establishment-simple-effective-rat-model-for-intraoperative

Establishment of a Simple and Effective Rat Model for Intraoperative Parathyroid Gland Imaging

Parathyroid gland (PG) identification is a critical unmet need in thyroidectomy. The identification of the PG is challenging in thyroid surgery as it is ...

Zhejiang Cancer Hospital

The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)

Nomogram has demonstrated its capability in individualized estimates of survival in diverse cancers. Here we retrospectively investigated 1195 patients with esophageal squamous-cell carcinoma (ESCC) who underwent radical esophagectomy at Zhejiang Cancer Hospital in Hangzhou, China. We randomly assigned two-thirds of the patients to a training cohort (n = 797) and one-third to a validation cohort (n = 398). Cox proportional hazards regression analyses were performed using the training cohort, and a nomogram was developed for predicting 3-year and 5-year overall survival rates. Multivariate analysis identified tumor length, surgical approach, number of examined lymph node, number of positive lymph node, extent of positive lymph node, grade, and depth of invasion as independent risk factors for survival. The discriminative ability of the nomogram was externally determined using the validation cohort, showing that the nomogram exhibited a sufficient level of discrimination according to the C-index (0.715, 95% CI 0.671-0.759). The C-index of the nomogram was significantly higher than that of the sixth edition (0.664, P-value < 0.0001) and the seventh edition (0.696, P-value < 0.0003) of the TNM classification. This study developed the first nomogram for ESCC, which can be applied in daily clinical practice for individualized survival prediction.

Prognostic Nomogram for Thoracic Esophageal Squamous Cell Carcinoma after Radical Esophagectomy.

Brain metastasis is a major cause leading to the failure of treatment management for non-small cell lung cancer (NSCLC) patients. The goal of this study was to establish an effective nomogram for prediction of brain metastases of resected NSCLC patients.

A Nomogram to Predict Brain Metastases of Resected Non-Small Cell Lung Cancer Patients.

We explored the influence of body mass index (BMI) on long-term outcomes in patients with esophageal squamous cell carcinoma (ESCC) who underwent esophagectomy as a primary treatment. BMI is a risk factor for development of esophageal cancer. However, the details of the relationship between BMI and cancer prognosis remains unclear. Patients who underwent esophagectomy as an initial treatment in 2000 to 2009 period were included. The patients were divided into 3 groups according to Asian-specific BMI cut-offs. The associations between BMI and long-term outcomes were explored. This study included 1082 ESCC patients between 2000 and 2009; all the patients underwent esophagectomy. The median overall survival (OS) of the BMI <18.5, 18.5 ≤ BMI <23, and BMI ≥23 kg/m groups were 21, 24, and 29.5 months, respectively; they differed significantly (P = 0.005). The 5-year survival rates of the 3 groups were 24.6%, 30.4%, and 35.3%, respectively. Multivariate analysis showed that lower BMI was an independent risk factor for a shorter OS (18.5 ≤ BMI <23 kg/m vs. BMI ≥23 kg/m, hazard ratio [HR] = 1.18; 95% confidence interval [CI] = 1.00-1.40, P = 0.054, BMI <18.5 kg/m vs. BMI ≥23 kg/m, HR = 1.38; 95% CI = 1.09-1.75, P = 0.007). The better OS of the BMI ≥23 kg/m patients remained statistically significant in never-smoking patients (P < 0.05). In conclusion, patients with BMIs ≥23 kg/m experienced better OS, and multivariate analysis further indicated that BMI ≥23 kg/m was an independent predictor of survival. When stratified by smoking status, BMI ≥23 kg/m was still a factor in better OS among never smokers. 

Influence of body mass index on the long-term outcomes of patients with esophageal squamous cell carcinoma who underwent esophagectomy as a primary treatment: A 10-year medical experience.

MicroRNAs (miRNAs) are important gene regulators that play key roles in tumor genesis. In this study, we investigate the role of miR-148a in the development of papillary thyroid cancer (PTC). Data from the cancer genome atlas (TCGA) indicate that miR-148a is downregulated in PTC tissues; we also find that miR-148a is downregulated in tissue samples from PTC patients and PTC cell lines. Overexpression of miR-148a significantly suppresses PTC cell proliferation, migration and invasiveness , and inhibits tumor growth  as well. We have identified the cyclin-dependent kinase 8 (CDK8) gene as a direct target of miR-148a using the online software packages TargetScan and miRanda. Overexpression of miR-148a significantly represses  expression by directly targeting the 3'-untranslated region (3'-UTR) of the  gene in PTC tissues and cell lines; overexpression of  reverses the inhibitory effects of miR-148a on PTC cell growth, migration and invasiveness. Taken together, our results indicate that miR-148a functions as a tumor suppressor in PTC by repressing  expression.

Downregulation of cyclin-dependent kinase 8 by microRNA-148a suppresses proliferation and invasiveness of papillary thyroid carcinomas.

This study aimed to assess the predictive factor of multifocality to identify patients at high risk of central lymph node metastasis (CLNM).

Multifocality is associated with central neck lymph node metastases in papillary thyroid microcarcinoma.

 This study aimed to investigate the feasibility of utilizing CytoSorter® system to detect circulating tumor cells (CTCs) and clinical value of CTCs in patients with locally advanced head and neck squamous cell carcinoma (LAHNSCC).  31 patients with LAHNSCC, 12 healthy volunteers, and 6 patients with benign tumor serving as controls were enrolled in this study. CTCs were enriched with the CytoSorter®, a microfluidic based immune capture system. CTC detection was performed before and after induction chemotherapy, as well as after surgery and/or radiotherapy. Correlations between CTC enumerations at different time points and survival outcome and recurrence risk were evaluated. The correlation between CTCs and clinicopathological characteristics was appraised. Follow-up of patients continued until March 2019.  While CTCs were not found in the controls, they were detected in 24 of 31 LAHNSCC patients. CTCs could be used to distinguish diseased people from the healthy (<0.0001). CTCs were statistically associated with patient age (=0.037, >60 years old vs<60 years old) and lymph node metastasis (= 0.034, N0N1 VS N2N3). Most patients had significantly reduced CTCs at the end of treatment. Patients with partial remission of tumor after induction therapy had more CTCs than those with complete remission of tumor. Patients with higher CTCs counts prior to treatment had higher chance of developing local recurrence of tumor after treatment (=0.0187).  CTCs were successfully isolated in LAHNSCC patients using CytoSorter® system with better sensibility. CTCs can be used to differentiate LAHNSCC patients from those with benign HNSCC tumor or healthy volunteers, and as markers to monitor patient's response to treatment and predict the local tumor recurrence after treatment. CTC detection at baseline has the greatest prognostic potency in LAHNSCC patients.

Evaluation of therapeutic efficacy with CytoSorter circulating tumor cell-capture system in patients with locally advanced head and neck squamous cell carcinoma.

This study aimed to explore the effects of miR-345-5p on papillary thyroid carcinoma (PTC) and uncover the possible mechanisms.

MiR-345-5p inhibits tumorigenesis of papillary thyroid carcinoma by targeting SETD7.

This study aims to explore the predictive factors of central lymph node metastasis (CLNM) in patients with papillary thyroid microcarcinoma (PTMC) without capsule invasion.

The relationship between central lymph node metastasis and the distance from tumor to thyroid capsule in papillary thyroid microcarcinoma without capsule invasion.

Minimally invasive testing for early detection of lung cancer to improve patient survival is a major unmet clinical need. This study aimed to develop and validate a serum multi-microRNA (multimiR) panel as a minimally invasive test for early detection of nonsmall cell lung cancer (NSCLC) regardless of smoking status, gender, and ethnicity. Our study included 744 NSCLC cases and 944 matched controls, including smokers and nonsmokers, male and female, with Asian and Caucasian subjects. Using RT-qPCR and a tightly controlled workflow, we quantified the absolute expression of 520 circulating microRNAs (miRNAs) in a Chinese cohort of 180 early stage NSCLC cases and 216 healthy controls (male smokers). Candidate biomarkers were verified in two case-control cohorts of 432 Chinese and 218 Caucasians, respectively (including females and nonsmokers). A multimiR panel for NSCLC detection was developed using a twofold cross-validation and validated in three additional Asian cohorts comprising 642 subjects. We discovered 35 candidate miRNA biomarkers, verified 22 of them, and developed a five-miR panel that detected NSCLC with area under curve (AUC) of 0.936-0.984 in the discovery and verification cohorts. The panel was validated in three independent cohorts with AUCs of 0.973, 0.916, and 0.917. The sensitivity of five-miR test was 81.3% for all stages, 82.9% for stages I and II, and 83.0% for stage I NSCLC, when the specificity is at 90.7%. We developed a minimally invasive five-miR serum test for detecting early stage NSCLC and validated its performance in multiple patient cohorts independent of smoking status, gender, and ethnicity.

Development of a serum miRNA panel for detection of early stage non-small cell lung cancer.

Ecto-5'-nucleotidase (cluster of differentiation 73/CD73) is an ectonucleotidase that is being evaluated as a biomarker for the diagnosis and prognosis of various types of cancer. However, the clinicopathological relationship between CD73 expression in monocytic MDSCs (M-MDSCs) and polymorphonuclear MDSC (PMN-MDSCs) in head and neck squamous cell carcinomas (HNSCCs) is not clear. Understanding the phenotypic and functional characteristics of human CD73 MDSCs in the tumor microenvironment could help elucidate the roles of these cells in the ontogeny, spread, and treatment of solid cancer.

CD73 expression in myeloid-derived suppressor cells is correlated with clinical stages in head and neck squamous cell carcinomas.

Given its role in the regulation of calcium and PTH levels, vitamin D was presumed as a potential predictor of postoperative hypoparathyroidism. However, the reports about their association were controversial. This study aims to reveal the relationship between preoperative vitamin D and postoperative parathyroid hormone (PTH).

Weihui Zheng

Key Laboratory of Head & Neck Cancer Translational Research of Zhejiang Province

Zhejiang Cancer Hospital

Establishment of a Simple and Effective Rat Model for Intraoperative Parathyroid Gland Imaging