scholarly journals Mesenchymal tumor organoid models recapitulate rhabdomyosarcoma subtypes

2022 ◽  
Author(s):  
Michael T. Meister ◽  
Marian J. A. Groot Koerkamp ◽  
Terezinha de Souza ◽  
Willemijn B. Breunis ◽  
Ewa Frazer-Mendelewska ◽  
...  

Rhabdomyosarcomas (RMS) are mesenchyme-derived tumors and the most common childhood soft tissue sarcomas. Treatment is intense, with a nevertheless poor prognosis for high-risk patients. Discovery of new therapies would benefit from additional preclinical models. Here we describe the generation of a collection of pediatric RMS tumor organoid (tumoroid) models comprising all major subtypes. For aggressive tumors, tumoroid models can often be established within four to eight weeks, indicating the feasibility of personalized drug screening. Molecular, genetic and histological characterization show that the models closely resemble the original tumors, with genetic stability over extended culture periods of up to six months. Importantly, drug screening reflects established sensitivities and the models can be modified by CRISPR/Cas9 with TP53 knockout in an embryonal RMS model resulting in replicative stress drug sensitivity. Tumors of mesenchymal origin can therefore be used to generate organoid models, relevant for a variety of preclinical and clinical research questions.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Dejun Wu ◽  
Zhenhua Yin ◽  
Yisheng Ji ◽  
Lin Li ◽  
Yunxin Li ◽  
...  

AbstractLncRNAs play a pivotal role in tumorigenesis and development. However, the potential involvement of lncRNAs in colon adenocarcinoma (COAD) needs to be further explored. All the data used in this study were obtained from The Cancer Genome Atlas database, and all analyses were conducted using R software. Basing on the seven prognosis-related lncRNAs finally selected, we developed a prognosis-predicting model with powerful effectiveness (training cohort, 1 year: AUC = 0.70, 95% Cl = 0.57–0.78; 3 years: AUC = 0.71, 95% Cl = 0.6–0.8; 5 years: AUC = 0.76, 95% Cl = 0.66–0.87; validation cohort, 1 year: AUC = 0.70, 95% Cl = 0.58–0.8; 3 years: AUC = 0.73, 95% Cl = 0.63–0.82; 5 years: AUC = 0.68, 95% Cl = 0.5–0.85). The VEGF and Notch pathway were analyzed through GSEA analysis, and low immune and stromal scores were found in high-risk patients (immune score, cor =  − 0.15, P < 0.001; stromal score, cor =  − 0.18, P < 0.001) , which may partially explain the poor prognosis of patients in the high-risk group. We screened lncRNAs that are significantly associated with the survival of patients with COAD and possibly participate in autophagy regulation. This study may provide direction for future research.


2021 ◽  
Author(s):  
Axel Bengtsson ◽  
Roland Andersson ◽  
Jonas Rahm ◽  
Karthik Ganganna ◽  
Bodil Andersson ◽  
...  

Abstract Background Pancreatic ductal adenocarcinoma has the lowest survival rate among all major cancers and is the third leading cause of cancer-related mortality. The stagnant survival statistics and dismal response rates to current therapeutics highlight the need for more efficient preclinical models. Patient-derived organoids (PDOs) offer new possibilities as powerful preclinical models able to account for interpatient variability. Organoid development can be divided into four different key phases: establishment, propagation, drug screening and response prediction. Establishment entails tailored tissue extraction and growth protocols, propagation requires consistent multiplication and passaging, while drug screening and response prediction will benefit from shorter and more precise assays, and clear decision-making tools. Conclusions This review attempts to outline the most important challenges that remain in exploiting organoid platforms for drug discovery and clinical applications. Some of these challenges may be overcome by novel methods that are under investigation, such as 3D bioprinting systems, microfluidic systems, optical metabolic imaging and liquid handling robotics. We also propose an optimized organoid workflow inspired by all technical solutions we have presented.


2021 ◽  
Author(s):  
Wenming Bao ◽  
Liming Deng ◽  
haitao Yu ◽  
bangjie He ◽  
Zixia Lin ◽  
...  

Abstract Background Intrahepatic cholangiocarcinoma (ICC) is a malignant neoplasm with a poor prognosis. Prediction of prognosis is critical for the individualized clinical management of patients with ICC. The purpose of this study is to establish a nomogram based on the psoas muscle index (PMI) and prognostic nutritional index (PNI) to identify the high risk-patient with ICC after curative resection. Methods ICC Patients after hepatectomy in multi-hospital from August 2012 to October 2019 were enrolled. The overall survival (OS) and recurrence-free survival (RFS) rates were analyzed by Kaplan-Meier. The independent factors were identified by univariate and multivariate Cox regression analyses. A nomogram based on independent factors was established to predict ICC patient prognosis. Results 178 ICC patients were included. The OS was worst in the patients with a combination of low PMI combined low PNI (p < 0.01). PMI, PNI, lymph node metastasis and tumor differentiation were the independent prognostic risk factors; these factors were used to establish the nomogram was established by it. The calibration curve revealed that the nomogram survival probability prediction model was in good agreement with the actual observation results. The nomogram has good reliability in predicting ICC patient prognosis (OS C-index = 0.692). The area under the receiver operating characteristic curve (AUC) for the nomogram's 3-year predicted survival was 0.752. Based on the stratified by nomogram, the median survival for low-risk patients was 59.8 months, compared with 16.2 months for high-risk patients (p༜0.001). Conclusion The nomogram based on the PMI and PNI can identify patients with the highest risk of poor prognosis after curative hepatectomy. It is a good decision-making tool for individualized treatment.


2020 ◽  
Vol 67 (3) ◽  
pp. 154-158
Author(s):  
Nikola Milosevic ◽  
Suzana Stojanovic-Rundic ◽  
Srdjan Milanovic ◽  
Marko Dozic

Leiomyosarcomas belong to one of the histological subtypes of soft tissue sarcomas. They most often occur in genital, gastrointestinal tract and extremities, and the appearance of these tumors in the bones (especially head and neck) is very rare. Clinically, leiomyosarcomas are aggressive tumors. Treatment is multidisciplinary and includes surgery, radiotherapy, and chemotherapy. This case report presents a 61-year-old patient who was referred to a maxillofacial surgeon due to congestion of the right side of the nose, pain in the right eye, and occasional epistaxis. After complete examination, including biopsy with histopathology and immunohistochemistry, primary intraosseous leiomyosarcoma of the nose and paranasal cavities was diagnosed. Since the tumor lesion was assessed as inoperable, the treatment started with radiotherapy. Two and half years after the radiotherapy was completed, there was good local control of the disease and no dissemination. The case report illustrates the rarity of localization, challenges and difficulties in multimodal treatment, and contribution of radiotherapy to good treatment results.


2020 ◽  
Vol 04 (02) ◽  
pp. 148-156
Author(s):  
David S. Shin ◽  
Hong Vo ◽  
Guy Johnson ◽  
Raimund Pichler ◽  
Scott W. Biggins

AbstractCirrhosis with complications of portal hypertension portends a poor prognosis. Transjugular intrahepatic portosystemic shunts (TIPS) can successfully treat some of these complications in select patients. While the safety and efficacy of TIPS have improved significantly over the past decade, certain patients are categorized as high-risk based on various demographic, laboratory, and comorbid factors. Herein, we provide an in-depth review of TIPS in these settings, including high model for end-stage liver disease score, hepatic malignancy, advanced age, cardiac disease, renal dysfunction, and pregnancy, and discuss their impact on patient selection and procedural considerations.


PLoS ONE ◽  
2013 ◽  
Vol 8 (12) ◽  
pp. e82870 ◽  
Author(s):  
Jung Ryul Kim ◽  
Young Jae Moon ◽  
Keun Sang Kwon ◽  
Jun Sang Bae ◽  
Sajeev Wagle ◽  
...  

2013 ◽  
Author(s):  
Ymera Pignochino ◽  
Federica Capozzi ◽  
Carmine Dell'aglio ◽  
Marco Basiricò ◽  
Lorenzo D'ambrosio ◽  
...  

2020 ◽  
Author(s):  
Shuyang S. Qin ◽  
Booyeon J. Han ◽  
Alyssa Williams ◽  
Katherine M. Jackson ◽  
Rachel Jewell ◽  
...  

AbstractSynchronous metastatic melanoma, clinically defined as multiple lesions diagnosed within 6 months, has a poor prognosis. Despite recent advances in systemic immunotherapy, a majority of patients fail to respond or exhibit lesion-specific responses. While intertumoral heterogeneity has been clinically associated with lesion-specific therapeutic responses, no clear mechanism has been identified, largely due to the scarcity of preclinical models. We developed a novel murine synchronous melanoma model that recapitulates clinical intertumoral heterogeneity. We show that genetic differences between tumors generate distinct tumor immune microenvironments (TIME). These TIMEs can independently upregulate PD-1/PD-L1 expression in response to ongoing anti-tumor immunity and the presence of interferon-gamma. The simultaneous presence of multiple tumors can additionally alter the TIME of each tumor. As such, our model provides a unique approach to investigate the effects of intertumoral heterogeneity on mechanisms of immunotherapy resistance.


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