A novel panel of biomarkers predicts radioresistance in patients with squamous cell carcinoma of the head and neck

Åkervall, Jan; Nandalur, S.R.; Zhang, Jacob; Qian, Chao Nan; Goldstein, Neal S.; Gyllerup, Paulina; Gårdinger, Ylva; Alm, Jens; Lorenc, Katarina; Nilsson, Karolina; Resau, James H.; Wilson, George; Teh, Bin Tean

doi:10.1016/j.ejca.2013.11.007

Cited by 76 publications

(56 citation statements)

References 47 publications

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“…In rectal cancer patients undergoing concurrent chemoradiotherapy, high expression of metastasis-associated in colon cancer-1 and c-MET was revealed to be associated with a reduced relapse-free survival rate and an adverse prognosis (23). Therefore, targeting c-MET may exhibit a synergistic effect with chemotherapy or radiotherapy (24,25). The present findings are consistent with previous studies (26)(27)(28)(29).…”

Section: Discussionsupporting

confidence: 83%

c-MET inhibition enhances the response of the colorectal cancer cells to irradiation in vitro and in vivo

et al. 2016

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Abstract. The aim of the present study was to investigate the effect of hepatocyte growth factor receptor (c-MET) inhibition on the viability of colon cancer cells and xenografts exposed to irradiation using short hairpin (sh)RNA or the c-MET inhibitor PHA665752. The underlying mechanisms were also investigated. Human colorectal adenocarcinoma HT-29 cells were infected with a lentivirus expressing shRNAs against c-MET and were irradiated at 0, 2, 4, 6 and 8 Gy. The viability of the cells was assessed by alamarBlue ® assays. Mice bearing human colon carcinoma SW620 xenografts were randomly selected to receive 2.5% dimethyl sulfoxide (DMSO), 25 mg/kg PHA665752 intraperitoneally once every 2 days for 3 weeks, irradiation at 10 Gy, or 25 mg/kg PHA665752 intraperitoneally once every 2 days for 3 weeks followed 24 h later by irradiation at 10 Gy. The mean tumor volume (MTV) was measured. The apoptotic rate of cells was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assays, and double stranded break marker antibody γ-H2AX and hypoxia inducible factor (HIF)-1α expression was examined by immunohistochemistry. alamarBlue assays revealed that c-MET downregulation by shRNA markedly accentuated the irradiation-induced reduction in the viability of HT-29 cells compared with HT-29 cells irradiated at the same doses (P<0.05). A combination of irradiation and PHA665752 caused an additional reduction in the MTV (382.8±42.4 mm 3 ; P<0.01 vs. irradiation and PHA665752, 998.0±180.6 and 844.8±190.0 mm 3 , respectively). TUNEL assays revealed that irradiation and PHA665752 alone caused significant apoptosis of the SW620 cells in the tumor xenografts (P<0.01 vs. DMSO). The apoptotic index in the tumor xenografts of mice treated with a combination of irradiation and PHA665752 was significantly increased compared with mice treated with either agent alone (P<0.01). The combination of irradiation and PHA665752 was also associated with a marked increase in γ-H2AX levels and a significant decrease in HIF-1α expression in the xenografts (P<0.01). In conclusion, c-MET inhibition sensitizes colorectal cancer cells to irradiation by enhancing the formation of DNA double strand breaks and possibly alleviating tumor hypoxia. IntroductionWorldwide, colorectal cancer (CRC) is the third most common cancer (1). Currently, the standard regimen for newly diagnosed patients with locally advanced rectal cancer (grade, cT3/T4 and cN + ) is surgery in combination with neoadjuvant radiochemotherapy (2,3). However, the majority of patients have mid to advanced stage CRC at the time of diagnosis. Neoadjuvant radiochemotherapy improves the survival and anus-preservation rates by shrinking tumors, decreasing the clinical stage and reducing the pathological grade (4). While patients with local CRC have a more favorable outcome, with a 5-year survival rate of 90%, patients with metastatic CRC have a poor 5-year survival rate of 12%, despite the good therapeutic regimens that are available, including surgical resection, ad...

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Section: Discussionsupporting

confidence: 83%

c-MET inhibition enhances the response of the colorectal cancer cells to irradiation in vitro and in vivo

et al. 2016

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“…A strong correlation of claudin-4 expression and poor patient survival was also reported in a few cancers, such as gastric adenocarcinoma and endometrial carcinoma [15,37]. In addition, based on a recent gene expression profiling study, claudin-4 was found to be a predictive marker for the poor response to radiation therapy of patients with head and neck SCC [38]. However, we did not find any significant relationships between the claudin-4 expression and patient clinical-pathologic features or survival data.…”

Section: Discussionmentioning

confidence: 98%

Overexpression of Claudin-1 is Associated with Advanced Clinical Stage and Invasive Pathologic Characteristics of Oral Squamous Cell Carcinoma

Sappayatosok

Phattarataratip

2014

Head and Neck Pathol

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Claudins constitute a group of principal proteins forming the tight junctional complex. The altered expression of selected claudins has been reported in several human cancers. The purpose of this study was to investigate the expression of claudin-1 and claudin-4 in oral squamous cell carcinoma (OSCC) and examine its relationship with patient clinical-pathologic features. Fortyfive OSCC cases were enrolled. Patient clinical, pathologic and follow-up data were reviewed and the claudin-1 and claudin-4 expression was analyzed immunohistochemically. Positive claudin-1 and claudin-4 immunoreactivities were noted in 86.7 and 80 % of cases, respectively. The majority of cases showed the staining in less than 25 % of cancer cells. The increased claudin-1 expression was significantly associated with the high pathologic grade, the presence of microscopic perineural invasion, vascular invasion, nodal metastasis, and advanced clinical stage. No relationship between various clinico-pathologic parameters and differential claudin-4 expression was observed.Claudin-1 may play a role in OSCC progression and could serve as a prognostic marker of advanced disease.

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“…With this personalized approach the chance of cure could be increased in sensitive, normal and resistant patients. The molecular mechanisms for the known hypersensitivity still remain obscure and there are no universally valid predictive biomarkers for radio-sensitivity available (Akervall et al, 2014;Chua and Rothkamm, 2013;Horn et al, 2013;Mabert et al, 2014;Pernot et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

The inter-individual variability outperforms the intra-individual variability of differentially expressed proteins prior and post irradiation in lymphoblastoid cell lines

Guertler

Hauptmann

Pautz

et al. 2014

Archives of Physiology and Biochemistry

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A novel panel of biomarkers predicts radioresistance in patients with squamous cell carcinoma of the head and neck

Cited by 76 publications

References 47 publications

c-MET inhibition enhances the response of the colorectal cancer cells to irradiation in vitro and in vivo

c-MET inhibition enhances the response of the colorectal cancer cells to irradiation in vitro and in vivo

Overexpression of Claudin-1 is Associated with Advanced Clinical Stage and Invasive Pathologic Characteristics of Oral Squamous Cell Carcinoma

The inter-individual variability outperforms the intra-individual variability of differentially expressed proteins prior and post irradiation in lymphoblastoid cell lines

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