Simultaneous detection of epidermal growth factor receptor (EGF‐R), epidermal growth factor (EGF) and ras p21 in cholangiocarcinoma by an immunocytochemical method

Nonomura, Akitaka; Ohta, Goroku; Nakanuma, Yasuni; Izumi, Ryohei; Mizukami, Yuji; Matsubara, Fujitsugu; Hayashi, Morimoto; Watanabe, Kishichiro; Takayanagi, Nobutatsu

doi:10.1111/j.1600-0676.1988.tb00985.x

Cited by 43 publications

(21 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It is known that a subset of ICC exhibit overexpression of the EGF and HER-2 receptor [34] . Indeed, in our study group 21.3% (13/61) of ICC showed strong EGFR overexpression, which was confirmed by others [35] . Due to the relatively large subset of ICC with EGF or HER-2 expression activation of these ligands might be relevant for the progression of ICC.…”

Section: Activation By Growth Factorssupporting

confidence: 77%

AKT and ERK1/2 signaling in intrahepatic cholangiocarcinoma

Kj¹,

Schmitz²,

Lang³

et al. 2007

WJG

View full text Add to dashboard Cite

Intrahepatic cholangiocarcinomas (ICC) are neoplasms that originate from cholangiocytes and can occur at any level of the biliary tree. Surgical resection is the current therapy of choice for this highly aggressive cancer. However, the 5-year survival still is poor, with high recurrence rates. Due to the intrahepatic growth a significant proportion of patients present with advanced disease and are not candidates for curative surgery or transplantation. The existing palliative options are of limited benefit and there is a great necessity for novel therapeutic options. In this article we review the role of the phosphoinositide 3-kinase(PI3K)/ AKT and extracellular regulated kinase (ERK) signaling pathways in ICC and present new data on the prognostic value of these protein kinases. Finally, we discuss future upcoming therapeutic options based on targeting these signaling pathways.

show abstract

Section: Activation By Growth Factorssupporting

confidence: 77%

AKT and ERK1/2 signaling in intrahepatic cholangiocarcinoma

Kj¹,

Schmitz²,

Lang³

et al. 2007

WJG

View full text Add to dashboard Cite

show abstract

“…The epidermal growth factor receptor (EGFR), a transmembrane tyrosine kinase receptor, is widely expressed in various solid tumors, and its expression level is correlated with malignancy, metastatic phenotype and poor prognosis [1][2][3]. For these reasons, EGFR is considered an important target for cancer therapeutic reagents, including therapeutic antibodies.…”

Section: Introductionmentioning

confidence: 99%

Multimerization of anti‐(epidermal growth factor receptor) IgG fragments induces an antitumor effect: the case for humanized 528 scFv multimers

et al. 2013

View full text Add to dashboard Cite

The construction of antibody fragments has the potential to reduce the high cost of therapeutic antibody production, but the structures of these fragments, with monovalency and the lack of an Fc region, can lead to reduced function. Multimerization is one strategy for recovering function that also yields better tumor-to-blood ratios than IgGs or monomeric antibody fragments because of rapid tumor uptake and clearance. Here, we constructed single-chain variable fragment (scFv) multimers by modifying the linker length and domain order of humanized anti-(epidermal growth factor receptor) IgG 528 (h528) and tested their ability to inhibit tumor growth. h528 scFv multimers, expressed using a bacterial expression system, were successfully fractionated and inhibited cancer growth in a multimerization-dependent manner, whereas the h528 scFv monomer showed no inhibition. h528 scFv trimers with variable heavy-light domain order and no linkers showed the highest in vitro and in vivo antitumor effects, which were comparable with those of the approved anti-(epidermal growth factor receptor) therapeutic IgG Cetuximab and Panitumumab. The trimers were also structurally stable in vitro and in vivo, which may be attributable to a strong interaction between the variable heavy and variable light domains of h528 Fv. Thus, h528 scFv multimers, especially trimers, are attractive as the next generation of anti-(epidermal growth factor receptor) therapeutic IgG and offer the possibility of low-cost production.

show abstract

“…Some studies have demonstrated overexpression of EGFR and VEGFR, or mutations of their signaling pathways in biliary tract cancer [27]. Nonomura et al [28] reported overexpression rates by 32.4% of EGFR, by 59.5% of EGF, and by 89.2% of ras p21 in 37 intrahepatic cholangiocarcinomas, with all the rates being statistically significantly different as compared with those in normal tissues. Recently, Yoshikawa et al [29] demonstrated EGFR, VEGF and human epidermal growth factor receptor (HER) 2 overexpression in 27.4, 53.8 and 0.9% cases of intrahepatic cholangiocarcinoma, and in 19.2, 59.2 and 8.5% of cases of extrahepatic cholangiocarcinoma, respectively.…”

Section: Preclinical Studies Of the Molecular Biology Of Biliary Tracmentioning

confidence: 99%

Targeted therapy for biliary-tract cancer

Furuse

2010

The Lancet Oncology

View full text Add to dashboard Cite

Abstract:It is necessary to establish effective chemotherapy to improve the survival of patients with biliary tract cancer, because most of these patients are unsuitable candidates for surgery, and even patients undergoing curative surgery often have recurrence. Recently, the combination of cisplatin plus gemcitabine was reported to show survival benefits over gemcitabine alone in randomized clinical trials conducted in the United Kingdom and Japan. Thus, the combination of cisplatin plus gemcitabine is now recognized as the standard therapy for unresectable biliary tract cancer. One of the next issues that need to be addressed is whether molecular targeted agents might also be effective against biliary tract cancer. Although some targeted agents have been investigated as monotherapy for first-line chemotherapy, none were found to exert satisfactory efficacy. On the other hand, monoclonal antibodies such as bevacizumab and cetuximab have also been investigated in combination with a gemcitabine-based regimen and have been demonstrated to show promising activity. Furthermore, clinical trials using new targeted agents for biliary tract cancer are also proposed. This cancer is a relatively rare and heterogeneous tumor consisting of cholangiocarcinoma and gallbladder carcinoma. Therefore, a large randomized clinical trial is necessary to confirm the efficacy of chemotherapy, and international collaboration is important.

show abstract

Simultaneous detection of epidermal growth factor receptor (EGF‐R), epidermal growth factor (EGF) and ras p21 in cholangiocarcinoma by an immunocytochemical method

Cited by 43 publications

References 20 publications

AKT and ERK1/2 signaling in intrahepatic cholangiocarcinoma

AKT and ERK1/2 signaling in intrahepatic cholangiocarcinoma

Multimerization of anti‐(epidermal growth factor receptor) IgG fragments induces an antitumor effect: the case for humanized 528 scFv multimers

Targeted therapy for biliary-tract cancer

Contact Info

Product

Resources

About