ABSTRACT
We report a 60-year-old man with humidifier lung showing diffusely distributed centrilobular micronodules and branching opacities on chest computed tomography (CT). Fever and dyspnea occurred 2 months after using an ultrasonic humidifier. KL-6 and SP-D were within normal ranges. Bronchoalveolar lavage showed elevated lymphocytes (53 %) and histological findings of transbronchial lung biopsy demonstrated organizing pneumonia. His condition improved after cessation of the humidifier. A provocation test exhibited a positive response to the humidifier. Humidifier lung should be considered as a differential diagnosis in patients with these CT findings. Detailed clinical, pathological and microbiological examinations are needed to exclude other diseases.
ABSTRACT
We propose an augmented reality (AR)-based training system for basketball free-throws. The optimal shot trajectory for free-throws is projected by a head-mounted display according to the shooter's release point. The efficacy of the training system was assessed in novice shooters by comparing changes in success rates and eye-gaze behavior (quiet eye [QE]) between AR-training and control-training groups. The success rate during the AR training with the optimal trajectory did not differ from the pre-training rate; however, in post-AR training, i.e., after removal of the optimal trajectory, the success rate increased. Additionally, AR training increased the QE duration (QED) compared with that recorded during pre- and post-training blocks. In contrast, the control group showed no change in the success rate or QED. These findings imply that our AR training system affected QE behavior and improved free-throwing shooting performance after training. Thus, our system is expected to enhance basketball free-throw shooting performance.
ABSTRACT
We report a 68-year-old woman with tracheobronchitis and laryngitis associated with Crohn's disease (CD), which was discovered during the evaluation of suspected lung cancer. She had no symptoms induced by these upper airway diseases (UADs). Bronchoscopy revealed swelling of the epiglottis with edematous change and a mass like epiglottis fold. There were nodular and edematous changes in the trachea and bilateral main bronchus. Histological findings demonstrated infiltration by numerous lymphocytes and plasma cells. Dexamethasone as the premedication for chemotherapy against lung cancer was efficacious for these extraintestinal manifestations of CD. Our case was rare in that bronchial lesion and UADs appeared concomitantly.
ABSTRACT
BACKGROUND: Recently, deaths due to mucormycosis in immunocompromised hosts have increased; however, the clinical and pathological features of mucormycosis are not fully understood, especially in view of the associated high mortality and rare incidence in immunocompetent patients. CASE PRESENTATION: We have described a rare autopsy case of a 67-year-old Japanese man with chronic obstructive pulmonary disease who contracted mucormycosis. He had not been on any immunosuppressants, and his immune functions were intact. Since 3 days prior to admission to our hospital, he had experienced progressive dyspnea, productive cough, and fever. Chest computed tomography revealed pleural effusion in the left lower hemithorax and consolidation in the right lung field. Although he was administered with tazobactam-piperacillin hydrate (13.5 g/day), renal dysfunction occurred on the ninth disease day. Therefore, it was switched to cefepime (2 g/day). However, his general condition and lung-field abnormality worsened gradually. Cytological analysis of the sputum sample at admission mainly revealed sporangiophores and unicellular sporangioles, while repeated sputum culture yielded Cunninghamella species. Therefore, he was diagnosed with pulmonary mucormycosis. Liposomal amphotericin B (5 mg/kg/day) was initiated on the 28th disease day. However, chest radiography and electrocardiography detected cardiomegaly and atrial fibrillation, respectively, and he died on the 37th disease day. A postmortem examination revealed clusters of fungal hyphae within the arteries of the right pulmonary cavity wall, the subpericardial artery, intramyocardial capillary blood vessels, and the esophageal subserosa vein. Direct sequencing revealed that all fungal culture samples were positive for Cunninghamella bertholletiae. CONCLUSIONS: Cunninghamella bertholletiae could rapidly progress from colonizing the bronchi to infecting the surrounding organs via vascular invasion even in immunocompetent patients.
Subject(s)
Lung Diseases, Fungal , Mucormycosis , Male , Humans , Aged , Mucormycosis/diagnosis , Autopsy , Lung Diseases, Fungal/diagnosisABSTRACT
Severe immune thrombocytopenia is a rare side-effect of rifampicin (RFP) and can be life-threatening. Here, we report the case of a 74-year-old male with tuberculous pleurisy who developed severe thrombocytopenia after first exposure to RFP. Platelet count decreased to 1 × 103/µL after 7 days of treatment with RFP, isoniazid, ethambutol, and pyrazinamide. After all the drugs were discontinued, the platelet count recovered. As thrombocytopenia did not occur after re-administration of drugs other than RFP, the patient was diagnosed with RFP-induced thrombocytopenia. Clinicians should be aware that RFP can induce acute and severe thrombocytopenia even without previous exposure to this drug.
ABSTRACT
RATIONALE: The relationship between rheumatoid arthritis (RA) and eosinophilic inflammation is unclear. According to recent studies, it has been suggested that T helper 2 cell responses play a role in the inhibition of RA. It is unclear how the immunological response after coronavirus disease-2019 (COVID-19) vaccination affects T cell immune reactions. PATIENT CONCERNS AND DIAGNOSES: Here, we report the case of an 88-year-old woman diagnosed with RA and chronic eosinophilic pneumonia (CEP). She was diagnosed with CEP about 20 years ago, and, through steroid treatment, she improved and had no relapse for 16 years. At the time of diagnosis of CEP, the rheumatoid factor (RF) was increased; however, there were no joint symptoms. After receiving the COVID-19 vaccine, joint and respiratory symptoms gradually worsened. Laboratory examinations showed increased RF, anti-cyclin citrullinated peptide antibody, and peripheral absolute eosinophil count. Musculoskeletal ultrasonography showed synovitis. INTERVENTION AND OUTCOME: Methylprednisolone pulse therapy improved respiratory and joint symptoms immediately; RA and CEP stabilized with no relapses. LESSONS: Eosinophilic and rheumatoid reactions following COVID-19 vaccination were an-reported adverse events. Eosinophilic inflammation might be reflected on an anti-inflammatory reaction in initial phase of RA.
Subject(s)
Arthritis, Rheumatoid , COVID-19 Vaccines , COVID-19 , Pulmonary Eosinophilia , Aged, 80 and over , Anti-Inflammatory Agents , Arthritis, Rheumatoid/complications , Arthritis, Rheumatoid/diagnosis , Arthritis, Rheumatoid/drug therapy , BNT162 Vaccine , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Female , Humans , Inflammation , Methylprednisolone/therapeutic use , Pulmonary Eosinophilia/etiology , Rheumatoid Factor , VaccinationABSTRACT
Anti-melanoma differentiation-associated gene 5 (MDA5) and anti-aminoacyl-tRNA synthetase (ARS) antibodies are two major myositis-specific autoantibodies with distinct clinical features. However, the clinical course remains unclear in patients with clinically amyopathic dermatomyositis (CADM)-interstitial lung disease (ILD) who have co-existing anti-MDA5 and anti-ARS antibodies. Here, we describe the case of a 32-year-old woman with CADM-ILD who had anti-MDA5 and anti-PL12 antibodies. Her serum ferritin level was within the normal range. However, chest computed tomography revealed bilateral lower-lobe consolidation and ground-glass opacities. Treatment with prednisolone and immunosuppressants was successful in improving the skin lesion and ILD, but relapse occurred on reducing the dose of prednisolone. These clinical features match those of anti-ARS antibody-positive dermatomyositis-ILD. Because these two conditions show significantly different clinical features and require different intensities of treatment, clinicians should carefully follow-up these patients throughout the course of the disease.
ABSTRACT
We aimed to assess the prognostic and predictive significance of pretreatment Geriatric Nutritional Risk Index (GNRI) and Prognostic Nutritional Index (PNI) measurements on advanced non-small cell lung cancer (NSCLC) patients treated with first-line therapy. Patients with advanced NSCLC treated between February 2014 and August 2020 were retrospectively analyzed. The optimal cutoff points for GNRI and PNI were measured with receiver operating characteristic (ROC) curve analysis according to overall survival (OS). The predictive factors for progression-free survival (PFS) and OS were evaluated with univariate and multivariate analyses via the Cox hazards regression. A total of 160 patients were included in the study. Significant differences between the low and high-GNRI or PNI groups were found regarding ECOG-PS. The low-GNRI and low-PNI groups had significantly shorter PFS and OS than the high-GNRI and high-PNI groups. A multivariate analysis using a Cox regression model revealed that the high-GNRI group was an independent prognostic factor of OS and PFS, and the PNI group was an independent prognostic factor of OS. Pretreatment GNRI and PNI may therefore be a potential effective predictor of the survival of advanced NSCLC patients undergoing first-line treatment.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Aged , Carcinoma, Non-Small-Cell Lung/therapy , Humans , Nutrition Assessment , Prognosis , Retrospective StudiesABSTRACT
Many aging related diseases such as cancer implicate the myofibroblast in disease progression. Furthermore genesis of the myofibroblast is associated with manifestation of cellular senescence of unclear significance. In this study we investigated the role of a common regulator, namely telomerase reverse transcriptase (TERT), in order to evaluate the potential significance of this association between both processes. We analyzed the effects of TERT overexpression or deficiency on expression of CDKN2A and ACTA2 as indicators of senescence and differentiation, respectively. We assess binding of TERT or YB-1, a repressor of both genes, to their promoters. TERT repressed both CDKN2A and ACTA2 expression, and abolished stress-induced expression of both genes. Conversely, TERT deficiency enhanced their expression. Altering CDKN2A expression had no effect on ACTA2 expression. Both TERT and YB-1 were shown to bind the CDKN2A promoter but only YB-1 was shown to bind the ACTA2 promoter. TERT overexpression inhibited CDKN2A promoter activity while stimulating YB-1 expression and activation to repress ACTA2 gene. TERT repressed myofibroblast differentiation and senescence via distinct mechanisms. The latter was associated with TERT binding to the CDKN2A promoter, but not to the ACTA2 promoter, which may require interaction with co-factors such as YB-1.
Subject(s)
Cell Differentiation/physiology , Cellular Senescence/physiology , Myofibroblasts/physiology , Telomerase/physiology , Actins/metabolism , Cyclin-Dependent Kinase Inhibitor p16/metabolism , Humans , Male , Promoter Regions, Genetic , RNA, Small Interfering , Telomerase/biosynthesis , Telomerase/geneticsABSTRACT
RATIONALE: Lung pleomorphic carcinoma (LPC) is generally resistant to chemotherapy or radiotherapy. However, a combination of immune checkpoint inhibitors and radiotherapy has a remarkable efficacy against LPC. PATIENT CONCERNS AND DIAGNOSES: Here, we report the case of a 50-year old man diagnosed with progressive LPC. The tumor invaded the carina and predominantly obstructed the right main bronchus; therefore, a combination of palliative chemoradiotherapy and atezolizumab was initiated. However the trachea was gradually obstructed. INTERVENTION AND OUTCOME: Argon plasma coagulation (APC) was performed to prevent tumor invasion. After three APC sessions, the tumor showed a necrotic change and was easily excised using biopsy forceps. LESSONS: A combination of chemoradiotherapy, atezolizumab, and APC showed a good efficacy, and the patient had a good response to atezolizumab maintenance therapy. Multidisciplinary treatments, such as a combination of immune checkpoint inhibitors and APC, could have synergistic efficacy in lung cancer.
Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Antineoplastic Agents/therapeutic use , Carcinoma, Non-Small-Cell Lung/therapy , Immune Checkpoint Inhibitors/therapeutic use , Laser Coagulation , Lasers, Gas/therapeutic use , Lung Neoplasms/therapy , Bronchi/pathology , Carcinoma, Non-Small-Cell Lung/pathology , Chemoradiotherapy , Humans , Lung Neoplasms/pathology , Male , Middle Aged , Necrosis , Trachea/pathology , Treatment OutcomeABSTRACT
BACKGROUND: Immune checkpoint inhibitors have potential applications in treating various cancers but are associated with immune-related adverse events, such as inflammation, in a wide range of organs; however, allergic inflammation caused by these agents has not been extensively studied. CASE PRESENTATION: A 65-year-old man was diagnosed with a kidney neuroendocrine carcinoma. Three months after kidney resection surgery, the tumor cells had metastasized to his liver and lymph nodes. Subsequently, the patient started chemotherapy; however, regardless of treatment, the tumor grew, and the patient experienced a series of adverse effects, such as taste disorder, anorexia, and general fatigue. Finally, he was administered a programmed cell death (PD)-1 inhibitor, nivolumab (biweekly, toal 200 mg/body), which was effective against kidney carcinoma. However, the patient had a bronchial asthma attack at 22 cycles of nivolumab treatment and chest computed tomography (CT) revealed an abnormal bilateral shadow after 37 cycles of nivolumab treatment. Bronchoscopy findings revealed eosinophil infiltration in the lungs along with severe alveolar hemorrhage. Paranasal sinus CT scanning indicated sinusitis and nerve conduction analysis indicated a decrease in his right ulnar nerve conduction velocity. Based on these findings, the patient was diagnosed with eosinophilic granulomatosis with polyangiitis; he was treated with prednisolone, which alleviated his bronchial asthma. To restart nivolumab treatment, the dose of prednisolone was gradually tapered, and the patient was administered a monthly dose of mepolizumab and biweekly dose of nivolumab. To date, there have been no bronchial attacks or CT scan abnormalities upon follow up. CONCLUSIONS: We present a rare case in which a patient with cancer was diagnosed with eosinophilic granulomatosis with polyangiitis following treatment with a PD-1 inhibitor. Blockade of PD-1 and the programmed cell death ligand (PD-L) 1/PD-1 and PD-L2/PD-1 signaling cascade may cause allergic inflammation. Further studies are needed to identify the specific mechanisms underlying allergic inflammation after PD-1 blockade.
Subject(s)
Churg-Strauss Syndrome/chemically induced , Immune Checkpoint Inhibitors/adverse effects , Nivolumab/adverse effects , Aged , Carcinoma, Neuroendocrine/drug therapy , Churg-Strauss Syndrome/drug therapy , Humans , Kidney Neoplasms/drug therapy , Male , Prednisolone/therapeutic use , Tomography, X-Ray ComputedABSTRACT
One of the human natural defense systems protects against nontuberculous mycobacterial (NTM) infection by IFN-γ producing T lymphocyte cells. Most disseminated NTM infections usually occur in severe immune-compromised patients, such as HIV infection or after organ transplant patients. However, there have been several reports of non-compromised patients with disseminated NTM infection, including antibiotic resistance cases and the presence of a neutralizing antibody against IFN-γ. We elucidated the anti-IFN-γ neutralizing antibody in a 65 year-old Japanese man whose legs were paralyzed because of multiple abscesses in vertebral bodies. Although his vertebral bodies were released due to an operation and antibiotics were administered, this treatment efficacy was poor. Patient's plasma demanded not only IFN-γ expression in peripheral blood mononuclear cells (PBMC) obtained from healthy controls, but also recombinant human IFN-γ expression. Furthermore, IFN-γ receptor expression was increased, compared to the healthy control. Finally, anti-IFN-γ antibody was detected in his plasma. These results suggested that anti-IFN-γ antibody induced an incurable NTM infection. IFN-γ was subcutaneously administrated with antibiotics, and then the abscesses diminished and his general condition was successfully improved. This therapy might be useful against severe NTM infections.
Subject(s)
HIV Infections , Mycobacterium Infections, Nontuberculous , Aged , Autoantibodies , Humans , Injections, Subcutaneous , Interferon-gamma , Leukocytes, Mononuclear , Male , Mycobacterium Infections, Nontuberculous/drug therapyABSTRACT
Background: The validity of four-dimensional dynamic-ventilation CT scan for distinguishing COPD from asthma has not been established. Purpose: To assess whether four-dimensional dynamic-ventilation CT scan can aid in the diagnosis of COPD by comparing local lung movement during tidal breathing between COPD and asthma. Patients and Methods: Thirty-three COPD patients (30 males and three females; median age 74; range 44-89 years) and 11 asthma patients (five males and six females; median age 55; range: 32-75 years) underwent whole-lung dynamic-ventilation CT scan. CT data were reconstructed, one respiratory cycle to 10 phases, and in addtion we reconstructed threefold new phase data sets. We then analyzed local lung movement during tidal breathing using unpaired t-tests and chi-squared tests. Results: The local lung movement in COPD patients was significantly smaller than in asthma patients, especially in the ventral part of the lung. This was so even in patients who had mild emphysema (Goddard score <8). Conclusion: Quantitative evaluation using four-dimensional dynamic-ventilation CT scan demonstrated that local lung movement during tidal breathing, particularly in the ventral lung, was smaller in COPD than in asthma patients, which may help distinguish COPD from asthma.
Subject(s)
Asthma , Pulmonary Disease, Chronic Obstructive , Adult , Aged , Aged, 80 and over , Asthma/diagnostic imaging , Female , Four-Dimensional Computed Tomography , Humans , Lung/diagnostic imaging , Male , Middle Aged , Pulmonary Disease, Chronic Obstructive/diagnostic imaging , RespirationABSTRACT
Epidermal growth factor receptor (EGFR) exon 20 insertion is not associated with sensitivity to EGFR tyrosine kinase inhibitors and chemotherapy. Here, we report the case of a 41-year-old man who presented a right lower lobe nodule and mediastinal lymph node enlargement diagnosed as EGFR exon 20 insertion adenocarcinoma with high-expression programmed cell death ligand 1 (PD-L1). He showed stable disease to chemoradiation treatment at the primary tumor site. However, durvalumab treatment has good response. Non-small cell lung cancer with EGFR exon 20 insertion and high PD-L1 expression may be treated with immunotherapy exposure.
ABSTRACT
Immunoglobulin type G4 -related disease (IgG4-RD) is known as a chronic systemic inflammatory disease, which is sometimes associated with lung cancer. However, the detailed association between IgG4-RD and lung cancer in clinical settings is still poorly understood. An 80-year-old man was diagnosed with progressive lung adenocarcinoma carrying an EGFR point mutation at L858R, and osimertinib treatment was administered. Two months later, although osimertinib treatment showed good response to the primary tumor, fever and anorexia appeared, and multiple lymph nodes, in particular in the left axillary, became swollen. Ultrasonography-guided biopsy of the axillary lymph node revealed infiltration of lymphocytes with IgG4-positive plasma cells and fibrosis. Serum IgG4 levels were also increased. These results suggested that the multiple swollen lymph nodes were not metastasis, but IgG4-related disease. Based on these results, therapy using prednisolone was initiated. Multiple lymphadenopathy gradually decreased, and his symptoms improved. Currently, his good responses to osimertinib treatment have been maintained. Like in our case, multiple lymphadenopathy with IgG4-positive plasma cell infiltration during successful anti-cancer treatment is quite rare. In this case, it was hypothesized that anti-cancer treatment with osimertinib induced IgG4-positive plasma cell infiltration in multiple lymph nodes. When lymphadenopathy occurs during lung cancer treatment, IgG4-RD has to be considered other than lung cancer metastasis.
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Chest computed tomography (CT) findings of minute pulmonary meningothelial-like nodules (MPMNs) usually show tiny nodules (2-5 mm in diameter) of ground-glass attenuation. However, diffuse, thin-walled cavities have rarely been reported. We herein report a 56-year-old woman with MPMNs showing diffuse, thin-walled cystic lesions on a thin-section chest CT scan. Clinicians need to be aware of the imaging characteristics of this conditions to guide appropriate management of lung diseases, as these CT findings may resemble certain metastatic lung neoplasias and primary adenocarcinoma of the lung.
Subject(s)
Lung Neoplasms/pathology , Lung/pathology , Multiple Pulmonary Nodules/pathology , Diagnosis, Differential , Female , Humans , Lung/diagnostic imaging , Lung Neoplasms/diagnostic imaging , Male , Middle Aged , Multiple Pulmonary Nodules/diagnostic imaging , Tomography, X-Ray ComputedABSTRACT
An 84-year-old man visited our hospital with a prolonged productive cough. Chest computed tomography showed a thick wall cavity and bilateral consolidations. Laboratory findings revealed peripheral blood eosinophilia, increased total IgE and elevated myeloperoxidase anti-neutrophil cytoplasmic antibody. Specific IgE and IgG antibodies and an immediate skin reaction against Aspergillus showed positive results. The histological findings of the lung parenchyma were compatible with eosinophilic pneumonia and bronchial biopsy showed eosinophilic vasculitis. Bronchoalveolar lavage fluid culture yielded Aspergillus fumigatus. These results met the diagnosis criteria for both allergic bronchopulmonary aspergillosis (ABPA) and eosinophilic granulomatosis with polyangiitis (EGPA). This case thus suggests that A. fumigatus might be a pathogen common to both diseases, and prolonged exposure to A. fumigatus in some patients with ABPA may promote progression to EGPA.
ABSTRACT
OBJECTIVES: It is unclear whether family medical history influences the willingness to undergo genetic testing. This study aimed to determine how family history affected the willingness to undergo genetic testing for salt-sensitive hypertension in patients with and without hypertension. DESIGN: Cross-sectional study using a self-administered questionnaire. SETTING: Six primary care clinics and hospitals in Japan. PARTICIPANTS: Consecutive 1705 outpatients aged >20 years, 578 of whom had hypertension. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome variable was the willingness to undergo genetic testing to determine the risk of salt-sensitive hypertension, and the secondary variables were age, sex, education level, family history and concerns about hypertension. Factors associated with a willingness to undergo genetic testing were evaluated in patients with and without hypertension using a logistic regression model. RESULTS: In the hypertension and non-hypertension groups, 323 (55.9%) and 509 patients (45.2%), respectively, were willing to undergo genetic testing. This willingness was related with a high level of education (adjusted OR (ad-OR): 1.81, 95% CI 1.12 to 2.93), family history of stroke (1.55, 1.04 to 2.31) and concerns about hypertension (2.04, 1.27 to 3.28) in the hypertension group, whereas in the non-hypertension group, it was influenced by education level (ad-OR: 1.45, 95% CI 1.13 to 1.86), family history of hypertension (1.52, 1.17 to 1.98) and concerns about hypertension (2.03, 1.53 to 2.68). CONCLUSIONS: The influence of family history on the willingness to undergo genetic testing for risk of salt-sensitivity hypertension differed between participants with and without hypertension. In particular, participants without hypertension wished to know their likelihood of developing hypertension, whereas those with hypertension were interested to know the risk of stroke (a complication of hypertension). Family history could help better counsel patients about genetic testing on the basis of their medical history.
Subject(s)
Health Knowledge, Attitudes, Practice , Hypertension/genetics , Medical History Taking , Patient Acceptance of Health Care , Sodium Chloride, Dietary/administration & dosage , Adult , Aged , Cross-Sectional Studies , Female , Genetic Testing/statistics & numerical data , Humans , Hypertension/complications , Hypertension/epidemiology , Japan , Logistic Models , Male , Middle Aged , Multivariate Analysis , Outpatients/psychology , Outpatients/statistics & numerical data , Self Report , Sodium Chloride, Dietary/adverse effects , Stroke/epidemiologyABSTRACT
BACKGROUND: For achieving equity of the accessibility to primary healthcare, measuring potential geographical accessibility is essential. The provider-to-population ratio is the most frequently used measure. However, it is difficult to be used in closer region because it does not take into consideration the people and health services beyond its boundary. In order to overcome this problem, we measured the potential access to hospital, using both distance measures and the enhanced two-step floating catchment area (E2SFCA) method. The aim of this study was to compare the number of hospitals in the neighborhood and the E2SFCA score with regard to the amount and equity for access to hospitals. METHODS: This descriptive study used publicly available data from 2010. The E2SFCA score and number of neighborhood hospitals were obtained from Tochigi province in Japan using a geographic information system. Dataset of four measures by each census tract was obtained. The measures were E2SFCA score, number of hospitals within the 5 km range, number of hospitals within the 10 km range, and number of hospitals within the 15 km range. Correlation and disparity analyses with the Lorenz curve and Gini coefficient were performed. RESULTS: The measures were obtained in a smaller area than municipality considering adjacent areas using a geographical approach. The E2SFCA score was 5.3 [3.2-7.3] hospitals/million (median [quantile range]), compared to 5.6 hospitals/million in total for the given district. The median number of hospitals within the 5 km, 10 km, and 15 km ranges were 1, 39, and 47, respectively. There was no hospital within the 5 km range in one third of the blocks. Both the number of hospitals within the 10 km range and those within the 15 km range were well correlated. Regional difference became smaller as the distance to count the number of hospitals increased. The gap between small number of hospitals and the high E2SFCA score indicated the location of community hospital in depopulated areas. CONCLUSIONS: The E2SFCA method is superior for analyzing spatial access to hospital, because it provides information in the closer sub-regions. Regional differences were hardly seen in access to hospital beyond the 10 km range. Further studies in other regions and countries are needed for precise assessment.
Subject(s)
Health Services Accessibility , Hospitals/supply & distribution , Catchment Area, Health , Geographic Information Systems , Hospitals/statistics & numerical data , Japan , Primary Health Care , Spatial AnalysisABSTRACT
The known oncogene cyclin D1 (CCND1) participates in progression of the cell cycle from G1 to S-phase. Expression of cyclin D1 is frequently promoted in multiple human cancers including non-small cell lung cancer (NSCLC). However, a relationship between cyclin D1 expression and the prognosis of NSCLC has not been confirmed. NKX2-1 is a homeobox transcription factor involved in pulmonary development as a differentiation-promoting factor. In NSCLC, it acts as a metastasis suppressor and correlates with a good prognosis. Here, NKX2-1-binding motifs were identified in the cyclin D1 promoter, but it has not been clarified whether NKX2-1 is involved in cyclin D1 expression in NSCLC. To shed light on this issue, endogenous NKX2-1 was depleted in NSCLC cell lines, which resulted in decreased cyclin D1 mRNA and protein. In contrast, forced overexpression of NKX2-1 increased cyclin D1 levels. Moreover, NKX2-1 directly bound to the cyclin D1 promoter and enhanced its activity. Finally, using human NSCLC clinical specimens, it was determined that both NKX2-1 protein and mRNA were significantly correlated with cyclin D1 expression status in adenocarcinomas. These results indicate that NKX2-1 directly and positively regulates transcription of cyclin D1 Finally, expression of NKX2-1, but not cyclin D1, was significantly associated with metastatic incidence as an independent good prognostic factor of adenocarcinoma.Implications: NKX2-1-expressing adenocarcinomas, whereas NKX2-1 promoted cyclin D1 expression, may show good prognosis features by the metastasis inhibition potency of NKX2-1 regardless cyclin D1 expression. Mol Cancer Res; 15(10); 1388-97. ©2017 AACR.