scholarly journals Fibrolamellar Carcinoma: 2012 Update

Scientifica ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-15 ◽  
Author(s):  
Michael Torbenson
Keyword(s):  
Tumor Cells ◽  
Primary Liver Cancer ◽  
Neuroendocrine Differentiation ◽  
Science Literature ◽  
Unique Type ◽  
Younger Age ◽  
Genetic Abnormalities ◽  
Fibrolamellar Carcinoma ◽  
Prognostic Feature ◽  
Children And Young Adults

Fibrolamellar carcinomas are a unique type of primary liver cancer. They occur most commonly in children and young adults. Their etiology remains a mystery, as they are not associated with chronic liver disease. Fibrolamellar carcinomas are not indolent tumors, but have an overall better prognosis than typical hepatocellular carcinomas, in part because of the younger age at presentation and the lack of cirrhosis. The most important prognostic feature is whether the tumor is resectable. Histologically, the tumor is made up of large cells that contain abundant mitochondria. The nuclei of the tumor cells have prominent nucleoli. The tumor cells induce the formation of extensive intratumoral fibrosis, which often grows in parallel, or lamellar bands. The tumor cells clearly show hepatocellular features but are also unique in showing both biliary and neuroendocrine differentiation. The uniqueness of fibrolamellar carcinoma extends to their molecular findings. While the genetic abnormalities that lead to fibrolamellar carcinomas are not yet known, studies have shown that they lack mutations in the genes most commonly mutated in typical hepatocellular carcinoma (TP53andCTNNB1). In this paper, the clinical, pathological, and basic science literature on fibrolamellar carcinoma is comprehensively reviewed. Key areas of needed research are also discussed.

scholarly journals Natural Killer–Dendritic Cell Interactions in Liver Cancer: Implications for Immunotherapy

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2184
Author(s):  
Valentina Cazzetta ◽  
Sara Franzese ◽  
Claudia Carenza ◽  
Silvia Della Bella ◽  
Joanna Mikulak ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Immune Responses ◽  
Nk Cells ◽  
Natural Killer ◽  
Tumor Cells ◽  
Primary Liver Cancer ◽  
Circulating Antigens ◽  
Direct Cytotoxicity ◽  
Immune Changes

Natural killer (NK) and dendritic cells (DCs) are innate immune cells that play a crucial role in anti-tumor immunity. NK cells kill tumor cells through direct cytotoxicity and cytokine secretion. DCs are needed for the activation of adaptive immune responses against tumor cells. Both NK cells and DCs are subdivided in several subsets endowed with specialized effector functions. Crosstalk between NK cells and DCs leads to the reciprocal control of their activation and polarization of immune responses. In this review, we describe the role of NK cells and DCs in liver cancer, focusing on the mechanisms involved in their reciprocal control and activation. In this context, intrahepatic NK cells and DCs present unique immunological features, due to the constant exposure to non-self-circulating antigens. These interactions might play a fundamental role in the pathology of primary liver cancer, namely hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). Additionally, the implications of these immune changes are relevant from the perspective of improving the cancer immunotherapy strategies in HCC and ICC patients.

scholarly journals Regulation of Neuroendocrine Differentiation in Gastrointestinal Carcinoid Tumor Cells by Notch Signaling

2005 ◽  
Vol 90 (7) ◽  
pp. 4350-4356 ◽  
Author(s):  
Eric K. Nakakura ◽  
Virote R. Sriuranpong ◽  
Muthusamy Kunnimalaiyaan ◽  
Edward C. Hsiao ◽  
Kornel E. Schuebel ◽  
...  
Keyword(s):  
Notch Signaling ◽  
Tumor Cells ◽  
Carcinoid Tumor ◽  
Neuroendocrine Differentiation ◽  
Gastrointestinal Carcinoid

scholarly journals Phenotypic Characteristics of Tumor Cells in Patients with Chronic Lymphocytic Leukemia into Different Prognostic Groups

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5276-5276
Author(s):  
Aleksei Kuvshinov ◽  
Sergei Voloshin ◽  
Irina Martynkevich ◽  
Ludmila Martynenko ◽  
Andrei Garifullin ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Tumor Cells ◽  
Conflicts Of Interest ◽  
Lymphocytic Leukemia ◽  
Phenotypic Characteristics ◽  
Hla Dr ◽  
Number Of Patients ◽  
Genetic Abnormalities ◽  
Prognostic Groups ◽  
The Relationship

Abstract Background. The presence or absence of certain cluster of differentiation on the tumor cells of chronic lymphocytic leukemia may affect the course of the disease. Influence of genetic abnormalities on the prognosis of the disease was also proved. Aim. To determine the relationship of the phenotype of tumor cells with genetic prognostic groups of patients with chronic lymphocytic leukemia (CLL). Methods. Thirty-five adult pts (median age 61 year, range 44 - 82; male 24, female 11) with diagnosed CLL were included in the study. The CLL was diagnosed according to the standard basic examination (complete blood count with differential, multicolor flow cytometry (MFC) of blood and bone marrow (BM), lymph node and BM immunohistochemistry (IHC), computered tomography). Cytogenetic studies were performed on blood samples using standard GTG-method. Interphase FISH analyses were performed according to the manufacturer's protocol using DNA probes: LSI 13(RB1)13q14, LSI ATM (11q22), CEP12, LSI TP53 (17p13.1) (Abbott). Immunophenotype (IFT) of CLL cells assessed with combinations: CD3/CD19, CD19/CD5, CD19/CD11c, CD19/CD20, CD19/CD22, CD19/CD23, CD19/CD25, CD19/CD38, CD19/CD43, CD19/CD81, CD19/HLA-DR, and CD19/CD5/CD23. Results. Stratification of patients into prognostic groups was performed based on identified GA. Favorable prognosis - patients with del(13q) (n = 9); neutral prognosis - normal karyotype (n = 14) or trisomy of chromosome 12 (n = 4); unfavorable prognosis - del(17p) (n = 3), del(11q) (n = 3) and the complex karyotype (n = 2). Expression of CD20 was lower, and CD38 - higher in adverse group (51.0±16.31 % and 36.02±10.35 %, respectively) versus neutral or favorable groups (CD20+ - 83.17±5.52 % and 84.41±4.7 %; CD38 - 10.46±4.8 %, and 12.44±4.1 %, respectively, p <0.05). The expression level of CD20 and CD38 did not differ between the neutral and favorable groups. The number of patients with CD38 expression more than 10% was higher in the unfavorable group (7/8) versus favorable (4/8) (p <0.05). At the same time overexpression of CD38 was observed more frequently in patients with a lack of expression of CD23 on CD5 tumor cells (CD5+CD23-) (p<0.05). Expression of HLA-DR was higher in patients with MRD-negative remissions (3/4) versus patients with MRD-positive remissions (1/8) (p<0.05). Conclusions. The study of the influence of various factors on the prognosis and course of CLL requires a comprehensive approach. Further researches are needed to determine the relationship between CLL affecting factors like genetic abnormalities, phenotypic characteristics of the tumor cells and MRD. Disclosures No relevant conflicts of interest to declare.

scholarly journals DNAJB1-PRKACA in HEK293T cells induces LINC00473 overexpression that depends on PKA signaling

2021 ◽  
Author(s):  
Stephanie S Kim ◽  
Ina Kycia ◽  
Michael Karski ◽  
Rosanna K Ma ◽  
Evan A Bordt ◽  
...  
Keyword(s):  
Fusion Gene ◽  
Mitochondrial Dynamics ◽  
Primary Liver Cancer ◽  
Mitochondrial Fission ◽  
Normal Liver ◽  
Chemotherapeutic Agents ◽  
Cellular Effects ◽  
Cellular Models ◽  
Fibrolamellar Carcinoma ◽  
Insight Into

Fibrolamellar carcinoma (FLC) is a primary liver cancer that most commonly arises in adolescents and young adults in a background of normal liver tissue and has an poor prognosis due to lack of effective chemotherapeutic agents. The DNAJB1-PRKACA gene fusion (DP) has been reported in the majority of FLC tumors, however its oncogenic mechanisms remain unclear. Given the paucity of cellular models, in particular FLC tumor cell lines, we hypothesized that engineering the DP fusion gene in HEK293T cells would provide insight into the cellular effects of the fusion gene. We used CRISPR/Cas9 to engineer HEK293T clones expressing DP fusion gene (HEK-DP) and performed transcriptomic, proteomic, and mitochondrial studies to characterize this cellular model. Proteomic analysis of DP interacting partners identified mitochondrial proteins as well as proteins in other subcellular compartments. HEK-DP cells demonstrated significantly elevated mitochondrial fission, which suggests a role for DP in altering mitochondrial dynamics. Transcriptomic analysis of HEK-DP cells revealed a significant increase in LINC00473 expression, similar to what has been observed in primary FLC samples. LINC00473 overexpression was reversible with siRNA targeting of PRKACA as well as pharmacologic targeting of PKA and Hsp40 in HEK-DP cells. Therefore, our model suggests that LINC00473 is a candidate marker for DP activity.

scholarly journals A Rare Case of Acute Myeloblastic Leukemia With Blast Count Less Than 20% in Bone Marrow

2019 ◽  
Author(s):  
Pardis Nematollahi ◽  
Behnaz Sabaghi ◽  
Alireza Moafi
Keyword(s):  
Bone Marrow ◽  
Cell Count ◽  
Bone Marrow Aspiration ◽  
Final Diagnosis ◽  
Blast Cell ◽  
Acute Myeloblastic Leukemia ◽  
Genetic Abnormalities ◽  
Laboratory Results ◽  
Blast Count ◽  
Children And Young Adults

One of the diagnostic criteria for Acute Myeloblastic Leukemia (AML) is the presence of 20% myeloid blasts in peripheral blood or bone marrow. Some cases with recurrent cytogenetic abnormalities also fall in this category with blast cell count less than 20%. Thus, in the presence of these genetic abnormalities, the patients are classified as AML regardless of blast cell count. One of these genetic heterogeneities is t(8; 21) (q22, q22.1) which is more commonly seen in children and young adults. In this study, a 14-year-old boy is reported with a final diagnosis of AML, which was presented with fever and bicytopenia, clinically suspicious for acute leukemia. Laboratory results reported less than 20% blasts in bone marrow aspiration smears but genetic alteration t(8; 21) (q22, q22.1) was detected by molecular exams.

scholarly journals Single-cell analysis of hepatoblastoma identifies distinct tumor cell signatures that predict susceptibility to chemotherapy using patient-specific tumor spheroids

2021 ◽  
Author(s):  
Hanbing Song ◽  
Simon Bucher ◽  
Katherine Rosenberg ◽  
Margaret Tsui ◽  
Deviana Burhan ◽  
...  
Keyword(s):  
Single Cell ◽  
Tumor Cells ◽  
Tumor Heterogeneity ◽  
Single Cell Analysis ◽  
Primary Liver Cancer ◽  
Patient Specific ◽  
Precision Oncology ◽  
Cell Of Origin ◽  
Specific Tumor ◽  
Transcriptomic Signature

Pediatric hepatoblastoma (HB) is the most common primary liver cancer in infants and children. Studies of HB that focus exclusively on tumor cells demonstrate sparse somatic mutations and a common cell of origin, the hepatoblast, across patients. In contrast to the homogeneity these studies would suggest, HB tumors have a high degree of heterogeneity that can portend poor prognosis. In this study, we used single- cell genomic techniques to analyze resected human pediatric HB specimens. This study establishes that tumor heterogeneity can be defined by the relative proportions of five distinct subtypes of tumor cells. Notably, patient-derived HB spheroid cultures predict differential responses to treatment based on the transcriptomic signature of each tumor, suggesting a path forward for precision oncology for these tumors. Collectively, these results define HB tumor heterogeneity with single-cell resolution and demonstrate that patient-derived spheroids can be used to evaluate responses to chemotherapy.

scholarly journals Fibrolamellar Carcinoma: Recent Advances and Unresolved Questions on the Molecular Mechanisms

2018 ◽  
Vol 38 (01) ◽  
pp. 051-059 ◽  
Author(s):  
Gadi Lalazar ◽  
Sanford Simon
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Primary Liver Cancer ◽  
Rare Form ◽  
Fibrolamellar Hepatocellular Carcinoma ◽  
Underlying Liver Disease ◽  
Recent Advances ◽  
Fibrolamellar Carcinoma

AbstractFibrolamellar hepatocellular carcinoma (FLC) is a rare form of primary liver cancer that affects adolescents and young adults without underlying liver disease. Surgery remains the mainstay of therapy; however, most patients are either not surgical candidates or suffer from recurrence. There is no approved systemic therapy and the overall survival remains poor. Historically classified as a subtype of hepatocellular carcinoma (HCC), FLC has a unique clinical, histological, and molecular presentation. At the genomic level, FLC contains a single 400kB deletion in chromosome 19, leading to a functional DNAJB1-PRKACA fusion protein. In this review, we detail the recent advances in our understanding of the molecular underpinnings of FLC and outline the current knowledge gaps.

Dissecting the molecular interplay between tumor cells and –stroma in primary liver cancer

2021 ◽  
Author(s):  
N Ganjian ◽  
Z Abadi ◽  
O Trompak ◽  
R Geffers ◽  
L Zender ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Tumor Cells ◽  
Primary Liver Cancer
Sign in / Sign up

Export Citation Format

Share Document