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Hepatobiliary cancer

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https://www.readbyqxmd.com/read/28530407/a-gadolinium-complex-of-1-4-7-10-tetraazacyclododecane-1-4-7-trisacetic-acid-do3a-ethoxybenzyl-eob-conjugate-as-a-new-macrocyclic-hepatobiliary-mri-contrast-agent
#1
Ah Rum Baek, Hee-Kyung Kim, Subin Park, Gang Ho Lee, Hyo Jeung Kang, Jae Chang Jung, Joon-Suk Park, Hun-Kyu Ryeom, Tae-Jeong Kim, Yongmin Chang
We report the synthesis of a macrocyclic Gd chelate based on a 1,4,7,10-tetraazacyclododecane-1,4,7-trisacetic acid (DO3A) coordination cage bearing an ethoxybenzyl (EOB) moiety and discuss its use as a T1 hepatobiliary magnetic resonance imaging (MRI) contrast agent. The new macrocyclic liver agent shows high chelation stability and high r1 relaxivity compared with linear-type Gd chelates, which are the current clinically approved liver agents. Our macrocyclic, liver-specific Gd chelate was evaluated in vivo through biodistribution analysis and liver MRI, which demonstrated its high tumor detection sensitivity and suggested that the new Gd complex is a promising contrast agent for liver cancer imaging...
May 22, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28527946/the-microbiome-and-hepatobiliary-pancreatic-cancers
#2
Kosuke Mima, Shigeki Nakagawa, Hiroshi Sawayama, Takatsugu Ishimoto, Katsunori Imai, Masaaki Iwatsuki, Daisuke Hashimoto, Yoshifumi Baba, Yo-Ichi Yamashita, Naoya Yoshida, Akira Chikamoto, Hideo Baba
The human intestinal microbiome encompasses at least 100 trillion microorganisms that can influence host immunity and disease conditions, including cancer. Hepatobiliary and pancreatic cancers have been associated with poor prognosis owing to their high level of tumor invasiveness, distant metastasis, and resistance to conventional treatment options, such as chemotherapy. Accumulating evidence from animal models suggests that specific microbes and microbial dysbiosis can potentiate hepatobiliary-pancreatic tumor development by damaging DNA, activating oncogenic signaling pathways, and producing tumor-promoting metabolites...
May 17, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28511073/preparation-and-evaluation-of-l-and-d-5-18-f-fluorotryptophan-as-pet-imaging-probes-for-indoleamine-and-tryptophan-2-3-dioxygenases
#3
Tang Tang, Herman S Gill, Annie Ogasawara, Jeff N Tinianow, Alexander N Vanderbilt, Simon-Peter Williams, Georgia Hatzivassiliou, Sharla White, Wendy Sandoval, Kevin DeMent, Mengling Wong, Jan Marik
Indoleamine and tryptophan 2,3-dioxygenases (IDO1 and TDO2) are pyrrolases catalyzing the oxidative cleavage of the 2,3-double bond of L-tryptophan in kynurenine pathway. In the tumor microenvironment, their increased activity prevents normal immune function, i.e. tumor cell recognition and elimination by cytotoxic T-cells. Consequently, inhibition of the kynurenine pathway may enhance the activity of cancer immunotherapeutics by reversing immune dysfunction. We sought to investigate the properties of radiolabeled 5-[(18)F]fluorotryptophan with respect to its ability for measuring IDO1 and TDO2 activity by positron emission tomography (PET)...
May 5, 2017: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/28506361/igg4-related-disease-and-the-liver
#4
REVIEW
Jonathan H Chen, Vikram Deshpande
Pathologists are likely to encounter IgG4-related disease in several organ systems. This article focuses on helping pathologists diagnose IgG4-related disease in the hepatobiliary system. Missing the diagnosis can result in unnecessary organ damage and/or unnecessary surgical and cancer therapy. In the liver, tumefactive lesion(s) involving the bile ducts with storiform fibrosis and an IgG4-enriched lymphoplasmacytic infiltrate are highly concerning for IgG4-related disease. The recent identification of oligoclonal populations of T cells and B cells in IgG4-related disease may lead to molecular tests, new therapeutics, and a greater mechanistic understanding of the disease...
June 2017: Gastroenterology Clinics of North America
https://www.readbyqxmd.com/read/28498235/hospital-minimally-invasive-surgery-utilization-for-gastrointestinal-cancer
#5
Meredith C Mason, Hop S Tran Cao, Samir S Awad, Farhood Farjah, George J Chang, Nader N Massarweh
OBJECTIVE: The aim of the study was to evaluate the impact of receiving care at high minimally invasive surgery (MIS)-utilizing hospitals BACKGROUND:: MIS techniques are used across surgical specialties. The extent of MIS utilization for gastrointestinal (GI) cancer resection and impact of receiving care at high utilizing hospitals is unclear. METHODS: This is a retrospective cohort study of 137,581 surgically resected esophageal, gastric, pancreatic, hepatobiliary, colon, and rectal cancer patients within the National Cancer Data Base (2010-2013)...
May 11, 2017: Annals of Surgery
https://www.readbyqxmd.com/read/28485270/a-review-of-the-scaffold-protein-menin-and-its-role-in-hepatobiliary-pathology
#6
Laurent Ehrlich, Chad Hall, Fanyin Meng, Terry Lairmore, Gianfranco Alpini, Shannon Glaser
Multiple endocrine neoplasia type I (MEN1) is a familial cancer syndrome with neuroendocrine tumorigenesis of the parathyroid glands, pituitary gland, and pancreatic islet cells. The MEN1 gene codes for the canonical tumor suppressor protein, menin. Its protein structure has recently been crystallized, and it has been investigated in a multitude of other tissues. In this review, we summarize recent advancements in understanding the structure of the menin protein and its function as a scaffold protein in histone modification and epigenetic gene regulation...
April 28, 2017: Gene Expression
https://www.readbyqxmd.com/read/28480070/chemotherapy-in-patients-with-hepatobiliary-cancers-and-abnormal-hepatic-function
#7
REVIEW
Jun Gong, May Cho, Marwan Fakih
Sorafenib and cisplatin plus gemcitabine currently represent first-line treatment standards in advanced hepatocellular carcinoma and biliary cancer, respectively. Conventional cytotoxic agents (monotherapy or combination therapy) have demonstrated activity in the second-line setting or in those in which first-line agents are contraindicated. A strategy for safe yet effective administration of such systemic therapies in patients with advanced hepatobiliary cancer and abnormal liver function needs to be strongly considered...
April 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28479363/circadian-clock-is-involved-in-regulation-of-hepatobiliary-transport-mediated-by-multidrug-resistance-associated-protein-2
#8
Ju-Hee Oh, Joo Hyun Lee, Dong-Hee Han, Sehyung Cho, Young-Joo Lee
There has been a growing interest in circadian regulation of the expression and function of drug transporters. In this study, we investigated circadian rhythm in the expression and function of multidrug resistance-associated protein 2 (Mrp2) in mouse liver and involvement of circadian clock in their regulations by using the circadian clock genes (period 1 and period 2) knockout mice. The mRNA and protein expression of Mrp2, P-glycoprotein, and breast cancer resistance protein was measured in the mouse liver at different times of the day...
May 4, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28477007/tissue-recommendations-for-precision-cancer-therapy-using-next-generation-sequencing-a-comprehensive-single-cancer-center-s-experiences
#9
Minho Cho, Soomin Ahn, Mineui Hong, Heejin Bang, Michael Van Vrancken, Seungtae Kim, Jeeyun Lee, Se Hoon Park, Joon Oh Park, Young Suk Park, Ho Yeong Lim, Won Ki Kang, Jong-Mu Sun, Se Hoon Lee, Myung-Ju Ahn, Keunchil Park, Duk Hwan Kim, Seunggwan Lee, Woongyang Park, Kyoung-Mee Kim
To generate accurate next-generation sequencing (NGS) data, the amount and quality of DNA extracted is critical. We analyzed 1564 tissue samples from patients with metastatic or recurrent solid tumor submitted for NGS according to their sample size, acquisition method, organ, and fixation to propose appropriate tissue requirements.Of the 1564 tissue samples, 481 (30.8%) consisted of fresh-frozen (FF) tissue, and 1,083 (69.2%) consisted of formalin-fixed paraffin-embedded (FFPE) tissue. We obtained successful NGS results in 95...
April 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28476736/nccn-guidelines-insights-hepatobiliary-cancers-version-1-2017
#10
Al B Benson, Michael I D'Angelica, Daniel E Abbott, Thomas A Abrams, Steven R Alberts, Daniel Anaya Saenz, Chandrakanth Are, Daniel B Brown, Daniel T Chang, Anne M Covey, William Hawkins, Renuka Iyer, Rojymon Jacob, Andrea Karachristos, R Kate Kelley, Robin Kim, Manisha Palta, James O Park, Vaibhav Sahai, Tracey Schefter, Carl Schmidt, Jason K Sicklick, Gagandeep Singh, Davendra Sohal, Stacey Stein, G Gary Tian, Jean-Nicolas Vauthey, Alan P Venook, Andrew X Zhu, Karin G Hoffmann, Susan Darlow
The NCCN Guidelines for Hepatobiliary Cancers provide treatment recommendations for cancers of the liver, gallbladder, and bile ducts. The NCCN Hepatobiliary Cancers Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize the panel's discussion and most recent recommendations regarding locoregional therapy for treatment of patients with hepatocellular carcinoma...
May 2017: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/28468016/treating-hepatobiliary-cancers-the-oncology-way
#11
Peter Robert Galle
Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related deaths worldwide. HCC represents more than 90% of primary liver cancers. There is growing incidence of HCC worldwide. In the western world, HCC arises in a cirrhotic background in up to 90% of cases, and cirrhosis itself is a progressive disease that affects patient survival. Thus, outcome in patients with HCC and the chances for anti-tumor treatment and it is results are dependent not only on tumor-associated factors but also on the liver function...
2017: Digestive Diseases
https://www.readbyqxmd.com/read/28468006/treating-hepatobiliary-cancer-the-immunologic-approach
#12
A G Duffy, T F Greten
Hepatobiliary cancer comprises a heterogeneous group of malignancies in which the standard treatments for advanced disease are minimally effective and evolve slowly over time. Like the majority of gastrointestinal cancers, with some notable exceptions, the impact of immune-based approaches is yet to be experienced. Notwithstanding this, the etiological background of hepatobiliary cancer - overlapping in almost every known causative or associated factor with inflammation - provides a strong clue that these approaches may have an impact on this group of diseases...
2017: Digestive Diseases
https://www.readbyqxmd.com/read/28451831/enhancing-the-therapeutic-range-of-a-targeted-small-molecule-tubulysin-conjugate-for-folate-receptor-based-cancer-therapy
#13
Christopher P Leamon, Joseph A Reddy, Iontcho R Vlahov, Ryan Dorton, Alicia Bloomfield, Marilynn Vetzel, Patrick J Klein, Elaine Westrick, Le-Cun Xu, Yu Wang
PURPOSE: EC0305 represents a folate-tubulysin B construct capable of specifically eradicating folate receptor (FR)-positive subcutaneous tumors from mice (Leamon et al., Cancer Res 68:9839-9844, 8). Herein we report on the use of multiple polar carbohydrate segments (e.g. 1-amino-1-deoxy-glucitolyl-γ-glutamate) placed in-between the folate and tubulysin B moieties of EC0305 creating a new conjugate, herein referred to as EC0531, with more desirable biological properties. METHODS: The synthesis of EC0531 and its tritium-labeled counterpart are described...
June 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28418841/circulating-uric-acid-levels-and-subsequent-development-of-cancer-in-493-281-individuals-findings-from-the-amoris-study
#14
Andrew Yiu, Mieke Van Hemelrijck, Hans Garmo, Lars Holmberg, Håkan Malmström, Mats Lambe, Niklas Hammar, Göran Walldius, Ingmar Jungner, Wahyu Wulaningsih
OBJECTIVES: Serum uric acid has been suggested to be associated with cancer risk. We aimed to study the association between serum uric acid and cancer incidence in a large Swedish cohort. RESULTS: A positive association was found between uric acid levels and overall cancer risk, and results were similar with adjustment for glucose, triglycerides and BMI. Hazard ratio (HR) for overall cancer for the 4th quartile of uric acid compared to the 1st was 1.08 (95% CI: 1...
March 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28417463/pharmacological-interventions-for-primary-sclerosing-cholangitis-an-attempted-network-meta-analysis
#15
REVIEW
Francesca Saffioti, Kurinchi Selvan Gurusamy, Neil Hawkins, Clare D Toon, Emmanuel Tsochatzis, Brian R Davidson, Douglas Thorburn
BACKGROUND: Primary sclerosing cholangitis is a chronic cholestatic liver disease that is associated with both hepatobiliary and colorectal malignancies, which can result in liver cirrhosis and its complications. The optimal pharmacological treatment for patients with primary sclerosing cholangitis remains controversial. OBJECTIVES: To assess the comparative benefits and harms of different pharmacological interventions in people with primary sclerosing cholangitis by performing a network meta-analysis, and to generate rankings of available pharmacological interventions according to their safety and efficacy...
March 28, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28404115/advances-in-primary-sclerosing-cholangitis
#16
REVIEW
Jennifer L Horsley-Silva, Elizabeth J Carey, Keith D Lindor
Primary sclerosing cholangitis is a chronic, progressive cholangiopathy that frequently affects men and is associated with inflammatory bowel disease. Although the cause of the disease is still debated, a genetic association and link to immune-mediated disease triggered by environmental factors are thought to contribute. The disease can present as isolated imaging abnormalities, biochemical changes, cholangiocarcinoma, or end-stage complications such as cirrhosis. Symptoms of primary sclerosing cholangitis include fatigue, jaundice, pruritus, or steatorrhoea...
September 2016: Lancet. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28385087/design-synthesis-and-evaluation-of-18-f-labeled-cationic-carbonic-anhydrase-ix-inhibitors-for-pet-imaging
#17
Zhengxing Zhang, Joseph Lau, Chengcheng Zhang, Nadine Colpo, Alessio Nocentini, Claudiu T Supuran, François Bénard, Kuo-Shyan Lin
Carbonic anhydrase IX (CA-IX) is a marker for tumor hypoxia, and its expression is negatively correlated with patient survival. CA-IX represents a potential target for eliminating hypoxic cancers. We synthesized fluorinated cationic sulfonamide inhibitors 1-3 designed to target CA-IX. The binding affinity for CA-IX ranged from 0.22 to 0.96 μM. We evaluated compound 2 as a diagnostic PET imaging agent. Compound 2 was radiolabeled with (18)F in 10 ± 4% decay-corrected radiochemical yield with 85.1 ± 70...
December 2017: Journal of Enzyme Inhibition and Medicinal Chemistry
https://www.readbyqxmd.com/read/28383652/th1-and-innate-lymphoid-cells-accumulate-in-primary-sclerosing-cholangitis-associated-inflammatory-bowel-disease
#18
Agnes Gwela, Priya Siddhanathi, Roger W Chapman, Simon Travis, Fiona Powrie, Carolina V Arancibia-Cárcamo, Alessandra Geremia
Background and Aims: Primary sclerosing cholangitis (PSC) is an idiopathic chronic disorder of the hepatobiliary system associated with inflammatory bowel disease (IBD), mainly ulcerative colitis (UC). Colitis in patients with PSC and UC (PSC-UC) exhibits characteristic features and is linked to increased colon cancer risk. Genetic studies have identified immune-related susceptibility genes that only partially overlap with those involved in IBD. These observations suggest that PSC-UC may represent a distinct form of IBD...
April 5, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/28378832/glypican-3-as-a-serum-marker-for-hepatoblastoma
#19
Shengmei Zhou, Maurice R G O'Gorman, Fusheng Yang, Kevin Andresen, Larry Wang
Hepatoblastoma (HB) is the most common primary liver cancer in children. The conventional serum marker for HB, alpha-fetoprotein (AFP), has its limitations. Novel serum markers need to be explored. Glypican 3 (GPC3) has been reported to be an excellent histological immunomarker for HB. However, the clinical value of serum GPC3 in patients with HB is unknown. A total of 184 serum samples were tested for both GPC3 by ELISA, and AFP by immunometric assay. Of these, 134 were from 32 patients with HB at three treatment stages, 30 from age-matched patients with benign hepatobiliary disorders (BHD) and 20 from age-matched "normal controls"(NC)...
April 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28377057/synthesis-and-evaluation-of-18-f-labeled-cj-042794-for-imaging-prostanoid-ep4-receptor-expression-in-cancer-with-positron-emission-tomography
#20
Zhengxing Zhang, Joseph Lau, Hsiou-Ting Kuo, Chengcheng Zhang, Nadine Colpo, François Bénard, Kuo-Shyan Lin
The potent and selective prostanoid EP4 receptor antagonist CJ-042794 was radiolabeled with (18)F, and evaluated for imaging EP4 receptor expression in cancer with positron emission tomography (PET). The fluorination precursor, arylboronic acid pinacol ester 4, was prepared in 4 steps with 42% overall yield. (18)F-CJ-042794 was synthesized via a copper-mediated (18)F-fluorination reaction followed by base hydrolysis, and was obtained in 1.5±1.1% (n=2) decay-corrected radiochemical yield. PET/CT imaging and biodistribution studies in mice showed that (18)F-CJ-042794 was excreted through both renal and hepatobiliary pathways with significant retention in blood...
March 27, 2017: Bioorganic & Medicinal Chemistry Letters
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