RESUMO
Fibroblast activation proteins (FAP) are overexpressed in the tumor stroma and have received attention as target molecules for radionuclide therapy. The FAP inhibitor (FAPI) is used as a probe to deliver nuclides to cancer tissues. In this study, we designed and synthesized four novel 211At-FAPI(s) possessing polyethylene glycol (PEG) linkers between the FAP-targeting and 211At-attaching moieties. 211At-FAPI(s) and piperazine (PIP) linker FAPI exhibited distinct FAP selectivity and uptake in FAPII-overexpressing HEK293 cells and the lung cancer cell line A549. The complexity of the PEG linker did not significantly affect selectivity. The efficiencies of both linkers were almost the same. Comparing the two nuclides, 211At was superior to 131I in tumor accumulation. In the mouse model, the antitumor effects of the PEG and PIP linkers were almost the same. Most of the currently synthesized FAPI(s) contain PIP linkers; however, in our study, we found that PEG linkers exhibit equivalent performance. If the PIP linker is inconvenient, a PEG linker is expected to be an alternative.
Assuntos
Fibroblastos , Polietilenoglicóis , Humanos , Animais , Camundongos , Células HEK293 , Piperazina/farmacologia , Polietilenoglicóis/farmacologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Radioisótopos de GálioRESUMO
A 69-year-old woman was diagnosed with a germ cell tumor in the anterior mediastinum. Following 3 years follow-up, she experienced chest pain and an enlarging of the anterior mediastinal tumor and bilateral lung metastases were detected by chest X-ray. The tumor was diagnosed as a primary malignant mediastinal non-seminomatous germ cell tumor by needle biopsy. After initial radiotherapy (12 Gy/4 Fr), she was subsequently treated with EP chemotherapy which achieved a partial response. Complete resection of the residual tumors in the mediastinum and right lung was performed. No recurrence has been noted for 5 years post-operatively.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia , Neoplasias do Mediastino/terapia , Neoplasias Embrionárias de Células Germinativas/terapia , Idoso , Biópsia por Agulha , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/terapia , Neoplasias do Mediastino/diagnóstico por imagem , Neoplasias do Mediastino/patologia , Neoplasias Embrionárias de Células Germinativas/diagnóstico por imagem , Resultado do TratamentoRESUMO
The reported patient was a 90-year-old woman with anorexia. She was diagnosed with advanced gallbladder cancer that occurred concurrently with stomach cancer. Subsequent to intestinal bypass surgery, S-1(80mg/day)was administered for 14 days, followed by 7 days of rest for one course. Tumor marker levels returned to normal after 4 months. Computed tomography results indicated that, in regard to the gallbladder cancer, the patient had stable disease after 8 months. In addition, gastroscopy revealed a complete response of the gastric cancer after a year. The patient was able to continue treatment as an outpatient until she experienced aspiration pneumonia. The administration of S-1 was terminated after 4 years and 4 months. Treatment with S-1 monotherapy is considered safe for elderly patients, and has the additional benefit that it is deliverable as an outpatient treatment.
Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Neoplasias da Vesícula Biliar/tratamento farmacológico , Neoplasias Primárias Múltiplas/tratamento farmacológico , Ácido Oxônico/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Tegafur/uso terapêutico , Idoso de 80 Anos ou mais , Combinação de Medicamentos , Evolução Fatal , Feminino , Humanos , Fatores de TempoRESUMO
For the targeted delivery of genes and drugs to the human liver, hepatitis B virus (HBV) envelope L particles, which form hollow nanoparticles and display a peptide that is indispensable for liver-specific infection by HBV in humans, should be a useful tool. To test the efficacy of these particles in vivo, in the present study we generated a small animal model harboring a functional human liver tissue xenograft. An anti-asialo GM1 antibody was administered to SCID mice to induce the depletion of natural-killer-cell-dependent immune responsibility and then the mice underwent transplantation of a noncancerous liver tissue originating in humans into the kidney capsule. Interestingly, human liver tissues were engrafted in 58% of the animals at least for 14 days shown by a human hepatocyte-specific antibody. The engineered HBV nanoparticles which contained fluorescent chemicals could selectively bind to the xenograft in these immune-deficient mice when they were administered systemically. These results suggested that the model animal was usable to demonstrate the efficacy of the nanoparticles that could deliver chemicals specific to the normal human liver tissue by systemic administration, which will facilitate the study of human liver cell biology, drug metabolism and infections with hepatotropic viruses.
Assuntos
Portadores de Fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Nanopartículas , Animais , Sistemas de Liberação de Medicamentos , Fluoresceínas/administração & dosagem , Humanos , Transplante de Fígado , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos SCID , Modelos Animais , Transplante Heterólogo , Proteínas do Envelope Viral/administração & dosagemRESUMO
A 78-year-old woman was admitted because of persistent cough, fever and sputum for one week. She had been treated with radiation therapy for inoperable thymoma complicated by severe heart failure and had been suffering from recurrent pneumonia and otitis media since then. A chest radiograph on admission showed an anterior mediastinal mass shadow and infiltrates in the bilateral lower lung fields. Serum gamma globulin was decreased and erythroid cells in the bone marrow were markedly decreased. Thymoma with hypogammaglobulinemia is called Good syndrome. We reported this very rare case of Good syndrome. After improving the infection, cyclosporine A was administered for PRCA and hypo-gamma globulinemia, but we discontinued this due to liver dysfunction. We have been currently continuing her treatment with red blood cell transfusion and immunoglobulin supplement only.
Assuntos
Agamaglobulinemia/complicações , Aplasia Pura de Série Vermelha/complicações , Timoma/complicações , Neoplasias do Timo/complicações , Agamaglobulinemia/terapia , Idoso , Transfusão de Eritrócitos , Feminino , Humanos , Imunoglobulinas/uso terapêutico , Aplasia Pura de Série Vermelha/terapia , SíndromeRESUMO
We report a case of tuberculosis associated with hemophagocytic syndrome (HPS) which was complicated by treatment with infliximab for Crohn's disease. A 48-year-old woman was admitted because of fever, diarrhea and general malaise. Her condition did not improve with treatment for recurrence of Crohn's disease, and an abnormal shadow was pointed out on chest imaging. She was referred to our department and received a diagnosis of tuberculosis based on the results of smear and polymerase chain reaction examination of the sputum and bone marrow. HPS was suspected based on subsequent results such as hepatosplenomegaly, leukocytopenia, elevated ferritin, disseminated intravascular coagulation, hemophagocytosis of nucleated red cells, and leukocytes in the bone marrow. She was treated with antituberculous drugs, steroids and gamma globulin, and improved. A diagnosis of tuberculosis during the administration of infliximab therapy was very difficult because of atypical clinical symptoms and images e.g. the abscence of cavities or nodular shadows on her chest roentgenogram. To the best of our knowledge this case is the first report of tuberculosis associated with HPS, which was complicated by treatment with infliximab.
Assuntos
Anticorpos Monoclonais/efeitos adversos , Fármacos Gastrointestinais/efeitos adversos , Linfo-Histiocitose Hemofagocítica/etiologia , Tuberculose Pulmonar/etiologia , Doença de Crohn/complicações , Doença de Crohn/tratamento farmacológico , Feminino , Humanos , Infliximab , Linfo-Histiocitose Hemofagocítica/complicações , Pessoa de Meia-Idade , Tuberculose Pulmonar/complicaçõesRESUMO
A 61-year-old man was admitted for evaluation of an abnormal chest abnormal with progressive swelling in both hands, clubbing of all fingers and toes, and polyarthroceles. He was given a diagnosis of pulmonary hypertrophic osteoarthropathy (PHO) associated with primary lung cancer, and underwent an upper left lobectomy. Histopathological analysis revealed stage IIB adenocarcinoma of the lung with K-ras mutation, but with no evidence of epidermal growth factor receptor (EGFR). Postoperatively, his symptoms rapidly improved, and the preoperatively observed high levels of serum vascular endothelial growth factor (VEGF) and interleukin 6 (IL-6) decreased to normal levels after just 1 month. VEGF and IL-6 caused by the genetic mutation of K-ras might play a role in the pathogenesis of PHO with lung cancer.
Assuntos
Adenocarcinoma/complicações , Adenocarcinoma/cirurgia , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/cirurgia , Osteoartropatia Hipertrófica Secundária/etiologia , Osteoartropatia Hipertrófica Secundária/terapia , Adenocarcinoma/genética , Genes ras/genética , Humanos , Interleucina-6/sangue , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Mutação , Pneumonectomia , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/sangueRESUMO
Acute interstitial pneumonia is a rare and fulminant form of idiopathic interstitial lung disease. Here, we report a case of a giant malignant sarcomatoid tumor of the left lung with unilateral lung infiltration. The tumor was resected under venovenous extracorporeal membrane oxygenation support. Right middle lung lobe biopsy revealed alveolar epithelial hyperplasia, mild interstitial fibrosis, and interstitial edema. The patient was diagnosed with acute interstitial pneumonitis, and effectively treated with steroid pulse therapy followed by prednisolone. In this case, the contralateral lung expansion accomplished with tumor resection, definitive diagnosis based on lung biopsy, and corticosteroid treatment possibly improved the outcome.
Assuntos
Síndrome de Hamman-Rich/terapia , Neoplasias Pulmonares/cirurgia , Sarcoma/cirurgia , Síndrome de Hamman-Rich/complicações , Síndrome de Hamman-Rich/diagnóstico , Síndrome de Hamman-Rich/patologia , Humanos , Pulmão/patologia , Neoplasias Pulmonares/complicações , Metilprednisolona/administração & dosagem , Prednisolona/administração & dosagem , Pulsoterapia , Sarcoma/complicaçõesRESUMO
We reported a case of overlap syndrome involving severe obstructive sleep apnea syndrome (OSAS) associated with chronic obstructive lung disease (COPD). This patient was a 52-year-old heavy smoking man, who had suffered from snoring and apnea for five years, and was admitted to our hospital because of worsening dyspnea. His BMI was 25 Kg/M2, His jaw was very small and he had a narrow upper airway. Chest X-ray showed hyperlucency throughout both lung fields with a markedly dilatation pulmonary arteries. His PaO2 was 62Torr, PaCO2 was 47Torr, FEV(1.0%) was 59%, mean pulmonary artery pressure was 27 mmHg, PSG showed that AHI was 70, were most pronounced during rapid eye movement sleep. He was given a diagnosis of overlap syndrome of OSAS associated with COPD. Generally, Overlap syndrome was believed that chronic bronchitis type (blue bloater) was more frequent than emphysema type. This case was a very rare case, with no obesity, moderate COPD, associated with pulmonary hypertension and hypercapnea, and then to be severe OSAS. However we should be more careful about the OSAS associated with overlap syndrome of the Japanese patients, because to be one factor of exacerbation of respiratory failure.
Assuntos
Doença Pulmonar Obstrutiva Crônica/complicações , Apneia Obstrutiva do Sono/complicações , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Prader-Willi syndrome (PWS) is a genetic disorder, characterized by shorter height, severe obesity and muscular hypotonicity. In particular, sleep disordered breathing (SDB) is a well-known complication in PWS. We encountered one case of PWS, complicated by typical obesity hypoventilation syndrome. A 23-year-old woman had been given a diagnosis of PWS as age 1, therefore she was treated with growth hormone replacement therapy, and with uvulopalatopharyngoplasty (UPPP) for her narrow throat. Her weight increased greatly to 96kg, body mass index (BMI) 51 kg/m2, resulting in hypersomnolence, cyanosis, heavy snoring, and nocturnal awakening. Eventually, she was admitted because of urinary incontinuence and loss of consciousness. On admission, she had severe hypoxia plus substantial hypercapnia, and her chest X-ray film showed severe cardiomegaly with massive pleural and pericardial effusion. On polysomnography (PSG) one week later, her apnea hypopnea index (AHI) was 16 with a mean nocturnal arterial saturation of 74%, mean percutaneous PCO2 59 Torr, which rose to 73 Torr during REM sleep. Non-invasive positive pressure ventilation (NPPV) was initiated, and improved her condition greatly. She was discharged, but continued to recieve NPPV, and her condition has stayed improved.
Assuntos
Síndrome de Hipoventilação por Obesidade/etiologia , Síndrome de Prader-Willi/complicações , Adulto , Feminino , Humanos , Síndrome de Hipoventilação por Obesidade/terapia , Respiração com Pressão Positiva , Síndrome de Prader-Willi/terapia , Resultado do TratamentoRESUMO
OBJECTIVES: Several American and Japanese guidelines recommend surgery for patients with c-stage I small-cell lung cancer (SCLC), whereas the European Society of Medical Oncology (ESMO) guidelines recommend surgery for patients with not only c-stage I but also c-stage II (T2N1) SCLC. In addition, previous studies identified various factors other than clinical stage that are related to survival in these patients. Thus, further validation and examination of the association of clinical stage and other clinical variables with survival are required for establishing practical management of early-stage SCLC. PATIENTS AND METHODS: We reviewed the clinical courses of 156 SCLC patients who had undergone surgery at 17 institutions between January 2003 and January 2013. RESULTS: Clinical stages (tumor-node-metastasis [TNM] version 7) of the 156 patients were 98 cases in IA, 14 in IB, 16 in IIA, 7 in IIB, 18 in IIIA, and 3 in IIIB. Median overall survival (OS) was 33.3 months (95% confidence interval: 20.9-45.8). Multivariate analysis revealed that OS was longer in patients either at c-stage II and under, with a maximum tumor diameter of <20mm, with preoperative diagnosis, without a history or presence of other types of cancer, or who underwent prophylactic cranial irradiation (PCI). CONCLUSION: These results indicate that a history or presence of other types of cancer might be a major decisive factor for surgery. Patients with c-stages I and II (c-T2N1) can be considered for surgery, and PCI may be useful in patients undergoing surgery in a practical setting, partly supporting the ESMO guidelines.(1).