ABSTRACT
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.
ABSTRACT
STUDY OBJECTIVES: High-concentration oxygen therapy is used to treat tissue hypoxia, but hyperoxia causes lung injury. Overproduction of nitric oxide by nitric oxide synthase (NOS) is thought to promote hyperoxic lung injury. The present study was conducted to examine the role of inducible nitric oxide synthase (iNOS) in hyperoxic lung injury in mice. MEASUREMENTS AND RESULTS: Mice were exposed to >98% oxygen for 72 h, and ONO-1714 (0.05 mg/kg) (ONO) was subcutaneously administered to block iNOS. Hyperoxia significantly increased total cell count, protein concentration, and nitrites/nitrates in the bronchoalveolar lavage fluid and proinflammatory cytokines in the lung tissue. ONO significantly prevented the increases in all of these variables. ONO suppressed histologic evidence of lung injury. ONO markedly inhibited iNOS protein expression and nitrotyrosine production in lung homogenates. After exposure to hyperoxia, alveolar epithelial cells stained positively for 8-hydroxy-2'-deoxyguanosine, a proper marker of oxidative DNA damage by reactive oxygen species. ONO attenuated this finding. CONCLUSIONS: NOS play important roles in the pathogenesis of hyperoxic lung injury. Selective iNOS inhibitors may be useful for the treatment of hyperoxic lung injury.
Subject(s)
Amidines/administration & dosage , Enzyme Inhibitors/administration & dosage , Hyperoxia/prevention & control , Lung Diseases/prevention & control , Nitric Oxide Synthase Type II/antagonists & inhibitors , Animals , Blotting, Western/methods , Bronchoalveolar Lavage Fluid/chemistry , Cell Differentiation/physiology , Cytokines/analysis , Drug Administration Schedule , Heterocyclic Compounds, 2-Ring/administration & dosage , Hyperoxia/metabolism , Hyperoxia/physiopathology , Immunohistochemistry/methods , Injections, Subcutaneous , Lung/chemistry , Lung/drug effects , Lung/pathology , Lung Diseases/metabolism , Lung Diseases/physiopathology , Male , Mice , Mice, Inbred C57BL , Nitric Oxide Synthase Type II/analysis , Nitrogen Oxides/analysis , Tyrosine/analogs & derivatives , Tyrosine/analysisABSTRACT
We report 4 cases of spinal cord metastases of lung cancer detected by MRI. Histologically, 3 of the 4 cases were small cell carcinoma and the other was adenocarcinoma. All 3 cases of small cell carcinoma had neoplastic meningitis. MRI taken in these cases showed the multiple nodules in the cauda equina, which were seeded from brain metastases. One of them had intramedullary spinal cord metastases, which appeared as enlargement of the spinal cord or nodules in the spinal cord on MRI. Leg paralysis and incontinence progressed in all cases. The other case of adenocarcinoma had epidural spinal cord compression due to spinal metastasis. In this case irradiation and corticosteroids relieved her leg and back pain. Spinal cord metastases should be considered as a differential diagnosis in patients with numbness, pain or weakness in the extremities.
Subject(s)
Lung Neoplasms/pathology , Magnetic Resonance Imaging , Spinal Cord Neoplasms/secondary , Adenocarcinoma/diagnosis , Adenocarcinoma/secondary , Aged , Carcinoma, Small Cell/diagnosis , Carcinoma, Small Cell/secondary , Diagnosis, Differential , Female , Gadolinium DTPA , Humans , Male , Middle Aged , Spinal Cord Neoplasms/diagnosisABSTRACT
A 27-year-old woman was admitted because of right dry eye and blurred vision. She was given a diagnosis of uveitis due to sarcoidosis. Chest X-ray film showed bilateral hilar lymphadenopathy and multiple nodules in both lungs. The nodules were considered to be associated with sarcoidosis. However chest CT demonstrated that the nodules were well-defined and connected with two vessels. We diagnosed diffuse pulmonary arteriovenous malformations (AVMs) by 3D-CT. In three of sixteen AVMs, the feeding vessels were more than 3 mm wide in diameter on pulmonary arteriography, and those were embolized by platinum coils. The embolotherapy of diffuse AVMs could not ameliorate the shunt fraction sufficiently, but should reduce the possibility of the catastrophic complication of brain abscess.
Subject(s)
Arteriovenous Malformations/complications , Pulmonary Artery/abnormalities , Pulmonary Veins/abnormalities , Sarcoidosis/complications , Adult , Arteriovenous Malformations/therapy , Embolization, Therapeutic , Female , Humans , Imaging, Three-Dimensional , Sarcoidosis/diagnostic imaging , Tomography, X-Ray Computed/methodsABSTRACT
Thymic carcinoma is rarer than thymoma and carries a very poor prognosis. No standard treatment has yet been established. Chemotherapy and radiation therapy are usually given to patients in whom surgery is not indicated. We clinically review six patients with thymic carcinoma (three men and three women) who were admitted to our hospital from 1992 through 2002. Their ages ranged from 56 to 81 years (median 70.5). Four patients had chest pain, two were unable to swallow, and in one, who was asymptomatic, the tumor was detected by chance. Histologically, five cases were squamous cell carcinomas, and one was a lymphoepithelioma-like carcinoma. Four of the six patients had distant metastasis at diagnosis. Only one patient was able to undergo surgery, two received radiation therapy alone, and three were administered chemoradiation. The response to the chemoradiation was progression of the disease in two patients and no change in one. The response to radiation therapy was partial response in one patient and no change in one. In summary, chest pain is the most common symptom of thymic carcinoma. A symptomatic case suggests a poor prognosis resulting from the clinical behavior of thymic carcinoma, such as early distant metastasis or direct invasion of surrounding organs. Histologically, squamous cell carcinoma is the most common, and thymic carcinoma appears to be generally resistant to chemotherapy and radiotherapy.