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Artikel ; Online: Large-vessel vasculitis possibly induced by BRAF and MEK inhibitors for BRAF V600E positive lung adenocarcinoma.

Ichikawa, Kento / Ohno, Shigeru / Kubo, Sousuke / Nakajima, Hideaki

BMJ case reports

2024 Band 17, Heft 5

Abstract: The combination therapy of v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) and mitogen-activated protein kinase kinase (MEK) inhibitors is approved for treating patients with BRAF V600E-positive tumours, including melanoma and lung cancer. Several ... ...

Abstract	The combination therapy of v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) and mitogen-activated protein kinase kinase (MEK) inhibitors is approved for treating patients with BRAF V600E-positive tumours, including melanoma and lung cancer. Several case reports indicated autoimmune side effects associated with the use of BRAF and MEK inhibitors. Still, the effects of these drugs on the immune system were not fully elucidated. Here, we report a patient with large-vessel vasculitis diagnosed after initiation of treatment with dabrafenib and trametinib for BRAF V600E-positive metastatic lung adenocarcinoma. She was a never-smoker woman in her early 70s who presented with a chronic cough and was diagnosed with BRAF V600E-positive metastatic lung adenocarcinoma by transbronchial lung biopsy. She was successfully treated with prednisolone and methotrexate while BRAF and MEK inhibitors were continued. We should be careful about autoimmune diseases using BRAF and MEK inhibitors.
Mesh-Begriff(e)	Humans ; Proto-Oncogene Proteins B-raf/antagonists & inhibitors ; Proto-Oncogene Proteins B-raf/genetics ; Female ; Pyridones/adverse effects ; Pyridones/therapeutic use ; Pyrimidinones/therapeutic use ; Pyrimidinones/adverse effects ; Lung Neoplasms/drug therapy ; Aged ; Adenocarcinoma of Lung/drug therapy ; Imidazoles/adverse effects ; Imidazoles/therapeutic use ; Oximes/adverse effects ; Oximes/therapeutic use ; Vasculitis/chemically induced ; Protein Kinase Inhibitors/adverse effects ; Protein Kinase Inhibitors/therapeutic use ; Prednisolone/therapeutic use ; Methotrexate/therapeutic use ; Methotrexate/adverse effects ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use
Chemische Substanzen	Proto-Oncogene Proteins B-raf (EC 2.7.11.1) ; Pyridones ; Pyrimidinones ; trametinib (33E86K87QN) ; Imidazoles ; dabrafenib (QGP4HA4G1B) ; Oximes ; Protein Kinase Inhibitors ; BRAF protein, human (EC 2.7.11.1) ; Prednisolone (9PHQ9Y1OLM) ; Methotrexate (YL5FZ2Y5U1)
Sprache	Englisch
Erscheinungsdatum	2024-05-08
Erscheinungsland	England
Dokumenttyp	Case Reports ; Journal Article
ISSN	1757-790X
ISSN (online)	1757-790X
DOI	10.1136/bcr-2023-255958
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Regional differences in epidermal growth factor receptor-tyrosine kinase inhibitor therapy in lung cancer treatment using a national database in Japan.

Matsumoto, Hiromi / Kobayashi, Nobuaki / Shinoda, Satoru / Goto, Atsushi / Kaneko, Ayami / Fukuda, Nobuhiko / Kamimaki, Chisato / Kubo, Sousuke / Watanabe, Keisuke / Horita, Nobuyuki / Hara, Yu / Ishikawa, Yoshihiro / Kaneko, Takeshi

Scientific reports

2023 Band 13, Heft 1, Seite(n) 5208

Abstract: Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are extensively used in the treatment of non-small cell lung cancer (NSCLC); hence, equal access to them is important. Therefore, this study aimed to identify regional differences in ...

Abstract	Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are extensively used in the treatment of non-small cell lung cancer (NSCLC); hence, equal access to them is important. Therefore, this study aimed to identify regional differences in the prescription of EGFR-TKIs and the factors contributing to these differences. In this ecological study, we collected data using the National Database Open Data and the National Cancer Registry. The standardized claim ratio (SCR) was used as an indicator of the number of EGFR-TKI prescriptions. Additionally, we examined the association between SCR and various factors to identify the factors associated with this difference. The average SCR for the top three provinces was 153.4, while the average for the bottom three provinces was 61.6. Multivariate analysis used for evaluating the association of SCR with variables revealed that the number of designated cancer hospitals and radiation therapies were independent factors associated with the SCR of EGFR-TKIs. There were significant regional differences in the prescriptions of EGFR-TKIs in Japan based on the number of coordinated designated cancer hospitals and the number of patients receiving radiotherapy alone. These findings emphasize the need to implement policies to increase the number of hospitals to reduce regional differences.
Mesh-Begriff(e)	Humans ; Lung Neoplasms/drug therapy ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Tyrosine Kinase Inhibitors ; Japan ; ErbB Receptors/genetics ; Protein Kinase Inhibitors/therapeutic use ; Protein Kinase Inhibitors/pharmacology ; Mutation
Chemische Substanzen	Tyrosine Kinase Inhibitors ; ErbB Receptors (EC 2.7.10.1) ; Protein Kinase Inhibitors
Sprache	Englisch
Erscheinungsdatum	2023-03-30
Erscheinungsland	England
Dokumenttyp	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-31856-6
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Thymic atypical carcinoid tumors with elevated mitotic counts in a patient with multiple endocrine neoplasia: A case report.

Hiro, Shuntaro / Teranishi, Shuhei / Sawazumi, Tomoe / Nagaoka, Satoshi / Sugimoto, Chihiro / Nagayama, Hirokazu / Segawa, Wataru / Kajita, Yukihito / Maeda, Chihiro / Kubo, Sousuke / Seki, Kenichi / Tashiro, Ken / Kobayashi, Nobuaki / Yamamoto, Masaki / Kudo, Makoto / Kaneko, Takeshi

Thoracic cancer

2023 Band 14, Heft 14, Seite(n) 1311–1315

Abstract: Thymic neuroendocrine tumors associated with multiple endocrine neoplasia are only defined as carcinoid and are not associated with large-cell neuroendocrine carcinoma (LCNEC). We report the case of a multiple endocrine neoplasia type 1 patient with ... ...

Abstract	Thymic neuroendocrine tumors associated with multiple endocrine neoplasia are only defined as carcinoid and are not associated with large-cell neuroendocrine carcinoma (LCNEC). We report the case of a multiple endocrine neoplasia type 1 patient with atypical carcinoid tumors with elevated mitotic counts (AC-h), an intermediate condition between carcinoid and LCNEC. A 27-year-old man underwent surgery for an anterior mediastinal mass and was diagnosed with thymic LCNEC. Fifteen years later, a mass appeared at the same site, which was determined to be a postoperative recurrence based on the pathological results of a needle biopsy and the clinical course. The patient's disease remained stable for 10 months on anti-programmed death-ligand 1 antibody and platinum-containing chemotherapy. The needle biopsy specimen was submitted for next-generation sequencing, which revealed a MEN1 gene mutation, and after further examination, a diagnosis of multiple endocrine neoplasia type 1 was made. A re-examination of the surgical specimen from 15 years prior showed that it corresponded to AC-h. Although thymic AC-h is classified as thymic LCNEC according to the current definition, our data suggests that a search for multiple endocrine neoplasia is warranted in such patients.
Mesh-Begriff(e)	Male ; Humans ; Adult ; Multiple Endocrine Neoplasia Type 1/complications ; Multiple Endocrine Neoplasia Type 1/genetics ; Multiple Endocrine Neoplasia Type 1/pathology ; Carcinoid Tumor/genetics ; Carcinoid Tumor/pathology ; Multiple Endocrine Neoplasia ; Neuroendocrine Tumors/pathology ; Thymus Neoplasms/diagnosis ; Thymus Neoplasms/genetics ; Thymus Neoplasms/surgery ; Thymoma/complications ; Carcinoma, Neuroendocrine/genetics
Sprache	Englisch
Erscheinungsdatum	2023-03-20
Erscheinungsland	Singapore
Dokumenttyp	Case Reports
ZDB-ID	2625856-0
ISSN	1759-7714 ; 1759-7706
ISSN (online)	1759-7714
ISSN	1759-7706
DOI	10.1111/1759-7714.14863
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Primary tracheal small-cell carcinoma detected 11 months after surgery for pulmonary large-cell neuroendocrine carcinoma: A case report.

Sugimoto, Chihiro / Teranishi, Shuhei / Sawazumi, Tomoe / Nagaoka, Satoshi / Nagayama, Hirokazu / Segawa, Wataru / Hiro, Shuntaro / Kajita, Yukihito / Maeda, Chihiro / Kubo, Sousuke / Seki, Kenichi / Tashiro, Ken / Kobayashi, Nobuaki / Yamamoto, Masaki / Kudo, Makoto / Kaneko, Takeshi

Thoracic cancer

2023 Band 14, Heft 13, Seite(n) 1212–1216

Abstract: Primary tracheal small-cell carcinoma is rare, and is often treated using small-cell lung cancer guidelines given that no standard treatment has been established for it. We report a patient in whom nodules appeared in the trachea and left main bronchus ... ...

Abstract	Primary tracheal small-cell carcinoma is rare, and is often treated using small-cell lung cancer guidelines given that no standard treatment has been established for it. We report a patient in whom nodules appeared in the trachea and left main bronchus 11 months after surgery for pulmonary large-cell neuroendocrine carcinoma; a biopsy revealed small-cell carcinoma. Given the absence of malignant lesions elsewhere in the body, the lesions were diagnosed as primary tracheal small-cell carcinoma. Respiratory failure progressed rapidly owing to airway stenosis caused by the growing lesion, and the patient required nasal high-flow therapy. However, the lesions shrank a few days after commencing first-line chemotherapy, and his respiratory failure resolved. Accelerated hyperfractionated radiotherapy was administered in conjunction with the third course of chemotherapy, and the patient ultimately achieved a complete response. Although the lesions were initially suspected of being postoperative recurrence of pulmonary large-cell neuroendocrine carcinoma, the fact that the biopsy revealed them to be primary tracheal small-cell carcinoma indicates that intra-airway nodules that appear after lung cancer surgery may possibly be primary tracheal tumors.
Mesh-Begriff(e)	Humans ; Trachea/pathology ; Lung Neoplasms/pathology ; Carcinoma, Small Cell/pathology ; Carcinoma, Neuroendocrine/pathology ; Small Cell Lung Carcinoma/pathology ; Carcinoma, Large Cell/pathology ; Respiratory Insufficiency/pathology
Sprache	Englisch
Erscheinungsdatum	2023-03-28
Erscheinungsland	Singapore
Dokumenttyp	Case Reports
ZDB-ID	2625856-0
ISSN	1759-7714 ; 1759-7706
ISSN (online)	1759-7714
ISSN	1759-7706
DOI	10.1111/1759-7714.14860
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Influence of age, IGRA results, and inflammatory markers on mortality in hospitalized tuberculosis patients.

Kobayashi, Nobuaki / Tanaka, Katsushi / Muraoka, Suguru / Somekawa, Kohei / Kaneko, Ayami / Kubo, Sousuke / Matsumoto, Hiromi / Fujii, Hiroaki / Watanabe, Keisuke / Horita, Nobuyuki / Hara, Yu / Kaneko, Takeshi

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy

2023 Band 30, Heft 1, Seite(n) 48–52

Abstract: Introduction: Tuberculosis (TB) remains a leading cause of death globally. Identifying the factors associated with mortality during hospitalization for TB is crucial for improving patient outcomes. This study aimed to investigate the potential risk ... ...

Abstract	Introduction: Tuberculosis (TB) remains a leading cause of death globally. Identifying the factors associated with mortality during hospitalization for TB is crucial for improving patient outcomes. This study aimed to investigate the potential risk factors, including T-SPOT.TB test results and routine laboratory markers of inflammation, associated with death during hospitalization due to TB. Methods: A retrospective analysis was conducted on 244 hospitalized TB patients. Demographic data, clinical characteristics, T-SPOT.TB results, and laboratory parameters were collected. Univariate and multivariate analyses were performed to identify independent risk factors for in-hospital mortality. Results: Among the patients, 206 survived and 38 died during hospitalization. Multivariate analysis revealed that age (HR: 1.08, 95% CI: 1.02-1.15, p = 0.001), a negative T-SPOT.TB test result (HR: 4.01, 95% CI: 1.78-9.01, p < 0.001), elevated C-reactive protein (CRP) levels (HR: 1.04, 95% CI: 1.01-1.08, p = 0.007), and increased neutrophil-to-lymphocyte ratio (NLR) (HR: 1.04, 95% CI: 1.00-1.07, p = 0.025) were independent risk factors for mortality. Conclusions: This study identified age, a negative T-SPOT.TB result, elevated CRP levels, and a high NLR as significant independent risk factors for death in hospitalized TB patients. These findings underscore the importance of these parameters in the risk stratification and management of hospitalized TB patients. Further research is warranted to elucidate the mechanisms behind these associations and to validate these results in different populations.
Mesh-Begriff(e)	Humans ; Interferon-gamma Release Tests ; Retrospective Studies ; Tuberculosis ; Risk Factors ; Hospital Mortality
Sprache	Englisch
Erscheinungsdatum	2023-09-12
Erscheinungsland	Netherlands
Dokumenttyp	Journal Article
ZDB-ID	1355399-9
ISSN	1437-7780 ; 1341-321X
ISSN (online)	1437-7780
ISSN	1341-321X
DOI	10.1016/j.jiac.2023.09.011
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Atezolizumab addition to platinum doublet: evaluating survival outcomes for patients with extensive disease small cell lung cancer.

Kubo, Sousuke / Kobayashi, Nobuaki / Matsumoto, Hiromi / Somekawa, Kohei / Kaneko, Ayami / Hashimoto, Hisashi / Teranishi, Shuhei / Watanabe, Keisuke / Horita, Nobuyuki / Hara, Yu / Kudo, Makoto / Kaneko, Takeshi

Journal of cancer research and clinical oncology

2023 Band 149, Heft 19, Seite(n) 17419–17426

Abstract: Background: The efficacy of adding atezolizumab to the platinum doublet regimen for extensive disease small cell lung cancer (ED-SCLC) remains marginally limited.: Methods: We retrospectively assessed the real-world efficacy and safety of ... ...

Abstract	Background: The efficacy of adding atezolizumab to the platinum doublet regimen for extensive disease small cell lung cancer (ED-SCLC) remains marginally limited. Methods: We retrospectively assessed the real-world efficacy and safety of atezolizumab in addition to carboplatin and etoposide (EP + A), versus carboplatin and etoposide (EP) alone in previously untreated ED-SCLC patients. Results: From a total of 99 patients, 46 were assigned to the EP + A group, and 53 to the EP group. No significant difference was observed in progression-free survival between the groups. However, the overall survival (OS) was significantly longer in the EP + A group (20.8 vs 12.1 months; HR: 0.52; p = 0.0127). Patients older than 70 years, male, with performance status 0-1, without liver metastasis, and low levels of C-reactive protein and neutrophil-lymphocyte ratio, experienced longer OS in the EP + A group compared to the EP group. Conclusion: The addition of atezolizumab to the platinum doublet regimen significantly extended OS in ED-SCLC patients, particularly among certain subgroups, suggesting its potential value in personalized treatment strategies. Further investigation is warranted to validate these findings.
Mesh-Begriff(e)	Humans ; Male ; Small Cell Lung Carcinoma/pathology ; Lung Neoplasms/pathology ; Carboplatin/adverse effects ; Etoposide/adverse effects ; Platinum/therapeutic use ; Cisplatin/adverse effects ; Retrospective Studies ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use
Chemische Substanzen	Carboplatin (BG3F62OND5) ; Etoposide (6PLQ3CP4P3) ; atezolizumab (52CMI0WC3Y) ; Platinum (49DFR088MY) ; Cisplatin (Q20Q21Q62J)
Sprache	Englisch
Erscheinungsdatum	2023-10-25
Erscheinungsland	Germany
Dokumenttyp	Journal Article
ZDB-ID	134792-5
ISSN	1432-1335 ; 0171-5216 ; 0084-5353 ; 0943-9382
ISSN (online)	1432-1335
ISSN	0171-5216 ; 0084-5353 ; 0943-9382
DOI	10.1007/s00432-023-05457-9
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel: Computed tomography imaging-based observation of the aggressive growth of angiosarcoma: a case study.

Kubo, Sousuke / Kobayashi, Nobuaki / Kaneko, Ayami / Aiko, Hiroko / Kudo, Makoto / Kaneko, Takeshi

Respirology case reports

2019 Band 7, Heft 8, Seite(n) e00479

Abstract: An 82-year-old man with chronic tuberculous empyema visited our hospital for an annual computed tomography (CT) scan. No differences were noted between the CT scan at presentation and a scan performed a year previously in August 2017. He began ... ...

Abstract	An 82-year-old man with chronic tuberculous empyema visited our hospital for an annual computed tomography (CT) scan. No differences were noted between the CT scan at presentation and a scan performed a year previously in August 2017. He began experiencing right chest, epigastrium, and back pain since the end of October 2017. A CT scan taken in November of 2017 to evaluate the pain in his right chest, epigastrium, and back showed an irregular thickening of the pleura adjacent to the empyema and an abnormal right seventh costal mass infiltrating the vertebral body. CT-guided needle biopsy of the mass showed angiosarcoma. Positron emission tomography/CT revealed multiple metastases in his bones and liver. Chemotherapy was not recommended owing to his poor performance status, which was related to angiosarcoma. Therefore, he was offered palliative radiotherapy for the metastasis to the vertebral body.
Sprache	Englisch
Erscheinungsdatum	2019-08-26
Erscheinungsland	United States
Dokumenttyp	Case Reports
ZDB-ID	2750180-2
ISSN	2051-3380
ISSN	2051-3380
DOI	10.1002/rcr2.479
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel: Improved diagnostic accuracy with three lung tumor markers compared to six-marker panel.

Translational lung cancer research

2024 Band 13, Heft 3, Seite(n) 503–511

Abstract: Background: Combining multiple tumor markers increases sensitivity for lung cancer diagnosis in the cost of false positive. However, some would like to check as many as tumor markers in the fear of missing cancer. We though to propose a panel of fewer ... ...

Abstract	Background: Combining multiple tumor markers increases sensitivity for lung cancer diagnosis in the cost of false positive. However, some would like to check as many as tumor markers in the fear of missing cancer. We though to propose a panel of fewer tumor markers for lung cancer diagnosis. Methods: Patients with suspected lung cancer who simultaneously underwent all six tests [carcinoembryonic antigen (CEA), cytokeratin-19 fragment (CYFRA), squamous cell carcinoma-associated antigen (SCC), neuron-specific enolase (NSE), pro-gastrin-releasing peptide (ProGRP), and sialyl Lewis-X antigen (SLX)] were included. Tumor markers with significant impact on the lung cancer in a logistic regression model were included in our panel. Area under the curve (AUC) was compared between our panel and the panel of all six. Results: We included 1,733 [median 72 years, 1,128 men, 605 women, 779 (45%) confirmed lung cancer]. Logistic regression analysis suggested CEA, CYFRA, and NSE were independently associated with the lung cancer diagnosis. The panel of these three tumor markers [AUC =0.656, 95% confidence interval (CI): 0.630-0.682, sensitivity 0.650, specificity 0.662] had better (P<0.001) diagnostic performance than six tumor markers (AUC =0.575, 95% CI: 0.548-0.602, sensitivity 0.829, specificity 0.321). Conclusions: Compared to applying all six markers (at least one marker above the upper limit of normal), the panel with three markers (at least one marker above the upper limit of normal) led to a better predictive value by lowering the risk of false positives.
Sprache	Englisch
Erscheinungsdatum	2024-03-15
Erscheinungsland	China
Dokumenttyp	Journal Article
ZDB-ID	2754335-3
ISSN	2226-4477 ; 2218-6751
ISSN (online)	2226-4477
ISSN	2218-6751
DOI	10.21037/tlcr-23-855
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Predictors of lung injury during durvalumab maintenance therapy following concurrent chemoradiotherapy in unresectable locally advanced non-small cell lung carcinoma.

Hirama, Nobuyuki / Yamamoto, Masaki / Nagaoka, Satoshi / Segawa, Wataru / Sugimoto, Chihiro / Nagayama, Hirokazu / Hiro, Shuntaro / Kajita, Yukihito / Maeda, Chihiro / Kubo, Sousuke / Seki, Kenichi / Nagahara, Yoshinori / Teranishi, Shuhei / Tashiro, Ken / Hara, Yu / Kobayashi, Nobuaki / Watanabe, Shigenobu / Kudo, Makoto / Kaneko, Takeshi

Thoracic cancer

2023 Band 14, Heft 25, Seite(n) 2601–2607

Abstract: Background: Based on the results of the PACIFIC trial, maintenance with durvalumab has emerged as the standard treatment following concurrent chemoradiotherapy in patients with unresectable locally advanced non-small cell lung carcinoma (NSCLC). However, ...

Abstract	Background: Based on the results of the PACIFIC trial, maintenance with durvalumab has emerged as the standard treatment following concurrent chemoradiotherapy in patients with unresectable locally advanced non-small cell lung carcinoma (NSCLC). However, adverse events attributed to durvalumab, especially lung injuries, including immune-related adverse events, and radiation pneumonitis, are concerning. This study retrospectively investigated the factors related to lung injury in patients receiving the PACIFIC regimen. Methods: Patients with unresectable locally advanced NSCLC who received durvalumab maintenance therapy following concurrent chemoradiotherapy at Yokohama City University Medical Centre between July 2018 and March 2022 were included. Clinical data, volume of normal lung receiving 20 or 5 Gy or more (V20 or V5), planning target volume (PTV), and relative lung parenchyma volume in emphysematous lung receiving 20 or 5 Gy or more (RLPV20 or 5; V20 or V5/100-percentage of low-attenuation volume) were evaluated. Results: Performance status (PS), V20, V5, PTV, RLPV20, and RLPV5 were significantly higher in the lung injury group in the univariate analysis. Furthermore, RLPV20 was the most significant factor in the lung injury group in the multivariate analysis comprising PS, PTV, V20, and RLPV20. Conclusion: RLPV20 and RLPV5 are useful in estimating lung inflammation. RLPV20 could be considered the most reliable risk factor for maintenance therapy with durvalumab following concurrent chemoradiotherapy in patients with unresectable locally advanced NSCLC.
Mesh-Begriff(e)	Humans ; Carcinoma, Non-Small-Cell Lung/pathology ; Lung Neoplasms/pathology ; Lung Injury/etiology ; Retrospective Studies ; Chemoradiotherapy/methods
Chemische Substanzen	durvalumab (28X28X9OKV)
Sprache	Englisch
Erscheinungsdatum	2023-08-02
Erscheinungsland	Singapore
Dokumenttyp	Journal Article
ZDB-ID	2625856-0
ISSN	1759-7714 ; 1759-7706
ISSN (online)	1759-7714
ISSN	1759-7706
DOI	10.1111/1759-7714.15042
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Class A CpG oligodeoxynucleotide inhibits IFN-γ-induced signaling and apoptosis in lung cancer.

Teranishi, Shuhei / Kobayashi, Nobuaki / Katakura, Seigo / Kamimaki, Chisato / Kubo, Sousuke / Shibata, Yuji / Yamamoto, Masaki / Kudo, Makoto / Piao, Hongmei / Kaneko, Takeshi

Thoracic cancer

2020 Band 11, Heft 4, Seite(n) 983–992

Abstract: Background: Currently, anticancer immunotherapy based on PD-1/PD-L1 blockade with immune checkpoint inhibitors (ICIs) is being used as a standard therapy for non-small cell lung cancer (NSCLC). However, more effective treatments are required as these ... ...

Abstract	Background: Currently, anticancer immunotherapy based on PD-1/PD-L1 blockade with immune checkpoint inhibitors (ICIs) is being used as a standard therapy for non-small cell lung cancer (NSCLC). However, more effective treatments are required as these tumors are often resistant and refractory. Here, we aimed to determine the effects of immunomodulatory oligodeoxynucleotides (ODNs) in terms of the presence or absence of CpG motifs and the number of consecutive guanosines. Methods: Western blots were used to measure the molecules which regulate the expression of PD-L1 in human lung cancer cell lines after incubation with several cytokines and ODNs. The expression of PD-L1 and β2-microglobulin (β2-MG) on A549 cells, and IFN-γ-induced apoptosis with ODNs were examined by flow cytometry. The relationship between IFN-γ receptor and ODN was analyzed by ELISA and immunofluorescence chemistry. Results: Our results verified that A-CpG ODNs suppress the upregulation of IFN-γ-induced PD-L1 and β2-MG expression. In addition, we found that ODNs with six or more consecutive guanosines (ODNs with poly-G sequences) may competitively inhibit the IFN-γ receptor and abolish the effect of IFN-γ, thereby suppressing apoptosis and indoleamine 2,3-dioxygenase 1 expression in human lung cancer cells. The tumor microenvironment regulates whether this action will promote or suppress tumor immunity. Thus, in immunotherapy with CpG ODNs, it is essential to consider the effect of ODNs with poly-G sequences. Conclusions: This study suggests that ODNs containing six or more consecutive guanosines may inhibit the binding of IFN-γ to IFN-γ receptor. However, it does not directly show that ODNs containing six or more consecutive guanosines competitively inhibit the IFN-γ receptor, and further studies are warranted to confirm this finding. Key points: Significant findings of the study: Oligodeoxynucleotides with a contiguous sequence of six or more guanosines may competitively inhibit the IFN-γ receptor and abolish the action of IFN-γ. This may suppress IFN-γ-induced apoptosis and indoleamine-2,3-dioxygenase-1 expression in human lung cancer cells. What this study adds: A-CpG and poly-G ODN may overcome tolerance if the cause of ICI tolerance is high IDO expression. However, IFN-γ also has the effect of suppressing apoptosis of cancer cells, and it is necessary to identify the cause of resistance.
Mesh-Begriff(e)	Antiviral Agents/pharmacology ; B7-H1 Antigen/genetics ; B7-H1 Antigen/metabolism ; Biomarkers, Tumor/genetics ; Biomarkers, Tumor/metabolism ; Cell Proliferation ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Indoleamine-Pyrrole 2,3,-Dioxygenase/genetics ; Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism ; Interferon-gamma/pharmacology ; Lung Neoplasms/drug therapy ; Lung Neoplasms/genetics ; Lung Neoplasms/metabolism ; Lung Neoplasms/pathology ; Oligodeoxyribonucleotides/pharmacology ; Tumor Cells, Cultured ; beta 2-Microglobulin/genetics ; beta 2-Microglobulin/metabolism
Chemische Substanzen	Antiviral Agents ; B7-H1 Antigen ; Biomarkers, Tumor ; CD274 protein, human ; CPG-oligonucleotide ; IDO1 protein, human ; Indoleamine-Pyrrole 2,3,-Dioxygenase ; Oligodeoxyribonucleotides ; beta 2-Microglobulin ; Interferon-gamma (82115-62-6)
Sprache	Englisch
Erscheinungsdatum	2020-02-17
Erscheinungsland	Singapore
Dokumenttyp	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2625856-0
ISSN	1759-7714 ; 1759-7706
ISSN (online)	1759-7714
ISSN	1759-7706
DOI	10.1111/1759-7714.13351
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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