scholarly journals Novel Preclinical Human Salivary Gland Cancer Models Established Using Organoid Culture And Patient-Derived Xenografting

Author(s):  
Yoshihiro Aizawa ◽  
Kentaro Takada ◽  
Jun Aoyama ◽  
Daisuke Sano ◽  
Shoji Yamanaka ◽  
...  

Abstract Salivary gland carcinoma (SGC) has poor prognosis depending on the histological subtype. However, due to the scarcity of preclinical experimental models, its pathogenesis remains largely unknown, hampering the development of new treatment modalities for patients with these malignancies. Here, we first report the establishment of a large collection of human SGC experimental models for multiple histological subtypes using patient-derived xenograft (PDX) and organoid culture techniques with our previously optimized method. Additionally, we successfully generated organoids by culturing established PDXs (PDX-derived organoids). Through passaging, each pre-clinical model was confirmed to maintain the pathological characteristics of the original tumor and the genetic traits of corresponding histological subtypes. Finally, we confirmed that these organoids were available for pharmacologic studies. Thus, our comprehensive models of SGC could be a powerful resource for the development of novel therapeutic agents and investigating the pathogenesis of these malignancies.

2014 ◽  
Vol 7 ◽  
pp. CMENT.S13770 ◽  
Author(s):  
Katri Aro ◽  
Tuomas Klockars ◽  
llmo Leivo ◽  
Antti Mäkitie

Background Salivary gland cancer (SGC) accounts for 3–5% of head and neck malignancies, and register-based studies estimate the familial proportion to be 0.15%. Objective We studied familial predisposition for SGC in the genetically distinct Finnish population. Patients and Methods We sent a patient questionnaire to 161 Finnish SGC patients, 86 of whom responded. Results A total of 76% of the patients reported having one or more relatives with cancer, 30% two or more, and 9% three or more but only one patient reported having a relative with SGC. Tracing the birthplaces of the SGC patients’ grandparents showed no regional clustering suggestive of a founder effect. Conclusions Lack of familial SGC patients and the absence of a founder effect strongly suggest that familial predisposition for SGC is insignificant in the Finnish population. Various histological subtypes and the rarity of these neoplasms make it impossible to draw conclusions about site-specific association between SGC and other malignancies.


VASA ◽  
2012 ◽  
Vol 41 (3) ◽  
pp. 163-176 ◽  
Author(s):  
Weidenhagen ◽  
Bombien ◽  
Meimarakis ◽  
Geisler ◽  
A. Koeppel

Open surgical repair of lesions of the descending thoracic aorta, such as aneurysm, dissection and traumatic rupture, has been the “state-of-the-art” treatment for many decades. However, in specialized cardiovascular centers, thoracic endovascular aortic repair and hybrid aortic procedures have been implemented as novel treatment options. The current clinical results show that these procedures can be performed with low morbidity and mortality rates. However, due to a lack of randomized trials, the level of reliability of these new treatment modalities remains a matter of discussion. Clinical decision-making is generally based on the experience of the vascular center as well as on individual factors, such as life expectancy, comorbidity, aneurysm aetiology, aortic diameter and morphology. This article will review and discuss recent publications of open surgical, hybrid thoracic aortic (in case of aortic arch involvement) and endovascular repair in complex pathologies of the descending thoracic aorta.


2020 ◽  
Vol 16 (35) ◽  
pp. 2997-3013
Author(s):  
Kentaro Kogushi ◽  
Michael LoPresti ◽  
Shunya Ikeda

Background: Synovial sarcoma (SS) is a rare, aggressive soft tissue sarcoma with a poor prognosis after metastasis. The objective of this study was to conduct a systematic review of the clinical evidence for therapeutic options for adults with metastatic or advanced SS. Materials & methods: Relevant databases were searched with predefined keywords. Results: Thirty-nine publications reported clinical data for systemic treatment and other interventions. Data on survival outcomes varied but were generally poor (progression-free survival: 1.0–7.7 months; overall survival: 6.7–29.2 months) for adults with metastatic and advanced SS. A high frequency of neutropenia with systemic treatment and low quality of life post-progression were reported. Conclusion: Reported evidence suggests poor outcomes in adults with metastatic and advanced SS and the need for the development of new treatment modalities.


Toxins ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 157 ◽  
Author(s):  
Adriana Tomoko Nishiya ◽  
Marcia Kazumi Nagamine ◽  
Ivone Izabel Mackowiak da Fonseca ◽  
Andrea Caringi Miraldo ◽  
Nayra Villar Scattone ◽  
...  

Canine oral mucosal melanomas (OMM) are the most common oral malignancy in dogs and few treatments are available. Thus, new treatment modalities are needed for this disease. Bacillus anthracis (anthrax) toxin has been reengineered to target tumor cells that express urokinase plasminogen activator (uPA) and metalloproteinases (MMP-2), and has shown antineoplastic effects both, in vitro and in vivo. This study aimed to evaluate the effects of a reengineered anthrax toxin on canine OMM. Five dogs bearing OMM without lung metastasis were included in the clinical study. Tumor tissue was analyzed by immunohistochemistry for expression of uPA, uPA receptor, MMP-2, MT1-MMP and TIMP-2. Animals received either three or six intratumoral injections of the reengineered anthrax toxin prior to surgical tumor excision. OMM samples from the five dogs were positive for all antibodies. After intratumoral treatment, all dogs showed stable disease according to the canine Response Evaluation Criteria in Solid Tumors (cRECIST), and tumors had decreased bleeding. Histopathology has shown necrosis of tumor cells and blood vessel walls after treatment. No significant systemic side effects were noted. In conclusion, the reengineered anthrax toxin exerted inhibitory effects when administered intratumorally, and systemic administration of this toxin is a promising therapy for canine OMM.


2021 ◽  
pp. 455-469
Author(s):  
Janakiraman Subramanian ◽  
Lara Kujtan

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Sebastian Kühn ◽  
Joanna Freyse ◽  
Passant Atallah ◽  
Jörg Rademann ◽  
Uwe Freudenberg ◽  
...  

Abstract The delivery of chemotactic signaling molecules via customized biomaterials can effectively guide the migration of cells to improve the regeneration of damaged or diseased tissues. Here, we present a novel biohybrid hydrogel system containing two different sulfated glycosaminoglycans (sGAG)/sGAG derivatives, namely either a mixture of short heparin polymers (Hep-Mal) or structurally defined nona-sulfated tetrahyaluronans (9s-HA4-SH), to precisely control the release of charged signaling molecules. The polymer networks are described in terms of their negative charge, i.e. the anionic sulfate groups on the saccharides, using two parameters, the integral density of negative charge and the local charge distribution (clustering) within the network. The modulation of both parameters was shown to govern the release characteristics of the chemotactic signaling molecule SDF-1 and allows for seamless transitions between burst and sustained release conditions as well as the precise control over the total amount of delivered protein. The obtained hydrogels with well-adjusted release profiles effectively promote MSC migration in vitro and emerge as promising candidates for new treatment modalities in the context of bone repair and wound healing.


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