CellSearch, the only approved epithelial cell adhesion molecule (EpCAM)‑dependent capture system approved for clinical use, overlooks circulating tumor cells (CTCs) undergoing epithelial‑mesenchymal transition (EMT‑CTCs), which is considered a crucial subtype responsible for metastasis. To address this limitation, a novel polymeric microfluidic device 'CTC‑chip' designed for the easy introduction of any antibody was developed, enabling EpCAM‑independent capture. In this study, antibodies against EpCAM and cell surface vimentin (CSV), identified as cancer‑specific EMT markers, were conjugated onto the chip (EpCAM‑chip and CSV‑chip, respectively), and the capture efficiency was examined using lung cancer (PC9, H441 and A549) and colon cancer (DLD1) cell lines, classified into three types based on EMT markers: Epithelial (PC9), intermediate (H441 and DLD1) and mesenchymal (A549).
View Article and Find Full Text PDFWe investigated the effect of preoperative therapy for non-small cell lung cancer on programmed death-ligand 1 (PD-L1), programmed death-1 (PD-1), poliovirus receptor (CD155), and T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT) expression and prognosis with the cases of 28 patients received preoperative concurrent chemo-radiotherapy (cCRT) and 27 received preoperative drug therapy. The post-treatment PD-L1 expression was higher in cCRT group than in the drug therapy (50.0% vs 5.
View Article and Find Full Text PDFCD155 serves an important role in tumor progression by promoting cell proliferation and migration. CD155 is also involved in the immune evasion of tumor cells, which may cause the development and progression of tumors. Accordingly, CD155 has emerged as a novel target in cancer immunotherapy; however, its expression in lung cancer remains unclear.
View Article and Find Full Text PDFDetecting rare circulating tumor cells (CTCs) in the bloodstream is extremely challenging. We had previously developed a novel polymeric microfluidic device, "CTC-chip," for capturing CTCs and have shown high capture efficiency in lung cancer cell lines by conjugating Abs against epithelial cell adhesion molecules (EpCAM). This study aimed to optimize the EpCAM-chip and clarify the prognostic impact of CTCs in lung cancer patients.
View Article and Find Full Text PDFAnaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKIs) have improved clinical outcomes in non-small cell lung cancer (NSCLC) harboring ALK- rearrangements. However, a small population of tumor cells survives due to adaptive resistance under drug pressure and ultimately acquires drug resistance. Thus, it is necessary to elucidate the mechanisms underlying the prevention of drug resistance to improve the prognosis of patients with ALK-rearranged NSCLC.
View Article and Find Full Text PDFIn our previous study, a microfluidic system was developed based on podoplanin detection for capturing circulating tumor cells (CTCs), derived from malignant pleural mesothelioma (MPM). However, non-epithelioid MPM shows low podoplanin protein expression compared with that in epithelioid MPM; thus, some CTC populations may be missed. To overcome this limitation, a new CTC-detection chip was developed by combining the conventional podoplanin antibody (clone: NZ-1.
View Article and Find Full Text PDFCirculating tumor cell (CTC) is a potentially useful surrogate of micro-metastasis, but detection of rare tumor cells contaminated in a vast majority of normal hematologic cells remains technical challenges. To achieve effective detection of a variety of CTCs, we have developed a novel microfluidic system (CTC-chip) in which any antibody to capture CTCs is easily conjugated. In previous studies, we employed an antibody (clone E-1) against podoplanin that was strongly expressed on mesothelioma cells.
View Article and Find Full Text PDFThe prognostic impact of tumoral programmed death-ligand 1 (PD-L1) expression in correlation with neutrophil-to-lymphocyte ratio (NLR) was retrospectively assessed in 83 patients with completely resected stage I squamous cell carcinoma of the lung, as PD-L1 is a potent regulator of cancer immunity and NLR is a potential surrogate of immune status. Forty-three patients (51.8%) had tumor with positive PD-L1 expression.
View Article and Find Full Text PDFGen Thorac Cardiovasc Surg
June 2020
Purpose: The impact of perioperative heparin bridging (HB) for lung surgery in patients on anti-clotting drugs remains unclear. We performed a retrospective study to assess its effect on surgical safety by comparing HB and non-HB groups.
Methods: This study included 274 consecutive patients on anti-clotting drugs who underwent surgery for lung cancer.
Purpose: To assess the efficacy and feasibility of perioperative pirfenidone treatment (PPT) in lung cancer patients with idiopathic pulmonary fibrosis (IPF).
Methods: The subjects of this retrospective review were 100 patients diagnosed with IPF, who underwent surgical resection for primary lung cancer between January 2011 and April 2018 at our institution. We compared the clinical outcomes of patients treated with pirfenidone (PPT group; n = 28) and those of patients not treated with pirfenidone (non-PPT group; n = 72).
Background: Consolidation treatment with an anti-PD-L1 antibody, durvalumab, following concurrent chemo-radiotherapy (cCRT) has become a new standard of care for locally advanced non-small cell lung cancer (NSCLC). The rationale of PD-L1 blockade after cCRT is based on preclinical evidence suggesting that chemotherapy and radiotherapy up-regulate tumoural PD-L1 expression, which has not been shown in clinical studies.
Methods: To examine alteration in tumoural PD-L1 expression (tumour proportion score, TPS) and density of stromal CD8-positive tumour-infiltrating lymphocytes (CD8 + TILs) after cCRT, paired NSCLC samples obtained before and after cCRT were reviewed in comparison with those obtained before and after drug therapy.
Background: Recent retrospective studies have shown that salvage surgery can improve survival with acceptable adverse events, and this procedure has been adapted for lung cancer. However, there are no reports demonstrating the efficacy of salvage surgery combined with aortic resection.
Case Presentation: A 73-year-old man had received definitive concurrent chemoradiotherapy (carboplatin/paclitaxel, 70 Gy) for lung cancer originated from the left upper lobe and infiltrating the thoracic aorta (cT4N1M0 stage IIIA).
The discovery of activating mutations in the epidermal growth factor receptor (EGFR) gene and development of tyrosine kinase inhibitors (TKIs) of EGFR have achieved a paradigm shift in treatment strategy of non-small cell lung cancer (NSCLC). For advanced NSCLC harboring activating EGFR mutations, an EGFR-TKI is preferably prescribed as it provides a superior survival benefit over platinum-based chemotherapy. To further improve the therapeutic outcomes, more potent EGFR-TKIs through irreversible inhibition of tyrosine kinase have been developed.
View Article and Find Full Text PDFBackground: Although immune checkpoint inhibitors (ICIs) for non-small cell lung cancer (NSCLC) have been established as one of standard therapy, the prognostic factors of ICIs remain unclear, aside from the programed cell death-ligand 1 (PD-L1) expression of tumor cells. The aim of this study was to determine the prognostic factors of ICIs.
Methods: We analyzed the clinicopathological data of 44 cases of advanced NSCLC targeted with ICIs in our hospital, between February 2016 and February 2018, in order to determine the prognostic factors of ICIs.
Gen Thorac Cardiovasc Surg
February 2020
We herein report the case of a 62-year-old man who underwent extrapleural pneumonectomy (EPP) for pleural epithelial hemangioendothelioma (EHE) diagnosed by a pleural biopsy. Pre-operative computed tomography revealed diffuse pleural thickening and pleural effusion in the right thoracic cavity, although metastasis to neither the lymph nodes nor distant organs was detected. We decided to perform EPP based on surgical findings that the tumor had invaded the lung parenchyma.
View Article and Find Full Text PDFBackground: Fenestration is performed in patients with bronchopleural fistula to avoid a life-threatening situation. However, usually, this procedure is required 9-cm mean length of the incision with rib resection.
Case Presentation: A 73-year-old man underwent right lower lobectomy with lymph node dissection (ND2a-2) for primary lung cancer (cT1cN2M0 Stage IIIA) with combined pulmonary fibrosis and emphysema.
Background: Pulmonary neuroendocrine tumor (NET) occurs with 20% of all lung cancers, and there are a limited number of literatures about the molecular aberrations, treatment and prognosis; especially in resected cases, as the operation indication for large cell neuroendocrine carcinoma (LCNEC) and small cell lung carcinoma (SCLC) is rare due to their aggressive behaviors. We investigated the relationship between postoperative survival and molecular expression patterns of pulmonary NET to establish a more effective treatment strategy.
Methods: In the present study, the curative surgical resection of pulmonary NET was reviewed retrospectively.
Gen Thorac Cardiovasc Surg
October 2019
We report the case of a 56-year-old woman who underwent pleural biopsy to identify the cause of the right pleural effusion. The pathological diagnosis was epithelial malignant pleural mesothelioma. The patient worked as a junior high school teacher and strongly hoped for continuing work.
View Article and Find Full Text PDFDetection of rare tumor cells circulating in the blood (CTCs) presents technical challenges. CellSearch, the only approved system for clinical use, fails to capture epithelial cell adhesion molecule-negative CTCs such as malignant pleural mesothelioma (MPM). We have developed a novel microfluidic device (CTC-chip) in which any Ab to capture CTCs is conjugated.
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