scholarly journals Conversion Therapy of Intrahepatic Cholangiocarcinoma Is Associated with Improved Prognosis and Verified by a Case of Patient-Derived Organoid

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1179
Author(s):  
Zhiwei Wang ◽  
Yun Jin ◽  
Yinghao Guo ◽  
Zhenhua Tan ◽  
Xiaoxiao Zhang ◽  
...  
Keyword(s):  
Overall Survival ◽  
Intrahepatic Cholangiocarcinoma ◽  
Screening Tests ◽  
Conversion Therapy ◽  
Inhibitory Effects ◽  
Kaplan Meier ◽  
Whole Exome ◽  
Hematoxylin And Eosin ◽  
Hematoxylin And Eosin Staining ◽  
Immunohistological Staining

This study was performed to determine the efficacy of conversion therapy in intrahepatic cholangiocarcinoma (IHCC) and explore the feasibility of cancer organoid to direct the conversion therapy of IHCC. Patient data were retrospectively reviewed in this study and cancer organoids were established using tissues obtained from two patients. A total of 42 patients with IHCC received conversion therapy, 9 of whom were downstaged successfully, and another 157 patients were initially resectable. Kaplan–Meier curves showed that the successfully downstaged patients had a significantly improved overall survival compared to those in whom downstaging was unsuccessful (p = 0.017), and had a similar overall survival to that of initially resectable patients (p = 0.965). The IHCC organoid was successfully established from one of two obtained tissues. Routine hematoxylin and eosin staining and immunohistological staining found the organoid retained the histopathological characteristics of the original tissues. Whole exome sequencing results indicated the IHCC organoid retained appropriately 87% of the variants in the original tissue. Gemcitabine and paclitaxel exhibited the strongest inhibitory effects on the cancer organoid as determined using drug screening tests, consistent with the levels of efficacy observed in the patient from whom it was derived. This study indicates that conversion therapy could improve the survival of patients with IHCC despite its low success rate, and it may be directed by cancer organoids though this is merely a proof of feasibility.

scholarly journals Whole-exome Sequencing Analysis for Mutations Characteristics in Recurrent or Metastatic Gastrointestinal Stromal Tumors

2021 ◽  
Author(s):  
Lingquan Wang ◽  
Wei Xu ◽  
Wenjing Zhang ◽  
Zhentian Ni ◽  
Xufeng wang ◽  
...  
Keyword(s):  
Overall Survival ◽  
Survival Time ◽  
Primary Tumor ◽  
Tumor Resection ◽  
Metastatic Tumor ◽  
Tumor Evolution ◽  
Sequencing Analysis ◽  
Driver Genes ◽  
Kaplan Meier ◽  
Whole Exome

Abstract Background: Surgical resection for the metastasis and recurrence of GIST was controversial. It is increasingly important to identify clinical factors related with survival and explore the driver genes and mutations in GIST.Methods: GIST patients who received two surgery for primary and recurrent and/or metastatic tumors between January 2003 and December 2018 were reviewed. Primary outcome was overall survival after reoperation. Kaplan-Meier , Cox proportional hazard regressions, and mean survival time were used to evaluate outcomes. Paired PT(primary tumor), RMT(recurrent and/or metastatic tumor) and normal DNA was whole- exome sequenced to generate comparable data for those specific 8 GIST cases. Results: We identified 39 eligible patients with a median overall survival time of 56.7 months(IQR:9.6-190.3months). Regular TKI(Imatinib) after primary tumor resection (HR:0.568; 95% confidence interval(CI):0.211-0.874; P=0.043) was associated with better OS, while presence of liver metastasis were prognostic for worse OS(HR:1.45; 95% CI:1.13-2.02;P=0.032) for those GIST patients who received re-surgery due to recurrent and/or metastatic tumor. Compared with normal tissue, we detected mutation on MUC family both in 8 PT and 7 RMT among the 8 patients. Only in irregular(TKI) group, the KIT mutations between PT and RMT contain correlations and differences, while its influence exist less on other cases. We also found that 31 genes which were direct correlation with coding regions may associated with RMT. We attained that the Spatial heterogeneity and temporal heterogeneity of the tumor reflected on mutation signature and subclone.Conclusions: The MUC mutations were supposed to be a potential predict to recurrent and/or metastatic GIST. The treatment of TKI could influence the KIT mutations on RMT of GIST. As the heterogeneity exist in PT and RMT, the direction of tumor evolution and progression were not stable and regular.

The Expression of FAT1 is Associated with Overall Survival in Children with Medulloblastoma

2016 ◽  
Vol 103 (1) ◽  
pp. 44-52 ◽  
Author(s):  
Jianzhong Yu ◽  
Hao Li
Keyword(s):  
Overall Survival ◽  
Protein Expression ◽  
Wnt Signaling ◽  
Mrna Expression ◽  
Wnt Signaling Pathway ◽  
Rank Test ◽  
Missense Mutations ◽  
Kaplan Meier ◽  
Whole Exome ◽  
Mrna And Protein Expression

Purpose The FAT1 gene is involved in some cancers; however, its role in medulloblastoma is less clear. This study investigated the effects of FAT1 expression on the prognosis of medulloblastoma patients. Methods Whole exome sequencing was undertaken in 40 medulloblastoma patient samples. FAT1 mRNA and protein expression levels in normal and brain tumor tissues were determined by fluorescence quantitative PCR and immunohistochemistry, respectively. The association of FAT1 expression with overall survival (OS) was examined by Kaplan-Meier curve analysis with a log-rank test. Following lentiviral-mediated FAT1 knockdown using shRNA in Daoy cells, proliferation, Wnt signaling, and β-catenin protein expression were determined. Results Eight FAT1 missense mutations were detected in 7 patients. FAT1 mRNA expression in tumors was significantly lower than in adjacent normal tissue ( p = 0.043). The OS of patients with high FAT1 protein expression was significantly longer than that of patients with low FAT1 protein expression (median survival time: 24.3 vs 4.8 months, respectively; p = 0.002). shFAT1 cells had significantly higher proliferation rates than shControl cells ( p≤0.028). Furthermore, the mRNA expression of LEF1, β-catenin, and cyclin D1 was significantly upregulated in shFAT1-Daoy cells ( p≤0.018). Conclusions Low FAT1 expression was associated with poor prognosis in children with medulloblastoma. Furthermore, FAT1 may act on Wnt signaling pathway to exert its antitumor effect.

Overall survival and resection margin after hepatectomy for intrahepatic cholangiocarcinoma at academic cancer centers versus community cancer centers.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 339-339
Author(s):  
Nicholas Gerard Berger ◽  
Abdulrahman Y Hammad ◽  
John Thomas Miura ◽  
Fabian McCartney Johnston ◽  
Kathleen K. Christians ◽  
...  
Keyword(s):  
Overall Survival ◽  
Intrahepatic Cholangiocarcinoma ◽  
Survival Rates ◽  
Margin Status ◽  
Disease Stage ◽  
Resection Margins ◽  
R0 Resection ◽  
Readmission Rates ◽  
Cancer Centers ◽  
Kaplan Meier

339 Background: Margin status is an important prognostic factor of survival following hepatectomy for intrahepatic cholangiocarcinoma (ICC). R0 resection for ICC correlates with improved recurrence-free survival and overall survival (OS). The present study hypothesized that surgical resection margins and survival rates vary between centers. Methods: Patients with ICC undergoing hepatectomy were identified from the National Cancer Database (1998-2011). Treating centers were categorized as Academic Cancer Centers (ACC), and Community Cancer Centers (CCC). Rates of R0 vs. R1/2 resection were examined. OS was analyzed by Kaplan-Meier method, and Cox multivariate modeling identified independent predictors of survival. Results: A total of 2,774 patients were identified. Hepatectomy was most often performed at ACC compared to CCC: 1,928 (69.5%) vs. 846 (30.5%). Hepatectomy at ACC was associated with higher rates of R0 resections compared to CCC (72.5% vs. 68.1%, p= 0.018). Higher 30-day readmission rates were seen following hepatectomy at ACC (9.9% vs. 5.7%, p= 0.002). Improved median OS was seen in ACC across all stages (25.8 months vs. 20.1 months; p< 0.001). After adjusting for age, sex, ethnicity, cirrhosis, alpha-feto protein level, comorbidity, disease stage, and margin status, hepatectomy at ACC was independently associated with improved OS (Hazards ratio: 0.79 [95%CI 0.62-0.99, p= 0.046]). Conclusions: ACC have higher rates of negative resection margins for ICC, but higher readmission rates following surgery. Survival is higher at ACC compared to CCC, suggesting that site of care plays a role in patient outcomes.

Presence and significance of NK cells in glioblastomas

1989 ◽  
Vol 70 (5) ◽  
pp. 728-731 ◽  
Author(s):  
Jesús Vaquero ◽  
Santiago Coca ◽  
Santiago Oya ◽  
Roberto Martínez ◽  
Josefa Ramiro ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Nk Cells ◽  
Survival Time ◽  
Tumor Cells ◽  
Lymphocytic Infiltration ◽  
Surface Marker ◽  
Content Type ◽  
Hematoxylin And Eosin ◽  
Hematoxylin And Eosin Staining ◽  
Fine Print

✓ A monoclonal antibody against the surface marker IOT-10 of natural killer (NK) cells was used to investigate the presence of these cells in a series of 25 glioblastomas. In 40% of the tumors, IOT-10-positive NK cells were found in small numbers scattered among the tumor cells. The presence of IOT-10-positive NK cells was not related to the degree of lymphocytic infiltration in the tumor as demonstrated by hematoxylin and eosin staining, nor did it appear to influence the survival time of the patients studied.

Higher CD1a Levels Correlate with PD-L1 Expression and Predict Worse Overall Survival in Triple-Negative Breast Carcinoma

Breast Care ◽  
2021 ◽  
pp. 1-9
Author(s):  
Jian Zheng ◽  
Yuntao Wei ◽  
Xiaoxi Li ◽  
Zhan Shen ◽  
Yong Zhang ◽  
...  
Keyword(s):  
Overall Survival ◽  
Dendritic Cells ◽  
Lymph Node ◽  
Breast Carcinoma ◽  
Triple Negative ◽  
Carcinoma Tissue ◽  
Kaplan Meier ◽  
Immature Dendritic Cells ◽  
Triple Negative Breast Carcinoma ◽  
High Median

Objective: The aim of this study was to measure the expression of PD-L1, CD1a (a marker for immature dendritic cells), and CD83 (a marker for mature dendritic cells) and further examine the associations of PD-L1, CD83, and CD1a with overall survival (OS) in triple-negative breast carcinoma patients. Methods: PD-L1, CD1a, and CD83 expression in breast carcinoma tissues and CD83 expression in lymph node tissues were examined by immunohistochemistry and tissue microarray in 159 patients. Patients were classified into the low, medium, and high PD-L1, CD1a, and CD83 levels. Pearson χ2 test was used to analyze the correlations between PD-L1, CD1a, and CD83. The Kaplan-Meier method was used to calculate the OS. Multivariate analysis was used to identify determinants of 3- and 5-year OS. Results: 25.1, 25.8, and 49.1% of the patients had low, medium, and high PD-L1 levels, respectively. PD-L1 levels significantly correlated with CD1a (r = 0.30409, p < 0.001) and CD83 levels (r = 0.6146, p < 0.001) in breast carcinoma tissue, as well as CD83 levels (r = 0.17508, p = 0.027) in lymph node. The median OS was 83 months (range 12–106), and the 3- and 5-year OS rates were 94.97% (95% CI 91.57–98.37) and 86.79% (95% CI 81.53–92.06), respectively. Moreover, patients with high median CD1a levels had a significantly lower 5-year OS rate (75.6%) than those with low median CD1a levels (93.5%, p = 0.038). Conclusion: PD-L1, CD1a, and CD83 are variably expressed in triple-negative breast carcinoma tissues, and PD-L1 expression correlates with CD1a and CD83. Higher CD1a levels correlate with PD-L1 expression and predict worse OS in triple-negative breast carcinoma.

scholarly journals Complement C9 expression is associated with damaged myocardial cells in pediatric sudden death cases of fulminant myocarditis

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Akari Takaya Uno ◽  
Masahito Hitosugi ◽  
Mami Nakamura ◽  
Tomoyuki Nakanishi ◽  
Takahiro Mima ◽  
...  
Keyword(s):  
Sudden Death ◽  
Acute Myocarditis ◽  
Lymphocytic Infiltration ◽  
Pericardial Fluid ◽  
Sirtuin 1 ◽  
Fulminant Myocarditis ◽  
Myocardial Cells ◽  
Hematoxylin And Eosin ◽  
Hematoxylin And Eosin Staining ◽  
Complement C9

Abstract Background Because disease progression is so fast in sudden death of acute fulminant myocarditis, damage of myocardial cells is not evident in routine hematoxylin and eosin staining. To understand damage to myocardial cells and the mechanism of sudden death, immunohistochemical staining was performed for two forensic autopsy cases. Case presentation The patients were a healthy 5-year-old girl and 8-year-old boy. They suddenly died within 2 days of appearance of flu-like symptoms. An autopsy showed accumulation of yellowish-clear pericardial fluid containing fibrin deposits, fluid blood in the heart, and congestion of visceral organs. Histologically, minor necrosis or degeneration of myocardial cells with mainly lymphocytic infiltration was observed sometimes in tissue sections. Immunohistochemically, positive complement C9 staining and negative sirtuin 1 staining were found. These findings suggested wide damage of myocardial cells, even in regions with no marked changes in myocardial cells with hematoxylin and eosin staining. These areas corresponded to those with strong accumulation of lymphocytes. Conclusions Immunohistochemistry for complement C9 and sirtuin 1 might become a new tool for evaluating damage of myocardial cells of fulminant acute myocarditis.

scholarly journals Comprehensive analysis of genomic mutation signature and tumor mutation burden for prognosis of intrahepatic cholangiocarcinoma

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Rui Zhang ◽  
Qi Li ◽  
Jialu Fu ◽  
Zhechuan Jin ◽  
Jingbo Su ◽  
...  
Keyword(s):  
Intrahepatic Cholangiocarcinoma ◽  
Cox Regression ◽  
Tnm Stage ◽  
Gene Set Enrichment Analysis ◽  
Functional Enrichment ◽  
Tumor Mutation Burden ◽  
Kaplan Meier ◽  
Mutation Burden ◽  
Significant Difference ◽  
Genomic Mutation

Abstract Background Intrahepatic cholangiocarcinoma (iCCA) is a highly lethal malignancy of the biliary tract. Analysis of somatic mutational profiling can reveal new prognostic markers and actionable treatment targets. In this study, we explored the utility of genomic mutation signature and tumor mutation burden (TMB) in predicting prognosis in iCCA patients. Methods Whole-exome sequencing and corresponding clinical data were collected from the ICGC portal and cBioPortal database to detect the prognostic mutated genes and determine TMB values. To identify the hub prognostic mutant signature, we used Cox regression and Lasso feature selection. Mutation-related signature (MRS) was constructed using multivariate Cox regression. The predictive performances of MRS and TMB were assessed using Kaplan–Meier (KM) analysis and receiver operating characteristic (ROC). We performed a functional enrichment pathway analysis using gene set enrichment analysis (GSEA) for mutated genes. Based on the MRS, TMB, and the TNM stage, a nomogram was constructed to visualize prognosis in iCCA patients. Results The mutation landscape illustrated distributions of mutation frequencies and types in iCCA, and generated a list of most frequently mutated genes (such as Tp53, KRAS, ARID1A, and IDH1). Thirty-two mutated genes associated with overall survival (OS) were identified in iCCA patients. We obtained a six-gene signature using the Lasso and Cox method. AUCs for the MRS in the prediction of 1-, 3-, and 5-year OS were 0.759, 0.732, and 0.728, respectively. Kaplan–Meier analysis showed a significant difference in prognosis for patients with iCCA having a high and low MRS score (P < 0.001). GSEA was used to show that several signaling pathways, including MAPK, PI3K-AKT, and proteoglycan, were involved in cancer. Conversely, survival analysis indicated that TMB was significantly associated with prognosis. GSEA indicated that samples with high MRS or TMB also showed an upregulated expression of pathways involved in tumor signaling and the immune response. Finally, the predictive nomogram (that included MRS, TMB, and the TNM stage) demonstrated satisfactory performance in predicting survival in patients with iCCA. Conclusions Mutation-related signature and TMB were associated with prognosis in patients with iCCA. Our study provides a valuable prognostic predictor for determining outcomes in patients with iCCA.

scholarly journals Predicted CD4+ T cell infiltration levels could indicate better overall survival in sarcoma patients

2021 ◽  
Vol 49 (1) ◽  
pp. 030006052098153
Author(s):  
Qing Bi ◽  
Yang Liu ◽  
Tao Yuan ◽  
Huizhen Wang ◽  
Bin Li ◽  
...  
Keyword(s):  
Overall Survival ◽  
T Cell ◽  
Survival Data ◽  
Tumor Infiltrating Lymphocytes ◽  
The Cancer Genome Atlas ◽  
Cell Infiltration ◽  
T Cell Infiltration ◽  
Whole Exome ◽  
Cancer Genome Atlas ◽  
Infiltrating Lymphocytes

Objective The role of tumor-infiltrating lymphocytes (TILs) has not yet been characterized in sarcomas. The aim of this bioinformatics study was to explore the effect of TILs on sarcoma survival and genome alterations. Methods Whole-exome sequencing, transcriptome sequencing, and survival data of sarcoma were obtained from The Cancer Genome Atlas. Immune infiltration scores were calculated using the Tumor Immune Estimation Resource. Potential associations between abundance of infiltrating TILs and survival or genome alterations were examined. Results Levels of CD4+ T cell infiltration were associated with overall survival of patients with pan-sarcomas, and higher CD4+ T cell infiltration levels were associated with better survival. Somatic copy number alterations, rather than mutations, were found to correlate with CD4+ T cell infiltration levels. Conclusions This data mining study indicated that CD4+ T cell infiltration levels predicted from RNA sequencing could predict sarcoma prognosis, and higher levels of CD4+ T cells infiltration indicated a better chance of survival.

scholarly journals 18F-FDG PET/CT and Urothelial Carcinoma: Impact on Management and Prognosis—A Multicenter Retrospective Study

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 700 ◽  
Author(s):  
Fabio Zattoni ◽  
Elena Incerti ◽  
Fabrizio Dal Moro ◽  
Marco Moschini ◽  
Paolo Castellucci ◽  
...  
Keyword(s):  
Overall Survival ◽  
Urothelial Carcinoma ◽  
Fdg Pet ◽  
Patient Management ◽  
Survival Prediction ◽  
Primary Tumor Site ◽  
Kaplan Meier ◽  
Pet Ct ◽  
18F Fdg ◽  
Fdg Pet Ct

Objectives: To evaluate the ability of 18F-labeled fluoro-2-deoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) to predict survivorship of patients with bladder cancer (BC) and/or upper urinary tract carcinoma (UUTC). Materials: Data from patients who underwent FDG PET/CT for suspicion of recurrent urothelial carcinoma (UC) between 2007 and 2015 were retrospectively collected in a multicenter study. Disease management after the introduction of FDG PET/CT in the diagnostic algorithm was assessed in all patients. Kaplan-Meier and log-rank analysis were computed for survival assessment. A Cox regression analysis was used to identify predictors of recurrence and death, for BC, UUTC, and concomitant BC and UUTC. Results: Data from 286 patients were collected. Of these, 212 had a history of BC, 38 of UUTC and 36 of concomitant BC and UUTC. Patient management was changed in 114/286 (40%) UC patients with the inclusion of FDG PET/CT, particularly in those with BC, reaching 74% (n = 90/122). After a mean follow-up period of 21 months (Interquartile range: 4–28 mo.), 136 patients (47.4%) had recurrence/progression of disease. Moreover, 131 subjects (45.6%) died. At Kaplan-Meier analyses, patients with BC and positive PET/CT had a worse overall survival than those with a negative scan (log-rank < 0.001). Furthermore, a negative PET/CT scan was associated with a lower recurrence rate than a positive examination, independently from the primary tumor site. At multivariate analysis, in patients with BC and UUTC, a positive FDG PET/CT resulted an independent predictor of disease-free and overall survival (p < 0,01). Conclusions: FDG PET/CT has the potential to change patient management, particularly for patients with BC. Furthermore, it can be considered a valid survival prediction tool after primary treatment in patients with recurrent UC. However, a firm recommendation cannot be made yet. Further prospective studies are necessary to confirm our findings.

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