Development and reliability and validity test of the Fear of Cancer Scale (FOCS).

OBJECTIVE: To develop a Fear of Cancer Scale (FOCS) for non-cancer populations. METHODS: FOCS was developed by classical measurement theory. A total of 15 college students were invited to conduct semi-structured interviews. Seven experts were invited for expert consultation. A total of 2012 Chinese college students who had completed the electronic questionnaire on WJX.cn platform was included. The reliability and validity of FOCS were verified. Multiple linear regression analysis was adopted to explore the influencing factors of cancer fear among college students and further verify the validity of FOCS. RESULTS: There were 17 items in the FOCS, including two subscales - direct fear (8 items), and indirect fear (9 items). FOCS had good validity and reliability. Multiple linear regression showed that GAD-7 score, CSDS score, negative coping score, positive coping score, guardian's highest education, gender, life satisfaction, nationality and major were the influencing factors of cancer fear (p < .05). CONCLUSIONS: The 17-item FOCS was a reliable and valid measure to examine the level of cancer fear in non-cancer populations.

Upregulation of CCT3 predicts poor prognosis and promotes cell proliferation via inhibition of ferroptosis and activation of AKT signaling in lung adenocarcinoma.

BACKGROUND: Chaperonin containing TCP1 subunit 3 (CCT3) acts as an oncogene in cancers, whereas its role and underlying mechanisms in lung adenocarcinoma (LUAD) are poorly understood. This study investigated the clinical relevance and function of CCT3 in LUAD. METHODS: Clinical relevance of CCT3 in LUAD and lung squamous cell carcinoma (LUSC) was analyzed based on TCGA database. qRT-PCR and Western blot were used to detect mRNA and protein expression, respectively. CCK8 and colony formation were performed to measure cell viability. PI and PI/Annexin V-FITC assay kit was used to determine cell cycle and cell death, respectively. Luciferase activity was performed to check whether CCT3 regulated slc7a11's transcription activity. Ferroptosis was determined by incubating the cells with ferroptosis and apoptosis inducer, their inhibitor and autophagy inhibitor, followed by cell viability examination. RESULTS: We found that CCT3 was overexpressed in LUAD and LUSC tissues. Overexpression of CCT3 predicted the poor prognosis of LUAD patients. Loss-of-function and gain-of-function experiments demonstrated that CCT3 promoted the proliferation and colony formation of LUAD cells. In addition, CCT3 promoted cell cycle progression and suppressed slc7a11-mediated cell ferroptosis, but not apoptosis. We also found that CCT3 activated AKT. MK2206 significantly reduced the viability of CCT3 overexpressed LUAD cells, while had smaller inhibitory effect on the proliferation of control cells, suggesting that CCT3 dictates the sensitivity of LUAD cells to AKT inhibition. CONCLUSION: Our study demonstrates that CCT3 contributes to the proliferation and growth of LUAD cells through inhibition of ferroptosis and activation of AKT.

Development and validation of a computed tomography-based immune ecosystem diversity index as an imaging biomarker in non-small cell lung cancer.

OBJECTIVES: To date, there are no data on the noninvasive surrogate of intratumoural immune status that could be prognostic of survival outcomes in non-small cell lung cancer (NSCLC). We aimed to develop and validate the immune ecosystem diversity index (iEDI), an imaging biomarker, to indicate the intratumoural immune status in NSCLC. We further investigated the clinical relevance of the biomarker for survival prediction. METHODS: In this retrospective study, two independent NSCLC cohorts (Resec1, n = 149; Resec2, n = 97) were included to develop and validate the iEDI to classify the intratumoural immune status. Paraffin-embedded resected specimens in Resec1 and Resec2 were stained by immunohistochemistry, and the density percentiles of CD3+, CD4+, and CD8+ T cells to all cells were quantified to estimate intratumoural immune status. Then, EDI features were extracted using preoperative computed tomography to develop an imaging biomarker, called iEDI, to determine the immune status. The prognostic value of iEDI was investigated on NSCLC patients receiving surgical resection (Resec1; Resec2; internal cohort Resec3, n = 419; external cohort Resec4, n = 96; and TCIA cohort Resec5, n = 55). RESULTS: iEDI successfully classified immune status in Resec1 (AUC 0.771, 95% confidence interval [CI] 0.759-0.783; and 0.770 through internal validation) and Resec2 (0.669, 0.647-0.691). Patients with higher iEDI-score had longer overall survival (OS) in Resec3 (unadjusted hazard ratio 0.335, 95%CI 0.206-0.546, p < 0.001), Resec4 (0.199, 0.040-1.000, p < 0.001), and TCIA (0.303, 0.098-0.944, p = 0.001). CONCLUSIONS: iEDI is a non-invasive surrogate of intratumoural immune status and prognostic of OS for NSCLC patients receiving surgical resection. KEY POINTS: • Decoding tumour immune microenvironment enables advanced biomarkers identification. • Immune ecosystem diversity index characterises intratumoural immune status noninvasively. • Immune ecosystem diversity index is prognostic for NSCLC patients.

The Combination Therapy of Fluorouracil and Oxaliplatin Suppress the Progression of Colon Cancer Through miR-183-5p/SOCS3 Axis and Downregulating PD-L1.

PURPOSE: The purpose of this study was to investigate the mechanism of combination of fluorouracil (FU) and oxaliplatin (OXA) on the progression of colon cancer via miR-183-5p/SOCS3 axis and regulating PD-L1. METHODS: HCT116 cells were treated with 4 µM OXA and 10.5 µM FU, or exogenous regulation of the expression of miR-183-5p, SOCS3 and PD-L1 in HCT116 cells. CCK-8 assay was employed to detect cell viability of HCT116 cells. Flow cytometry was performed to assess the apoptosis and cell cycle. The expression level of SOCS3, PD-L1, chemokines (CCL1, CCL4 and CCL7) and immune escapes related proteins (EGFR, STARD1 and STARD3) in HCT116 cells were assessed by Western blotting. In addition, dual-luciferase reporter gene was carried out to verify the targeted relationship between miR-183-5p with SOCS3. RESULTS: Our study demonstrated that the combination of OXA and FU remarkably suppressed proliferation, promoted apoptosis and arrest cells in G0/G1 phrase of HCT116 cells, and observably downregulated the expression of PD-L1, CCL1, CCL4, CCL7, EGFR, STARD1 and STARD3. Meanwhile, the combination of OXA and FU significantly downregulated miR-183-5p expression. Knockdown of miR-183-5p also repressed the proliferation, promoted apoptosis and arrest cells in G0/G1 phrase of HCT116 cells, and downregulated the expression of PD-L1, CCL1, CCL4, CCL7, EGFR, STARD1 and STARD3. In addition, our study proved that miR-183-5p upregulated PD-L1 by targeting downregulated SOCS3 expression. Finally, we demonstrated that the combination therapy of OXA and FU inhibited the proliferation, promote apoptosis and arrest cells in G0/G1 phrase by downregulating PD-L1 via miR-183-5p/SOCS3 axis. CONCLUSION: The combination therapy of OXA and FU could suppress the malignant biological behavior, and the mechanism was realized by inhibiting PD-L1 through miR-183-5p/SOCS3 axis.

Immune Microenvironment: New Insight for Familial Adenomatous Polyposis.

Currently, the main treatment for familial adenomatous polyposis (FAP) is surgery, however, surgery is far from ideal as there are many complications such as uncontrollable bowel movements, pouch inflammation, anastomotic stricture, and secondary fibroids. Therefore, it is necessary to further expand the understanding of FAP and develop new treatments for FAP. The immune microenvironment including immune cells and cytokines, plays an important role in FAP and the progression of FAP to adenocarcinoma, thus it may be a promising treatment for FAP. In the current review, we summarized the recent progress in the immune microenvironment of FAP.

Development and validation of the cancer symptoms discrimination scale: a cross-sectional survey of students in Yunnan, China.

BACKGROUND: This study aimed to devise a Cancer symptoms Discrimination Scale (CSDS) suitable for China based on a cross-sectional survey. METHODS: The CSDS was developed using the classical measurement theory. A total of 3610 students from Yunnan province, China, participated in the cross-sectional survey. The test version of the scale was modified by the item analysis method, and after the official version of CSDS was developed, its reliability and validity were verified. A univariate analysis of variance and a multiple linear regression model were used to analyze the influencing factors of cancer symptoms discrimination among the university/college students. RESULTS: There were 21 items in total for the CSDS, including 3 subscales --- common clinical manifestations (11 items), physical appearance defects (6 items), and drainage tube(s) wearing (4 items). This CSDS had good validity (GFI = 0.930, AGFI = 0.905, RMR = 0.013, I-CVIs> 0.80, and the Pearson correlation coefficient was satisfactory.) and reliability (Cronbach's alpha = 0.862, spearman-brown coefficient = 0.875). The multiple linear regression showed that certain factors may affect the students' discrimination level against cancer symptoms (P < 0.05), including gender, major, current education degree, guardian's highest record of formal schooling, self-rated health status, history of care for cancer patients, family relationship, ways of cancer knowledge acquisition, good/poor understanding of cancer-related information, degree of cancer fear, and their perception of cancer infectiousness. CONCLUSION: This CSDS, with good reliability and validity, can be used for the evaluation of the discrimination risk and levels against cancer symptoms among healthy students.

Predictive Value of Postoperative Peripheral CD4+ T Cells Percentage in Stage I-III Colorectal Cancer: A Retrospective Multicenter Cohort Study of 1028 Subjects.

OBJECTIVE: Association of postoperative peripheral CD4+ T cells percentage and recurrence in colorectal cancer (CRC) remains to be explored. Therefore, we aimed to investigate the association between the postoperative peripheral CD4+ T cells percentage and recurrence in CRC patients. PATIENTS AND METHODS: Consecutive stage I-III CRC patients without neoadjuvant treatment undergoing curative resection from January 2010 to July 2016 were identified in two Chinese centers. The association between the postoperative CD4+ T cells percentage, measured within 12 weeks after surgery, and recurrence-free survival (RFS) was analyzed. RESULTS: A total of 1028 patients were identified (training set: 913 patients, validation set: 115 patients). In the training set, the 5-year RFS rate of the 441 patients with abnormal postoperative CD4+ T cells percentage was significantly lower than that of those with normal percentage (70.3% [95% CI 65.7-75.2%] vs 77.6% [95% CI 73.7-81.7%] and unadjusted hazard ratio [HR] 1.36 [95% CI 1.04-1.78], P=0.02). The result was confirmed in the validation set. Multivariable Cox regression analysis demonstrated that the association of postoperative CD4+ T cells percentage with 5-year RFS was independent both in the training and validation sets. In propensity score matching analysis, patients with normal postoperative CD4+ T cells percentage were found to have a favourable response to adjuvant chemotherapy (HR 0.29 [95% CI 0.12-0.72], P=0.008). CONCLUSION: Postoperative peripheral CD4+ T cells percentage is a predictive biomarker for RFS in patients with CRC, which can identify those who will benefit from adjuvant chemotherapy.

Hyperresponsiveness to interferon gamma exposure as a response mechanism to anti-PD-1 therapy in microsatellite instability colorectal cancer.

Colorectal cancer (CRC) with high-level microsatellite instability (MSI-H) tends to be associated with a better response to programmed death receptor-1 (PD-1) blockade than does microsatellite stable CRC. However, emerging evidence makes the use of programmed death ligand-1 (PD-L1) as a biomarker problematic. Here, we sought to characterize the interactions between PD-L1 expression and the response to PD-1 blockade therapy in BALB/c mice with a subcutaneous tumor challenge. We further focused on interferon gamma (IFNγ)-induced PD-L1 expression in an in vitro setting to evaluate the responsiveness to IFNγ exposure and the specific signaling of PD-1 in HCT116 and SW480 cell lines. In this study, enhanced PD-L1 expression increased survival in CT26 cells, and PD-1 blockade increased the CTL profile and apoptotic cells in mice with CRC. Our in vitro findings showed that PD-L1 expression was significantly upregulated by a low-dose IFNγ treatment, and the MSI-H cell line might exhibit hyperresponsiveness to IFNγ exposure partly through the JAK-STAT pathway. These results suggest that intrinsic PD-L1 in cooperation with extrinsic IFNγ exposure in CRC may be more responsive to anti-PD-1 therapy, mainly through the CTL profile in the tumor microenvironment.

Psychometric properties of the Chinese version of the Swanson, Nolan, and Pelham, version IV scale - parent form.

This study aimed to establish the psychometric properties of parent ratings on the Chinese version of the Swanson, Nolan, and Pelham IV scale (SNAP-IV) in a school-based sample of 3534 students in grades 1 to 8 from two cities and two suburbs in Taiwan and 189 children diagnosed with attention deficit/hyperactivity disorder (ADHD) (aged 6 to 15) consecutively recruited from a medical center in Taipei. Parents completed the Chinese versions of the SNAP-IV, Strengths and Difficulties Questionnaire, and Child Behavior Checklist. The Chinese SNAP-IV demonstrated similar three factor structure (Inattention, Hyperactivity/Impulsivity, and Oppositional) as its English version, and satisfactory test-retest reliability (intraclass correlation = 0.59 approximately 0.72), internal consistency (alpha = 0.88 approximately 0.90), concurrent validity (Pearson correlations = 0.56 approximately 0.72), and discriminant validity. Boys scored higher than girls across the eight school grade levels. The SNAP-IV clearly distinguished children with ADHD from school-based participants. Comorbidity with oppositional defiant disorder/conduct disorder predicted higher SNAP-IV scores among children with ADHD. Our findings suggest that the Chinese SNAP-IV is a reliable and valid instrument for rating ADHD-related symptoms in both clinical and community settings in Taiwan.