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1.
Esophagus ; 18(3): 566-573, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33661456

RESUMO

BACKGROUND: Circulating tumor cells (CTCs) are known to be a systemic process of malignant progression of cancer cells and there is a possibility that analysis for CTCs as a liquid biopsy become predictive or prognostic tools for cancer patients. METHODS: In the present study with the novel CTCs detection system (Celsee system®), we performed quantitative and qualitative analysis of CTCs in patients with esophageal squamous cell carcinoma (ESCC) receiving neoadjuvant chemotherapy (NAC) with 5FU + CDDP regimen. CTCs are defined as having both DAPI positive and CD45 negative. Vimentin-positive CTCs were defined as mesenchymal-type CTCs (M-CTCs), while epithelial-type CTCs (E-CTCs) were only positive for pan-cytokeratin. RESULTS: At the baseline, there are detectable amounts of CTCs in all patients (n = 30) at all stages, and there were no significant differences of total CTCs, E-CTCs, or M-CTCs numbers between stages. Of importance, among total CTCs, M-CTCs are more dominant than E-CTCs in number. Also, there was no significant change of detectable amounts and phenotype of CTCs before and after NAC (n = 24). Of note, early recurrent group indicated that there was an elevated total CTCs number before NAC and an increased M-CTCs after NAC in comparison to those in non-recurrent group. CONCLUSIONS: Quantitative and qualitative analysis of CTCs may provide useful complementary predictive and prognostic information in ESCC.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Células Neoplásicas Circulantes , Biomarcadores Tumorais , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/patologia , Humanos , Terapia Neoadjuvante , Células Neoplásicas Circulantes/patologia
2.
Esophagus ; 15(1): 1-9, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29892809

RESUMO

BACKGROUND: Immunotherapy has become a promising treatment strategy for cancer. Immune checkpoint blockade with anti-CTLA4 mAb and anti-PD-1 mAb has demonstrated clear evidence of objective responses including improved overall survival and tumor shrinkage, driving renewed enthusiasm for cancer immunotherapy in multiple cancer types including esophageal squamous cell carcinoma (ESCC). There are several clinical trials using anti-PD1 mAb for ESCC in early phases and the results are currently promising. RESULTS AND CONCLUSIONS: In this review, recent advances in cancer immunotherapy for ESCC are discussed with particular focus on immune checkpoint inhibitors and cancer vaccine.


Assuntos
Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias Esofágicas/tratamento farmacológico , Imunoterapia/métodos , Anticorpos Monoclonais/uso terapêutico , Vacinas Anticâncer/uso terapêutico , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Carcinoma de Células Escamosas do Esôfago , Humanos , Terapia de Alvo Molecular/métodos
3.
Cancer Med ; 7(7): 3321-3330, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29855157

RESUMO

Esophageal squamous cell carcinoma (ESCC) is an aggressive tumor, and it is urgently needed to develop novel therapeutic strategies including immunotherapy. In this study, we investigated the upregulation of the programmed death ligand 1 (PD-L1) due to epithelial-mesenchymal transition (EMT) in ESCC using an in vitro treatment system with the EMT inducer, glycogen synthase kinase (GSK)-3 inhibitor, and we also analyzed the correlation of EMT and PD-L1 expression in the clinical tumor samples of both tissue microarray (TMA) samples (n = 177) and whole tissue samples (n = 21). As a result, the inhibition of GSK-3ß induces EMT phenotype with upregulated vimentin and downregulated E-cadherin as well as increased Snail and Zinc finger E box-binding homeobox (ZEB)-1 gene expression. Simultaneously, we showed that EMT-converted ESCC indicated the upregulation of PD-L1 at both protein (total and surface) and mRNA levels. Of importance, we showed that EMT-converted tumor cells have a capability to induce T-cell apoptosis to a greater extent in comparison to original epithelial type tumor cells. Furthermore, the immunohistochemical stains of ESCC showed that PD-L1 expression on tumor cells was positively correlated with EMT status in TMA samples (P = .0004) and whole tissue samples (P = .0029). In conclusion, our in vitro and in vivo study clearly demonstrated that PD-L1 expression was upregulated in mesenchymal type tumors of ESCC. These findings provide a strong rationale for the clinical use of anti-PD-1/anti-PD-L1 monoclonal antibodies for advanced ESCC patients.

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