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Article ; Online: Cholangiocarcinoma: Current Knowledge and New Developments.

Blechacz, Boris

2017 Volume 11, Issue 1, Page(s) 13–26

Abstract: Cholangiocarcinoma (CCA) is the second most common primary malignancy. Although it is more common in Asia, its incidence in Europe and North America has significantly increased in recent decades. The prognosis of CCA is dismal. Surgery is the only ... ...

Abstract	Cholangiocarcinoma (CCA) is the second most common primary malignancy. Although it is more common in Asia, its incidence in Europe and North America has significantly increased in recent decades. The prognosis of CCA is dismal. Surgery is the only potentially curative treatment, but the majority of patients present with advanced stage disease, and recurrence after resection is common. Over the last two decades, our understanding of the molecular biology of this malignancy has increased tremendously, diagnostic techniques have evolved, and novel therapeutic approaches have been established. This review discusses the changing epidemiologic trends and provides an overview of newly identified etiologic risk factors for CCA. Furthermore, the molecular pathogenesis is discussed as well as the influence of etiology and biliary location on the mutational landscape of CCA. This review provides an overview of the diagnostic evaluation of CCA and its staging systems. Finally, new therapeutic options are critically reviewed, and future therapeutic strategies discussed.
MeSH term(s)	Asia/epidemiology ; Bile Duct Neoplasms/diagnosis ; Bile Duct Neoplasms/epidemiology ; Bile Duct Neoplasms/pathology ; Bile Duct Neoplasms/therapy ; Caroli Disease/epidemiology ; Chemoradiotherapy ; Cholangiocarcinoma/diagnosis ; Cholangiocarcinoma/epidemiology ; Cholangiocarcinoma/pathology ; Cholangiocarcinoma/therapy ; Cholangitis, Sclerosing/epidemiology ; Choledochal Cyst/epidemiology ; Diabetes Mellitus/epidemiology ; Hepatectomy ; Hepatitis B/epidemiology ; Hepatitis C/epidemiology ; Humans ; Klatskin Tumor/diagnosis ; Klatskin Tumor/epidemiology ; Klatskin Tumor/pathology ; Klatskin Tumor/therapy ; Liver Cirrhosis/epidemiology ; Liver Diseases, Parasitic/epidemiology ; Liver Transplantation ; Neoadjuvant Therapy ; Neoplasm Staging ; Obesity/epidemiology ; Prognosis ; Risk Factors
Language	English
Publishing date	2017-01-15
Publishing country	Korea (South)
Document type	Journal Article ; Review
ZDB-ID	2399010-7
ISSN	2005-1212 ; 1976-2283
ISSN (online)	2005-1212
ISSN	1976-2283
DOI	10.5009/gnl15568
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Book ; Thesis: Parvovirus H-1

Blechacz, Boris

Infektiösität und Zytotoxizität für humane Hepatomzellinien und seine Eignung als Vektorsystem für eine tumorzellspezifische Gentherapie

2001

Author's details	vorgelegt von Boris Blechacz
Language	German
Size	III, 88 Bl., Ill., graph. Darst., 30 cm
Publishing country	Germany
Document type	Book ; Thesis
Thesis / German Habilitation thesis	Heidelberg, Univ., Diss., 2001
HBZ-ID	HT013178880
Database	Catalogue ZB MED Medicine, Health

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Shelf mark	Loan status	Location
2001 E 2852	order for loan	Magazin

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Article ; Online: Biopsy for liver cancer: How to balance research needs with evidence-based clinical practice.

Blechacz, Boris / Mishra, Lopa

Hepatology (Baltimore, Md.)

2015 Volume 62, Issue 5, Page(s) 1645

MeSH term(s)	Carcinoma, Hepatocellular/pathology ; Humans ; Liver/pathology ; Liver Neoplasms/pathology
Language	English
Publishing date	2015-03-25
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	604603-4
ISSN	1527-3350 ; 0270-9139
ISSN (online)	1527-3350
ISSN	0270-9139
DOI	10.1002/hep.27746
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Article ; Online: Analysis of the c-KIT Ligand Promoter Using Chromatin Immunoprecipitation.

Zhang, Pingyu / Rojas, Andres / Blechacz, Boris

Journal of visualized experiments : JoVE

2017 , Issue 124

Abstract: Multiple cellular processes, including DNA replication and repair, DNA recombination, and gene expression, require interactions between proteins and DNA. Therefore, DNA-protein interactions regulate multiple physiological, pathophysiological, and ... ...

Abstract	Multiple cellular processes, including DNA replication and repair, DNA recombination, and gene expression, require interactions between proteins and DNA. Therefore, DNA-protein interactions regulate multiple physiological, pathophysiological, and biological functions, such as cell differentiation, cell proliferation, cell cycle control, chromosome stability, epigenetic gene regulation, and cell transformation. In eukaryotic cells, the DNA interacts with histone and nonhistone proteins and is condensed into chromatin. Several technical tools can be used to analyze DNA-protein interactions, such as the Electrophoresis (gel) Mobility Shift Assay (EMSA) and DNase I footprinting. However, these techniques analyze the protein-DNA interaction in vitro, not within the cellular context. Chromatin immunoprecipitation (ChIP) is a technique that captures proteins at their specific DNA binding sites, thereby allowing for the identification of DNA-protein interactions within their chromatin context. It is done by fixation of the DNA-protein interaction, followed by immunoprecipitation of the protein of interest. Subsequently, the genomic site that the protein was bound to is characterized. Here, we describe and discuss ChIP and demonstrate its analytical value for the identification of the Transforming Growth Factor-β (TGF-β)-induced binding of the transcription factor SMAD2 to SMAD Binding Elements (SBE) within the promoter region of the tyrosine-protein kinase Kit (c-KIT) receptor ligand Stem Cell Factor (SCF).
MeSH term(s)	Chromatin Immunoprecipitation/methods ; Humans ; Promoter Regions, Genetic ; Proto-Oncogene Proteins c-kit/genetics
Chemical Substances	Proto-Oncogene Proteins c-kit (EC 2.7.10.1)
Language	English
Publishing date	2017-06-27
Publishing country	United States
Document type	Journal Article ; Video-Audio Media
ISSN	1940-087X
ISSN (online)	1940-087X
DOI	10.3791/55689
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Hepatocellular carcinoma biology.

Blechacz, Boris / Mishra, Lopa

Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer

2012 Volume 190, Page(s) 1–20

Abstract: Hepatocellular carcinoma (HCC) is the most common primary hepatic malignancy. Its incidence and prevalence is globally heterogeneous with the highest rates in Southeast Asia and Sub-Saharan Africa. In Western Industry nations, its incidence has ... ...

Abstract	Hepatocellular carcinoma (HCC) is the most common primary hepatic malignancy. Its incidence and prevalence is globally heterogeneous with the highest rates in Southeast Asia and Sub-Saharan Africa. In Western Industry nations, its incidence has significantly increased throughout the previous three decades. Its global heterogeneity is in part a reflection of the global distribution of its risk factors. Its prognosis is dismal with a 5-year survival of 11 %. The only potentially curative treatment is surgical with either resection or orthotopic liver transplantation. However, the majority of HCC patients are diagnosed at an advanced stage at which surgical therapies are not feasible. HCC is considered chemotherapy-resistant-a characteristic thought to be mediated in part through stem-like tumor initiating cells (STICs). Recent studies have provided significant insights in the hepatocarcinogenesis and the molecular signaling pathways of this malignancy resulting in the development of novel, molecular targeted therapies with modest therapeutic benefit. Our growing understanding of the biology of this malignancy will help in the development of novel, molecular-targeted therapies.
MeSH term(s)	Carcinoma, Hepatocellular/drug therapy ; Carcinoma, Hepatocellular/metabolism ; Carcinoma, Hepatocellular/mortality ; Carcinoma, Hepatocellular/surgery ; Cytokines/metabolism ; Humans ; Intracellular Signaling Peptides and Proteins/metabolism ; Liver Neoplasms/drug therapy ; Liver Neoplasms/metabolism ; Liver Neoplasms/mortality ; Liver Neoplasms/surgery ; Liver Transplantation ; Neoplastic Stem Cells/physiology ; Proto-Oncogene Proteins/metabolism ; Signal Transduction ; Survival Rate
Chemical Substances	Cytokines ; Intracellular Signaling Peptides and Proteins ; Proto-Oncogene Proteins
Language	English
Publishing date	2012-09-04
Publishing country	Germany
Document type	Journal Article ; Review
ISSN	0080-0015
ISSN	0080-0015
DOI	10.1007/978-3-642-16037-0_1
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Article: Cancer review: Cholangiocarcinoma.

Ghouri, Yezaz Ahmed / Mian, Idrees / Blechacz, Boris

Journal of carcinogenesis

2015 Volume 14, Page(s) 1

Abstract: Cholangiocarcinoma (CCA) is the most common biliary tract malignancy. CCA is classified as intrahepatic, perihilar or distal extrahepatic; the individual subtypes differ in their biologic behavior, clinical presentation, and management. Throughout the ... ...

Abstract	Cholangiocarcinoma (CCA) is the most common biliary tract malignancy. CCA is classified as intrahepatic, perihilar or distal extrahepatic; the individual subtypes differ in their biologic behavior, clinical presentation, and management. Throughout the last decades, CCA incidence rates had significantly increased. In addition to known established risk factors, novel possible risk factors (i.e. obesity, hepatitis C virus) have been identified that are of high importance in developed countries where CCA prevalence rates have been low. CCA tends to develop on the background of inflammation and cholestasis. In recent years, our understanding of the molecular mechanisms of cholangiocarcinogenesis has increased, thereby, providing the basis for molecularly targeted therapies. In its diagnostic evaluation, imaging techniques have improved, and the role of complementary techniques has been defined. There is a need for improved CCA biomarkers as currently used ones are suboptimal. Multiple staging systems have been developed, but none of these is optimal. The prognosis of CCA is considered dismal. However, treatment options have improved throughout the last two decades for carefully selected subgroups of CCA patients. Perihilar CCA can now be treated with orthotopic liver transplantation with neoadjuvant chemoradiation achieving 5-year survival rates of 68%. Classically considered chemotherapy-resistant, the ABC-02 trial has shown the therapeutic benefit of combination therapy with gemcitabine and cisplatin. The benefits of adjuvant treatments for resectable CCA, local ablative therapies and molecularly targeted therapies still need to be defined. In this article, we will provide the reader with an overview over CCA, and discuss the latest developments and controversies.
Language	English
Publishing date	2015-02-23
Publishing country	India
Document type	Journal Article ; Review
ZDB-ID	2098237-9
ISSN	1477-3163
ISSN	1477-3163
DOI	10.4103/1477-3163.151940
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Positron emission tomography scan for a hepatic mass.

Blechacz, Boris / Gores, Gregory J

Hepatology (Baltimore, Md.)

2010 Volume 52, Issue 6, Page(s) 2186–2191

MeSH term(s)	Aged ; Cholangiocarcinoma/diagnostic imaging ; Humans ; Liver/diagnostic imaging ; Liver Neoplasms/diagnostic imaging ; Male ; Positron-Emission Tomography ; Ultrasonography
Language	English
Publishing date	2010-10-21
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	604603-4
ISSN	1527-3350 ; 0270-9139
ISSN (online)	1527-3350
ISSN	0270-9139
DOI	10.1002/hep.24002
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Article: Analysis of the c-kit ligand promoter using chromatin immunoprecipitation

Zhang, Pingyu / Rojas, Andres / Blechacz, Boris

Journal of visualized experiments. 2017 June 27, , no. 124

2017

Abstract	Multiple cellular processes, including DNA replication and repair, DNA recombination, and gene expression, require interactions between proteins and DNA. Therefore, DNA-protein interactions regulate multiple physiological, pathophysiological, and biological functions, such as cell differentiation, cell proliferation, cell cycle control, chromosome stability, epigenetic gene regulation, and cell transformation. In eukaryotic cells, the DNA interacts with histone and nonhistone proteins and is condensed into chromatin. Several technical tools can be used to analyze DNA-protein interactions, such as the Electrophoresis (gel) Mobility Shift Assay (EMSA) and DNase I footprinting. However, these techniques analyze the protein-DNA interaction in vitro, not within the cellular context. Chromatin immunoprecipitation (ChIP) is a technique that captures proteins at their specific DNA binding sites, thereby allowing for the identification of DNA-protein interactions within their chromatin context. It is done by fixation of the DNA-protein interaction, followed by immunoprecipitation of the protein of interest. Subsequently, the genomic site that the protein was bound to is characterized. Here, we describe and discuss ChIP and demonstrate its analytical value for the identification of the Transforming Growth Factor-β (TGF-β)-induced binding of the transcription factor SMAD2 to SMAD Binding Elements (SBE) within the promoter region of the tyrosine-protein kinase Kit (c-KIT) receptor ligand Stem Cell Factor (SCF).
Keywords	DNA ; DNA replication ; binding sites ; cell cycle ; cell differentiation ; cell proliferation ; chromatin ; deoxyribonuclease I ; electrophoresis ; epigenetics ; eukaryotic cells ; gels ; gene expression ; genes ; genomics ; histones ; ligands ; mothers against decapentaplegic homolog proteins ; precipitin tests ; promoter regions ; stem cell factor ; transcription factors ; transforming growth factor beta
Language	English
Dates of publication	2017-0627
Size	p. e55689.
Publishing place	Journal of Visualized Experiments
Document type	Article
ZDB-ID	2259946-0
ISSN	1940-087X
ISSN	1940-087X
DOI	10.3791/55689
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Hepatocellular Carcinoma Diagnosis and Management in 2021: A National Veterans Affairs Quality Improvement Project.

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association

2023 Volume 22, Issue 2, Page(s) 324–338

Abstract: Background & aims: The coronavirus disease-2019 pandemic profoundly disrupted preventative health care services including cancer screening. As the largest provider of cirrhosis care in the United States, the Department of Veterans Affairs (VA) National ... ...

Abstract	Background & aims: The coronavirus disease-2019 pandemic profoundly disrupted preventative health care services including cancer screening. As the largest provider of cirrhosis care in the United States, the Department of Veterans Affairs (VA) National Gastroenterology and Hepatology Program aimed to assess factors associated with hepatocellular carcinoma (HCC) stage at diagnosis, treatment, and survival. Methods: Veterans with a new diagnosis of HCC in 2021 were identified from electronic health records (N = 2306). Structured medical record extraction was performed by expert reviewers in a 10% random subsample of Veterans with new HCC diagnoses. Factors associated with stage at diagnosis, receipt of treatment, and survival were assessed using multivariable models. Results: Among 199 patients with confirmed HCC, the average age was 71 years and most (72%) had underlying cirrhosis. More than half (54%) were at an early stage (T1 or T2) at diagnosis. Less-advanced liver disease, number of imaging tests adequate for HCC screening, HCC diagnosis in the VA, and receipt of VA primary care were associated significantly with early stage diagnosis. HCC-directed treatments were administered to 145 (73%) patients after a median of 37 days (interquartile range, 19-54 d) from diagnosis, including 70 (35%) patients who received potentially curative treatments. Factors associated with potentially curative (vs no) treatments included HCC screening, early stage at diagnosis, and better performance status. Having fewer comorbidities and better performance status were associated significantly with noncurative (vs no) treatment. Early stage diagnosis, diagnosis in the VA system, and receipt of curative treatment were associated significantly with survival. Conclusions: These results highlight the importance of HCC screening and engagement in care for HCC diagnosis, treatment, and survival while demonstrating the feasibility of developing a national quality improvement agenda for HCC screening, diagnosis, and treatment.
MeSH term(s)	Humans ; United States ; Aged ; Carcinoma, Hepatocellular/diagnosis ; Carcinoma, Hepatocellular/therapy ; Liver Neoplasms/diagnosis ; Liver Neoplasms/therapy ; Veterans ; Quality Improvement ; Liver Cirrhosis/diagnosis ; Liver Cirrhosis/therapy ; Liver Cirrhosis/complications ; Retrospective Studies
Language	English
Publishing date	2023-07-15
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural
ZDB-ID	2119789-1
ISSN	1542-7714 ; 1542-3565
ISSN (online)	1542-7714
ISSN	1542-3565
DOI	10.1016/j.cgh.2023.07.002
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Article ; Online: Adult cancer-related hemophagocytic lymphohistiocytosis - a challenging diagnosis: a case report.

Hust, Michael A / Blechacz, Boris R A / Bonilla, Diana L / Daver, Naval / Rojas-Hernandez, Cristhiam M

Journal of medical case reports

2017 Volume 11, Issue 1, Page(s) 172

Abstract: Background: Adult hemophagocytic lymphohistiocytosis is a secondary immunopathologic phenomenon, mainly secondary to malignancy, infection, or autoimmune disorders. The performance of diagnostic criteria, studied in the pediatric population, is yet to ... ...

Abstract	Background: Adult hemophagocytic lymphohistiocytosis is a secondary immunopathologic phenomenon, mainly secondary to malignancy, infection, or autoimmune disorders. The performance of diagnostic criteria, studied in the pediatric population, is yet to be validated in the adult population. Some of the criteria include cytopenias and organomegaly that are inherent features to malignant processes, thus making the diagnosis of hemophagocytic lymphohistiocytosis a challenge in patients with cancer. Case presentation: We describe the case of a 54-year-old white man with history of metastatic maxillary sinus adenoid cystic carcinoma who had severe liver injury and cytopenias with progressive clinical deterioration. We performed an evaluation, by flow cytometry, of the expression of surface markers in his natural killer cells that revealed remarkable abnormalities. His syndrome eventually fulfilled criteria for hemophagocytic lymphohistiocytosis and he received therapy with steroids with interval clinical improvement. Unfortunately, he refused further cytotoxic treatment and died 2 weeks later. Conclusions: The conventional criteria for the diagnosis of hemophagocytic lymphohistiocytosis are suboptimal for adult patients with cancer resulting in delays in diagnosis and timely initiation of treatment. The diagnostic criteria have to be re-evaluated in patients with cancer; novel, easily available, and accurate diagnostic methods are needed.
Language	English
Publishing date	2017-06-27
Publishing country	England
Document type	Journal Article
ZDB-ID	2269805-X
ISSN	1752-1947 ; 1752-1947
ISSN (online)	1752-1947
ISSN	1752-1947
DOI	10.1186/s13256-017-1344-x
Database	MEDical Literature Analysis and Retrieval System OnLINE

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