• Journal of Life Science
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• v.29 no.4
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• pp.499-508
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• 2019

Cancer stem cells (CSCs), which are primarily responsible for metastasis and recurrence, have self-renewal, differentiation, therapeutic resistance, and tumor formation abilities. Numerous studies have demonstrated the signaling pathways essential for the acquisition and maintenance of CSC characteristics, such as WNT/${\beta}$-catenin, Hedgehog, Notch, B lymphoma Mo-MLV insertion region 1 homolog (BMI1), Bone morphogenetic protein (BMP), and TGF-${\beta}$ signals. However, few therapeutic strategies have been developed that can selectively eliminate CSCs. Recently, neutralizing antibodies against Cytotoxic T-lymphocyte associated protein 4 (CTLA-4) and Programmed cell death protein 1 (PD-1)/Programmed death-ligand 1 (PD-L1), immune checkpoint inhibitors (ICIs), have shown promising outcomes in clinical trials of melanoma, lung cancer, and pancreatic cancer, as well as in hematologic malignancies. ICIs are considered to outperform conventional anticancer drugs by maintaining long-lasting anti-cancer effects, with less severe side effects. Several studies reported that ICIs successfully blocked CSC properties in head and neck squamous carcinomas, melanomas, and breast cancer. Together, these findings suggest that novel and effective anticancer therapeutic modalities using ICIs for selective elimination of CSCs may be developed in the near future. In this review, we highlight the origin and characteristics of CSCs, together with critical signaling pathways. We also describe progress in ICI-mediated anticancer treatment to date and present perspectives on the development of CSC-targeting ICIs.

• Radiation Oncology Journal
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• v.24 no.1
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• pp.11-20
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• 2006

Puroose: In order to find out whether stereotactic radiation therapy (RT) using CyberKnife (CK) could improve survival rate and lower acute toxicity compared to conventional RT. Materials and Methods: From April 2003 through April 2004, 19 patients with Eastern Cooperative Oncology Group (ECOG) performance status ${\leq}3$ and locally advanced pancreas cancer without distant metastasis, evaluated by CT or PET/CT, were included. We administered stereotactic RT consisting of either 33 Gy, 36 Gy or 39 Gy in 3 fractions to 6, 4 and 9 patients, respectively, in an effort to increase the radiation dose step by step, and analyzed the survival rate and gastrointestinal toxicities by the acute radiation morbidity criteria of Radiation Therapeutic Oncology Group (RTOG). Prognostic factors of age, sex, ECOG performance score, chemotherapy, bypass surgery, radiation dose, CA 19-9, planning target volume (PTV), and adjacent organ and vessel invasion on CT scan were evaluated by Log Rank test. Results: The median survival time was 11 months with 1-year survival rate of 36.8%. During follow-up period (range $3{\sim}20$ months, median 10 months), no significant gastrointestinal acute toxicity (RTOG grade 3) was observed. In univariate analysis, age, sex, ECOG performance score, chemotherapy, bypass surgery, radiation dose, CA 19-9 level, and adjacent organ and vessel invasion did not show any significant changes of survival rate, however, patients with PTV (80 cc showed more favorable survival rate than those with PTV>80 cc (p-value<0.05). In multivariate analysis, age younger than 65 years and PTV>80 cc showed better survival rate. Conclusion: In terms of survival, the efficacy of stereotactic radiation therapy using CK was found to be superior or similar to other recent studies achieved with conventional RT with intensive chemotherapy, high dose conformal RT, intraoperative RT (IORT), or intensity modulated RT (IMRT). Furthermore, severe toxicity was not observed. Short treatment time in relation to the short life expectancy gave patients more convenience and, finally, quality of life would be increased. Consequently, this could be regarded as an effective novel treatment modality for locally advanced, unresectable pancreas cancer. PTV would be a helpful prognostic factor for CK.

• Journal of Gastric Cancer
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• v.9 no.3
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• pp.110-116
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• 2009

Purpose: The aim of this study was to examine the usefulness of positron emission tomography (PET)-computed tomography (CT) in the pre-operative staging of gastric cancer. Materials and Methods: Between February 2006 and August 2008, PET-CT and CT were performed on 70 patients diagnosed with gastric cancer by gastrofiberscopic biopsy. The sensitivities, specificities, Positive predictive value (PPV), and negative predictive value (NPV) of PET-CT and CT imaging for the detection of gastric cancer TNM staging were compared. Results: The detection rates for the primary tumor were as follows: PET-CT, 81.4% (57/70); and CT, 42.9% (30/70). For both early gastric cancer (EGC) and advanced gastric cancer (AGC), PET-CT was more accurate than CT in detecting the lesions. As the size of the tumor exceeded 3 cm, the detection rate increased. The sensitivities, specificities, PPV, and NPV of PET-CT for lymph node staging were 55.6%, 81%, 86.2%, and 45.9%, while the sensitivities, specificities, PPV, and NPV of CT were 40.0%, 85.7%, 85.7% and 40%, respectively. One case of multiple liver metastasis and two cases of dual primary cancer (rectal and pancreatic cancers) were detected by PET-CT. PET-CT also had a higher detection rate for all histologic types of primary tumors. PET-CT was more accurate than CT in detecting primary gastric cancer lesions. The detection of nodal metastasis by PET-CT was similar to CT; small-sized tumors or EGC detection rates were not high. However, PET-CT provided additional information to detect distant metastases and dual primary cancers and reduced unnecessary laparotomies to detect peritoneal seeding or carcinomatosis. Conclusion: It would be useful to make a pre-operative diagnosis of gastric cancer and determine treatment if PET-CT were added to other routine pre-operative studies.