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Cancer Cell Oct 2019Cellular diversity in tumors is a key factor for therapeutic failures and lethal outcomes of solid malignancies. Here, we determined the single-cell transcriptomic... (Observational Study)
Observational Study
Cellular diversity in tumors is a key factor for therapeutic failures and lethal outcomes of solid malignancies. Here, we determined the single-cell transcriptomic landscape of liver cancer biospecimens from 19 patients. We found varying degrees of heterogeneity in malignant cells within and between tumors and diverse landscapes of tumor microenvironment (TME). Strikingly, tumors with higher transcriptomic diversity were associated with patient's worse overall survival. We found a link between hypoxia-dependent vascular endothelial growth factor expression in tumor diversity and TME polarization. Moreover, T cells from higher heterogeneous tumors showed lower cytolytic activities. Consistent results were found using bulk genomic and transcriptomic profiles of 765 liver tumors. Our results offer insight into the diverse ecosystem of liver cancer and its impact on patient prognosis.
Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Immunological; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Biopsy; Carcinoma, Hepatocellular; Cholangiocarcinoma; DNA Copy Number Variations; Drug Resistance, Neoplasm; Female; Gene Expression Regulation, Neoplastic; Genetic Variation; Hepatectomy; Humans; Liver; Liver Neoplasms; Male; Middle Aged; Prognosis; Progression-Free Survival; RNA-Seq; Single-Cell Analysis; Tumor Microenvironment; Vascular Endothelial Growth Factor A
PubMed: 31588021
DOI: 10.1016/j.ccell.2019.08.007 -
International Journal of Molecular... Aug 2021Cholangiocarcinoma (CC) is an aggressive malignancy with an inferior prognosis due to limited systemic treatment options. As preclinical models such as CC cell lines are...
Cholangiocarcinoma (CC) is an aggressive malignancy with an inferior prognosis due to limited systemic treatment options. As preclinical models such as CC cell lines are extremely rare, this manuscript reports a protocol of cholangiocarcinoma patient-derived organoid culture as well as a protocol for the transition of 3D organoid lines to 2D cell lines. Tissue samples of non-cancer bile duct and cholangiocarcinoma were obtained during surgical resection. Organoid lines were generated following a standardized protocol. 2D cell lines were generated from established organoid lines following a novel protocol. Subcutaneous and orthotopic patient-derived xenografts were generated from CC organoid lines, histologically examined, and treated using standard CC protocols. Therapeutic responses of organoids and 2D cell lines were examined using standard CC agents. Next-generation exome and RNA sequencing was performed on primary tumors and CC organoid lines. Patient-derived organoids closely recapitulated the original features of the primary tumors on multiple levels. Treatment experiments demonstrated that patient-derived organoids of cholangiocarcinoma and organoid-derived xenografts can be used for the evaluation of novel treatments and may therefore be used in personalized oncology approaches. In summary, this study establishes cholangiocarcinoma organoids and organoid-derived cell lines, thus expanding translational research resources of cholangiocarcinoma.
Topics: Adult; Aged; Aged, 80 and over; Animals; Antineoplastic Agents; Bile Duct Neoplasms; Biomarkers, Tumor; Cell Line, Tumor; Cholangiocarcinoma; Female; Gene Expression Regulation, Neoplastic; High-Throughput Nucleotide Sequencing; Humans; Male; Mice; Middle Aged; Organ Culture Techniques; Organoids; Precision Medicine; Sequence Analysis, RNA; Tumor Cells, Cultured; Exome Sequencing; Xenograft Model Antitumor Assays
PubMed: 34445380
DOI: 10.3390/ijms22168675 -
Materials Today. Bio Dec 2022Thyroid cancer, as one of the most common endocrine cancers, has seen a surge in incidence in recent years. This is most likely due to the lack of specificity and... (Review)
Review
Thyroid cancer, as one of the most common endocrine cancers, has seen a surge in incidence in recent years. This is most likely due to the lack of specificity and accuracy of its traditional diagnostic modalities, leading to the overdiagnosis of thyroid nodules. Although there are several treatment options available, they are limited to surgery and I radiation therapy that come with significant side effects and hence cannot meet the treatment needs of anaplastic thyroid carcinoma with very high malignancy. Optical imaging that utilizes optical absorption, refraction and scattering properties, not only observes the structure and function of cells, tissues, organs, or even the whole organism to assist in diagnosis, but can also be used to perform optical therapy to achieve targeted non-invasive and precise treatment of thyroid cancer. These applications of screening, diagnosis, and treatment, lend to optical imaging's promising potential within the realm of thyroid cancer surgical navigation. Over the past decade, research on optical imaging in the diagnosis and treatment of thyroid cancer has been growing year by year, but no comprehensive review on this topic has been published. Here, we review key advances in the application of optical imaging in the diagnosis and treatment of thyroid cancer and discuss the challenges and potential for clinical translation of this technology.
PubMed: 36388462
DOI: 10.1016/j.mtbio.2022.100441 -
Respiratory Medicine Oct 2019A chylothorax, also known as chylous pleural effusion, is an uncommon cause of pleural effusion with a wide differential diagnosis characterized by the accumulation of... (Review)
Review
A chylothorax, also known as chylous pleural effusion, is an uncommon cause of pleural effusion with a wide differential diagnosis characterized by the accumulation of bacteriostatic chyle in the pleural space. The pleural fluid will have either or both triglycerides >110 mg/dL and the presence of chylomicrons. It may be encountered following a surgical intervention, usually in the chest, or underlying disease process. Management of a chylothorax requires a multidisciplinary approach employing medical therapy and possibly surgical intervention for post-operative patients and patients who have failed medical therapy. In this review, we aim to discuss the anatomy, fluid characteristics, etiology, and approach to the diagnosis of a chylothorax.
Topics: Antineoplastic Agents, Hormonal; Chylothorax; Diagnosis, Differential; Exudates and Transudates; Humans; Lymphography; Lymphoscintigraphy; Octreotide; Pleural Effusion; Postoperative Period; Radiography, Thoracic; Suction; Thoracentesis; Thoracic Duct; Tomography, X-Ray Computed; Triglycerides
PubMed: 31454675
DOI: 10.1016/j.rmed.2019.08.014 -
Mediastinum (Hong Kong, China) 2022Chylopericardium is a rare pathologic condition consisting of the accumulation of excess amounts of chylous fluid within the pericardial cavity. Most patients are... (Review)
Review
Chylopericardium is a rare pathologic condition consisting of the accumulation of excess amounts of chylous fluid within the pericardial cavity. Most patients are asymptomatic at presentation; however, chest pressure, chest pain and lightheadedness have been reported, and the most common presenting symptom is shortness of breath. Patients are noted to have enlargement of the cardiac silhouette on routine chest radiograph, and evidence of a pericardial effusion on echocardiography. The diagnosis is only definitively confirmed with pericardiocentesis and fluid analysis. The fluid is typically turbid white or milky in appearance, with a triglyceride level in excess of 500 mg/dL. The mechanism by which chyle accumulates within the pericardium is believed to be secondary to abnormal or damaged lymphatics or due to elevated pressure within the thoracic duct that results in chyle reflux into the pericardium. Following drainage with a pericardiocentesis or pericardial drain, attempts at conservative therapy with nothing by mouth and parental nutrition can be made, but have a high rate of failure and subsequent reaccumulation of chyle. Surgical treatment provides the most definitive management and consists of ligation of the thoracic duct just above the level of the diaphragm and creation of a pericardial window. With this treatment, risk of recurrence is incredibly low (<5%).
PubMed: 35340832
DOI: 10.21037/med-20-64