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1.
Oncologist ; 27(11): 903-e834, 2022 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-36181763

RESUMO

BACKGROUND: Osimertinib is one of the standard first-line treatments for advanced non-small cell lung cancer in patients with epidermal growth factor receptor (EGFR) mutations, because it achieves significantly longer progression-free survival (PFS) than conventional first-line treatments (hazard ratio: 0.46). However, the efficacy and safety of osimertinib as a first-line treatment for patients aged ≥75 years remain unclear. METHODS: This phase II study was performed to prospectively investigate the efficacy and safety of osimertinib for elderly patients with EGFR mutation-positive advanced non-small cell lung cancer. The primary endpoint was 1-year PFS rate; secondary endpoints were overall response rate (ORR), PFS, overall survival (OS), and safety. RESULTS: Thirty-eight patients were included in the analysis. The 1-year PFS rate was 59.4% (95% confidence interval [CI], 46.1%-72.7%), which did not meet the primary endpoint (the threshold 1-year PFS rate of 50% predicted using data from the NEJ003 study). The most common grade 3/4 adverse events were rash/dermatitis acneiform/ALT increased/hypokalemia (2 patients, 5%). Seven patients developed pneumonitis (17.5%). There were no other cases of treatment discontinuation due to adverse events other than pneumonitis. CONCLUSION: Although this study did not meet the primary endpoint, osimertinib was tolerable for elderly patients with EGFR mutation-positive advanced non-small cell lung cancer. (Japan Registry of Clinical Trials [JRCT] ID number: jRCTs071180007).


Assuntos
Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Idoso , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Inibidores de Proteínas Quinases/efeitos adversos , Antineoplásicos/efeitos adversos , Compostos de Anilina/efeitos adversos , Receptores ErbB/genética , Receptores ErbB/uso terapêutico , Mutação
2.
Cancer Med ; 12(14): 15117-15127, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37269194

RESUMO

BACKGROUND: Dacomitinib significantly improves progression-free survival and overall survival (OS) compared with gefitinib in patients with non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR)-activating mutations. However, dacomitinib often causes skin toxicities, resulting in treatment discontinuation. We aimed to evaluate a prophylactic strategy for skin toxicity induced by dacomitinib. METHODS: We performed a single-arm, prospective, open-label, multi-institutional phase II trial for comprehensive skin toxicity prophylaxis. Patients with NSCLC harboring EGFR-activating mutations were enrolled and received dacomitinib with comprehensive prophylaxis. The primary endpoint was the incidence of skin toxicity (Grade ≥2) in the initial 8 weeks. RESULTS: In total, 41 Japanese patients participated between May 2019 and April 2021 from 14 institutions (median age 70 years; range: 32-83 years), 20 were male, and 36 had a performance status of 0-1. Nineteen patients had exon 19 deletions and L858R mutation. More than 90% of patients were perfectly compliant with prophylactic minocycline administration. Skin toxicities (Grade ≥2) occurred in 43.9% of patients (90% confidence interval [CI], 31.2%-56.7%). The most frequent skin toxicity was acneiform rash in 11 patients (26.8%), followed by paronychia in five patients (12.2%). Due to skin toxicities, eight patients (19.5%) received reduced doses of dacomitinib. The median progression-free survival was 6.8 months (95% CI, 4.0-8.6 months) and median OS was 21.6 months (95% CI, 17.0 months-not reached). CONCLUSION: Although the prophylactic strategy was ineffective, the adherence to prophylactic medication was quite good. Patient education regarding prophylaxis is important and can lead to improved treatment continuity.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Masculino , Idoso , Feminino , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Estudos Prospectivos , Inibidores de Proteínas Quinases/uso terapêutico , Receptores ErbB/genética , Mutação
3.
JTO Clin Res Rep ; 4(12): 100587, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38046380

RESUMO

Introduction: Osimertinib may be effective in treating central nervous system (CNS) metastasis, but its efficacy in treating radiation therapy (RT)-naive metastasis is unclear. The OCEAN study assessed the efficacy of osimertinib against RT-naive CNS metastasis in patients previously treated (T790M cohort) and untreated patients (first-line cohort) with EGFR mutation. Here, we report the results of the first-line cohort. Methods: Previously untreated patients with RT-naive CNS metastasis and EGFR mutation-positive NSCLC were treated with osimertinib. The brain metastasis response rate (BMRR), progression-free survival (PFS), and overall survival in the first-line cohort were secondary end points. Results: A total of 26 patients were enrolled in the study between September 2019 and July 2020. The median age was 72.0 years with 80.8% female. There were 20 patients who had multiple CNS metastases. BMRR assessed by PAREXEL criteria was 76.9% (90% confidence interval [CI]: 63.3%-90.5%), BMRR assessed by Response Evaluation Criteria in Solid Tumors was 76.9% (95% CI: 54.0%-99.8%), and median PFS of CNS metastasis was 22.0 months (95% CI: 9.7 mo-not reached). The overall response rate was 64.0% (95% CI: 45.2%-82.8%), median PFS was 11.5 months (95% CI: 6.9 mo-not reached), and median survival time was 23.7 months (95% CI: 16.5 mo-not reached). Paronychia and increased creatinine level were the most frequent nonhematological toxicities observed in 13 patients (50%). Grade three and higher adverse events were less than 10%, and there were no treatment-related deaths. Pneumonitis was observed in five patients (19.2%). Conclusions: These results suggest that osimertinib is effective in untreated patients with RT-naive asymptomatic CNS metastasis in a clinical practice first-line setting. Trial registration: UMIN identifier: UMIN000024218. jRCT identifier: jRCTs071180017.

4.
Thorac Cancer ; 13(18): 2616-2623, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35906784

RESUMO

BACKGROUND: It has long been thought that small-cell lung cancer (SCLC) is a central type of tumor that is located in the proximal bronchi and the mediastinum. However, several studies reported that SCLC exhibited several types of spread pattern on computed tomography (CT). The aim of this study is to investigate the relationship between CT images and clinical characteristics in patients with SCLC. METHODS: We retrospectively reviewed the CT images of 92 SCLC patients and classified them into six types of spreading patterns: central, peripheral, lymphangitic spread (LYM), pleural dissemination (PLE), lobar replacement (LOB), and air-space consolidation (AC). We also evaluated the correlation between primary tumor location and the clinical characteristics of patients. RESULTS: The most common type of imaging pattern was peripheral (n = 40, 44%), with the next most common type being central (n = 27, 29%). Atypical types of SCLC, such as LYM (n = 2, 2%), PLE (n = 4, 4%), LOB (n = 8, 9%), and AC (n = 11, 12%), were also recognized in our study. The prevalence of emphysema and interstitial lung disease (ILD) was significantly higher in the peripheral type than in the central type (p = 0.0056 and p = 0.0403, respectively). Meanwhile, no survival difference was seen between the central type and the peripheral type (median months 17.9 vs. 21.9, respectively, p = 0.720). CONCLUSIONS: The peripheral type of tumor was correlated with higher prevalence of emphysema and ILD in SCLC. Our result suggests different mechanisms of development and tumor characteristics according to tumor location.


Assuntos
Enfisema , Doenças Pulmonares Intersticiais , Neoplasias Pulmonares , Enfisema Pulmonar , Carcinoma de Pequenas Células do Pulmão , Humanos , Pulmão/patologia , Doenças Pulmonares Intersticiais/complicações , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Enfisema Pulmonar/complicações , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/complicações , Carcinoma de Pequenas Células do Pulmão/diagnóstico por imagem , Carcinoma de Pequenas Células do Pulmão/patologia
5.
Respirol Case Rep ; 10(3): e0913, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35198215

RESUMO

Edwardsiella tarda is an anaerobic, gram-negative rod bacterium associated with freshwater and marine life. Human E. tarda infections are rare, and most infections in humans cause gastroenteritis. Extraintestinal infections of E. tarda such as pleural empyema are particularly rare. A 72-year-old man was admitted with cough and purulent sputum. His medical history included periodontal disease and gastric cancer for which he had undergone total gastrectomy. Chest computed tomography showed left pleural effusion with foci of gas, and both E. tarda and Streptococcus constellatus were cultured from the pleural effusion. Thus, he was diagnosed with gas-forming empyema. He was successfully treated with therapeutic thoracentesis and antibiotics. Our case suggests that a dietary habit of raw fish, undernutrition, gastrectomy and oral infection may be predisposing factors for empyema caused by E. tarda.

6.
Respir Med Case Rep ; 37: 101642, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35360361

RESUMO

Werner syndrome (WS) is a rare progressive disorder that is characterized by premature aging of all organs. Malignancy is a frequent complication of WS, however, lung cancer patients with WS are much rare. In patients with WS, the treatment for malignancy is often limited due to other complications of severe skin ulcer, diabetes mellitus and cardiovascular disease. Currently, immune-checkpoint inhibitors (ICIs) are standard therapy for several cancer patients and the combination of nivolumab plus ipilimumab has also been approved for the treatment of non-small cell lung cancer (NSCLC). Recent studies have also reported that serious immune-related adverse events (irAEs) induced by ICIs may correlate with elderly or more vulnerable patients. However, the efficacy and safety of ICIs in NSCLC patients with WS remain unclear. To the best of our knowledge, this is the first case describing a NSCLC patient with WS receiving the combination immunotherapy of nivolumab and ipilimumab. Our case showed objective response to ICIs, however, several immune-related adverse events (irAEs) including hypothyroidism, adrenal insufficiency, hard rash and interstitial lung disease occurred, thus resulted in early treatment discontinuation. Our case suggests that immunotherapy for NSCLC patients with WS could be effective, but physicians may be aware of the possibility of multiple irAEs undergoing immunotherapy for NSCLC patients with WS.

7.
J Clin Tuberc Other Mycobact Dis ; 29: 100341, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36466135

RESUMO

Introduction: Acute respiratory distress syndrome (ARDS) is considered a poor prognostic factor for miliary tuberculosis (MTB), but little is known about the effectiveness of steroid pulse therapy for MTB complicated by ARDS. Patients and methods: Medical records were used to retrospectively investigate the prognosis and clinical information of 13 patients diagnosed with MTB complicated by ARDS among 68 patients diagnosed with MTB at our hospital between January 1994 and October 2016. None of the patients had multidrug resistant tuberculosis (TB). MTB was diagnosed by 1 radiologist and 2 respiratory physicians based on the observation of randomly distributed, uniformly sized diffuse bilateral nodules on chest computed tomography and the detection of mycobacterium TB from clinical specimens. ARDS was diagnosed based on the Berlin definition of ARDS. The effect of steroid pulse therapy on death within 3 months of hospitalization was examined using Cox proportional hazards models. Variables were selected by the stepwise method (variable reduction method). Results: Six of 8 patients with MTB complicated by ARDS were alive 3 months after hospitalization in the steroid pulse therapy group, whereas only 1 of 5 patients was alive in the non-steroid pulse therapy group. Analysis of factors related to the survival of patients with MTB complicated by ARDS revealed that steroid pulse therapy was the strong prognostic factor (hazard ratio = 0.136 (95 % CI: 0.023-0.815)). Conclusion: Our findings suggest that steroid pulse therapy improves the short-term prognosis of patients with MTB complicated by ARDS.

8.
Transl Lung Cancer Res ; 11(9): 1847-1857, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36248326

RESUMO

Background: Topoisomerase is an essential enzyme for deoxyribonucleic acid replication, and its inhibitors suppress tumor progression. Amrubicin, a topoisomerase II inhibitor, is mainly used in the second-line treatment of patients with extensive-stage small cell lung cancer (ES-SCLC). However, the impact of different types of topoisomerase inhibitors for first-line chemotherapy on the efficacy of amrubicin remains unclear. In the present study, we aimed to evaluate the efficacy of second-line amrubicin in patients with relapsed SCLC who were previously treated with platinum-based chemotherapy, including topoisomerase I and II inhibitors. Methods: This study retrospectively analyzed patients with ES-SCLC who experienced recurrence and were treated with amrubicin at 22 institutions in Japan between April 2015 and November 2020. The progression-free survival of amrubicin monotherapy was investigated using the Kaplan-Meier method. Results: A total of 320 patients were enrolled in this study, with 59 (18%) receiving platinum plus topoisomerase I inhibitor irinotecan and 261 (82%) receiving platinum plus topoisomerase II inhibitor etoposide as first-line treatment. The progression-free survival of amrubicin was significantly longer in the irinotecan group than in the etoposide group (3.2 vs. 2.5 months; P=0.034). Conclusions: These results showed that different types of topoisomerase inhibitors could affect the efficacy of amrubicin monotherapy in the second-line treatment of patients with relapsed ES-SCLC.

9.
Respirology ; 15(5): 809-12, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20497387

RESUMO

BACKGROUND AND OBJECTIVE: Although the association of hypertrophic pulmonary osteoarthropathy (HPO) with lung cancer was investigated in the 1960s, the recent incidence of clinically apparent HPO is not known. Data from a large series of patients with lung cancer were analysed, in order to assess the incidence of possible HPO, based on bone scintigraphy, as well as the incidence of clinically confirmed HPO. The clinical features of confirmed HPO were also evaluated. METHODS: The medical records of patients admitted with lung cancer between January 1986 and August 2004 were reviewed. Bone scintigraphy showing symmetrical, abnormally high uptake in joints and/or long bones was considered to be suggestive of HPO. Patients who also had finger clubbing and joint pain were considered to have a confirmed diagnosis of HPO. Clinical histories and hormone levels were then investigated in these patients, to identify possible causal factors. RESULTS: Among the 1226 lung cancer patients, 55 (4.5%) demonstrated abnormally high uptake on bone scintigraphy, suggesting possible HPO. Ten (0.8%) patients had clubbed fingers and joint pain and were eventually confirmed as having HPO. Serum hormone concentrations were abnormally high in the patients with confirmed HPO. CONCLUSIONS: This retrospective study indicated that 4.5% of lung cancer patients showed findings suggestive of HPO, a frequency similar to that reported previously. However, patients with HPO rarely showed the complete triad of signs. Although increased hormone concentrations may have caused the HPO, further investigation is required to confirm this.


Assuntos
Adenocarcinoma/complicações , Carcinoma de Células Pequenas/complicações , Carcinoma de Células Escamosas/complicações , Neoplasias Pulmonares/complicações , Osteoartropatia Hipertrófica Secundária/epidemiologia , Osteoartropatia Hipertrófica Secundária/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Artralgia/epidemiologia , Artralgia/etiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
10.
Nihon Kokyuki Gakkai Zasshi ; 48(10): 769-73, 2010 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-21066867

RESUMO

A 56-year-old man receiving hemodialysis treatment was hospitalized for examination of a mass in the right middle lobe. Chest computed tomography showed a right hilar mass shadow accompanied by pleural effusion. Non-small cell lung cancer (NSCLC) was diagnosed by cytological examination of the pleural effusion. No epidermal growth factor receptor (EGFR) mutation was found. He was treated with 6 courses of docetaxel as first-line chemotherapy. Docetaxel was administered on the same day as hemodialysis. Adverse events, including hematotoxicity, were managed safely and no delay in administration occurred. This chemotherapy resulted in a partial response. Because docetaxel is metabolized in the liver and does not affect renal function, it can be administered as a standard regimen. This suggests that docetaxel monotherapy is an efficient therapy for non-small cell lung cancer patients receiving hemodialysis.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Diálise Renal , Taxoides/uso terapêutico , Docetaxel , Humanos , Masculino , Pessoa de Meia-Idade
11.
Medicine (Baltimore) ; 99(43): e22561, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33120743

RESUMO

Although sedation for bronchoscopy improves patient comfort, there is a risk of oversedation in elderly patients. Only a few studies have evaluated the efficacy and safety of sedation for bronchoscopy in elderly patients.This study retrospectively analyzed records of 210 patients who underwent transbronchial brushing and/or biopsy under midazolam sedation at National Hospital Organization Omuta National Hospital between June 2017 and October 2019. Patients were administered 1 mg midazolam following 10 mL 4% lidocaine inhalation. When sedation was insufficient, 0.5 mg midazolam was administered additionally. Diagnostic yield, incidence of complications, amount of oxygen supplementation, decreases in percutaneous oxygen saturation (SpO2), changes in blood pressure, and degree of comfort were analyzed.Patients were divided into the elderly (n = 102) and non-elderly (n = 108) groups. No significant differences were observed in diagnostic yield and procedure time between the 2 groups, and no severe adverse events were noted in the elderly group. The degree of comfort during bronchoscopy was significantly higher in the elderly group. In patients administered < 2 mg midazolam, the amount of oxygen supplementation and decreases in SpO2 were significantly smaller in the elderly group compared to the non-elderly group.The risk of adverse events related to midazolam sedation in bronchoscopy does not increase with age, and sedation improves comfort during flexible bronchoscopy in elderly patients. Moreover, a total dose of midazolam <2 mg is safe for elderly patients undergoing bronchoscopy.


Assuntos
Broncoscopia , Sedação Consciente , Hipnóticos e Sedativos/uso terapêutico , Midazolam/uso terapêutico , Conforto do Paciente , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Oxigênio/sangue , Oxigenoterapia/estatística & dados numéricos , Estudos Retrospectivos
12.
Nihon Kokyuki Gakkai Zasshi ; 47(12): 1156-60, 2009 Dec.
Artigo em Japonês | MEDLINE | ID: mdl-20058697

RESUMO

We report a case of a 28-year-old man with a dry cough and chest pain. Chest X-ray film showed a huge mass in the right lung field. Computed tomography (CT) and magnetic resonance imaging (MRI) showed a huge mass which occupied most of the right thoracic cavity and invaded the superior vena cava, heart atrium and right pulmonary vein. Positron emission tomography (PET) showed metastasis of bone, right adrenal grand and lymph nodes. A tumor specimen was biopsied percutaneously, and the diagnosis was pathologically confirmed as an inflammatory myofibroblastic tumor. Immunohistochemical staining also showed an overexpression of ALK in the tumor. He was treated with a non-steroid anti-inflammation drug and steroid, but they were ineffective. He underwent chemotherapy with bleomicin, etoposide and cisplatin. After two cycles of chemotherapy, the tumor slightly reduced in size, but was eventually refractory to the regimen finally. He also underwent with paclitaxel and carboplatin. At present, if operative extirpation is not possible, there is no way to treat an inflammatory myofibroblastic tumor. In the future, new therapy incorporating ALK inhibitors would be expected to treat those cases of IMT in which local recurrences and distant metastases occur.


Assuntos
Granuloma de Células Plasmáticas , Pneumopatias , Adulto , Granuloma de Células Plasmáticas/tratamento farmacológico , Humanos , Pneumopatias/tratamento farmacológico , Masculino
13.
Respirology ; 13(1): 103-7, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18197918

RESUMO

BACKGROUND AND OBJECTIVE: A multi-institutional phase II trial combining uracil-tegafur (UFT) and cisplatin (CDDP) was conducted in patients with previously untreated advanced non-small cell lung cancer (NSCLC) to evaluate the safety and efficacy of this combined treatment regimen. METHODS: The entry criteria for this study were previously untreated NSCLC, measurable disease, age <80 years, performance status <2, and adequate haematological, hepatic and renal function. Patients were treated with 400 mg/m(2) oral UFT from day 1 to day 14 and 80 mg/m(2) cisplatin on day 15. The treatment course was repeated every 3 weeks. RESULTS: Of the 68 patients enrolled, 64 (27 with stage IIIB and 37 with stage IV disease) were eligible for treatment. Twenty of the 64 patients responded to the chemotherapy (response rate 31.3%; 95% CI 21.2-43.4%). The median survival time was 8.6 months, and the 1-year survival was 41.5%. Haematological toxicity >or=WHO grade 3 was seen in 3 (4.7%) patients. For non-haematological toxicities, anorexia with WHO grade 3 was seen in 8 (12.5%) patients, nausea and vomiting with WHO grade 3 in 4 (6.3%), diarrhoea with WHO grade 4 in 1 (1.6%), and liver dysfunction with WHO grade 4 in 1 (1.6%) patient. CONCLUSIONS: The combination of oral UFT plus cisplatin was found to be a safe and active treatment against advanced NSCLC. The observed low toxicity of this combined regimen may warrant its application to the treatment of elderly patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Fatores Etários , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Taxa de Sobrevida , Tegafur/administração & dosagem , Tegafur/efeitos adversos , Resultado do Tratamento , Uracila/administração & dosagem , Uracila/efeitos adversos
14.
J Clin Tuberc Other Mycobact Dis ; 12: 66-72, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31720401

RESUMO

BACKGROUND AND PURPOSE: Acute respiratory distress syndrome (ARDS) complication has long been considered a factor associated with poor prognosis in patients with miliary tuberculosis. However, few reports exist on the prognostic factors of miliary tuberculosis including those complicating ARDS. SUBJECTS AND METHODS: We retrospectively examined prognoses and other clinical information obtained from medical records of a total of 68 patients diagnosed with miliary tuberculosis. Clinical findings were compared between patients who died within three months (non-survivor group) and those who survived beyond three months (survivor group), and risk factors for death within three months of diagnosis were examined using logistic regression analysis. RESULTS: Fifteen of 68 patients diagnosed with miliary tuberculosis died within three months. Most patients were aged 60 years or older (63 patients; 91.2%), with a peak in the 80 s (32 patients; 47.1%). Of the 68 patients with miliary tuberculosis, 13 (19%) had ARDS. The risk of death within three months increased with increasing age and ARDS onset during the disease course. The results of multivariate analysis revealed that, in addition to age (odd ratio (OR): 15.5) and the presence/absence of ARDS (OR: 12.0), consciousness disturbance (OR: 81.53) and high BUN levels (OR: 5.71) were independent factors for death within three months. CONCLUSION: In patients with miliary tuberculosis, old age, ARDS, consciousness disturbance, and high BUN levels were factors associated with poor prognosis.

15.
Lung Cancer ; 55(2): 145-56, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17113184

RESUMO

Conventional treatments are not adequate for the majority of lung cancer patients. Conditionally replicating adenoviruses (CRAds) represent a promising new modality for the treatment of neoplastic diseases, including non-small cell lung cancer. Specifically, following cellular infection, the virus replicates selectively in the infected tumor cells and kills the cells by cytolysis. Next, the progeny virions infect a new population of surrounding target cells, replicate again and eradicate the infected tumor cells while leaving normal cells unaffected. However, to date, there have been two main limitations to successful clinical application of these CRAd agents; i.e. poor infectivity and poor tumor specificity. Here we report the construction of a CRAd agent, CRAd-CXCR4.RGD, in which the adenovirus E1 gene is driven by a tumor-specific CXCR4 promoter and the viral infectivity is enhanced by a capsid modification, RGD4C. This agent CRAd-CXCR4.RGD, as expected, improved both of the viral infectivity and tumor specificity as evaluated in an established lung tumor cell line and in primary tumor tissue from multiple patients. As an added benefit, the activity of the CXCR4 promoter was low in human liver as compared to three other promoters regularly used for targeting tumors. In addition, this agent has the potential of targeting multiple other tumor cell types. From these data, the CRAd-CXCR4.RGD appears to be a promising novel CRAd agent for lung cancer targeting with low host toxicity.


Assuntos
Adenoviridae/genética , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/terapia , Terapia Viral Oncolítica/métodos , Regiões Promotoras Genéticas , Receptores CXCR4/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Vetores Genéticos , Humanos , Fígado/metabolismo , Neoplasias Pulmonares/genética , Reação em Cadeia da Polimerase , Células Tumorais Cultivadas , Replicação Viral
16.
Anticancer Res ; 27(6C): 4351-8, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-18214043

RESUMO

Determining an effective predictor of clinical drug resistance in small cell lung cancer (SCLC) is considered to be important. In this study, the relationship between the expression of P-glycoprotein (P-gp), multidrug resistance-associated protein 1 (MRP1) and MRP2, which are the members of ATP-binding cassette superfamily transporter, and of the p53 tumor suppressor gene and the response to chemotherapy were analysed. The expression of P-gp, MRP1, MRP2, and p53 was determined by an immunohistochemical analysis of transbronchial biopsy (TBB) specimens from 61 SCLC patients. The relationship of such expression was also investigated regarding chemotherapy and clinicopathological factors. The response rate in the MRP2-negative group was significantly higher than that in the MRP2-positive group (88% versus 50%). The P-gp-negative group responded significantly better to chemotherapy than the P-gp-positive group, with a response rate of 81% versus 39%. No relationship could be found between the response to chemotherapy and immunostaining for MRP1 or p53. In 37 patients treated with platinum-based chemotherapy, the response rate of patients in the MRP2-negative group was significantly higher than that in the positive group (92% versus 50%). In a multiple logistic regression analysis, MRP2 as well as P-gp were shown to be statistically significant predictors of chemotherapy resistance. These results suggest that immunostaining of MRP2 for TBB specimens may help to predict clinical resistance to platinum agents. This is the first report which indicates that the immunohistochemical expression of MRP2 is positively related to a clinical resistance to platinum.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Pequenas/metabolismo , Resistencia a Medicamentos Antineoplásicos/fisiologia , Neoplasias Pulmonares/metabolismo , Proteínas de Membrana Transportadoras/biossíntese , Proteínas Associadas à Resistência a Múltiplos Medicamentos/biossíntese , Compostos de Platina/uso terapêutico , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/biossíntese , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Pequenas/tratamento farmacológico , Resistência a Múltiplos Medicamentos/fisiologia , Feminino , Expressão Gênica , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Proteína 2 Associada à Farmacorresistência Múltipla
17.
Respir Investig ; 55(1): 16-23, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28012488

RESUMO

BACKGROUND: The prognostic significance of serial measurements of serum KL-6 levels in patients with idiopathic pulmonary fibrosis (IPF) is unclear; hence, it was assessed in this study. METHODS: Medical records of 66 patients with IPF, who were not treated with pirfenidone prior to enrollment, were retrospectively reviewed for information on clinical progress, forced vital capacity (FVC), survival, and serum KL-6 levels. We assessed initial serum levels of KL-6, serial changes in serum KL-6 levels, yearly decline in FVC (ΔFVC), and the rate of decline (%ΔFVC). RESULTS: Patients with increased serum KL-6 levels during follow-up had a significantly steeper decline in ΔFVC than those with no KL-6 increase (-201 vs. -50.7ml/year; p=0.0001). Patients with both initial serum KL-6 ≥1000U/ml and serial increases in serum KL-6 had the steepest decline, while those with both initial serum KL-6 <1000ml and no serial increases in KL-6 had the least decline in ΔFVC and %ΔFVC. Relative to the non-increased KL-6 group, survival in the increased KL-6 group tended to be poorer (p=0.0530). Patients with both initial serum KL-6 values <1000U/ml and no serial increase in KL-6 had more favorable prognoses than those with serial increases in KL-6 or initial serum KL-6 values ≥1000U/ml (p<0.0044). Prognosis was significantly poorer in patients with serial KL-6 changes >51.8U/ml/year than in those with serial KL-6 changes <51.8U/ml/year (p=0.0009). CONCLUSION: Thus, serial serum KL-6 measurements can be useful for assessing prognosis in patients with IPF.


Assuntos
Fibrose Pulmonar Idiopática/diagnóstico , Mucina-1/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Feminino , Seguimentos , Humanos , Fibrose Pulmonar Idiopática/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Prognóstico , Piridonas/uso terapêutico , Estudos Retrospectivos
18.
Clin Cancer Res ; 8(11): 3480-6, 2002 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-12429638

RESUMO

Vascular endothelial growth factor (VEGF) is well known to be produced by many human tumors, and it also plays an important role in tumor neovasculature formation. In addition to angiogenesis promotion, recent basic research has shown that VEGF has another function that allows it to inhibit dendritic cell (DC) maturation. However, very little is known about VEGF-dependent DC inhibition in a clinical setting. In this study, we analyzed the immunohistochemical expression of VEGF, microvessel density (MVD), and intratumoral DC infiltration in 132 surgically resected lung cancer specimens. We also evaluated the influence of these factors on their survival by a multivariate statistical analysis. VEGF expression was positively related to MVD (P = 0.0003) and negatively related to the degree of DC infiltration (P = 0.0232). A multivariate analysis also showed the VEGF expression, MVD, and DC infiltration to be independent prognostic factors. Moreover, we also accurately analyzed patient prognoses using the double stratification method for determining VEGF expression and DC infiltration. The patient group with a high VEGF expression/low DC infiltration showed a worse prognosis (P < 0.0001), whereas the group with a low VEGF expression/high DC infiltration had a better prognosis (P = 0.0001).


Assuntos
Células Dendríticas/patologia , Fatores de Crescimento Endotelial/biossíntese , Peptídeos e Proteínas de Sinalização Intercelular/biossíntese , Neoplasias Pulmonares/diagnóstico , Linfocinas/biossíntese , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/patologia , Células Dendríticas/citologia , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/patologia , Masculino , Microcirculação , Pessoa de Meia-Idade , Análise Multivariada , Neoplasias/irrigação sanguínea , Prognóstico , Fatores de Tempo , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio Vascular
19.
Pulm Med ; 2015: 218253, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26693350

RESUMO

OBJECTIVE: This study aimed to examine the nutritional status and nutrient intake of patients with MAC lung disease with a focus on visceral fat area. PATIENTS AND METHODS: Among 116 patients of our hospital with nontuberculous mycobacteriosis who were registered between May 2010 and August 2011, 103 patients with MAC lung disease were included in this study. In all patients, nutritional status and nutrient intake were prospectively examined. RESULTS: Patients were 23 men and 80 women (mean age, 72.3±10.9 years). BMI (kg/m2) at the time of registration was 20.4±2.7 in men and 19.2±2.9 in women. Visceral fat area (cm2) was significantly lower in women (35.7±26.6) than in men (57.5±47.4) (p=0.0111). The comparison with general healthy adults according to age revealed a markedly reduced visceral fat area among patients with MAC lung disease. With respect to nutrient intake, energy adequacy (86.1±15.7%), protein adequacy (82.4±18.2%), lipid adequacy (78.1±21.8%), and carbohydrate adequacy (89.6±19.2%) ratios were all low at the time of registration. BMI was significantly correlated with protein adequacy (p=0.0397) and lipid adequacy (p=0.0214) ratios, while no association was found between visceral fat area and nutrient intake. CONCLUSION: Patients with MAC lung disease had a low visceral fat area and low nutrient intake.


Assuntos
Ingestão de Energia/fisiologia , Gordura Intra-Abdominal/fisiologia , Pneumopatias/fisiopatologia , Infecções por Mycobacterium não Tuberculosas/fisiopatologia , Estado Nutricional/fisiologia , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
20.
Kekkaku ; 77(6): 457-63, 2002 Jun.
Artigo em Japonês | MEDLINE | ID: mdl-12136600

RESUMO

The aim of the study is to search the efficient way for the prevention of nosocomial tuberculosis (TB) infection in a university teaching hospital. Through a questionnaire, informations on the degree of interest in TB, on the way how they try to learn about TB infection, and on basic knowledge of TB epidemiology were obtained. The study subjects were most employees including physicians, nursing staffs, medical technicians, pharmacists, clerks as well as medical and dental students, who were younger than 40 years. The study was done from 1999 through 2001, and a total of 2,159 questionnaires in which age, sex and occupational category were completely described were analyzed. Out of total participants, 61.8% participants showed interest in TB, however, only 3.0% had actually attended lecture meeting or collected materials on TB infection. Out of 619 nursing staffs, 431 (69.6%) felt anxiety for TB infection and the disease, and it was significantly higher than the other occupational groups. Of 2,159 participants, 1,472 (68.2%) participants desired to have health examination for TB. On the other hand, less than 50% participants including physicians answered correctly to questions about basic knowledge of TB epidemiology. Through the present study, it was suggested that employees and students in a university hospital do not voluntarily learn about TB, or do not have enough knowledge on TB in spite of their anxiety or interest, but that they are well prepared to obtain essential informations on the prevention of TB infection. Thus, it would be worthwhile to establish a system of education and health examination for the prevention of nosocomial TB infection. On the other hand, the degree of interest in and anxiety about TB in clerical employees was relatively low. Since they have some risk of TB infection through a service at window, the strengthening of health education on TB for them would be necessary.


Assuntos
Atitude do Pessoal de Saúde , Infecção Hospitalar/prevenção & controle , Conhecimentos, Atitudes e Prática em Saúde , Controle de Infecções , Recursos Humanos em Hospital/psicologia , Estudantes de Odontologia/psicologia , Estudantes de Medicina/psicologia , Tuberculose/prevenção & controle , Adulto , Pessoal Técnico de Saúde/psicologia , Ansiedade , Infecção Hospitalar/epidemiologia , Feminino , Educação em Saúde , Hospitais Universitários , Humanos , Masculino , Corpo Clínico Hospitalar/psicologia , Recursos Humanos de Enfermagem Hospitalar/psicologia , Inquéritos e Questionários , Tuberculose/epidemiologia , Recursos Humanos
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