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2.
Cancer Sci ; 2021 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-34618997

RESUMEN

Chemoradiation therapy (CRT) of locally advanced esophageal cancer (LAEC), although improving outcomes of patients, still results in 50% of local failure. An early prediction could identify the patients at high-risk of poor response for individualized adaptive treatment. We aimed to investigate physiological changes in LAEC using diffusion and perfusion MRI for early prediction of treatment response. In the study, 115 LAEC patients treated with CRT were enrolled (67 in the discovery cohort and 48 in the validation cohort). MRI scans were performed pre-RT and at week 3 during RT (mid-RT). Gross tumour volume (GTV) of primary tumor was delineated on T2 weighted images. Within the GTV, the hypercellularity volume (VHC ) and high blood volume (VHBV ) were defined based upon the analysis of ADC and Vp histogram distributions within the tumors in the discovery cohort. The median GTV were 28cc±2.2cc at pre-RT and 16.7cc±1.5cc at mid-RT. Respectively, VHC and VHBV decreased from 4.7cc±0.7cc and 5.7cc±0.7cc at pre-RT to 2.8cc±0.4cc and 3.5cc±0.5cc at mid-RT. Smaller VHC at mid-RT (AUC=0.67, p=0.05; AUC=0.66, p=0.05) and more decreasing in VHC at mid-RT (AUC=0.7, p=0.01; AUC=0.69, p=0.03) were associated with longer PFS in both discovery and validation cohort. No significant predictive effects were shown in GTV and VHBV at any time point. In conclusions, we demonstrated that VHC represent aggressive subvolumes in LAEC. Further analysis will be carried out to confirm the correlations between the changes in image-phenotype subvolumes with local failure to determine the radiation-resistant tumor subvolumes, which may be useful for dose escalation.

3.
Sci Rep ; 11(1): 18017, 2021 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-34504253

RESUMEN

This study explored the dosimetric difference between hypofractionated whole-breast irradiation (HFWBI) with sequential boost (SEB) and simultaneous integrated boost (SIB) based on supine and prone positions to identify the superior boost mode and superior position. Thirty breast cancer patients eligible for HFWBI after breast-conserving surgery were enrolled. All patients underwent 3DCT simulation scanning in both supine and prone positions. For the SEB-HFWBI plan, the dose prescribed for the planning target volume (PTV) of whole breast (WB) was 2.67 Gy per fraction with a total of 15 fractions, followed by a sequential boost of 3.2 Gy per fraction to the PTV of tumor bed (TB) in 3 fractions. For the SIB-HFWBI plan, the dose prescribed for the PTV of WB was 2.67 Gy per fraction with a total of 15 fractions, with a simultaneously integrated boost of 3.2 Gy per fraction to the PTV of TB with a total of 15 fractions. Regardless of the position, for the PTV of TB, the conformal index (CI) in the SIB-HFWBI plans was greater than those in the SEB-HFWBI plans (T = - 8.114, - 8.114; both P < 0.05). The CI for the PTV of WB increased significantly in the prone position relative to the supine position in both two plans(Z = - 3.340, - 3.501; all P < 0.05). The study suggested that prone SIB-HFWBI might be more suitable for postoperative radiotherapy after breast-conserving surgery for early-stage breast cancer patients.

4.
Health Qual Life Outcomes ; 19(1): 213, 2021 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-34488798

RESUMEN

BACKGROUND: Although physical activity (PA) and sedentary time in cancer survivors (CSs) were associated with health-related quality of life (HRQOL), it was not clear whether their associations were similar among CSs with different number of comorbid chronic diseases (CCDs). This study aimed to investigate the associations between PA, sedentary time and HRQOL in CSs with different number of CCDs. METHODS: A cross-sectional study was conducted among 1546 CSs between June and September 2018 in Shanghai, China. Data were collected with a self-reported questionnaire including sociodemographic characteristics, CCDs, PA, sedentary time and HRQOL. International Physical Activity Questionnaire and Cancer Quality of Life Questionnaire-Core30 were respectively used to measure PA and HRQOL of CSs. Associations of PA and sedentary time with HRQOL among CSs with different number of CCDs were evaluated by using logistic regression, adjusted for confounding factors. RESULTS: About seventy-five percent CSs had at least one CCD. Approximately three fifths CSs had high PA level and < 4 h/day sedentary time. Moderate PA level and high PA level were shown to be associated with better HRQOL among all participants. In CSs with ≤ 2 CCDs, high PA level was significantly associated with higher scores of physical function and lower scores of nausea and vomiting, appetite loss. However, there was a positive association between high PA level and constipation score among CSs with ≥ 3 CCDs. CSs with shorter sedentary time had better HRQOL in those with CCDs. CONCLUSIONS: High PA level and long sedentary time have significant association with worse HRQOL of CSs with ≥ 3 CCDs, while high PA level is positively associated with HRQOL in CSs with ≤ 2 CCDs. Our findings may support further studies of the causal association between PA, sedentary times and HRQOL to provide targeted proposal to improve the HRQOL of CSs according to their number of CCDs.


Asunto(s)
Supervivientes de Cáncer/psicología , Ejercicio Físico/fisiología , Neoplasias/mortalidad , Calidad de Vida/psicología , Conducta Sedentaria , Adulto , Anciano , Anciano de 80 o más Años , China/epidemiología , Estudios Transversales , Ejercicio Físico/psicología , Femenino , Conductas Relacionadas con la Salud , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/terapia , Encuestas y Cuestionarios , Terapéutica
5.
Bioengineered ; 12(1): 5632-5640, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34519257

RESUMEN

Acute coronary syndrome (ACS) is one of the main syndromes of coronary artery disease with high mortality. The identification of biomarkers associated with disease occurrence and progression could improve early detection and risk prediction. This study was aimed to reveal the clinical significance and function of miR-3646 in ACS.The expression of miR-3646 was evaluated in ACS patients, healthy volunteers, and non-ACS patients and estimated the clinical significance of miR-3646. The ACS modeling rats were also established in this study to explore the potential mechanism underlying the function of miR-3646. miR-3646 was upregulated in ACS patients compared with healthy volunteers and non-ACS patients. The expression of miR-3646 was positively correlated with the severity and progression of ACS patients and could discriminate ACS patients from healthy volunteers and non-ACS patients. The knockdown of miR-3646 could reverse the inflammatory response induced by ACS.miR-3646 serves as a diagnostic biomarker for ACS. The knockdown of miR-3646 could alleviate ACS by reversing inflammatory response. These results provide a potential therapeutic target of ACS.

6.
EMBO Rep ; : e52707, 2021 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-34472665

RESUMEN

Genome-wide association studies (GWAS) have identified multiple gastric cancer risk loci and several protein-coding susceptibility genes. However, the role of long-noncoding RNAs (lncRNAs) transcribed from these risk loci in gastric cancer development and progression remains to be explored. Here, we functionally characterize a lncRNA, lncPSCA, as a novel tumor suppressor whose expression is fine-regulated by a gastric cancer risk-associated genetic variant. The rs2978980 T > G change in an intronic enhancer of lncPSCA interrupts binding of transcription factor RORA, which down-regulates lncPSCA expression in an allele-specific manner. LncPSCA interacts with DDX5 and promotes DDX5 degradation through ubiquitination. Increased expression of lncPSCA results in low levels of DDX5, less RNA polymerase II (Pol II) binding with DDX5 in the nucleus, thus activating transcription of multiple p53 signaling genes by Pol II. These findings highlight the importance of functionally annotating lncRNAs in GWAS risk loci and the great potential of modulating lncRNAs as innovative cancer therapy.

7.
Cancer Med ; 10(18): 6291-6303, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34390218

RESUMEN

BACKGROUND: Many tools have been developed to predict the efficacy of immunotherapy, such as lung immune prognostic index (LIPI), EPSILoN [Eastern Cooperative Oncology Group performance status (ECOG PS), smoking, liver metastases, lactate dehydrogenase (LDH), neutrophil-to-lymphocyte ratio (NLR)], and modified lung immune predictive index (mLIPI) scores. The aim of this study was to determine the ability of three predictive scores to predict the outcomes in Chinese advanced non-small cell lung cancer (aNSCLC) patients treated with immune checkpoint inhibitors (ICIs). METHODS: We retrospectively analyzed 429 patients with aNSCLC treated with ICIs at our institution. The predictive ability of these models was evaluated using area under the curve (AUC) in receiver operating characteristic curve (ROC) analysis. Calibration was assessed using the Hosmer-Lemeshow test (H-L test) and Spearman's correlation coefficient. Progression-free survival (PFS) and overall survival (OS) curves were generated using the Kaplan-Meier method. RESULTS: The AUC values of LIPI, mLIPI, and EPSILoN scores predicting PFS at 6 months were 0.642 [95% confidence interval (CI):0.590-0.694], 0.720 (95% CI: 0.675-0.762), and 0.633 (95% CI: 0.585-0.679), respectively (p < 0.001 for all models). The AUC values of LIPI, mLIPI, and EPSILON scores predicting objective response rate (ORR) were 0.606 (95% CI: 0.546-0.665), 0.683 (95% CI: 0.637-0.727), and 0.666 (95% CI: 0.620-0.711), respectively (p < 0.001 for all models). The C-indexes of LIPI, mLIPI, and EPSILoN scores for PFS were 0.627 (95% CI 0.611-6.643), 0.677 (95% CI 0.652-0.682), and 0.631 (95% CI 0.617-0.645), respectively. CONCLUSIONS: As mLIPI scores had the highest accuracy when used to predict the outcomes in Chinese aNSCLC patients, this tool could be used to guide clinical immunotherapy decision-making.

8.
Chin Med J (Engl) ; 134(17): 2066-2072, 2021 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-34435978

RESUMEN

BACKGROUND: The mortality rate among patients with nasopharyngeal carcinoma (NPC) has improved significantly with the advent of chemoradiotherapy strategies. However, distant metastasis remains problematic. Tumor-specific reactivity in cancer patients has been detected exclusively in CD39+ T cells, particularly in CD39+CD103+ T cells. Circulating cancer-specific T cells are important for protecting against metastasis. This study aimed to evaluate the predictive value of circulating CD39+CD8+ T cells for metastasis in patients with NPC. METHODS: We performed a cross-sectional, longitudinal study of 55 patients with newly diagnosed NPC of stage III-IVa. All patients were initially treated with standard combined chemoradiotherapy. Blood samples were obtained from 24 patients before and at 1 month and 6 months after treatment. T cell expression of CD39 and CD103, together with the markers of T cell exhaustion programmed death-1 (PD-1)/T cell immunoglobulin and mucin domain-containing protein 3 (Tim-3) and markers of cell differentiation CD27/CC-chemokine receptor 7/CD45RA, was examined by flow cytometry. The Wilcoxon rank-sum test analysis was used to analyze the differences between two groups. Kaplan-Meier analysis was used for analysis of progression-free survival (PFS). RESULTS: The expression of circulating CD39+CD8+ and CD39+CD103+ CD8+ T cells was significantly higher in patients without distant metastasis (CD39+CD8+: 6.52% [1.24%, 12.58%] vs. 2.41% [0.58%, 5.31%], Z=-2.073, P=0.038 and CD39+CD103+CD8+: 0.72% [0.26%, 2.05%] vs. 0.26% [0.12%, 0.64%], Z=-2.313, P = 0.021). Most CD39+ T cells did not express PD-1 or Tim-3. Patients with high expression of CD39+CD103+CD8+ T cells had better PFS than patients with low expression (log rank value = 4.854, P = 0.028). CD39+CD8+ T cells were significantly elevated at 1-month post-treatment (10.02% [0.98%, 17.42%] vs. 5.91% [0.61%, 10.23%], Z = -2.943, P = 0.003). The percentage of advanced differentiated CD8+ T cells also increased at 1-month post-treatment compared with pre-treatment (33.10% [21.60%, 43.05%] vs. 21.00% [11.65%, 43.00%], Z = -2.155, P = 0.031). There was a significant correlation between elevated CD39+CD8+ T cells and increased effector memory T cells (intermediate stage: r = 0.469, P = 0.031; advanced stage: r = 0.508, P = 0.019). CONCLUSIONS: CD39+CD8+ circulating T cells have preserved effector function, contributing to an improved prognosis and a reduced risk of metastasis among NPC patients. These cells may thus be a useful predictive marker for a better prognosis in patients with NPC.


Asunto(s)
Linfocitos T CD8-positivos , Neoplasias Nasofaríngeas , Quimioradioterapia , Estudios Transversales , Humanos , Estudios Longitudinales , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/terapia , Pronóstico
9.
Sci Rep ; 11(1): 16794, 2021 Aug 18.
Artículo en Inglés | MEDLINE | ID: mdl-34408216

RESUMEN

Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer, but the prognosis of LUAD patients remains unsatisfactory. Here, we retrieved the RNA-seq data of LUAD cohort from The Cancer Genome Atlas (TCGA) database and then identified differentially expressed immune-related lncRNAs (DEirlncRNAs) between LUAD and normal controls. Based on a new method of cyclically single pairing along with a 0-or-1 matrix, we constructed a novel prognostic signature of 8 DEirlncRNA pairs in LUAD with no dependence upon specific expression levels of lncRNAs. This prognostic model exhibited significant power in distinguishing good or poor prognosis of LUAD patients and the values of the area under the curve (AUC) were all over 0.70 in 1, 3, 5 years receiver operating characteristic (ROC) curves. Moreover, the risk score of the model could serve as an independent prognostic factor for patients with LUAD. In addition, the risk model was significantly associated with clinicopathological characteristics, tumor-infiltrating immune cells, immune-related molecules and sensitivity of anti-tumor drugs. This novel signature of DEirlncRNA pairs in LUAD, which did not require specific expression levels of lncRNAs, might be used to guide the administration of patients with LUAD in clinical practice.

10.
Int J Biochem Cell Biol ; 138: 106040, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34246759

RESUMEN

Increased stemness is causally linked to development of drug resistance in cancers. JARID2 is a member of the Jumonji family of proteins and regulates differentiation of embryonic stem cells. However, the role of JARID2 in lung cancer stemness and drug resistance is still unclear. In this study, we investigated the expression of JARID2 in parental and cisplatin (CDDP) resistant non-small cell lung cancer (NSCLC) cells. The function of JARID2 in modulating CDDP sensitivity of NSCLC cells was determined. It was found that JARID2 is upregulated in CDDP resistant NSCLC cells, which depends on SOX2 expression. JARID2 overexpression promotes CDDP resistance in NSCLC cells, whereas JARID2 depletion restores CDDP sensitivity in CDDP resistant NSCLC cells. Moreover, JARID2 overexpression enhances cancer stem cell-like properties in NSCLC cells, which is coupled with increased expression of cancer stem cell markers. Mechanistically, JARID2-induced stemness and CDDP resistance is mediated by upregulation of Notch1. In clinical settings, high expression of JARID2 is significantly associated with advanced TNM stage, shorter overall survival, and poor chemotherapeutic response. These findings point toward an important role of JARID2 in CDDP resistance and stemness of NSCLC and provide a promising target for overcoming CDDP resistance.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/patología , Cisplatino/farmacología , Resistencia a Antineoplásicos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Células Madre Neoplásicas/patología , Complejo Represivo Polycomb 2/metabolismo , Receptor Notch1/metabolismo , Animales , Antineoplásicos/farmacología , Apoptosis , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Proliferación Celular , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Células Madre Neoplásicas/efectos de los fármacos , Complejo Represivo Polycomb 2/genética , Receptor Notch1/genética , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto
11.
Cancer Med ; 10(17): 6058-6069, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34254466

RESUMEN

OBJECTIVES: This study aims to explore the prevalence of sexual satisfaction among Chinese cancer survivors, and explore the association of sexual satisfaction with comorbidity and lifestyle factors. METHODS: A cross-sectional study was performed among 3996 Chinese cancer survivors recruited at Shanghai Cancer Rehabilitation Club from March to April 2017. Data were collected through self-reported questionnaires. The questionnaire includes information about demographic, cancer characteristics, comorbidities, lifestyle factors, and sexual satisfaction. Sexual satisfaction was measured by a single-item scale. The distribution of sexual satisfaction among different demographic and cancer characteristics was compared using the chi-squared test. Logistic regression models were conducted to assess the effects of lifestyle factors, comorbidities on sexual satisfaction after adjustment for demographic and cancer characteristics. RESULTS: More than 40% of male and female cancer survivors reported no sexual satisfaction. Sexual satisfaction of cancer survivors is significantly associated with both the number and the type of comorbidities. Heart disease, musculoskeletal system disease, diabetes, and hyperlipidemia are the comorbidities significantly associated with sexual satisfaction of cancer survivors. Lifestyle factors other than smoking, including exercise or fitness, drinking alcohol, and eating fruits and vegetables are significantly correlated with sexual satisfaction. Besides, all of the above associations show gender differences. In addition, demographic characteristics include sex, age, marital status, living status, and average monthly income are also significantly associated with sexual satisfaction of cancer survivors. CONCLUSION: Comorbidity and lifestyle factors are associated with sexual satisfaction of cancer survivors, and the associations show gender differences. Improving the lifestyles of cancer survivors, and controlling and reducing their comorbidities are important for improving their sexual satisfaction.

12.
Artículo en Inglés | MEDLINE | ID: mdl-34209159

RESUMEN

This study aimed to investigate prolonged screen time and using electronic devices before sleep and their associated factors in elderly people in Shaanxi province of China. We conducted a cross-sectional study among 2647 elderly participants aged 60-88 years. Data were collected through questionnaires. Demographic characteristics, screen time, using electronic devices before sleep, health status, lifestyles, sleep quality, and other associated factors were investigated. Logistic regression analysis was used to analyze the relationship between the associated factors of screen time and using electronic devices before sleep. The crude odds ratio (cOR) and adjusted odds ratio (aOR) and their 95% confidence intervals (CI) were calculated. A total of 1784 subjects completed the questionnaire. There were 6.89% participants with prolonged screen time and 13.45% using electronic devices before sleep frequently. Prolonged screen time was associated with personal monthly income (aOR = 1.205, p = 0.001), number of household residents (aOR = 0.860, p = 0.010), rural residents (aOR = 0.617, p = 0.038), and regular drinkers (aOR = 2.889, p < 0.001). Using electronic devices before sleep was associated with being female (aOR = 0.657, p = 0.007), family monthly income (aOR = 0.866, p = 0.002), being an occasional drinker (aOR = 1.891, p = 0.005), and self-reported sleep quality (aOR = 1.593, p = 0.007). In conclusion, several factors related to screen time or using electronic devices before sleep were identified. Only being a drinker was a common associated factor for both screen time and using electronic devices before sleep.


Asunto(s)
Tiempo de Pantalla , Sueño , Anciano , China/epidemiología , Estudios Transversales , Electrónica , Femenino , Humanos , Encuestas y Cuestionarios
13.
Cancer Lett ; 520: 91-99, 2021 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-34237407

RESUMEN

Despite advances in immunotherapy, extensive challenges remain in its clinical application. Positron emission tomography (PET)/computed tomography (CT) is widely used in the diagnosis and follow-up of malignant tumors and in the prediction of treatment outcomes. Successful cancer immunotherapy requires systemic immune activation. In addition to local immune responses, a systemic antitumor response involving primary and secondary lymphoid organs is required for tumor eradication. Immune-related adverse events (IRAEs) are considered to be a manifestation of excessive immune activation. PET/CT can monitor the metabolic changes in peripheral lymphoid organs and related organs. Thus, it can identify patients with effective immune activation and predict the efficacy and outcomes of immunotherapy. This review aimed to investigate the theoretical basis and feasibility of applying PET/CT for monitoring the immune activation status of peripheral lymphoid organs after immunotherapy and predict its effectiveness. Towards this goal, we reviewed the cellular components and structural composition of peripheral lymphoid organs, as well as their functions in the systemic immune response. We analyzed the theoretical basis and feasibility of applying PET/CT to monitor the immune activation status of peripheral lymphoid organs after immunotherapy to predict the effectiveness of immunotherapy.

14.
Cancer Lett ; 519: 150-160, 2021 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-34265397

RESUMEN

Calcium channel TRPV6 upregulation is associated with poor prognosis of breast cancer by promoting invasion and metastasis, and TRPV6 is a potential target for breast cancer therapy. However, the mechanism by which TRPV6 promotes breast metastasis remains unclear. Here, we report that TRPV6 expression is upregulated in metastatic breast cancers and that TRPV6 overexpression or upregulation accelerates primary breast cancer cell migration. In contrast, TRPV6 suppression decreases cell migration. Mechanistically, TRPV6 activates NFATC2 by increasing NFATC2IP phosphorylation at Ser204, and CDK5 is a candidate kinase that may perform this phosphorylation. Consequently, activated NFATC2 increases breast cancer metastasis by upregulating ADAMTS6 expression. These observations suggest that TRPV6 increases NFATC2 transcriptional activity by increasing NFATC2IP phosphorylation, which consequently upregulates ADAMTS6 expression to promote breast cancer metastasis.

15.
Radiother Oncol ; 162: 26-33, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34139210

RESUMEN

BACKGROUND: Effective dose to immune cell (EDIC), an estimated radiation dose to the circulating lymphocytes, is of significance for overall survival (OS) in non-small cell lung cancer. This study aimed to validate the EDIC's OS effect on limited-stage small cell lung cancer (LS-SCLC). METHOD AND MATERIALS: This study included LS-SCLC patients received definitive chemo-radiation in one single center from 2012 to 2017. All patients had multiple complete-blood-count tests including lymphocyte count at pre-, during- and end- radiotherapy. EDIC, computed according to doses of the lung, heart, and the total body, was assessed for its correlation with lymphocyte nadir, OS and progression free survival (PFS). RESULTS: Of 503 eligible patients, the mean EDIC was 7.34 Gy. The mean lymphocyte nadir was 0.48 × 109 cells/L, significantly lower than 1.65 × 109 cells/L at pre-radiotherapy (p < 0.001). EDIC was significantly correlated with lymphocyte nadir under both univariate (p < 0.001) and multivariable linear regression (p < 0.001). Multivariable analysis showed EDIC (HR = 0.1072, p = 0.005) and lymphocyte nadir (HR = 0.345, p = 0.003) were both significant for OS. EDIC was also significant for PFS (HR = 1.046, p = 0.026). The C-indexes of OS prediction were 0.593, 0.617, 0.676, and 0.684, for lymphocyte nadir alone, EDIC alone, combined lymphocyte nadir model, and combined EDIC model, respectively. CONCLUSIONS: This study demonstrated that EDIC is an independent predictor for lymphocyte nadir, PFS and OS. EDIC may serve as a predictor for lymphocyte nadir and a surrogate marker for OS in LS-SCLC. More attention should be paid to EDIC to decease the lymphocyte toxicity and improve survival.

16.
Radiat Oncol ; 16(1): 97, 2021 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-34098965

RESUMEN

INTRODUCTION: In this study, we performed a consecutive macropathologic analysis to assess microscopic extension (ME) in high-grade glioma (HGG) to determine appropriate clinical target volume (CTV) margins for radiotherapy. MATERIALS AND METHODS: The study included HGG patients with tumors located in non-functional areas, and supratotal resection was performed. The ME distance from the edge of the tumor to the microscopic tumor cells surrounding brain tissue was measured. Associations between the extent of ME and clinicopathological characteristics were evaluated by multivariate linear regression (MVLR) analysis. An ME predictive model was developed based on the MVLR model. RESULTS: Between June 2017 and July 2019, 652 pathologic slides obtained from 30 HGG patients were analyzed. The mean ME distance was 1.70 cm (range, 0.63 to 2.87 cm). The MVLR analysis identified that pathologic grade, subventricular zone (SVZ) contact and O6-methylguanine-DNA methyltransferase (MGMT) methylation, isocitrate dehydrogenase (IDH) mutation and 1p/19q co-deletion status were independent variables predicting ME (all P < 0.05). A multivariable prediction model was developed as follows: YME = 0.672 + 0.513XGrade + 0.380XSVZ + 0.439XMGMT + 0.320XIDH + 0.333X1p/19q. The R-square value of goodness of fit was 0.780. The receiver operating characteristic curve proved that the area under the curve was 0.964 (P < 0.001). CONCLUSION: ME was heterogeneously distributed across different grades of gliomas according to the tumor location and molecular marker status, which indicated that CTV delineation should be individualized. The model could predict the ME of HGG, which may help clinicians determine the CTV for individual patients. Trial registration The trial was registered with Chinese Clinical Trial Registry (ChiCTR2100046106). Registered 4 May 2021-Retrospectively registered.

17.
J Hematol Oncol ; 14(1): 92, 2021 06 12.
Artículo en Inglés | MEDLINE | ID: mdl-34118979

RESUMEN

Hypoxia inducible factor-1α (HIF-1α) up-regulates the expression of programmed death ligand-1 (PD-L1) in some extracranial malignancies. However, whether it could increase PD-L1 expression in intracranial tumor is still unknown. Here, we explored the relationship between HIF-1α and PD-L1 expression in glioma, and investigated their clinical significance. In glioma patients, HIF-1α and PD-L1 were overexpressed in high grade glioma tissues and were significantly associated with poor survival. In glioma cells, PD-L1 expression was induced under hypoxia condition, and the enhanced PD-L1 expression was abrogated by either HIF-1α knock-down or HIF-1α inhibitor treatment. Furthermore, ChIP-qPCR analysis showed the direct binding of HIF-1α to PD-L1 proximal promoter region, providing evidence that HIF-1α up-regulates PD-L1 in glioma. In glioma murine model, the combination treatment with HIF-1α inhibitor and anti-PD-L1 antibody caused a more pronounced suppressive effect on tumor growth compared to either monotherapy. Immunologically, the combination treatment improved both dendritic cell (DC) and CD8+ T cell activation. Overall, our results demonstrated that positive correlation between PD-L1 and HIF-1α in glioma, and provide an alternative strategy, inhibiting HIF-1α, as combination therapies with immunotherapies to advance glioma treatment.


Asunto(s)
Antígeno B7-H1/genética , Glioma/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Hipoxia Tumoral , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Humanos , Microambiente Tumoral
18.
Int J Radiat Oncol Biol Phys ; 111(2): 443-455, 2021 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-33974887

RESUMEN

PURPOSE: Our purpose was to construct a computed tomography (CT)-based delta-radiomics nomogram and corresponding risk classification system for individualized and accurate estimation of severe acute radiation pneumonitis (SARP) in patients with esophageal cancer (EC) after radiation therapy. METHODS AND MATERIALS: Four hundred patients with EC were enrolled from 2 independent institutions and were divided into the training (n = 200) and validation (n = 200) cohorts. Eight hundred fifty radiomics features of lung were extracted from treatment planning images, including the positioning CT before radiation therapy (CT1) and the resetting CT after receiving 40 to 45 Gy (CT2). The longitudinal net changes in radiomics features from CT1 to CT2 were calculated and defined as delta-radiomics features. Least absolute shrinkage and selection operator algorithm was performed to features selection and delta-radiomics signature building. Integrating the signature with multidimensional clinicopathologic, dosimetric, and hematological predictors of SARP, a novel CT-based delta-radiomics nomogram was established according to multivariate analysis. The clinical application values of nomogram were both evaluated in the training and validation cohorts by concordance index, calibration curves, and decision curve analysis. Recursive partitioning analysis was used to generate a risk classification system. RESULTS: The delta-radiomics signature consisting of 24 features was significantly associated with SARP status (P < .001). Incorporating it with other high-risk factors, Subjective Global Assessment score, pulmonary fibrosis score, mean lung dose, and systemic immune inflammation index, the developed delta-radiomics nomogram showed increased improvement in SARP discrimination accuracy with concordance index of 0.975 and 0.921 in the training and validation cohorts, respectively. Calibration curves and decision curve analysis confirmed the satisfactory clinical feasibility and utility of nomogram. The risk classification system displayed excellent performance on identifying SARP occurrence (P < .001). CONCLUSIONS: The delta-radiomics nomogram and risk classification system as low-cost and noninvasive means exhibited superior predictive accuracy and provided individualized probability of SARP stratification for patients with EC.


Asunto(s)
Neoplasias Esofágicas/radioterapia , Neumonitis por Radiación/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Anciano , Neoplasias Esofágicas/diagnóstico por imagen , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nomogramas , Dosificación Radioterapéutica , Estudios Retrospectivos
19.
BMC Cancer ; 21(1): 585, 2021 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-34022830

RESUMEN

BACKGROUND: Radiation-induced pneumonitis (RP) is a non-negligible and sometimes life-threatening complication among patients with thoracic radiation. We initially aimed to ascertain the predictive value of acute radiation-induced esophagitis (SARE, grade ≥ 2) to symptomatic RP (SRP, grade ≥ 2) among thoracic cancer patients receiving radiotherapy. Based on that, we established a novel nomogram model to provide individualized risk assessment for SRP. METHODS: Thoracic cancer patients who were treated with thoracic radiation from Jan 2018 to Jan 2019 in Shandong Cancer Hospital and Institute were enrolled prospectively. All patients were followed up during and after radiotherapy (RT) to observe the development of esophagitis as well as pneumonitis. Variables were analyzed by univariate and multivariate analysis using the logistic regression model, and a nomogram model was established to predict SRP by "R" version 3.6.0. RESULTS: A total of 123 patients were enrolled (64 esophageal cancer, 57 lung cancer and 2 mediastinal cancer) in this study prospectively. RP grades of 0, 1, 2, 3, 4 and 5 occurred in 29, 57, 31, 0, 3 and 3 patients, respectively. SRP appeared in 37 patients (30.1%). In univariate analysis, SARE was shown to be a significant predictive factor for SRP (P < 0.001), with the sensitivity 91.9% and the negative predictive value 93.5%. The incidence of SRP in different grades of ARE were as follows: Grade 0-1: 6.5%; Grade 2: 36.9%; Grade 3: 80.0%; Grade 4: 100%. Besides that, the dosimetric factors considering total lung mean dose, total lung V5, V20, ipsilateral lung mean dose, ipsilateral lung V5, and mean esophagus dose were correlated with SRP (all P < 0.05) by univariate analysis. The incidence of SRP was significantly higher in patients whose symptoms of RP appeared early. SARE, mean esophagus dose and ipsilateral mean lung dose were still significant in multivariate analysis, and they were included to build a predictive nomogram model for SRP. CONCLUSIONS: As an early index that can reflect the tissue's radiosensitivity visually, SARE can be used as a predictor for SRP in patients receiving thoracic radiation. And the nomogram containing SARE may be fully applied in future's clinical work.

20.
J Immunol Res ; 2021: 5531220, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34056008

RESUMEN

The nucleocapsid protein (NP) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contains immunogenic epitopes that can induce cytotoxic T lymphocyte (CTL) against viral infection. This makes the nucleocapsid protein a suitable candidate for developing a vaccine against SARS-CoV-2 infection. This article reports the intradermal delivery of NP antigen using dissolvable microneedle skin patches that could induce both significant B cell and T cell responses.


Asunto(s)
Anticuerpos Antivirales/sangre , Vacunas contra la COVID-19/inmunología , COVID-19/prevención & control , Proteínas de la Nucleocápside de Coronavirus/inmunología , SARS-CoV-2/inmunología , Linfocitos T Citotóxicos/inmunología , Animales , Linfocitos B/inmunología , Vacunas contra la COVID-19/administración & dosificación , Proteínas de la Nucleocápside de Coronavirus/administración & dosificación , Ensayo de Inmunoadsorción Enzimática , Inyecciones Intradérmicas/métodos , Ratones , Ratones Endogámicos BALB C , Fosfoproteínas/administración & dosificación , Fosfoproteínas/inmunología
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