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1.
Eur Radiol ; 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38834788

RESUMO

OBJECTIVES: To investigate the potential utility of [18F]fibroblast activation protein inhibitor (FAPI) positron emission tomography/computed tomography (PET/CT) for evaluating pulmonary artery (PA) masses, and compare it with [18F]fluorodeoxyglucose (FDG) PET/CT. METHODS: Participants with clinically suspected PA malignancy were prospectively enrolled and underwent dual-tracer PET/CT ([18F]FAPI-42 and [18F]FDG) imaging. Visual analysis and semi-quantitative parameters were compared between the two types of radiotracers. The tissue specimen underwent immunohistochemical staining to verify FAP expression in the tissue. RESULTS: Thirty-three patients (18 males/15 females; mean age 53.1 ± 15.4 years) were enrolled. All 21 patients with malignant PA masses were FDG-positive (100%), whereas 20 out of 21 patients were FAPI-positive (95.2%). All 12 patients with benign PA masses were both negative in FDG and FAPI PET. The mean maximum standardized uptake value (SUVmax) and target-to-background ratio (TBR) of FAPI and FDG in malignant PA masses were significantly higher than those of benign masses. Although there was no significant difference in SUVmax between FDG and FAPI in malignant PA masses (11.36 vs. 9.18, p = 0.175), the TBR (liver) and TBR (left ventricle) were more favorable for FAPI than for FDG (13.04 vs. 5.17, p < 0.001); (median: 7.75 vs. 2.75, p = 0.007). Immunohistochemical analysis (n = 16) validated that the level of FAP expression corresponded strongly to the uptake of FAPI in PET/CT scans (rs = 0.712, p = 0.002). For clinical management, FAPI PET found more metastatic lesions than FDG PET in 4 patients, with 2 patients upgrading and 1 patient changing treatment decisions. CONCLUSIONS: FAPI PET/CT is feasible in the diagnosis of PA masses. Although not superior to FDG PET/CT, FAPI PET/CT showed better target-to-background contrast. CLINICAL RELEVANCE STATEMENT: This study found that FAPI PET/CT is not superior to FDG PET/CT in diagnosing PA masses, but FAPI PET/CT displays better target-to-background contrast and more positive lesions, which may help improve disease management. KEY POINTS: Pulmonary malignancies lack specificity in clinical manifestations, laboratory tests, and routine imaging examinations. FAPI PET/CT is not diagnostically better than FDG PET/CT but displays better target-to-background contrast and more positive lesions. Dual-tracer PET/CT ([18F]FAPI-42 and [18F]FDG) imaging improves clinical management of pulmonary artery masses.

2.
Cancer Imaging ; 24(1): 68, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38831354

RESUMO

BACKGROUND: This study investigates the value of fluorine 18 ([18F])-labeled fibroblast activation protein inhibitor (FAPI) for lymph node (LN) metastases in patients with stage I-IIIA non-small cell lung cancer (NSCLC). METHODS: From November 2021 to October 2022, 53 patients with stage I-IIIA NSCLC who underwent radical resection were prospectively included. [18F]-fluorodeoxyglucose (FDG) and [18F]FAPI examinations were performed within one week. LN staging was validated using surgical and pathological findings. [18F]FDG and [18F]FAPI uptake was compared using the Wilcoxon signed-ranks test. Furthermore, the diagnostic value of nodal groups was investigated. RESULTS: In 53 patients (median age, 64 years, range: 31-76 years), the specificity of [18F]FAPI for detecting LN metastasis was significantly higher than that of [18F]FDG (P < 0.001). High LN risk category, greater LN short-axis dimension(≥ 1.0 cm), absence of LN calcification or high-attenuation, and higher LN FDG SUVmax (≥ 10.1) were risk factors for LN metastasis(P < 0.05). The concurrence of these four risk factors accurately predicted LN metastases (Positive Predictive Value [PPV] 100%), whereas the presence of one to three risk factors was unable to accurately discriminate the nature of LNs (PPV 21.7%). Adding [18F]FAPI in this circumstance improved the diagnostic value. LNs with an [18F]FAPI SUVmax<6.2 were diagnosed as benign (Negative Predictive Value 93.8%), and LNs with an [18F]FAPI SUVmax≥6.2 without calcification or high-attenuation were diagnosed as LN metastasis (PPV 87.5%). Ultimately, the integration of [18F]FDG and [18F]FAPI PET/CT resulted in the highest accuracy for N stage (83.0%) and clinical decision revisions for 29 patients. CONCLUSION: In patients with stage I-IIIA NSCLC, [18F]FAPI contributed additional valuable information to reduce LN diagnostic uncertainties after [18F]FDG PET/CT. Integrating [18F]FDG and [18F]FAPI PET/CT resulted in more precise clinical decisions. TRIAL REGISTRATION: The Chinese Clinical Trial Registry: ChiCTR2100044944 (Registered: 1 April 2021, https://www.chictr.org.cn/showprojEN.html?proj=123995 ).


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Fluordesoxiglucose F18 , Neoplasias Pulmonares , Metástase Linfática , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Compostos Radiofarmacêuticos , Humanos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Pessoa de Meia-Idade , Masculino , Feminino , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Estudos Prospectivos , Idoso , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Adulto , Metástase Linfática/diagnóstico por imagem , Linfonodos/diagnóstico por imagem , Linfonodos/patologia
3.
Clin Nucl Med ; 49(6): e295-e297, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38377375

RESUMO

ABSTRACT: We compared 18 F-FAPI and 18 F-FDG PET/CT findings of metastatic perivacular epitheliod cell tumor in a 23-year-old woman. Apart from showing strong uptake of a left upper lung mass that showed moderate uptake on 18 F-FDG, 18 F-FAPI PET/CT additionally presented hypermetabolism in diffuse multifocal lesion throughout the body. This case suggests that 18 F-FAPI PET/CT might play a more beneficial role than 18 F-FDG PET/CT in identifying and assessing the extent of perivascular epithelioid cell tumors.


Assuntos
Metástase Neoplásica , Neoplasias de Células Epitelioides Perivasculares , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Feminino , Neoplasias de Células Epitelioides Perivasculares/diagnóstico por imagem , Neoplasias de Células Epitelioides Perivasculares/patologia , Adulto Jovem , Fluordesoxiglucose F18
4.
Eur J Nucl Med Mol Imaging ; 51(7): 2124-2133, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38285206

RESUMO

PURPOSE: This paper discusses the optimization of pharmacokinetic modelling and alternate simplified quantification method for [18F]AlF-P16-093, a novel tracer for in vivo imaging of prostate cancer. METHODS: Dynamic PET/CT scans were conducted on eight primary prostate cancer patients, followed by a whole-body scan at 60 min post-injection. Time-activity curves (TACs) were obtained by drawing volumes of interest for primary prostatic and metastatic lesions. Optimal kinetic modelling involved evaluating three compartmental models (1T2K, 2T3K, and 2T4K) accounting for fractional blood volume (Vb). The simplified quantification method was then determined based on the correlation between the static uptake measure and total distribution volume (Vt) obtained from the optimal pharmacokinetic analysis. RESULTS: In total, 17 intraprostatic lesions, 10 lymph nodes, and 36 osseous metastases were evaluated. Visually, the contrast of the tumor increased and showed the steepest incline within the first few minutes, whereas background activity decreased over time. Full pharmacokinetic analysis revealed that a reversible two-compartmental (2T4K) model is the preferred kinetic model for the given tracer. The kinetic parameters K1, k3, Vb, and Vt were all significantly higher in lesions when compared with normal tissue (P < 0.01). Several simplified protocols were tested for approximating comprehensive dynamic quantification in tumors, with image-based SURmean (the ratio of tumor SUVmean to blood SUVmean) within the 28-34 min window found to be sufficient for approximating the total distribution Vt values (R2 = 0.949, P < 0.01). Both Vt and SURmean correlated significantly with the total serum prostate-specific antigen (tPSA) levels (P < 0.01). CONCLUSIONS: This study introduced an optimized pharmacokinetic modelling approach and a simplified acquisition method for [18F]AlF-P16-093, a novel PSMA-targeted radioligand, highlighting the feasibility of utilizing one static PET imaging (between 30 and 60 min) for the diagnosis of prostate cancer. Note that the image-derived input function in this study may not reflect the true corrected plasma input function, therefore the interpretation of the associated kinetic parameter estimates should be done with caution.


Assuntos
Modelos Biológicos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/metabolismo , Idoso , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Pessoa de Meia-Idade , Compostos Radiofarmacêuticos/farmacocinética , Cinética , Lisina/análogos & derivados , Ureia/análogos & derivados
5.
Eur J Nucl Med Mol Imaging ; 51(6): 1753-1762, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38212531

RESUMO

PURPOSE: This is a first-in-human study to evaluate the radiation dosimetry of a new prostate-specific membrane antigen (PSMA)-targeted radiopharmaceutical, [18F]AlF-P16-093, and also initial investigation of its ability to detect PSMA-positive tumors using PET scans in a cohort of prostate cancer (PCa) patients. METHODS: The [18F]AlF-P16-093 was automatically synthesized with a GE TRACERlab. A total of 23 patients with histopathologically proven PCa were prospectively enrolled. Dosimetry and biodistribution study investigations were carried out on a subset of six (6) PCa patients, involving multiple time-point scanning. The mean absorbed doses were estimated with PMOD and OLINDA software. RESULTS: [18F]AlF-P16-093 was successfully synthesized, and radiochemical purity was > 95%, and average labeling yield was 36.5 ± 8.3% (decay correction, n = 12). The highest tracer uptake was observed in the kidneys, spleen, and liver, contributing to an effective dose of 16.8 ± 1.3 µSv/MBq, which was ~ 30% lower than that of [68Ga]Ga-P16-093. All subjects tolerated the PET examination well, and no reportable side-effects were observed. The PSMA-positive tumors displayed rapid uptake, and they were all detectable within 10 min, and no additional lesions were observed in the following multi-time points scanning. Each patient had at least one detectable tumor lesion, and a total of 356 tumor lesions were observed, including intraprostatic, lymph node metastases, bone metastases, and other soft tissue metastases. CONCLUSIONS: We report herein a streamlined method for high yield synthesis of [18F]AlF-P16-093. Preliminary study in PCa patients has demonstrated its safety and acceptable radiation dosimetry. The initial diagnostic study indicated that [18F]AlF-P16-093 PET/CT is efficacious and potentially useful for a widespread application in the diagnosis of PCa patients.


Assuntos
Antígenos de Superfície , Glutamato Carboxipeptidase II , Neoplasias da Próstata , Radiometria , Humanos , Masculino , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Idoso , Glutamato Carboxipeptidase II/metabolismo , Pessoa de Meia-Idade , Antígenos de Superfície/metabolismo , Distribuição Tecidual , Compostos Radiofarmacêuticos/farmacocinética , Compostos Radiofarmacêuticos/química , Radioisótopos de Flúor/química , Idoso de 80 Anos ou mais , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada
6.
Biomed Rep ; 19(4): 73, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37746591

RESUMO

Fibrous dysplasia of bone (FDB) is a rare benign condition in which fibrous tissue replaces normal bone architecture. FDB rarely undergoes malignant transformation, but there are reports of locally aggressive fibrous dysplasia with cortical destruction and soft tissue extension. Diagnosis of FDB malignant transformation is not easy, especially in monostotic form, because of the overlap in imaging features of locally aggressive fibrous dysplasia and fibrous dysplasia with malignant transformation. The present case study reports a rare case of FDB in a 23-year-old man with polyostotic fibrous dysplasia arising in the left side of the pelvis and lower limb bones with partial transformation to fibrosarcoma. This study explored the multimodal imaging features of FDB malignant transformation, to achieve early detection and improve diagnostic accuracy of local FDB aggressiveness and its malignant transformation.

7.
Chinese Journal of Epidemiology ; (12): 544-551, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-985525

RESUMO

Objective: To describe the distribution characteristics of hyperlipidemia in adult twins in the Chinese National Twin Registry (CNTR) and explore the effect of genetic and environmental factors on hyperlipidemia. Methods: Twins recruited from the CNTR in 11 project areas across China were included in the study. A total of 69 130 (34 565 pairs) of adult twins with complete information on hyperlipidemia were selected for analysis. The random effect model was used to characterize the population and regional distribution of hyperlipidemia among twins. The concordance rates of hyperlipidemia were calculated in monozygotic twins (MZ) and dizygotic twins (DZ), respectively, to estimate the heritability. Results: The age of all participants was (34.2±12.4) years. This study's prevalence of hyperlipidemia was 1.3% (895/69 130). Twin pairs who were men, older, living in urban areas, married,had junior college degree or above, overweight, obese, insufficient physical activity, current smokers, ex-smokers, current drinkers, and ex-drinkers had a higher prevalence of hyperlipidemia (P<0.05). In within-pair analysis, the concordance rate of hyperlipidemia was 29.1% (118/405) in MZ and 18.1% (57/315) in DZ, and the difference was statistically significant (P<0.05). Stratified by gender, age, and region, the concordance rate of hyperlipidemia in MZ was still higher than that in DZ. Further, in within-same-sex twin pair analyses, the heritability of hyperlipidemia was 13.04% (95%CI: 2.61%-23.47%) in the northern group and 18.59% (95%CI: 4.43%-32.74%) in the female group, respectively. Conclusions: Adult twins were included in this study and were found to have a lower prevalence of hyperlipidemia than in the general population study, with population and regional differences. Genetic factors influence hyperlipidemia, but the genetic effect may vary with gender and area.


Assuntos
Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , China/epidemiologia , Doenças em Gêmeos/genética , Hiperlipidemias/genética , Doenças Metabólicas , Gêmeos Dizigóticos , Gêmeos Monozigóticos/genética
8.
Chem Commun (Camb) ; 58(18): 3015-3018, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-35147615

RESUMO

We have established a practical and concise method for the straightforward access of a universal deuterated methylthiolating reagent through a one-pot gram-scale operation under mild conditions. This odourless electrophilic SCD3 reagent was widely applied to react with numerous representative nucleophiles and approached various valuable SCD3 analogues with excellent levels of deuterium content (>99% D). The divergent further transformations were smoothly carried out to obtain the significant derivatives with different oxidative states in high efficiency.

9.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-935329

RESUMO

Objective: To assess the association of genetic polymorphisms and circulating levels of chemokine monocyte chemoattractant protein-1 (MCP1) with risk of breast cancer. Methods: A total of 820 patients with pathologically confirmed breast cancer and 900 age-and area-of-residence-matched healthy controls who visited the hospital for routine health screening during the same period were included in this case-control study. Mendelian randomization analysis was performed using three widely followed functional single nucleotide polymorphisms (SNPs) of the MCP1 gene rs1024611, rs2857656 and rs4586 to construct instrumental variables . Results: MCP1 rs1024611 (OR=1.26, P=0.002), rs2857656 (OR=1.23, P=0.006) and rs4586 (OR=1.23, P=0.003) were significantly associated with increased risk of breast cancer. SNP rs1024611 (β=1.194, P<0.001), rs2857656 (β=1.221, P<0.001) and rs4586 (β=1.137, P<0.001) were positively correlated with higher circulating level of MCP1. The case-control study showed that an increase of 23.7 pg/ml of circulating levels of MCP1 was associated with a 0.25-fold increased risk of breast cancer. MR analysis confirmed that the genetic predicted circulating levels of MCP1 were associated with an increased risk of breast cancer, and the risk of breast cancer increased by 0.20 times with an increase of 23.7 pg/ml in MCP1. Conclusion: Genetic variants and circulating levels of MCP1 are significantly associated with the risk of breast cancer and can be used as a biomarker for early prediction of breast cancer.


Assuntos
Feminino , Humanos , Neoplasias da Mama/genética , Estudos de Casos e Controles , Quimiocina CCL2/genética , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único
10.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-931742

RESUMO

DECIDE-Diet trial was taken as a case to introduce the methods of blinding and blinding assessment for feeding trials, report the details of blinding, conduct a blinding survey and calculate Jame's BI and Bang's BI. Jame's BI was 0.683 (95% CI: 0.593~0.772). The Bang's BI for the intervention group was 0.340 (95% CI: 0.199~0.481), and for the control group was 0.086 (95% CI: -0.060~0.231). The blinding of the DECIDE)-Diet was generally successful, but the intervention group may infer their group to a certain extent. Feeding trials should report the details of blinding and consider blinding assessment.

11.
Chinese Journal of Oncology ; (12): 743-760, 2022.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-940935

RESUMO

Objective: To systematically summarize and analyze the clinical research progress of therapeutic vaccines for cervical cancer or precancerous lesions. Methods: English databases (PubMed, Embase, Web of Science, Cochrane library, Proquest, and ClinicalTrails.gov) and Chinese databases (SinoMed, CNKI, WanFang, and VIP Database) were systematically searched to collect literature on therapeutic vaccines for cervical cancer or precancerous lesions from inception to February 18, 2021. After screening, we evaluated the risk of bias of included studies, and combed the basic information of the literature, research designs, information of vaccines, study patients, outcome indicators and so on, qualitatively summarized the clinical research progress. Results: A total of 71 studies were included in this systematic review, including 14 random controlled trials, 15 quasi-random controlled trials, 4 cohort studies, 1 case-control study, 34 case series studies and 3 case reports. The study patients included women aged 15~79 with cervical cancer or precancerous lesions in 18 countries from 1989 to 2021. On the one hand, there were 40 studies on therapeutic vaccines for cervical precancerous lesions (22 867 participants), involving 21 kinds of vaccines in 6 categories. Results showed 3 marketed vaccines (Cervarix, Gardasil, Gardasil 9) as adjuvant immunotherapies were significant effective in preventing the recurrence of precancerous lesions compared with the conization only. In addition, MVA E2 vaccine had been in phase Ⅲ clinical trials as a specific therapeutic vaccine, with relative literature showing it could eliminate most high-grade precancerous lesions. Therapeutic vaccines for precancerous lesions all showed good safety. On the other hand, there were 31 studies on therapeutic vaccines for cervical cancer (781 participants), involving 19 kinds of vaccines in 7categories, with none had been marketed. 25 studies were with no control group, showing the vaccines could effectively eliminate solid tumors, prevent recurrence, and prolong the median survival time. However, the vaccines effectiveness couldn't be statistically calculated due to the lack of a control group. As for the safety of therapeutic vaccines for cervical cancer, 9 studies showed that patients experienced serious adverse events after treatments, where 7 studies reported that serious adverse events occurred in patients couldn't be ruled out as the results of therapeutic vaccines. Conclusions: The literature review shows that the literature evidence for the therapeutic vaccines for cervical precancerous lesions is relatively mature compared with the therapeutic vaccines for cervical cancer. The four kinds of vaccines on the market are all therapeutic vaccines for precancerous lesions, but they are generally used as vaginal infection treatments or adjuvant immunotherapies for cervical precancerous lesions, not used for the specific treatments of cervical precancerous lesions. Other specific therapeutic vaccines are in the early stage of clinical trials, mainly phase Ⅰ/Ⅱ clinical trials with small sample size. The effectiveness and safety data are limited, and further research is still needed.


Assuntos
Feminino , Humanos , Vacinas Anticâncer/uso terapêutico , Displasia do Colo do Útero/prevenção & controle , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/uso terapêutico , Lesões Pré-Cancerosas/terapia , Neoplasias do Colo do Útero/prevenção & controle
12.
Cancer Immunol Immunother ; 67(2): 209-224, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29051990

RESUMO

Currently, little is known about the interactions between microRNAs (miRNAs) and the PD-1/PD-L1 signaling pathway in chordoma, and data discussing the role of the immune milieu in chordoma prognosis are limited. We aimed to analyze the relationship between PD-L1, miR-574-3p, microenvironmental tumor-infiltrating lymphocytes (TILs) and clinicopathological features of spinal chordoma patients. PD-L1 expression and TILs (including Foxp3+, CD8+, PD-1+ and PD-L1+) were assessed by immunohistochemistry in tumor specimens of 54 spinal chordoma patients. MiRNAs microarray and bioinformatical analysis were used to identify miRNAs potentially regulating PD-L1 expression, which were further validated by quantitative RT-PCR. miR-574-3p was identified to potentially regulate PD-L1 expression in chordoma, which inversely correlated with PD-L1. Positive PD-L1 expression on tumor cells was associated with advanced stages (P = 0.041) and TILs infiltration (P = 0.005), whereas decreased miR-574-3p level correlated with higher muscle invasion (P = 0.012), more severe tumor necrosis (P = 0.022) and poor patient survival. Importantly, a patient subgroup with PD-L1+/miR-574-3plow chordoma phenotype was significantly associated with worse local recurrence-free survival (LRFS) (P = 0.026). PD-1+ TILs density was associated with surrounding muscle invasion (P = 0.014), and independently portended poor LRFS (P = 0.040), while PD-L1+ TILs showed tendencies of less aggressive clinical outcomes. Multivariate analysis of OS only found CD8+/Foxp3+ ratio to be independent prognostic factor (P = 0.022). These findings may be useful to stratify patients into prognostic groups and provide a rationale for the use of checkpoint blockade therapy, possibly by administering miR-574-3p mimics, in spinal chordoma.


Assuntos
Antígeno B7-H1/imunologia , Linfócitos T CD8-Positivos/imunologia , Cordoma/imunologia , Fatores de Transcrição Forkhead/imunologia , MicroRNAs/imunologia , Neoplasias da Coluna Vertebral/imunologia , Adulto , Idoso , Antígeno B7-H1/biossíntese , Antígeno B7-H1/genética , Estudos de Casos e Controles , Cordoma/genética , Cordoma/patologia , Feminino , Humanos , Linfócitos do Interstício Tumoral/imunologia , Masculino , MicroRNAs/biossíntese , MicroRNAs/genética , Pessoa de Meia-Idade , Prognóstico , Neoplasias da Coluna Vertebral/genética , Neoplasias da Coluna Vertebral/patologia , Microambiente Tumoral/imunologia , Adulto Jovem
13.
Oncoimmunology ; 4(9): e1038017, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26405607

RESUMO

Postoperative non-small cell lung cancer (NSCLC) patients require adjuvant therapy to improve their prognosis. In this study, we investigated the efficacy of a sequential combination of autologous cellular immunotherapy (CIT) and chemotherapy for postoperative NSCLC. This retrospective study included 120 postoperative NSCLC patients: 60 cases received only chemotherapy; 33 cases received chemotherapy and sequential CIT with cytokine-induced killer (CIK) cells; and 27 cases received chemotherapy and sequential CIT with alternate CIK and natural killer (NK) cells. Survival analysis showed significantly higher overall survival rates in the CIT group compared with the control group. Overall survival was higher in patients who received CIT with alternate CIK and NK cells than those who received treatment with only CIK cells. Multivariate analysis showed that adjuvant CIT was an independent prognostic factor for overall survival of patients with NSCLC. In subgroup analyses, adjuvant CIT significantly improved the overall survival of patients with less than 60 y old and positive lymph node. In conclusions, these data indicate that adjuvant CIT, especially with alternate application of CIK and NK cells, is an effective therapeutic approach to prolong survival of patients with NSCLC, particularly for patients ≤60 y old with positive lymph nodes.

14.
Oncoimmunology ; 4(2): e976507, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25949875

RESUMO

Adoptive cell therapy (ACT) for cancers using autologous tumor-infiltrating lymphocytes (TILs) can induce immune responses and antitumor activity in metastatic melanoma patients. Here, we aimed to assess the safety and antitumor activity of ACT using expanded TILs following concurrent chemoradiotherapy (CCRT) in patients with locoregionally advanced nasopharyngeal carcinoma (NPC). Twenty-three newly diagnosed, locoregionally advanced NPC patients were enrolled, of whom 20 received a single-dose of TIL infusion following CCRT. All treated patients were assessed for toxicity, survival and clinical and immunologic responses. Correlations between immunological responses and treatment effectiveness were further studied. Only mild adverse events (AEs), including Grade 3 neutropenia (1/23, 5%) consistent with immune-related causes, were observed. Nineteen of 20 patients exhibited an objective antitumor response, and 18 patients displayed disease-free survival longer than 12 mo after ACT. A measurable plasma Epstein-Barr virus (EBV) load was detected in 14 patients at diagnosis, but a measurable EBV load was not found in patients after one week of ACT, and the plasma EBV load remained undetectable in 17 patients at 6 mo after ACT. Expansion and persistence of T cells specific for EBV antigens in peripheral blood following TIL therapy were observed in 13 patients. The apparent positive correlation between tumor regression and the expansion of T cells specific for EBV was further investigated in four patients. This study shows that NPC patients can tolerate ACT with TILs following CCRT and that this treatment results in sustained antitumor activity and anti-EBV immune responses. A larger phase II trial is in progress.

15.
Sci Rep ; 5: 9202, 2015 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-25776856

RESUMO

The benefits of adjuvant cytokine-induced killer (CIK) cell immunotherapy for hepatocellular carcinoma (HCC) remain mixed among patients. Here, we constructed a prognostic nomogram to enable individualized predictions of survival benefit of adjuvant CIK cell treatment for HCC patients. Survival analysis showed that the median overall survival (OS) and progression-free survival (PFS) for patients in the hepatectomy/CIK combination group were 41 and 16 months, respectively, compared to 28 and 12 months for patients in the hepatectomy alone group (control). Based on multivariate analysis of the entire cohort, independent factors for OS were tumor size, tumor capsule, pathological grades, total bilirubin, albumin, prothrombin time, alpha-fetoprotein, and tumor number, which were incorporated into the nomogram. The survival prediction model performed well, as assessed by the c-index and calibration curve. Internal validation revealed a c-index of 0.698, which was significantly greater than the c-index value of the TNM (tumor-node-metastasis) staging systems of 0.634. The calibration curves fitted well. In conclusions, our developed nomogram resulted in more accurate individualized predictions of the survival benefit from adjuvant CIK cell treatment after hepatectomy. The model may provide valuable information to aid in the decision making regarding the application of adjuvant CIK cell immunotherapy.


Assuntos
Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/terapia , Células Matadoras Induzidas por Citocinas/imunologia , Imunoterapia , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/mortalidade , Terapia Combinada , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Estudos Retrospectivos , Resultado do Tratamento , Carga Tumoral , Adulto Jovem
16.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-482351

RESUMO

Objective To analyse effect of ShenQi FuZheng injection on serum carbohydrate antigen 19-9(CA19-9), C-reaction protein(CRP) and CD4 +lymphocyte subsets in patients after laparoscopic radical resection of colon cancer.Methods 58 patients after laparoscopic radical resection of colon cancer were collected.All patients were randomly divided into experimental group and control group according to the different drugs, 29 cases in each group.Patients were given the corresponding drug treatment after operation, after the treatment, the serum levels of CA19-9, CRP and venous blood T lymphocyte level were detected in all patients.Results Compared with before treatment, CA19-9 and CRP level in serum were lower (P<0.05) , CD4 +cells, CD4 +/CD8 +, and NK cells were higher(P<0.05);Compared with control group after treatment, the serum CA19-9 and CRP level were lower in the experimental group (P<0.05); the levels of venousblood CD4 +cells, CD4 +/CD8 +and NK cells were higher in the experimental group (P<0.05).Conclusion ShenQi FuZheng injection can significantly reduce the serum CRP and CA19-9 levels in patients after laparoscopic radical resection of colon cancer, improve the levels of venous blood CD4 +cells, CD4 +/CD8 +and NK cells, improve immune function, and have a guiding significance for clinica.

17.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-482326

RESUMO

Objective To investigate the effect of glutamine on the serum carcino embryonie antigen (CEA) , alpha fetal protein (AFP) and T cell immune function in postoperative patients with gastric cancer.Methods 52 postoperative patients with gastric cancer from Yiwu Central Hospital were selected and randomly divided into control group and experimenal group, 26 cases in each group.The control group received routine nutritional therapy, and experimental group received alanyl -glutamine injection on the basis of control group.The serum nutritional parameters, CEA, AFP, CD4 +T, CD8 +T levels were compared post-treatment.Results Compared with control group post-treatment, the serum albumin (ALB) and pre-albumin (PA) levels were higher (P<0.05), the CEA and AFP levels were lower (P<0.05),the serum levels of CD4 +T and CD4 +T/CD8 +T were higher (P<0.05),CD8 +T level were lower (P<0.05).Conclusion Glutamine could significantly improve the clinical symptoms of patients with gastric cancer after surgery,and it is speculated that the mechanism may be the increase of serum ALB, PA levels, the decrease of CEA, AFP levels and the improvement of immune function.

18.
Clin Cancer Res ; 20(11): 3003-11, 2014 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-24668644

RESUMO

PURPOSE: Triple-negative breast cancer (TNBC) is a high risk form of this disease, even after surgery, due to the absence of targets for hormone treatment and anti-Her-2 therapy. Chemotherapy is the main therapeutic strategy for such patients with breast cancer, although the outcome is often unsatisfactory. Thus, the development of combination adjuvant therapies is essential for improved prognosis in patients with TNBC. In this study, we investigated the efficacy of a sequential combination of cytokine-induced killer cell (CIK) infusion and chemotherapy for patients with post-mastectomy TNBC. EXPERIMENTAL DESIGN: From 2008 to 2012, 90 patients with post-mastectomy TNBC were included in this retrospective study: 45 cases received chemotherapy alone or with sequential radiotherapy; a further 45 cases received chemotherapy with/without radiotherapy and sequential CIK infusion. RESULTS: Survival analysis showed significantly higher disease-free survival (DFS) and overall survival (OS) rates in the CIK treatment group compared with the control group (P = 0.0382, P = 0.0046, respectively; log-rank test). Multivariate survival analysis showed that CIK adjuvant treatment was an independent prognostic factor for OS of patients with TNBC. In subgroup analyses, CIK adjuvant treatment significantly increased the DFS rate of patients with pathologic grade 3, and significantly increased the OS rate of patients in N1, N2, N3, IIB, III TNM (tumor-node-metastasis) stages, and with pathologic grade 3. CONCLUSIONS: These data indicate that adjuvant CIK treatment combined with chemotherapy is an effective therapeutic strategy to prevent disease recurrence and prolong survival of patients with TNBC, particularly those with lymph node metastasis, advanced TNM stage, and poor pathologic grade. Clin Cancer Res; 20(11); 3003-11. ©2014 AACR.


Assuntos
Células Matadoras Induzidas por Citocinas/imunologia , Imunoterapia/métodos , Neoplasias de Mama Triplo Negativas/terapia , Adulto , Idoso , Antineoplásicos/uso terapêutico , Quimioterapia Adjuvante , Terapia Combinada , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Mastectomia , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Radioterapia , Estudos Retrospectivos , Neoplasias de Mama Triplo Negativas/mortalidade , Neoplasias de Mama Triplo Negativas/patologia
19.
Tumour Biol ; 35(1): 701-7, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23955802

RESUMO

Cytokine-induced killer (CIK) cells are ex vivo generated heterogeneous NK-like T lymphocytes. It is not very clear whether the phenotype of CIK cells is associated with their therapeutic efficacy to cancer patients. Thus, in this study, the association of phenotype of CIK cells and the overall survival of 121 patients with hepatocellular carcinoma (HCC), 74 patients with lung cancer and 42 patients with colorectal cancer, all of whom underwent surgical resection and received autogenous CIK cell therapy, was analyzed. We found that high ratio of the CD3+CD4+ subset was associated with poorer overall survival in colorectal cancer, but not HCC or lung cancer. A high ratio of the CD3+CD8+ subset was associated with improved overall survival in all three types of cancer. A high ratio of the CD3+CD56+ NK-like subset was associated with improved overall survival in lung and colorectal cancer, but not HCC. A high ratio of the CD3-CD56+ NK subset was associated with poorer overall survival in lung and colorectal cancer, but not HCC. In conclusion, the CD3+CD8+ and CD3+CD56+ subsets, especially the CD3+CD8+ subset, may be the major phenotypes responsible for anti-tumor immunity in vivo after autogenous CIK cell therapy.


Assuntos
Células Matadoras Induzidas por Citocinas/imunologia , Células Matadoras Induzidas por Citocinas/metabolismo , Neoplasias/imunologia , Neoplasias/mortalidade , Fenótipo , Antígenos CD/metabolismo , Feminino , Humanos , Imunofenotipagem , Imunoterapia Adotiva , Masculino , Neoplasias/terapia
20.
Biochem Biophys Res Commun ; 442(3-4): 171-6, 2013 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-24269822

RESUMO

A replication-deficient adenovirus (Ad) encoding secreted human endostatin (Ad-Endo) has been demonstrated to have promising antiangiogenic and antitumoral effects. The E1B55k-deleted Ad H101 can selectively lyse cancer cells. In this study, we explored the antitumor effects and cross-interactions of Ad-Endo and H101 on nasopharyngeal carcinoma (NPC). The results showed that H101 dramatically promoted endostatin expression by Ad-Endo via rescuing Ad-Endo replication in NPC cells, and the expressed endostatin proteins significantly inhibited the proliferation of human umbilical vein endothelial cells. E1A and E1B19k products are required for the rescuing of H101 to Ad-Endo replication in CNE-1 and CNE-2 cells, but not in C666-1 cells. On the other hand, Ad-Endo enhanced the cytotoxicity of H101 by enhancing Ad replication in NPC cells. The combination of H101 and Ad-Endo significantly inhibited CNE-2 xenografts growth through the increased endostatin expression and Ad replication. These findings indicate that the combination of Ad-Endo gene therapy and oncolytic Ad therapeutics could be promising in comprehensive treatment of NPC.


Assuntos
Adenoviridae/fisiologia , Endostatinas/genética , Terapia Genética/métodos , Neoplasias Nasofaríngeas/terapia , Neovascularização Patológica/terapia , Terapia Viral Oncolítica/métodos , Vírus Oncolíticos/fisiologia , Replicação Viral , Adenoviridae/genética , Animais , Carcinoma , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/irrigação sanguínea , Vírus Oncolíticos/genética , Proteínas Recombinantes/genética , Ensaios Antitumorais Modelo de Xenoenxerto
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