Current Management of Gallbladder Carcinoma

Zhu, Andrew X.; Hong, Theodore S.; Hezel, Aram F.; Kooby, David A.

doi:10.1634/theoncologist.2009-0302

Cited by 291 publications

(255 citation statements)

References 103 publications

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“…A recent review by Nakanishi and Toi (41) details the activation of NF-κB by chemotherapeutic agents as the major factor contributing to chemoresistance. MA can inhibit IKKα/β degradation, block p65 nuclear translocation and phosphorylation, and downregulate the expression levels of NF-κB-mediated genes/proteins involved in proliferation, apoptosis and invasion (42). As previously reported, proteins including cyclin D1, Bax, Bcl-2, MMP-2 and MMP-9, have been associated with tumor growth, apoptosis, invasion, and metastasis.…”

Section: Discussionsupporting

confidence: 56%

Maslinic acid potentiates the antitumor activities of gemcitabine in vitro and in vivo by inhibiting NF-κB-mediated survival signaling pathways in human gallbladder cancer cells

Wang

Xia

et al. 2015

Oncology Reports

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Abstract. Gemcitabine (GEM) is one of the first-line drugs in the treatment of gallbladder cancer (GBC), although the therapeutic effect is not sustained due to resistance to the drug over time. Maslinic acid (MA) has been shown to inhibit transcription factor nuclear factor-κB (NF-κB), resulting in the suppression of survival signaling. The authors of the present study investigated whether MA enhanced the antitumor activity of GEM in GBC. Anti-proliferative effects of MA, GEM and MA + GEM were assessed using the MTT assay. Apoptosis was assessed using Annexin V and by western blot analysis of various mediators of apoptosis. Xenograft tumors of EH-GB2 GBC cells were established in athymic nude mice and were monitored following treatment with MA, GEM and MA + GEM. Immunohistochemistry of the tumors was used to examine various survival proteins. MA inhibited the in vitro proliferation of various GBC cell lines and potentiated the apoptosis and cell invasion inhibition induced by GEM. Western blot analysis showed that the combination of MA and GEM inhibited constitutive NF-κB activation and NF-κB-regulated gene products, including cyclin D1, Bcl-2, Bax, MMP-2 and MMP-9, to a greater extent. In vivo, the group that was treated with MA + GEM showed significant reductions in tumor volume and a decreased expression of NF-κB-regulated gene products. In conclusion, the results suggest that MA potentiates the antitumor effects of GEM in human GBC cell lines by suppressing the activation of NF-κB and its dowstream gene products, which are involved in survival signaling. IntroductionGallbladder cancer (GBC) is the most common cancer of the bile duct system and is the fifth most lethal cancer of the digestive system (1). The incidence of GBC in China, Thailand, Chile and Northern India is higher when compared with the United States and European countries (2). At present, radical surgical resection is the most effective treatment of GBC. However, for the majority of patients, surgery is not curative because of late detection and/or early, regional or distant metastasis. Additionally, few patients experience complete responses to chemotherapy, mainly due to chemoresistance. Thus, identifying novel approaches to enhance the antitumor effects of chemotherapeutic drugs and reduce chemoresistance are imperative.Maslinic acid (MA), a pentacyclic triterpene acid, is widely present in dietary plants, especially in olive fruit skins and hawthorn berries (3). The compound has attracted much interest due to its proven pharmacological safety and its many biological activities, including anticancer such as anti-inflammation (2), anti-viral (4,5), anti-oxidation (6), anti-diabetogenic (7), anticolonic cancer (8,9) and anti-astrocytoma (10) activities. MA has been shown to potentiate the anticancer activity of TNF-α in pancreatic cancer cells through the inhibition of nuclear factor-κB (NF-κB) survival signaling pathways (11).NF-κB is a transcriptional activator that has been extensively studied for its role in controlling the expression of...

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Section: Discussionsupporting

confidence: 56%

Maslinic acid potentiates the antitumor activities of gemcitabine in vitro and in vivo by inhibiting NF-κB-mediated survival signaling pathways in human gallbladder cancer cells

Wang

Xia

et al. 2015

Oncology Reports

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“…This has poor prognosis due to aggressive biologic behavior and lack of screening tests for early diagnosis most of this type of malignances diagnosis in advance stage (9) and it is also most aggressive cancer of the biliary tract with shortest survival (10) . Chile has the highest rate of Gall Bladder cancer, followed by Bolivia and the Republic of Korea (South Korea).…”

Section: Discussionmentioning

confidence: 99%

Gall bladder Cancer Incidence Trend over the time period in Bengaluru Population Based Cancer Registry (1982-2012)

Vijay¹

2017

JMSCR

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“…However, GBC remains one of the understudied cancer types, with only a few studies on a limited number of samples (9)(10)(11). These studies and previous candidate gene-sequencing investigations indicate that GBC tumors from patients from different geographic regions may have different genetic architectures, suggesting the need for mutation exploration using a high-throughput NGS approach from varied populations (5,12).…”

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confidence: 91%

Targeted Gene Sequencing of Gallbladder Carcinoma Identifies High-impact Somatic and Rare Germline Mutations

Yadav

Sarkar

Kumari

et al. 2017

CGP

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Abstract. Background: Gallbladder carcinoma (GBC) isGallbladder carcinoma (GBC) is a type of biliary tract cancer, characterized by rapid progression and high mortality. Significant risk factors for GBC include presence of gallstones, chronic inflammation, anomalous pancreatobiliary ductal junctions, advancing age and female gender (1).Incidence and prevalence of GBC exhibit remarkable ethnic and geographical variability. This variability has been attributed to genetic predisposition and lifestyle habits or environmental exposure. The high incidence of GBC in the Indo-Gangetic belt and its poorly characterized molecular pathology have resulted in its reputation as an enigmatic Indian carcinoma (2). Until 2010, the genomic studies of GBC were limited to scanning a few common mutations in wellknown cancer-associated genes such as tumor protein p53 (TP53) and KRAS proto-oncogene, GTPase (KRAS) (3-5). Advancements in massively parallel sequencing technology, or next-generation sequencing (NGS), have propelled the area of cancer genomics and have greatly improved the understanding of tumorigenesis and tumor evolution linked with disease progression (6, 7). Application of NGS provides a means of high-throughput identification of cancer drivers and other genes that may be clinically relevant and or actionable for precision medicine (6). During the past decade, several large-scale cancer mutational landscape studies have contributed to the understanding of the existence of clonal variability within and across tumors in various common cancer types (8). However, GBC remains one of the understudied cancer types, with only a few studies on a limited number of samples (9-11). These studies and previous candidate gene-sequencing investigations indicate that GBC tumors from patients from different geographic regions may have different genetic architectures, suggesting the need for mutation exploration using a high-throughput NGS approach from varied populations (5, 12).The current treatment for patients with GBC is operative resection. However, resection is limited to cases that present at an early stage. GBCs which have progressed are largely incurable and the treatment mostly relies on focal radiation therapy and/or generic chemotherapy (12). The overall survival rate for patients with advanced GBC (stage 3 and 4) is very poor, and fewer than 10% survive for 5 years post 495 This article is freely accessible online.

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Current Management of Gallbladder Carcinoma

Abstract: ABSTRACT

Cited by 291 publications

References 103 publications

Maslinic acid potentiates the antitumor activities of gemcitabine in vitro and in vivo by inhibiting NF-κB-mediated survival signaling pathways in human gallbladder cancer cells

Maslinic acid potentiates the antitumor activities of gemcitabine in vitro and in vivo by inhibiting NF-κB-mediated survival signaling pathways in human gallbladder cancer cells

Gall bladder Cancer Incidence Trend over the time period in Bengaluru Population Based Cancer Registry (1982-2012)

Targeted Gene Sequencing of Gallbladder Carcinoma Identifies High-impact Somatic and Rare Germline Mutations

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