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1.
Cancer Sci ; 115(7): 2333-2345, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38676373

RESUMO

Doublecortin (DCX)-positive neural progenitor-like cells are purported components of the cancer microenvironment. The number of DCX-positive cells in tissues reportedly correlates with cancer progression; however, little is known about the mechanism by which these cells affect cancer progression. Here we demonstrated that DCX-positive cells, which are found in all major histological subtypes of lung cancer, are cancer-associated Schwann cells (CAS) and contribute to the chemoresistance of lung cancer cells by establishing an adrenergic microenvironment. Mechanistically, the activation of the Hippo transducer YAP/TAZ was involved in the acquisition of new traits of CAS and DCX positivity. We further revealed that CAS express catecholamine-synthesizing enzymes and synthesize adrenaline, which potentiates the chemoresistance of lung cancer cells through the activation of YAP/TAZ. Our findings shed light on CAS, which drive the formation of an adrenergic microenvironment by the reciprocal regulation of YAP/TAZ in lung cancer tissues.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Neoplasias Pulmonares , Neuropeptídeos , Células de Schwann , Fatores de Transcrição , Microambiente Tumoral , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neuropeptídeos/metabolismo , Células de Schwann/metabolismo , Células de Schwann/patologia , Linhagem Celular Tumoral , Fatores de Transcrição/metabolismo , Animais , Proteína Duplacortina , Camundongos , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas de Sinalização YAP/metabolismo , Proteínas de Sinalização YAP/genética , Proteínas com Motivo de Ligação a PDZ com Coativador Transcricional/metabolismo , Epinefrina/metabolismo , Epinefrina/farmacologia , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Masculino , Feminino
2.
Jpn J Clin Oncol ; 2024 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-38704243

RESUMO

BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) has been reported as a prognostic biomarker in non-small cell lung cancer (NSCLC); however, the underlying biological rationale remains unclear. The present study aimed to explore the potential utility of NLR as a surrogate biomarker for immune response to cancer and to elucidate the underlying mechanism. METHODS: This retrospective study included the medical records of 120 patients with NSCLC who underwent surgery at the study institution in 2012. NLR in peripheral blood was determined from blood test within 30 days before surgery. Tumor immune status was evaluated using immunohistochemical staining to identify CD3+, CD8+ and FOXP3+ tumor-infiltrating lymphocytes (TILs), and the relationship of NLR, with clinicopathologic characteristics including 5-year overall survival (OS), and the tumor immune status was investigated. The median values of NLR and TIL count were used as cutoff points. RESULTS: The 5-year OS was significantly better in patients with low NLR (<2.2) than in those with high NLR (≥2.2) (70.1% vs. 56.8%, P = 0.042) and in patients with high CD3+ TIL count (≥242) than in those with low CD3+ TIL count (<242) (70% vs. 56.8%, P = 0.019). Additionally, the CD3+ TIL count was negatively correlated with preoperative NLR (P = 0.005). CONCLUSION: NLR might potentially reflect the immune status of tumor microenvironment, explaining its impact on prognosis of patients with NSCLC.

3.
Heart Vessels ; 39(5): 446-453, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38300278

RESUMO

The early prediction of neurological outcomes is useful for out-of-hospital cardiac arrest (OHCA). The initial pH was associated with neurological outcomes, but the values varied among the studies. Patients admitted to our division with OHCA of cardiac origin between January 2015 and December 2022 were retrospectively examined (N = 199). A good neurological outcome was defined as a Glasgow-Pittsburgh cerebral performance category (CPC) of 1-2 at discharge. Patients were divided according to the achievement of recovery of spontaneous circulation (ROSC) on hospital arrival, and the efficacy of pH in predicting good neurological outcomes was compared. In patients with ROSC on hospital arrival (N = 100), the initial pH values for good and poor neurological outcomes were 7.26 ± 0.14 and 7.09 ± 0.18, respectively (p < 0.001). In patients without ROSC on hospital arrival (N = 99), the initial pH values for good and poor neurological outcomes were 7.06 ± 0.23 and 6.92 ± 0.15, respectively (p = 0.007). The pH associated with good neurological outcome was much lower in patients without ROSC than in those with ROSC on hospital arrival (P = 0.003). A higher initial pH is associated with good neurological outcomes in patients with OHCA. However, the pH for a good or poor neurological outcome depends on the ROSC status on hospital arrival.


Assuntos
Reanimação Cardiopulmonar , Parada Cardíaca Extra-Hospitalar , Humanos , Parada Cardíaca Extra-Hospitalar/diagnóstico , Parada Cardíaca Extra-Hospitalar/terapia , Estudos Retrospectivos , Hospitais , Concentração de Íons de Hidrogênio
4.
Surg Today ; 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38635055

RESUMO

PURPOSES: Robot-assisted thoracoscopic (RATS) segmentectomy is becoming increasingly common because of the expanded indications for segmentectomy and the widespread adoption of robotic surgery. The precise division of the intersegmental plane is necessary to ensure oncologic margins from the tumor and to preserve the lung function. In this study, we present a strategy for accurately dividing the intersegmental plane using a robotic stapler and review the surgical outcomes. METHODS: RATS portal segmentectomy was performed using the Da Vinci Xi system and the intersegmental plane was dissected using a robotic stapler. We evaluated the perioperative outcomes in 92 patients who underwent RATS portal segmentectomy between May 2020 and January 2023. These results were compared with those of 82 patients who underwent complete video-assisted thoracoscopic surgery (CVATS) during the same period. RESULTS: The operative and console times were 162 and 97 min, respectively. No intraoperative complications occurred, and postoperative complications were observed in four cases (4.3%). The operative time, blood loss, postoperative complications, and maximum incision size were significantly lower in the RATS group than in the CVATS group. However, RATS requires a significantly higher number of staplers than CVATS. CONCLUSIONS: The division of the intersegmental plane using a robotic stapler in RATS portal segmentectomy was, therefore, found to be safe and effective.

5.
Surg Today ; 54(4): 317-324, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37523071

RESUMO

PURPOSE: Chronic lung allograft dysfunction (CLAD) is a known long-term fatal disorder after lung transplantation. In this study, we evaluated the CLAD classification of the International Society for Heart and Lung Transplantation (ISHLT) for living-donor lobar lung transplantation (LDLLT). METHODS: We conducted a single-center retrospective review of data from 73 patients who underwent bilateral LDLLT between 1998 and 2019. Factors related to opacity on computed tomography (CT) and restriction on pulmonary function tests (PFTs) were also analyzed. RESULTS: Overall, 26 (36%) patients were diagnosed with CLAD, including restrictive allograft syndrome (RAS), n = 10 (38.5%); bronchiolitis obliterans syndrome (BOS), n = 8 (30.8%); mixed, n = 1 (3.8%); undefined, n = 2 (7.7%); and unclassified, n = 5 (19.2%). The 5-year survival rate after the CLAD onset was 60.7%. The survival of patients with BOS was significantly better than that of patients with RAS (p = 0.012). In particular, patients with restriction on PFT had a significantly worse survival than those without restriction (p = 0.001). CONCLUSIONS: CLAD after bilateral LDLLT does not have a major impact on the recipient survival, especially in patients with BOS. Restriction on PFT may predict a particularly poor prognosis in patients with CLAD after bilateral LDLLT.


Assuntos
Síndrome de Bronquiolite Obliterante , Bronquiolite Obliterante , Transplante de Pulmão , Disfunção Primária do Enxerto , Humanos , Bronquiolite Obliterante/etiologia , Bronquiolite Obliterante/cirurgia , Doadores Vivos , Aloenxertos , Estudos Retrospectivos , Disfunção Primária do Enxerto/etiologia , Pulmão
6.
Surg Today ; 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38451313

RESUMO

PURPOSE: Radiation pneumonitis (RP) is an obstacle for patients after surgery following induction chemoradiotherapy for locally advanced non-small cell lung cancer (LA-NSCLC). We performed a comparative analysis of the association between clinicopathological factors, including the neutrophil-to-lymphocyte ratio (NLR) and prognosis, in LA-NSCLC patients with or without RP during induction chemoradiotherapy followed by surgery. METHODS: The subjects of this analysis were 168 patients undergoing trimodality therapy for LA-NSCLC between January, 1999 and May, 2019. Patients were divided into two groups: the RP group (n = 41) and the non-RP group (n = 127). We compared the clinicopathological factors including the NLR between the groups and analyzed the association between the NLR and prognosis. RESULTS: The RP group had more patients with tumors located in the lower lobe, more bilobar resections, shorter operative times, no implementation of postoperative adjuvant chemotherapy, and a higher postoperative NLR than the non-RP group. There were no significant differences in serious postoperative complications and the prognosis. Patients with a low postoperative NLR had a significantly better prognosis in the non-RP group, and a trend toward a better prognosis even in the RP group. CONCLUSION: Postoperative NLR may be a useful prognostic factor, even for patients who suffer RP after trimodality therapy for LA-NSCLC.

7.
Ann Surg Oncol ; 30(13): 8727-8734, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37658268

RESUMO

BACKGROUND: The presence of tumor-infiltrating lymphocytes (TILs) and tertiary lymphoid structures (TLSs) in tumor tissue has been related to the prognosis in various malignancies. Meanwhile, neutrophil-to-lymphocyte ratio (NLR) as a systemic inflammation marker also has been associated with the prognosis in them. However, few reports have investigated the relationship between pulmonary metastases from sarcoma and these biomarkers. METHODS: We retrospectively recruited 102 patients undergoing metastasectomy for pulmonary metastases from uterine leiomyosarcoma at Okayama University Hospital from January 2006 to December 2019. TILs and TLSs were evaluated by immunohistochemical staining of surgically resected specimens of pulmonary metastases using anti-CD3/CD8/CD103/Foxp3/CD20 antibodies. NLR was calculated from the blood examination immediately before the most recent pulmonary metastasectomy. We elucidated the relationship between the prognosis and these factors. Because we considered that the status of tumor tissue and systemic inflammation were equally valuable, we also assessed the impact of the combination of TILs or TLSs and NLR on the prognosis. RESULTS: As for TILs, CD3-positive cells and CD8-positive cells were correlated with the prognosis. The prognosis was significantly better in patients with CD3-high group, CD8-high group, TLSs-high group, and NLR-low group, respectively. The prognosis of CD8-high/NLR-low group and TLSs-high/NLR-low group was significantly better than that of CD8-low/NLR-high group and TLSs-low/NLR-high group, respectively. CONCLUSIONS: CD3-positive TILs, CD8-positive TILs, TLSs, and NLR are correlated with the prognosis, respectively. The combination of CD8-positive TILs or TLSs and NLR may be the indicators to predict the prognosis of patients with pulmonary metastases from uterine leiomyosarcoma.


Assuntos
Leiomiossarcoma , Neoplasias Pulmonares , Neoplasias Pélvicas , Estruturas Linfoides Terciárias , Humanos , Linfócitos do Interstício Tumoral , Prognóstico , Leiomiossarcoma/patologia , Neutrófilos/patologia , Estruturas Linfoides Terciárias/patologia , Estudos Retrospectivos , Linfócitos/patologia , Neoplasias Pulmonares/patologia , Linfócitos T CD8-Positivos , Neoplasias Pélvicas/patologia , Inflamação/patologia
8.
Ann Surg Oncol ; 30(11): 6697-6702, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37355521

RESUMO

BACKGROUND: Primary lung tumors are sometimes resected when either pleural dissemination (PD) or malignant pleural effusion (MPE) exists. This study clarified the prognostic factors for non-small cell lung cancer (NSCLC) with either PD and MPE, or both, detected during or after surgery. PATIENTS AND METHODS: We examined patients with NSCLC from a multicenter database who had either PD, MPE, or both, detected during or after surgery between 2005 and 2015. Hazard ratios and 95% confidence intervals were estimated using the Cox proportional hazards model adjusted for potential confounding factors. RESULTS: Among 9463 registered patients, PD, MPE, or both, were found in 114 patients with NSCLC during or after surgery. Primary tumor resection and exploratory thoracotomy were performed in 65 and 49 patients, respectively. In univariate analysis, adenocarcinoma, clinically undetected lymph node metastasis (c-N0 or unknown), EGFR mutation, and combination of chemotherapy or tyrosine kinase inhibitors after surgery were better prognostic factors for overall survival (OS), whereas in the multivariate analysis, adenocarcinoma, clinically undetected lymph node metastasis, and EGFR mutation were favorable independent prognostic factors in OS. Additionally, limited to patients with EGFR mutation, patients with primary lung tumor resection showed a significantly better 5-year OS than those with exploratory thoracotomy (86.4 vs. 44.8%; p < 0.001). CONCLUSION: Our findings show that surgical resection of primary tumors could improve the prognosis of patients with PD, MPE, or both, detected during or after surgery when the tumors harbor an EGFR mutation.


Assuntos
Adenocarcinoma , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Derrame Pleural Maligno , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirurgia , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Prognóstico , Metástase Linfática , Adenocarcinoma/genética , Adenocarcinoma/cirurgia , Derrame Pleural Maligno/genética , Derrame Pleural Maligno/cirurgia , Mutação , Receptores ErbB/genética
9.
Clin Transplant ; 37(11): e15077, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37461238

RESUMO

INTRODUCTION: The percentage of low attenuation area (%LAA) on computed tomography (CT) is useful for evaluating lung emphysema, and higher %LAA was observed in patients with chronic lung allograft dysfunction (CLAD). This study investigated the relationship between the %LAA and the development of CLAD after bilateral lung transplantation (LT). METHODS: We conducted a single-center retrospective study of 75 recipients who underwent bilateral LT; the recipients were divided into a CLAD group (n = 30) and a non-CLAD group (n = 45). The %LAA was calculated using CT and compared between the two groups from 4 years before to 4 years after the diagnosis of CLAD. The relationships between the %LAA and the percent baseline values of the pulmonary function test parameters were also calculated. RESULTS: The %LAA was significantly higher in the CLAD group than in the non-CLAD group from 2 years before to 2 years after the diagnosis of CLAD (P < .05). In particular, patients with bronchiolitis obliterans syndrome (BOS) exhibited significant differences even from 4 years before to 4 years after diagnosis (P < .05). Significant negative correlations between the %LAA and the percent baseline values of the forced expiratory volume in 1 s (r = -.36, P = .0031), the forced vital capacity (r = -.27, P = .027), and the total lung capacity (r = -.40, P < .001) were seen at the time of CLAD diagnosis. CONCLUSION: The %LAA on CT was associated with the development of CLAD and appears to have the potential to predict CLAD, especially BOS, after bilateral LT.


Assuntos
Síndrome de Bronquiolite Obliterante , Bronquiolite Obliterante , Transplante de Pulmão , Humanos , Bronquiolite Obliterante/diagnóstico por imagem , Bronquiolite Obliterante/etiologia , Estudos Retrospectivos , Pulmão/diagnóstico por imagem , Transplante de Pulmão/efeitos adversos , Tomografia Computadorizada por Raios X , Aloenxertos
10.
Clin Transplant ; 37(4): e14927, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36738289

RESUMO

INTRODUCTION: Living-donor lobar lung transplantation is an alternative procedure to deceased donation lung transplantation. It involves graft donation from healthy donors; however, only a few reports have discussed its long-term prognosis in living lung donors and their associated health-related quality of life. This study aimed to examine living lung donors' health-related quality of life. METHODS: In our cross-sectional survey of living lung donors, we assessed health-related quality of life-based on three key aspects (physical, mental, and social health) using the 36-Item Short Form Health Survey. We also evaluated chronic postoperative pain and postoperative breathlessness using the numeric rating scale and the modified Medical Research Council Dyspnea scale, respectively. RESULTS: We obtained consent from 117 of 174 living lung donors. The average scores of the living lung donors on the 36-Item Short Form Health Survey were higher than the national average. However, some donors had poorer physical, mental, and social health, with lower summary scores than the national averages. Low mental component summary predictors included donor age (<40 years; odds ratio = 10.2; p < .001) and recipient age (<18 years; odds ratio = 2.73; p < .032). Low role-social component summary predictors included high lung allocation score (≥50; odds ratio = 3.94, p < .002) and recipient death (odds ratio = 3.64; p = .005). There were no predictors for a physical component summary. Additionally, many donors did not complain of pain or dyspnea. CONCLUSIONS: Living lung donors maintained an acceptable long-term health-related quality of life after surgery. Potential donors should be informed of relevant risk factors, and high-risk donors should receive appropriate support.


Assuntos
Transplante de Pulmão , Qualidade de Vida , Humanos , Adulto , Adolescente , Doadores Vivos , Estudos Transversais , Dispneia , Inquéritos e Questionários
11.
Clin Transplant ; 37(9): e15006, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37115007

RESUMO

OBJECTIVES: S100A8/A9 is a damage-associated molecule that augments systemic inflammation. However, its role in the acute phase after lung transplantation (LTx) remains elusive. This study aimed to determine S100A8/A9 levels after lung transplantation (LTx) and evaluate their impact on overall survival (OS) and chronic lung allograft dysfunction (CLAD)-free survival. METHODS: Sixty patients were enrolled in this study, and their plasma S100A8/A9 levels were measured on days 0, 1, 2, and 3 after LTx. The association of S100A8/A9 levels with OS and CLAD-free survival was assessed using univariate and multivariate Cox regression analyses. RESULTS: S100A8/A9 levels were elevated in a time-dependent manner until 3 days after LTx. Ischemic time was significantly longer in the high S100A8/9 group than in the low S100A8/A9 group (p = .017). Patients with high S100A8/A9 levels (> 2844 ng/mL) had worse prognosis (p = .031) and shorter CLAD-free survival (p = .045) in the Kaplan-Meier survival analysis than those with low levels. Furthermore, multivariate Cox regression analysis showed that high S100A8/A9 levels were a determinant of poor OS (hazard ratio [HR]: 3.7; 95% confidence interval [CI]: 1.2-12; p = .028) and poor CLAD-free survival (HR: 4.1; 95% CI: 1.1-15; p = .03). In patients with a low primary graft dysfunction grade (0-2), a high level of S100A8/A9 was also a poor prognostic factor. CONCLUSIONS: Our study provided novel insights into the role of S100A8/A9 as a prognostic biomarker and a potential therapeutic target for LTx.


Assuntos
Calgranulina A , Transplante de Pulmão , Humanos , Prognóstico , Transplante de Pulmão/efeitos adversos , Pulmão , Biomarcadores
12.
Circ J ; 87(2): 306-311, 2023 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-36351594

RESUMO

BACKGROUND: The effect of delayed ambulation on the outcome of coronary artery bypass grafting (CABG) remains to be clarified.Methods and Results: The long-term and in-hospital outcomes of 887 patients who underwent isolated CABG (455 off-pump cases, 135 urgent cases) were evaluated, with a focus on the timing of first ambulation. In-hospital mortality cases were excluded. Early ambulation (first ambulation within 3 days after operation) was achieved in 339 (38%) patients. In the multivariable logistic regression analysis, longer operation time and urgent case, EuroSCORE II, re-thoracotomy, and respiratory time were associated with delayed (≥4 days) ambulation. Delayed ambulation was associated with a high incidence of postoperative complications, such as pneumonia, and stroke (P<0.01). Following discharge, 22.2% of patients experienced major cardiac events and 13.8% died during the follow-up period (median follow-up 60 months). Cox hazards analysis revealed that delayed ambulation was associated with long-term adverse events (hazard ratio 1.04 per day, P<0.001). With adjustment for preoperative factors, the estimated future risk of adverse events was found to be increased day-by-day during the delay until initial ambulation. CONCLUSIONS: In isolated CABG patients, delayed ambulation was associated with poor outcomes, even in the long-term period. The results support the current guideline recommending early ambulation protocol after cardiac surgery.


Assuntos
Ponte de Artéria Coronária sem Circulação Extracorpórea , Doença da Artéria Coronariana , Humanos , Ponte de Artéria Coronária sem Circulação Extracorpórea/efeitos adversos , Deambulação Precoce/efeitos adversos , Resultado do Tratamento , Ponte de Artéria Coronária/métodos , Prognóstico , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Doença da Artéria Coronariana/etiologia , Fatores de Risco
13.
Acta Med Okayama ; 77(3): 331-334, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37357635

RESUMO

Masaoka stage I type A thymomas rarely recur. We report the case of an 82-year-old man who developed endobronchial metastasis after thymothymectomy for Masaoka stage I type A thymoma. Twenty years after surgery, the patient developed bloody sputum, and chest computed tomography revealed a neoplasm obstructing the right upper lobe bronchus of the lung with enlarged mediastinal lymph nodes. He underwent right upper lobectomy and mediastinal lymph node dissection. Although preoperative pathological diagnosis was squamous cell carcinoma of the lung, postoperative histopathology revealed endobronchial metastasis of the thymoma. Nine years later, at age 89, the patient is alive and well.


Assuntos
Neoplasias Pulmonares , Timoma , Neoplasias do Timo , Masculino , Humanos , Idoso de 80 Anos ou mais , Timoma/cirurgia , Timoma/patologia , Timoma/secundário , Neoplasias Pulmonares/patologia , Escarro , Recidiva Local de Neoplasia , Neoplasias do Timo/cirurgia , Neoplasias do Timo/patologia
14.
Cancer Sci ; 113(10): 3428-3436, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35871750

RESUMO

Cancer-associated fibroblasts (CAFs) are a major component of the tumor microenvironment that mediate resistance of cancer cells to anticancer drugs. Tranilast is an antiallergic drug that suppresses the release of cytokines from various inflammatory cells. In this study, we investigated the inhibitory effect of tranilast on the interactions between non-small cell lung cancer (NSCLC) cells and the CAFs in the tumor microenvironment. Three EGFR-mutant NSCLC cell lines, two KRAS-mutant cell lines, and three CAFs derived from NSCLC patients were used. To mimic the tumor microenvironment, the NSCLC cells were cocultured with the CAFs in vitro, and the molecular profiles and sensitivity to molecular targeted therapy were assessed. Crosstalk between NSCLC cells and CAFs induced multiple biological effects on the NSCLC cells both in vivo and in vitro, including activation of the STAT3 signaling pathway, promotion of xenograft tumor growth, induction of epithelial-mesenchymal transition (EMT), and acquisition of resistance to molecular-targeted therapy, including EGFR-mutant NSCLC cells to osimertinib and of KRAS-mutant NSCLC cells to selumetinib. Treatment with tranilast led to inhibition of IL-6 secretion from the CAFs, which, in turn, resulted in inhibition of CAF-induced phospho-STAT3 upregulation. Tranilast also inhibited CAF-induced EMT in the NSCLC cells. Finally, combined administration of tranilast with molecular-targeted therapy reversed the CAF-mediated resistance of the NSCLC cells to the molecular-targeted drugs, both in vitro and in vivo. Our results showed that combined administration of tranilast with molecular-targeted therapy is a possible new treatment strategy to overcome drug resistance caused by cancer-CAF interaction.


Assuntos
Antialérgicos , Antineoplásicos , Fibroblastos Associados a Câncer , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Antialérgicos/metabolismo , Antialérgicos/farmacologia , Antialérgicos/uso terapêutico , Antineoplásicos/uso terapêutico , Fibroblastos Associados a Câncer/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Reposicionamento de Medicamentos , Transição Epitelial-Mesenquimal , Receptores ErbB , Humanos , Interleucina-6/metabolismo , Neoplasias Pulmonares/patologia , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Microambiente Tumoral , ortoaminobenzoatos
15.
Cancer Sci ; 113(1): 287-296, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34689382

RESUMO

The mutation status of tumor tissue DNA (n = 389) of resected stage II-III non-squamous non-small-cell lung cancer (Ns-NSCLC) was analyzed using targeted deep sequencing as an exploratory biomarker study (JIPANG-TR) for the JIPANG study, a randomized phase III study of pemetrexed/cisplatin (Pem/Cis) vs vinorelbine/cisplatin (Vnr/Cis). The TP53 mutation, common EGFR mutations (exon 19 deletion and L858R), and KRAS mutations were frequently detected. The frequency of the EGFR mutation was significant among female patients. Patients with an EGFR mutation-positive status had a significantly shorter recurrence-free survival (RFS) time (24 mo vs not reached) (HR, 1.64; 95% CI, 1.22-2.21; P = .0011 for EGFR mutation status). Multivariable analysis identified both the pathological stage and EGFR mutation status as independent prognostic factors for RFS (HR, 1.78; 95% CI, 1.30-2.44; P = .0003 for disease stage; and HR, 1.57; 95% CI, 1.15-2.16; P = .0050 for EGFR mutation status). This study demonstrated that the EGFR mutation has either a poor prognostic or predictive impact on a poor response to postoperative chemotherapy with platinum doublet chemotherapy for stage II-III Ns-NSCLC patients. This result supports a role for mandatory molecular diagnosis of early-stage Ns-NSCLC for precision oncology and signifies the importance of adjuvant for the 3rd generation tyrosine kinase inhibitor rather than platinum-based chemotherapy. This study is registered with the UMIN Clinical Trial Registry (UMIN 000012237).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Mutação , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Quimioterapia Adjuvante , Cisplatino/uso terapêutico , Receptores ErbB/genética , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirurgia , Masculino , Pemetrexede/uso terapêutico , Medicina de Precisão , Prognóstico , Análise de Sequência de DNA , Análise de Sobrevida , Resultado do Tratamento , Vinorelbina/uso terapêutico
16.
Respir Res ; 23(1): 20, 2022 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-35130915

RESUMO

BACKGROUND: Tyrosine kinase activation plays an important role in the progression of pulmonary fibrosis. In this study, we analyzed the expression of 612 kinase-coding and cancer-related genes using next-generation sequencing to identify potential therapeutic targets for idiopathic pulmonary fibrosis (IPF). METHODS: Thirteen samples from five patients with IPF (Cases 1-5) and eight samples from four patients without IPF (control) were included in this study. Six of the thirteen samples were obtained from different lung segments of a single patient who underwent bilateral pneumonectomy. Gene expression analysis of IPF lung tissue samples (n = 13) and control samples (n = 8) was performed using SureSelect RNA Human Kinome Kit. The expression of the selected genes was further confirmed at the protein level by immunohistochemistry (IHC). RESULTS: Gene expression analysis revealed a correlation between the gene expression signatures and the degree of fibrosis, as assessed by Ashcroft score. In addition, the expression analysis indicated a stronger heterogeneity among the IPF lung samples than among the control lung samples. In the integrated analysis of the 21 samples, DCLK1 and STK33 were found to be upregulated in IPF lung samples compared to control lung samples. However, the top most upregulated genes were distinct in individual cases. DCLK1, PDK4, and ERBB4 were upregulated in IPF case 1, whereas STK33, PIM2, and SYK were upregulated in IPF case 2. IHC revealed that these proteins were expressed in the epithelial layer of the fibrotic lesions. CONCLUSIONS: We performed a comprehensive kinase expression analysis to explore the potential therapeutic targets for IPF. We found that DCLK1 and STK33 may serve as potential candidate targets for molecular targeted therapy of IPF. In addition, PDK4, ERBB4, PIM2, and SYK might also serve as personalized therapeutic targets of IPF. Additional large-scale studies are warranted to develop personalized therapies for patients with IPF.


Assuntos
Regulação da Expressão Gênica , Fibrose Pulmonar Idiopática/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Pulmão/enzimologia , Fosfotransferases/genética , RNA/genética , Idoso , Feminino , Seguimentos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Fibrose Pulmonar Idiopática/metabolismo , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Fosfotransferases/biossíntese , Estudos Retrospectivos
17.
World J Surg Oncol ; 20(1): 114, 2022 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-35395855

RESUMO

BACKGROUND: Soft-tissue sarcomas are rare malignancies that consist of many different histologic subtypes and arise in various locations in the body. In patients with lung metastases from retroperitoneal sarcomas, the long-term outcomes and prognostic factors are unknown. This study is a retrospective review of patients undergoing pulmonary metastasectomy for retroperitoneal sarcoma metastases at one institution, with the purpose of determining prognostic factors and clinical outcomes. METHODS: This is a single-center, retrospective cohort study of patients undergoing pulmonary metastasectomy for lung metastases from various sarcomas at Okayama University Hospital from January 2006 to December 2018. The Kaplan-Meier method and log-rank test were used for the analyses, and cut-off values of continuous variables were determined by a receiver operating characteristic curve analysis. RESULTS: Twenty-four patients underwent the first pulmonary metastasectomy for lung metastases from retroperitoneal sarcoma in our hospital. Leiomyosarcoma was the most common histologic subtype of retroperitoneal sarcoma (79.2%, n = 19). Median overall survival was 49.9 months, and the 3-year and 5-year survival rates after the first pulmonary metastasectomy were 62.5% and 26.4% respectively. In univariate analysis, age ≥56 years, disease-free interval < 15 months, and size of metastasis (≥ 27 mm) were associated with poor survival. CONCLUSION: Pulmonary metastasectomy can be considered as an effective management strategy in retroperitoneal sarcoma patients with lung metastases in appropriately selected cases, just as it is for other sarcomas.


Assuntos
Neoplasias Pulmonares , Metastasectomia , Neoplasias Retroperitoneais , Sarcoma , Neoplasias de Tecidos Moles , Intervalo Livre de Doença , Humanos , Neoplasias Pulmonares/patologia , Pessoa de Meia-Idade , Pneumonectomia/métodos , Prognóstico , Neoplasias Retroperitoneais/cirurgia , Estudos Retrospectivos , Sarcoma/patologia , Taxa de Sobrevida , Resultado do Tratamento
18.
Acta Med Okayama ; 76(1): 89-92, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35237004

RESUMO

Congenital lobar emphysema (CLE) is defined as the hyperinflation of pulmonary lobes due to obstruction of the flow of air via a known or unknown etiology, which causes pressure symptoms in the adjacent organs. CLE is mainly diagnosed in the neonatal period, and very few adult cases have been reported. Here we report a 34-year-old male with muscular dystrophy who was diagnosed with CLE on examination. He underwent a right lower lobectomy via 3-portal completely video-assisted thoracoscopic surgery, and his symptoms improved. Thoracoscopic surgery helped preserve the respiratory muscles and led to the improvement of respiratory function in this patient.


Assuntos
Enfisema Pulmonar/congênito , Cirurgia Torácica Vídeoassistida/métodos , Adulto , Humanos , Masculino , Distrofias Musculares/complicações , Enfisema Pulmonar/cirurgia
19.
Surg Today ; 52(2): 294-305, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34251508

RESUMO

PURPOSE: Decreased irisin levels may be associated with the development of emphysema. Similarly, emphysematous changes may develop in patients with chronic lung allograft dysfunction (CLAD) after living-donor lobar lung transplantation (LDLLT). We investigated the severity of emphysematous changes and the relationship between irisin levels and CLAD after bilateral LDLLT and cadaveric lung transplantation (CLT). METHODS: The subjects of this retrospective study were 59 recipients of bilateral LDLLT (n = 31) or CLT (n = 28), divided into a non-CLAD group (n = 41), a LDLLT-CLAD group (n = 11), and a CLT-CLAD group (n = 7). We compared the severity of emphysematous changes, the skeletal muscle mass, and the plasma irisin levels among the groups. RESULTS: The emphysematous changes were significantly more severe in the LDLLT-CLAD and CLT-CLAD groups (p = 0.046 and 0.036), especially in patients with bronchiolitis obliterans syndrome (BOS), than in the non-CLAD group. Although the skeletal muscle mass was similar in all the groups, the plasma irisin levels were significantly lower in the LDLLT-CLAD group (p = 0.022), especially in the patients with BOS after LDLLT, than in the non-CLAD group. CONCLUSION: Emphysematous changes and lower levels of plasma irisin were associated with CLAD, especially in patients with BOS, after bilateral LDLLT.


Assuntos
Bronquiolite Obliterante/diagnóstico , Bronquiolite Obliterante/etiologia , Enfisema/patologia , Fibronectinas/sangue , Doadores Vivos , Transplante de Pulmão/efeitos adversos , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Adulto , Biomarcadores/sangue , Enfisema/sangue , Enfisema/diagnóstico , Enfisema/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gravidade do Paciente , Síndrome , Adulto Jovem
20.
Surg Today ; 52(11): 1540-1550, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35357572

RESUMO

OBJECTIVES: We herein review the outcomes of paediatric lung transplantation (LTx) and analyse subgroups divided by age. METHODS: We retrospectively reviewed 43 consecutive paediatric LTx recipients (< 18 years old: cadaveric LTx [n = 9], living-donor lobar LTx [n = 34]). We also analysed subgroups of patients 1-6 years old (n = 10) and 7-17 years old (n = 33). RESULTS: The 1-, 5- and 10-year overall survival (OS) rates in paediatric recipients were 93%, 82% and 67%, respectively. The 1-, 5- and 10-year graft dysfunction (GD)-free survival rates in paediatric recipients were 85%, 59% and 31%, respectively. The 1- and 5-year OS in the 1- to 6-year-old vs. 7- to 17-year-old groups were 70% vs. 100% and 48% vs. 93%, respectively (p < 0.0001). The 1- and 5-year GD-free survival rates in the 1- to 6-year-old vs. 7- to 17-year-old groups were 60% vs. 93% and 24% vs. 69%, respectively (p = 0.024). The 1- to 6-year-old group showed higher rates of non-standard LTx (p = 0.0001), interstitial pneumonia (p = 0.004) and ventilator dependency (p = 0.007) than the 7- to 17-year-old group. CONCLUSION: Paediatric recipients under 7 years old seemed to have a higher risk of mortality and GD than those 7 years old and older.


Assuntos
Transplante de Pulmão , Humanos , Criança , Adolescente , Lactente , Pré-Escolar , Estudos Retrospectivos , Resultado do Tratamento , Doadores Vivos , Taxa de Sobrevida
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