glycolipids degradation, which potentially contribute to tea color and aroma quality. Specifically, the most prominent decrease of PAs content during green tea manufacture was identified for the first time. This study provides insights into the lipid metabolic fates upon green tea manufacture, and their roles in green tea sensory quality.


Assuntos
Lipidômica/métodos , Lipídeos/análise , Lipídeos/química , Chá/química , China , Cromatografia Líquida de Alta Pressão , Cor , Indústria de Processamento de Alimentos , Metabolismo dos Lipídeos , Espectrometria de Massas , Odorantes/análise
15.
Thorac Cancer ; 12(3): 407-408, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33325129

RESUMO

Askin's tumor is a kind of aggressive tumor and extremely rare. To date, the treatment is uncodified and the prognosis for patients with this tumor remains bleak. Herein we report a case of a giant Askin's tumor in the chest wall that following diagnosis was successfully treated with surgical resection.

16.
Biomaterials ; 268: 120585, 2020 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-33307364

RESUMO

Neural stem cells (NSCs) transplantation at the injury site of central nerve system (CNS) makes it possible for neuroregeneration. Long-term cell survival and low proliferation, differentiation, and migration rates of NSCs-graft have been the most challenging aspect on NSCs application. New multichannel electrical stimulation (ES) device was designed to enhance neural stem cells (NSCs) differentiation into mature neurons. Compared to controls, ES at nanoscale topography enhanced the expression of mature neuronal marker, growth of the neurites, concentration of BDNF and electrophysiological activity. RNA sequencing analysis validated that ES promoted NSC-derived neuronal differentiation through enhancing autophagy signaling. Emerging evidences showed that insufficient or excessive autophagy contributes to neurite degeneration. Excessive ES current were able to enhance neuronal autophagy, the neuronal cells showed poor viability, reduced neurite outgrowth and electrophysiological activity. Well-controlled autophagy not only protects against neurodegeneration, but also regulates neurogenesis. Current NSC treatment protocol efficiently enhanced NSC differentiation, maturation and survival through combination of proper ES condition followed by balance of autophagy level in the cell culture system. The successful rate of such protreated NSC at injured CNS site should be significantly improved after transplantation.

17.
World J Surg ; 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33230587

RESUMO

BACKGROUND: Whether video-assisted thoracoscopic surgery (VATS) sleeve lobectomy could be an alternative to traditional thoracotomy sleeve lobectomy in treating centrally located non-small cell lung cancer (NSCLC) remains unclear. Therefore, we conducted the first meta-analysis to compare the effects of VATS sleeve lobectomy with thoracotomy sleeve lobectomy. METHODS: We systematically searched relevant studies from Pubmed, Embase, and Web of Science on May 12, 2020. Data for analysis included short-term outcomes (blood loss, lymph node dissected, operation time, hospital stay, complications) and long-term outcomes (3-year overall survival (OS) and progression-free survival (PFS) rates). We calculated the weighted mean differences (WMDs) for continuous data and risk ratio (RR) for pooling categorical data. RESULTS: We finally included 5 retrospective cohort study consisting of 436 patients. VATS sleeve lobectomy yielded significantly less blood loss (WMD = -37.83; 95% confidence intervals (CIs) = [-58.56, -17.11]; P < 0.001) than thoracotomy sleeve lobectomy and comparable total number of dissected lymph node to thoracotomy sleeve lobectomy (WMD = - 0.07; 95%CI = [-1.14, 0.99]; P = 0.89). However, VATS sleeve lobectomy consumed significantly more operation time than thoracotomy sleeve lobectomy (WMD = 49.00; 95%CI = [14.67, 83.34]; P = 0.005). VATS sleeve lobectomy yielded significantly less postoperative hospital stay time than thoracotomy sleeve lobectomy (WMD = -1.68; 95%CI = [-2.98, -0.39]; P = 0.011) and comparable postoperative complication rate to thoracotomy sleeve lobectomy (RR = 0.84; 95%CI = [0.49, 1.44]; P = 0.52). Moreover, VATS sleeve lobectomy yielded comparable 3-year OS (RR = 1.08; 95%CI = [0.95, 1.22]; P = 0.23) and PFS (RR = 1.15; 95%CI = [0.96, 1.37]; P = 0.13) rates to thoracotomy sleeve lobectomy. No significant heterogeneities were observed. CONCLUSIONS: VATS sleeve lobectomy yielded less surgical trauma than thoracotomy sleeve lobectomy and improved postoperative recovery without compromising oncological prognosis. Even though VATS sleeve lobectomy may consume more operation time, it could be recommended as an alternative to thoracotomy sleeve lobectomy for treating centrally located NSCLC in carefully selected cases.

18.
Zhongguo Fei Ai Za Zhi ; 23(11): 961-969, 2020 Nov 20.
Artigo em Chinês | MEDLINE | ID: mdl-33203198

RESUMO

N6-methyladenosine is one of the most prevalent mRNA modification in eukaryotes. The regulation of this pervasive mark is a dynamic and reversible process. m6A RNA methylation is catalyzed by m6A writers, removed by m6A erasers and recognized by m6A readers, thereby regulating multiple RNA processes including alternative splicing, nuclear export, degradation and translation. Accumulated evidence suggests that m6A modification plays a crucial role in the pathogenic mechanism and malignant progression in non-small cell lung cancer (NSCLC), including cell survival, proliferation, migration, invasion, tumor metastasis and drug resistance. Moreover, the expression of m6A and its related proteins are dysregulated in clinical samples and circulating tumor cells (CTCs) of lung cancer patients, indicating that m6A modification may serve as a novel potential biomarker for the diagnosis and prognosis of lung cancer. In this review, by summarizing a great number of recent reports related to m6A's function and its modulators, we aim to provide a new insight on the early diagnosis and drug development in NSCLC therapy.
.

19.
Genet Med ; 2020 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-33100332

RESUMO

PURPOSE: Pregnancy loss ranging from spontaneous abortion (SAB) to stillbirth can result from monogenic causes of Mendelian inheritance. This study evaluated the clinical application of exome sequencing (ES) in identifying the genetic etiology for pregnancy loss. METHODS: A cohort of 102 specimens from products of conception (POC) with normal karyotype and absence of pathogenic copy-number variants were selected for ES. Abnormality detection rate (ADR) and variants of diagnostic value correlated with SAB and stillbirth were evaluated. RESULTS: ES detected 6 pathogenic variants, 16 likely pathogenic variants, and 17 variants of uncertain significance favor pathogenic (VUSfp) from this cohort. The ADR for pathogenic and likely pathogenic variants was 22% and reached 35% with the inclusion of VUSfp. The ADRs of SAB and stillbirth were 36% and 33%, respectively. Affected genes included those associated with multisystem abnormalities, neurodevelopmental disorders, cardiac anomalies, skeletal dysplasia, metabolic disorders, and renal diseases. CONCLUSION: These results supported the clinical utility of ES for detecting monogenic etiology of pregnancy loss. The identification of disease-associated variants provided information for follow-up genetic counseling of recurrence risk and management of subsequent pregnancies. Discovery of novel variants could provide insight for underlying molecular mechanisms causing fetal death.

20.
Cell Mol Immunol ; 2020 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-32939032

RESUMO

Vγ9Vδ2 T cells are promising candidates for cellular tumor immunotherapy. Due to their HLA-independent mode of action, allogeneic Vγ9Vδ2 T cells can be considered for clinical application. To apply allogeneic Vγ9Vδ2 T cells in adoptive immunotherapy, the methodology used to obtain adequate cell numbers with optimal effector function in vitro needs to be optimized, and clinical safety and efficacy also need to be proven. Therefore, we developed a novel formula to improve the expansion of peripheral γδ T cells from healthy donors. Then, we used a humanized mouse model to validate the therapeutic efficacy of expanded γδ T cells in vivo; furthermore, the expanded γδ T cells were adoptively transferred into late-stage liver and lung cancer patients. We found that the expanded cells possessed significantly improved immune effector functions, including proliferation, differentiation, and cancer cell killing, both in vitro and in the humanized mouse model. Furthermore, a phase I clinical trial in 132 late-stage cancer patients with a total of 414 cell infusions unequivocally validated the clinical safety of allogeneic Vγ9Vδ2 T cells. Among these 132 patients, 8 liver cancer patients and 10 lung cancer patients who received ≥5 cell infusions showed greatly prolonged survival, which preliminarily verified the efficacy of allogeneic Vγ9Vδ2 T-cell therapy. Our clinical studies underscore the safety and efficacy of allogeneic Vγ9Vδ2 T-cell immunotherapy, which will inspire further clinical investigations and eventually benefit cancer patients.

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