DCK expression, a potential predictive biomarker in the adjuvant gemcitabine chemotherapy for biliary tract cancer after surgical resection: results from a phase II study

Woo, Sang Myung; Yoon, Kyong–Ah; Hong, Eun Kyung; Park, Weon Seo; Han, Sung‐Sik; Park, Sang-Jae; Joo, Jungnam; Park, Eun Young; Kim, Yun-Hee; Kim, Tae Hyun; Lee, Woojin

doi:10.18632/oncotarget.19037

Cited by 15 publications

(16 citation statements)

References 29 publications

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“…In cancer chemotherapy, dCK is an enzyme needed for phosphorylation of several deoxyribonucleosides and their nucleoside analogs such as gemcitabine and cytarabine and is known as a rate limiting enzyme in activation of these drugs. Furthermore, in addition to a report that the deficiency of dCK is involved in resistance to gemcitabine and cytarabine, it has also been reported that these drugs show very high anti-tumor efficacy in cancer cells that overexpress dCK (14)(15)(16)(17). We found for the first time that the expression levels of dCK increase with the acquisition of resistance to cetuximabin this study.…”

Section: Discussionsupporting

confidence: 69%

Exploration of Proteins Involved in Acquisition of Resistance to Cetuximab

Nakamura¹,

Nagamine²,

Yashima³

et al. 2019

Indo J Pharm

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Anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (Mabs) show high efficacy in about 50% of colorectal cancer (CRC) patients with wild-type KRAS. However, < 20% of patients with KRAS wild-type CRC have continued therapeutic effects with these agents, and acquired resistance to treatment has become a serious clinical problem. In this study, to clarify the factors related to acquisition of resistance to cetuximab (Cmab) and establish countermeasures against such acquired resistance, we conducted a comprehensive protein analysis via a proteomics approach using acquired resistance cell lines derived from Cmab-sensitive CRC cell lines and original cell lines. Cmab-acquired resistance cell lines were generated by continuous exposure of SW48 and C99 cell lines to Cmab. Expression of dCK and zinc finger and BTB domain-containing protein 41 (ZBTB41) increased more than 10-fold, and dual specificity protein phosphatase 3 (DUS3) expression decreased by less than 1/10 with acquisition of resistance to Cmab in both C99 and SW48 cell lines. Because overexpression of dCK is known as a positive indicator of efficacy of nucleoside analogs such as cytarabine or gemcitabine, it is considered that nucleoside analogs activated by dCK may be useful agents in treatment of cancers with acquired Cmab-resistance. In the future, we need to clarify the usefulness of these drugs for the treatment of Cmab resistant CRC and to assess the possibility of restoration of Cmab sensitivity by regulation of ZBTB41 and DUS3 expression.Keyword : cetuximab, colorectal cancer, acquired resistance, protein, dCK, ZBTB41

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Section: Discussionsupporting

confidence: 69%

Exploration of Proteins Involved in Acquisition of Resistance to Cetuximab

Nakamura¹,

Nagamine²,

Yashima³

et al. 2019

Indo J Pharm

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“…32 In line with the essential roles of hENT1 and dCK in gemcitabine metabolism, the hENT1 knockdown in biliary tract cancer cells 20 and dCK knockdown in pancreatic cancer cells 19 attenuated cell sensitivity to gemcitabine, which is consistent with the present results. High expression levels of hENT1 or dCK were associated with better survival in gemcitabine-treated cholangiocarcinoma 20 , 21 and pancreatic cancer, 17 , 18 , 22 , 23 indicating that the functional roles of hENT1 and dCK in vitro reflect their roles in gemcitabine sensitivity in clinical settings. Therefore, the present results demonstrated that patients with meningiomas expressing high levels of hENT1 and dCK may benefit from gemcitabine-based chemotherapy and, thus, clinical trials to test the efficacy of gemcitabine in high-grade meningiomas are warranted.…”

Section: Discussionmentioning

confidence: 98%

Roles for hENT1 and dCK in gemcitabine sensitivity and malignancy of meningioma

et al. 2021

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Background High-grade meningiomas are aggressive tumors with high morbidity and mortality rates that frequently recur even after surgery and adjuvant radiotherapy. However, limited information is currently available on the biology of these tumors and no alternative adjuvant treatment options exist. Although we previously demonstrated that high-grade meningioma cells were highly sensitive to gemcitabine in vitro and in vivo, the underlying molecular mechanisms remain unknown. Methods We examined the roles of hENT1 and dCK in the gemcitabine sensitivity and growth of meningioma cells in vitro. Tissue samples from meningiomas (26 WHO grade I and 21 WHO grade II/III meningiomas) were immunohistochemically analyzed for hENT1 and dCK as well as for Ki-67 as a marker of proliferative activity. Results hENT1 and dCK, which play critical roles in the intracellular transport and activation of gemcitabine, respectively, were responsible for the high gemcitabine sensitivity of high-grade meningioma cells and were strongly expressed in high-grade meningiomas. hENT1 expression was required for the proliferation and survival of high-grade meningioma cells and dCK expression. Furthermore, high hENT1 and dCK expression levels correlated with stronger tumor cell proliferative activity and shorter survival in meningioma patients. Conclusions The present results suggest that hENT1 is a key molecular factor influencing the growth capacity and gemcitabine sensitivity of meningioma cells and also that hENT1, together with dCK, may be a viable prognostic marker for meningioma patients as well as a predictive marker of their responses to gemcitabine.

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“…Although the incidence of BTC is relatively low, the heavy disease burden is associated with poor survival outcome. Even if BTC is diagnosed at an early stage and curative resection is performed, a short recurrence-free survival (11–20 months) and a high recurrence rate (53–62%) have been reported in previous studies [ 2 – 5 ]. Furthermore, most patients are initially diagnosed with advanced stage hepatobiliary cancer [ 6 ].…”

Section: Introductionmentioning

confidence: 96%

“…Identifying indicators that can predict the survival outcome of patients with advanced hepatobiliary cancers will help practitioners provide optimal care and management of these patients. According to recent studies, Child-Pugh score, body mass index (BMI), and aspartate aminotransferase (AST) for HCC and Eastern Cooperative Oncology Group Performance Status (ECOG-PS), carcinoembryonic antigen, carbohydrate antigen 19–9, hemoglobin (Hb), white blood cell (WBC), and albumin for BTCs have been identified as potential prognostic biomarkers for predicting survival in advanced hepatobiliary cancers [ 2 , 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Significance of serum ferritin as a prognostic factor in advanced hepatobiliary cancer patients treated with Korean medicine: a retrospective cohort study

Song

Kim

et al. 2018

BMC Complement Altern Med

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BackgroundAdvanced hepatobiliary cancers are highly lethal cancers that require precise prediction in clinical practice. Serum ferritin level increases in malignancy and high serum ferritin level is associated with poor survival in various cancers. This study aimed to identify whether serum ferritin could independently predict the overall survival (OS) of patients with advanced hepatobiliary cancers.MethodsThe retrospective cohort study was performed by reviewing medical records of patients with advanced hepatobiliary cancers from June 2006 to September 2016. The demographic and clinicopathological characteristics as well as the biochemical markers were evaluated at the initiation of Korean medicine (KM) treatment. The OS was calculated using Kaplan-Meier estimates. The Cox proportional hazard model was used to identify the independent prognostic significance of serum ferritin for survival.ResultsThe median OS of all subjects was 5.1 months (range, 0.5–114.9 months). The median OS of group with low ferritin levels and that with high ferritin levels was 7.5 months (range, 0.7–114.9 months) and 2.8 months (range, 0.5–22.8 months), respectively (P < 0.001). The results of the univariate analysis showed that the Eastern Cooperative Oncology Group Performance Status (ECOG-PS) (P = 0.002), tumor type (P = 0.001), prior treatment (P = 0.023), serum ferritin (P < 0.001), hemoglobin (P = 0.002), total bilirubin (P = 0.002), gamma-glutamyl transpeptidase (P = 0.007), albumin (P = 0.013), white blood cell (P = 0.002), and C-reactive protein (CRP) (P < 0.001) were significant factors for the patients’ survival outcome. On multivariate analysis controlling confounding factors, ferritin (P = 0.041), CRP (P = 0.010), ECOG-PS (P = 0.010), and tumor type (P = 0.018) were identified as independent prognostic factors for survival.ConclusionsThese results indicate that serum ferritin is a valid clinical biochemical marker to predict survival of patients with advanced hepatobiliary cancers.

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DCK expression, a potential predictive biomarker in the adjuvant gemcitabine chemotherapy for biliary tract cancer after surgical resection: results from a phase II study

Abstract: ABSTRACT

Cited by 15 publications

References 29 publications

Exploration of Proteins Involved in Acquisition of Resistance to Cetuximab

Exploration of Proteins Involved in Acquisition of Resistance to Cetuximab

Roles for hENT1 and dCK in gemcitabine sensitivity and malignancy of meningioma

Significance of serum ferritin as a prognostic factor in advanced hepatobiliary cancer patients treated with Korean medicine: a retrospective cohort study

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