RESUMO
Skin irritancy to topically applied chemicals is a significant problem that affects millions of people worldwide. New or modified chemical entities must be tested for potential skin irritancy by industry as part of the safety and toxicity profiling process. Many of these tests have now moved to a non-animal-based format to reduce experiments on animals. However, these tests for irritancy potential often rely on monolayer cultures of keratinocytes that are not representative of the skin architecture or tissue-engineered human skin equivalents (HSE) using complex multi-gene expression panels that are often cumbersome and not amenable for high throughput. Here, we show that human skin equivalents increase abundance of several phosphorylated kinases (c-Src, c-Jun, p53, GSK3α/ß) in response to irritant chemical stimulation by phosphokinase array analysis. Specific phosphorylation of c-SrcY419 was confirmed by immunoblotting and was plasma membrane-associated in basal/spinous cells by phospho-specific immunohistochemistry. Moreover, c-SrcY419 phosphorylation in response to the irritants lactic acid and capsaicin was inhibited by the c-Src inhibitors KB-SRC and betaine trimethylglycine. These data provide the first evidence for c-Src specific activation in response to chemical irritants and point to the development of new modes of rapid testing by immunodetection for first-pass screening of potential irritants.
Assuntos
Irritantes , Dermatopatias , Animais , Humanos , Irritantes/farmacologia , Pele/metabolismo , Dermatopatias/metabolismo , Queratinócitos/metabolismo , AlérgenosRESUMO
Psoriasis is a persistent inflammatory skin disease thought to arise as a result of the infiltration of inflammatory cells and activation of keratinocytes. Recent advances in basic research and clinical experience revealed that the interleukin (IL)-23/IL-17 axis has been identified as a major immune pathway in psoriasis. However, it remains unclear how keratinocyte factors contribute to the pathology of psoriasis. Keratinocyte proline-rich protein (KPRP) is a proline-rich insoluble protein, which is present in the epidermis and is likely to be involved in the skin barrier function. Here, to investigate the potential roles of KPRP in psoriatic skin inflammation, Kprp-modified mice were applied in the imiquimod (IMQ)-induced skin inflammation model, which develops psoriasis-like epidermal hyperplasia and cutaneous inflammation features. Then, heterozygous knockout (Kprp+/- ) but not homozygous knockout (Kprp-/- ) mice displayed attenuated skin erythema compared to control wild-type mice. In addition, RNA sequencing, quantitative PCR and/or histological analysis detected changes in the expression of several molecules related to psoriatic inflammation or keratinocyte differentiation in Kprp+/- mice, but not Kprp-/- mice. Further analysis exhibited reduced IL-17-producing γδlow T cells and amplified epidermal hyperplasia in Kprp+/- mice, which were implied to be related to decreased expression of ß-defensins and increased expression of LPAR1 (Lysophosphatidic acid receptor 1), respectively. Thus, our results imply that KPRP has the potential as a therapeutic target in psoriatic skin inflammation.
Assuntos
Dermatite , Psoríase , Camundongos , Animais , Imiquimode , Interleucina-17/metabolismo , Hiperplasia/patologia , Epiderme/metabolismo , Dermatite/metabolismo , Queratinócitos/metabolismo , Psoríase/tratamento farmacológico , Inflamação/metabolismo , Modelos Animais de Doenças , Pele/metabolismoRESUMO
Bofutsushosan (BTS; fangfengtongshengsan in Chinese) is a formula in traditional Japanese Kampo and Chinese medicine comprising 18 crude drugs and used to treat obesity and metabolic syndrome. In our previous study, BTS boiling water extract inhibited the uptake of fructose absorbed via glucose transporter 5 into cultured cells. In this study, the inhibitory effect of BTS extract on the absorption of fructose from the intestine was investigated in vivo. The extract of BTS was orally administered to rats at doses equivalent to 25-fold of the daily dose for humans. One minute after sample administration, fructose was orally administered and blood samples were collected from the jugular vein 0.5, 1, 1.5, 2, and 4 h after the administration of fructose. The absorption of fructose from the intestine was significantly reduced by treatment with BTS extract, and this in vivo study reproduced previous in vitro results. Subsequently, the blood samples were collected from the portal vein 30 min after the oral administration of fructose in mice. BTS extract significantly reduced fructose absorption in mice, and compared the effect of modified BTS samples by removing one to several crude drugs from BTS. We found that the dried rhizome of Rheum palmatum (RR) significantly contributed to the inhibitory effect of BTS on fructose absorption. We found sennoside A to be the active ingredient of RR for the inhibition of fructose absorption, and that its effect almost saturated at a dose of 3 mg/kg. These results support the action mechanisms of BTS when used for the treatment of obesity in clinics and drug stores.
Assuntos
Medicamentos de Ervas Chinesas , Frutose , Humanos , Camundongos , Ratos , Animais , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Obesidade , Senosídeos/uso terapêuticoRESUMO
There are no physical or visual manifestations that define skin sensitivity or irritation; a subjective diagnosis is made on the basis of the evaluation of clinical presentations, including burning, prickling, erythema, and itching. Adverse skin reaction in response to topically applied products is common and can limit the use of dermatological or cosmetic products. The purpose of this study was to evaluate the use of human skin equivalents based on immortalized skin keratinocytes and evaluate the potential of a 22-gene panel in combination with multivariate analysis to discriminate between chemicals known to act as irritants and those that do not. Test compounds were applied topically to full-thickness human skin equivalent or human ex vivo skin and gene signatures determined for known irritants and nonirritants. Principle component analysis showed the discriminatory potential of the 22-gene panel. Linear discrimination analysis, performed to further refine the gene set for a more high-throughput analysis, identified a putative seven-gene panel (IL-6, PTGS2, ATF3, TRPV3, MAP3K8, HMGB2, and matrix metalloproteinase gene MMP-3) that could distinguish potential irritants from nonirritants. These data offer promise as an in vitro prediction tool, although analysis of a large chemical test set is required to further evaluate the system.
RESUMO
We report the autopsy findings of a 40- year- old woman with lung complications of rheumatoid arthritis. She has been suffering from rheumatoid arthritis and interstitial pneumonia without satisfactory therapies because of her poor compliance. At autopsy, diffuse pleural adhesions and many protruding cysts were observed. The cut surfaces had rich fibrous changes and honey-comb like appearances dominantly in the left lower lobe. Microscopically, remarkable fibrous changes were observed with destruction of the alveolar structure. These fibroses were temporally homogeneous and lacked prominent fibroblastic foci. The histological pattern was consistent with fibrous non- specific interstitial pneumonia. In peripheral pulmonary arterioles, some thrombi were detected with much recanalization. Systemic amyloidosis was observed in the submandibular gland, thyroid, heart, and arterioles of the lung, kidney, and digestive tract. In the left pulmonary artery, a large embolus was detected. This embolism was the direct cause of death. Her pulmonary findings, except for the embolism, were considered sober states of lung complications of rheumatoid arthritis without the influence of therapy.
Assuntos
Artrite Reumatoide/patologia , Pulmão/patologia , Adulto , Artrite Reumatoide/complicações , Evolução Fatal , Feminino , Humanos , Doenças Pulmonares Intersticiais/etiologia , Doenças Pulmonares Intersticiais/patologiaRESUMO
A novel histone deacetylase inhibitor, FK228, is a promising anticancer agent and has been proposed to modulate intracellular signaling, in addition to regulating gene transcription. We evaluated the effect of this agent on Akt-mediated signaling in relation to its cytotoxic activity using lung adenocarcinoma cell lines. Based on MTT assay and the appearance of cleaved poly (ADP-ribose) polymerase (PARP), we regarded A549 and PC14 cells as relatively sensitive and resistant cell lines, respectively. In A549 cells, FK228 suppressed the phosphorylation of Akt at Ser-473 and glycogen synthase kinase-3 without affecting these protein levels, indicating inhibition of the Akt-mediated signaling pathway. On the other hand, in PC14 cells, these biochemical reactions were not detected after treatment with FK228. The combination of FK228 and a phosphatidylinositol 3-kinase (PI3K)/Akt pathway inhibitor, LY294002, was determined to be synergistically cytotoxic in PC14 cells by isobologram analysis. This synergistic effect was attributable to the enhancement of apoptosis, as judged by flow cytometric analysis, and the appearance of cleaved PARP. The combination of FK228 with UCN-01, another PI3K/Akt pathway inhibitor, also exerted a synergistic effect. We concluded that FK228 suppresses the PI3K/Akt signaling pathway in a cell-specific manner, and this effect is a determinant of sensitivity to FK228.
Assuntos
Adenocarcinoma/patologia , Antibióticos Antineoplásicos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Depsipeptídeos/farmacologia , Neoplasias Pulmonares/patologia , Fosfatidilinositol 3-Quinases/biossíntese , Proteínas Serina-Treonina Quinases/biossíntese , Proteínas Proto-Oncogênicas/biossíntese , Humanos , Fosfatidilinositol 3-Quinases/farmacologia , Proteínas Serina-Treonina Quinases/farmacologia , Proteínas Proto-Oncogênicas/farmacologia , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Células Tumorais CultivadasRESUMO
BACKGROUND: Central airway obstruction (CAO) may be caused by various etiologies. However, conventional chest X-rays are rarely diagnostic for patients with CAO. CASE PRESENTATION: We here described a 64-year-old asymptomatic female with tracheal mucosa-associated lymphoid tissue lymphoma discovered on spirometric findings during a complete physical examination. The plateau of forced expiratory flow was consistent with CAO. A decreased peak expiratory flow rate was noted at least 3 years before the diagnosis, and was attributed to an insufficient effort by the patient. Impulse oscillometric measurements, which were taken during quiet breathing and were effort-independent, suggested elevated respiratory resistance. These abnormalities completely disappeared after radiation therapy. CONCLUSION: The addition of impulse oscillometry to spirometry may be useful for screening CAO in routine health examinations.
Assuntos
Obstrução das Vias Respiratórias/diagnóstico , Resistência das Vias Respiratórias , Linfoma de Zona Marginal Tipo Células B/diagnóstico , Espirometria , Neoplasias da Traqueia/diagnóstico , Obstrução das Vias Respiratórias/etiologia , Obstrução das Vias Respiratórias/fisiopatologia , Doenças Assintomáticas , Biópsia , Broncoscopia , Feminino , Humanos , Linfoma de Zona Marginal Tipo Células B/complicações , Linfoma de Zona Marginal Tipo Células B/fisiopatologia , Linfoma de Zona Marginal Tipo Células B/radioterapia , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Tomografia Computadorizada por Raios X , Neoplasias da Traqueia/complicações , Neoplasias da Traqueia/fisiopatologia , Neoplasias da Traqueia/radioterapia , Resultado do TratamentoRESUMO
Intracellular signaling through Rho-associated coiled-coil forming kinase (ROCK) is a target of antimetastatic therapy and is proposed to be involved in carcinogenesis. Focal adhesion kinase (FAK) functions downstream of ROCK and participates in anti-apoptotic signaling. We hypothesized that a specific ROCK inhibitor, Y-27632, may exert a pro-apoptotic effect in combination with anticancer agents through the suppression of FAK. A549 lung carcinoma cells were treated with Y-27632 and cisplatin. The simultaneous combination did not exert any additional effect, whereas sequential treatment, in which cisplatin followed Y-27632, enhanced cytotoxicity in concentration- and time-dependent manner. Y-27632 did not suppress tyrosine phosphorylation of FAK in A549-FAK, the active form of FAK expressing A549 cells, as observed in parental cells. Nevertheless, the pretreatment of A549-FAK cells with Y-27632 still enhanced cisplatin-induced cytotoxicity. It was concluded that the ROCK inhibitor enhances cisplatin-induced cytotoxicity through FAK suppression-independent mechanism(s). These observations raise the possibility that the inhibition of the ROCK-mediated signal enhances the effect of anti-cancer agents in addition to its antimetastatic property.
Assuntos
Carcinoma/tratamento farmacológico , Cisplatino/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/farmacologia , Proteínas Tirosina Quinases/antagonistas & inibidores , Amidas/farmacologia , Western Blotting , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/farmacologia , Citometria de Fluxo , Quinase 1 de Adesão Focal , Proteína-Tirosina Quinases de Adesão Focal , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Metástase Neoplásica , Fosforilação , Plasmídeos/metabolismo , Testes de Precipitina , Piridinas/farmacologia , Transdução de Sinais , Fatores de Tempo , Transfecção , Tirosina/metabolismo , Quinases Associadas a rhoRESUMO
Paclitaxel is used frequently in the treatment of advanced non-small cell lung cancer. This study was carried out in order to determine the role of extracellular signal-regulated kinases (ERK) and retinoblastoma protein (pRB) in the governing mechanism resistance to paclitaxel using two lung adenocarcinoma cell lines with differing sensitivities. In paclitaxel-sensitive Ma-10 cells, treatment with paclitaxel induced pRB phosphorylation at Ser795 and ERK activation. In contrast, in paclitaxel-resistant Ma-31 cells, paclitaxel dephosphorylated pRB at Ser795 without affecting ERK activity. A specific ERK inhibitor, PD98059, blocked paclitaxel-induced ERK activation and pRB phosphorylation at Ser795 in Ma-10 cells. Furthermore, PD98059 inhibited cell cycle progression during paclitaxel treatment, the accumulation of sub-G1 population, and the cytotoxic effect by paclitaxel in Ma-10 cells, suggesting that ERK activation by paclitaxel, subsequent pRB phosphorylation, and the cell cycle progression during paclitaxel treatment are important determinants of sensitivity to paclitaxel. These observations raise the possibility that the promotion of cell cycle during the exposure of lung cancer cells to paclitaxel may sensitize resistant cells to paclitaxel.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Resistencia a Medicamentos Antineoplásicos , Ativação Enzimática/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Neoplasias Pulmonares/metabolismo , Paclitaxel/farmacologia , Proteína do Retinoblastoma/metabolismo , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/metabolismo , Inibidores Enzimáticos/farmacologia , Fase G1/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Fosforilação/efeitos dos fármacos , Proteína do Retinoblastoma/efeitos dos fármacos , Células Tumorais CultivadasRESUMO
Elderly patients with advanced non-small cell lung cancer (NSCLC) require chemotherapy that is effective and minimally toxic. We evaluated the activity of a combination of vinorelbine and 5-fluorouracil (5-FU)/UFT (a fixed combination of tegafur and uracil) in vitro and in vivo to establish a rationale for clinical use. The cytotoxic activities of various combinations of vinorelbine and 5-FU, the active metabolite of tegafur, were analyzed by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazlium bromide (MTT) assay and isobologram technique in vitro, using 3 NSCLC cell lines (A549, PC14, and Ma10). Sequential exposure to vinorelbine followed by 5-FU showed additive or synergistic activity against all 3 NSCLC cell lines tested. The reverse sequence showed no synergism. Antitumor activity and survival prolongation after treatment with different combinations of vinorelbine and UFT were evaluated in nude mice bearing PC14 xenografts. Treatment with vinorelbine before UFT was associated with higher antitumor activity, less toxicity, and longer survival than the reverse sequence. To clarify the underlying mechanism by which the combination exerts the synergistic effects, the expression of thymidylate synthase (TS) was assessed by Western blot analysis in vitro and by immunohistochemical analysis in an animal model. Vinorelbine suppressed the 5-FU-induced increase in TS protein in A549 cells. In PC14 tumor tissues of animal models, TS expression in cancer cells was suppressed by vinorelbine. Our data suggest that treatment with vinorelbine injection before oral UFT may have synergistic activity against NSCLC. This synergistic activity may be attributed to increased chemosensitivity to UFT caused by vinorelbine-induced suppression of TS.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Western Blotting , Carcinoma Pulmonar de Células não Pequenas/patologia , Modelos Animais de Doenças , Esquema de Medicação , Interações Medicamentosas , Fluoruracila/administração & dosagem , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Análise de Sobrevida , Tegafur/administração & dosagem , Timidilato Sintase/biossíntese , Transplante Heterólogo , Células Tumorais CultivadasRESUMO
Cell migration is essential for invasive and metastatic phenotypes of cancer cells. Potential chemopreventive agents of cancer-sulindac sulfide, caffeic acid phenethyl ester (CAPE), curcumin, and (+)-catechin-have been reported to interfere with several types of intracellular signaling. In this study, we examined the effects of these agents on transforming growth factor-beta(TGF-beta)-induced motility and Akt phosphorylation in A549 cells. Judged by gold particle phagokinesis assay, sulindac sulfide, CAPE, and curcumin suppressed the motility of A549 cells promoted by TGF-beta. LY294002, a specific inhibitor of phosphatidylinositol 3-kinase(PI3K)/Akt signaling, also suppressed TGF-beta-induced motility and Akt phosphorylation. Sulindac sulfide and CAPE, but not curcumin, suppressed TGF-beta-induced Akt phosphorylation. We conclude that sulindac sulfide and CAPE suppress the motility promoted by TGF-beta in lung adenocarcinoma cells through the suppression of Akt. Our observations raise the possibility that these agents, except for (+)-catechin, can be applied not only as chemopreventive agents but also as anti-metastatic therapy.
Assuntos
Adenocarcinoma/patologia , Ácidos Cafeicos/farmacologia , Movimento Celular/efeitos dos fármacos , Neoplasias Pulmonares/patologia , Álcool Feniletílico/análogos & derivados , Álcool Feniletílico/farmacologia , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Sulindaco/análogos & derivados , Sulindaco/farmacologia , Fator de Crescimento Transformador beta/farmacologia , Adenocarcinoma/metabolismo , Antineoplásicos/farmacologia , Catequina/farmacologia , Curcumina/farmacologia , Humanos , Neoplasias Pulmonares/metabolismo , NF-kappa B/antagonistas & inibidores , Neovascularização Patológica , Inibidores de Fosfoinositídeo-3 Quinase , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt , Células Tumorais CultivadasRESUMO
This report describes a 49-year-old woman with a well-circumscribed nodule of liposarcoma. The patient noticed a soft, slowly growing mass at the right sural region. Both axial computed tomography and magnetic resonance imaging revealed a soft tissue tumor consisting of nonfatty lesion measuring 5 x 3 x 3 cm circumscribed by a 1-cm thickened fatty area. Histologically, the tumor was made of 2 distinct components: the inner component of the tumor was a classic myxoid liposarcoma with numerous lipoblasts; the outer component was a lipoma-like lesion consisting of mature adipocytes without atypical nuclei. Immunohistochemically, MDM2 overexpression was observed and p53 immunophenotype was negative in both components. Molecular analysis revealed that type 1 TLS/ CHOP fusion gene transcript, characteristic of myxoid/round cell liposarcoma, was detected in both areas.
Assuntos
Adipócitos/patologia , Proteínas Estimuladoras de Ligação a CCAAT/genética , Lipossarcoma Mixoide/genética , Lipossarcoma Mixoide/patologia , Proteínas de Fusão Oncogênica/genética , Proteína FUS de Ligação a RNA/genética , Neoplasias de Tecidos Moles/genética , Neoplasias de Tecidos Moles/patologia , Adipócitos/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Antígeno Ki-67/metabolismo , Perna (Membro)/patologia , Lipossarcoma Mixoide/metabolismo , Pessoa de Meia-Idade , Proteínas Nucleares/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas c-mdm2 , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Neoplasias de Tecidos Moles/metabolismo , Tomografia Computadorizada por Raios X , Fator de Transcrição CHOP , Proteína Supressora de Tumor p53/metabolismoRESUMO
Paternally expressed imprinted gene 1/mesoderm-specific transcript (PEG1/MEST) is an imprinted gene expressed from the paternal allele. Recently, frequent loss of imprinting (LOI) of PEG1/MEST has been reported in lung adenocarcinomas. It is suggested that the LOI may be involved in pathogenesis of lung adenocarcinoma. In the present study, incidence of LOI of PEG1/MEST was examined in lung cancer cell lines, including small cell lung cancer (SCLC). Among 50 cell lines tested, 20 cell lines were heterozygous for the AflIII site of the PEG1/MEST gene. In these heterozygotes, biallelic expression was observed in 9 cell lines (45%), monoallelic in 11 (55%). In cell lines of non-small cell lung cancer (NSCLC), 62% (8 of 13) exhibited biallelic expression. In SCLC, only 1 of 7 cell lines (14%) showed biallelic expression. LOI of PEG1/MEST in the NSCLC cell line is significantly frequent compared with that in SCLC cell lines (p=0.043). This result supports the possibility that LOI may be related to tumorigenesis and malignant transformation, especially in NSCLC.
Assuntos
Impressão Genômica , Neoplasias Pulmonares/genética , Proteínas/genética , Adenocarcinoma/genética , Carcinoma de Células Gigantes/genética , Carcinoma de Células Grandes/genética , Carcinoma de Células Pequenas/genética , Carcinoma de Células Escamosas/genética , Linhagem Celular Tumoral , Humanos , Polimorfismo GenéticoRESUMO
A 57-year-old man who is a general physician was admitted to our hospital. A chest X-ray and CT showed a large pulmonary nodule in the right lower lobe. A percutaneous transthoracic fine needle aspiration biopsy under computed tomographic guidance revealed an advanced lung cancer (adenocarcinoma T4N3M1 Stage IV). He was treated with chemotherapy of weekly paclitaxel as an outpatient because he desired to continue working. After the chemotherapy, good partial response of all lesions was achieved. He is now working as a doctor every day. The regimen of weekly paclitaxel is useful and improves QOL of patients who desire to have outpatient treatment.
Assuntos
Adenocarcinoma/tratamento farmacológico , Assistência Ambulatorial , Antineoplásicos Fitogênicos/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Paclitaxel/administração & dosagem , Adenocarcinoma/patologia , Esquema de Medicação , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de NeoplasiasRESUMO
Paclitaxel is known to be efficacious in treating non-small cell lung cancer (NSCLC). We initiated a phase II trial of weekly paclitaxel (W-PTX) therapy in advanced NSCLC, and found that W-PTX was feasible for advanced NSCLC patients. We evaluated the cost of W-PTX from receipts and compared it with a standard cisplatin-vinorelbine (VC) regimen. The aim of this study was to assess the cost of W-PTX therapy. Previously untreated patients with stage IV NSCLC and patients with stage III B/IV NSCLC after at least one previous cisplatin based regimen were eligible if they had preserved organ function for treatment. Paclitaxel was administered at a dose of 80 mg/m2 for 3 consecutive weeks on a 4-week cycle. Patients received at least 1 course of W-PTX in our hospital and then, if possible, were treated on outpatients basis. All patients receiving the VC regimen were treated in the hospital. The mean cost of W-PTX for one month was approximately 699,000 yen per inpatient and 236,000 yen per outpatient. On the other hand, the mean cost of VC for one month was approximately 816,000 yen per patient. Although the cost of W-PTX for inpatient did not differ greatly from the cost of VC, the cost of W-PTX for outpatients was significantly lower than that of VC. The findings of this study suggest that W-PTX is feasible as a cost-effective chemotherapy for patients with advanced NSCLC.
Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/economia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Paclitaxel/administração & dosagem , Paclitaxel/economia , Vimblastina/análogos & derivados , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/economia , Carcinoma Pulmonar de Células não Pequenas/economia , Cisplatino/administração & dosagem , Análise Custo-Benefício , Esquema de Medicação , Feminino , Humanos , Neoplasias Pulmonares/economia , Masculino , Pessoa de Meia-Idade , Vimblastina/administração & dosagem , VinorelbinaRESUMO
From 1997 to 2003, 40 patients (all <40 years of age) with non-metastatic osteosarcoma of the extremities were treated with OOS-D and definitive surgery. Two cycles of doxorubicin 90 mg/m(2) plus cisplatin 120 mg/m(2) and ifosfamide 15 g/m(2) were given as neoadjuvant chemotherapy, and two cycles of doxorubicin/cisplatin and ifosfamide, and two cycles of high-dose methotrexate (10-12 g/m(2)) were given post-operatively. All patients underwent limb salvage surgeries, and 66% showed good response to neoadjuvant chemotherapy. With a median follow-up period of 117 months, 31 of the evaluable 40 patients were continuously disease-free, 7 were currently alive with no evidence of disease, and 2 died of disease. There was no local recurrence. The 5-year event-free and overall survival rates were 83 and 98%, respectively. The 10-year event-free and overall survival rates were 80 and 95%, respectively. The major form of toxicity was haematological one.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Osteossarcoma/tratamento farmacológico , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Ósseas/patologia , Neoplasias Ósseas/cirurgia , Quimioterapia Adjuvante/efeitos adversos , Quimioterapia Adjuvante/métodos , Criança , Pré-Escolar , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Extremidades/patologia , Extremidades/cirurgia , Feminino , Seguimentos , Humanos , Ifosfamida/administração & dosagem , Ifosfamida/efeitos adversos , Lactente , Recém-Nascido , Japão , Salvamento de Membro/métodos , Masculino , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Terapia Neoadjuvante/efeitos adversos , Terapia Neoadjuvante/métodos , Osteossarcoma/patologia , Osteossarcoma/cirurgia , Taxa de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
Seventy-two small-sized (
Assuntos
Adenocarcinoma/genética , Desequilíbrio Alélico/genética , Genoma Humano , Neoplasias Pulmonares/genética , Invasividade Neoplásica/genética , Adenocarcinoma/patologia , Mapeamento Cromossômico , Cromossomos Humanos/genética , Receptores ErbB/genética , Feminino , Frequência do Gene , Humanos , Neoplasias Pulmonares/patologia , Masculino , Estadiamento de Neoplasias , Prognóstico , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas p21(ras) , Fumar/genética , Proteína Supressora de Tumor p53/genética , Proteínas ras/genéticaRESUMO
To clarify metastatic patterns, and histologic and radiologic features in skeletal metastases from gastric cancer, 48 patients were retrospectively analyzed. The mean age of the patients at the time of diagnosis of gastric cancer was 59 years. In 31 patients with a history of the radical surgery, the mean interval between surgery and diagnosis of skeletal metastasis was 14 months. The mean duration between diagnosis of skeletal metastasis and death was 60 days. Scintigraphic assessment showed that solitary osseous lesions were found in four patients, whereas the remaining 44 had multiple skeletal lesions. In 28 patients with bone-only metastases with absence of visceral metastases, a higher incidence of thoracolumbar metastases at the level nearest the stomach was found. The incidence of skeletal metastasis in each histologic type was intestinal in 19 and diffuse in 29. Radiologic examination revealed that the ratio between the presence and the absence of osteosclerosis was 1:2. Osteosclerosis was seen in three of 19 patients with intestinal type metastasis, whereas with the diffuse type 13 of 29 patients had osteosclerosis.
Assuntos
Neoplasias Ósseas/secundário , Neoplasias Gástricas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/cirurgia , Distribuição de Qui-Quadrado , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de SobrevidaRESUMO
OBJECTIVE: To characterize the radiological and clinicopathologic features of cystic synovial sarcoma. DESIGN AND PATIENTS: Seven patients with primary cystic synovial sarcoma were evaluated. Computed tomography (CT) and magnetic resonance (MR) imaging were undertaken at the first presentation. The diagnosis of synovial sarcoma was made on the basis of histological examinations followed by molecular analysis. Radiological and clinicopathologic findings were reviewed. RESULTS: CT showed well-defined soft tissue mass without cortical bone erosion and invasion. Calcification was seen at the periphery of the mass in three cases. T2-weighted MR images showed multilocular inhomogeneous intensity mass in all cases, five of which showed fluid-fluid levels. On gross appearance, old and/or fresh hematomas were detected in six cases. In the one remaining case, microscopic hemorrhage in the cystic lumen was proven. Four cases had poorly differentiated areas. In five cases prominent hemangiopericytomatous vasculature was observed. Histologic grade was intermediate in one tumor and high in six. One case had a history of misdiagnosis for tarsal tunnel syndrome, one for lymphadenopathy, two for sciatica and two for hematoma. CONCLUSION: All cystic synovial sarcomas demonstrated multilocularity with well-circumscribed walls and internal septae. Synovial sarcoma should be taken into consideration in patients with deeply situated multicystic mass with triple signal intensity on T2-weighted MR imaging.
Assuntos
Sarcoma Sinovial/patologia , Cisto Sinovial/patologia , Adolescente , Adulto , Biópsia por Agulha Fina , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/patologia , Criança , Diagnóstico Diferencial , Feminino , Doenças do Pé/diagnóstico por imagem , Doenças do Pé/patologia , Virilha/diagnóstico por imagem , Virilha/patologia , Quadril/diagnóstico por imagem , Quadril/patologia , Humanos , Japão , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Sarcoma Sinovial/diagnóstico por imagem , Neoplasias de Tecidos Moles/diagnóstico por imagem , Neoplasias de Tecidos Moles/patologia , Estatística como Assunto , Cisto Sinovial/diagnóstico por imagem , Coxa da Perna/diagnóstico por imagem , Coxa da Perna/patologia , Tomografia Computadorizada por Raios XRESUMO
Pleomorphic malignant fibrous histiocytoma (MFH) is occasionally associated with inflammatory paraneoplastic syndrome (PNS). Recently, we reported that interleukin (IL)-6, one of the candidate cytokines, which induces such systemic inflammatory reaction, may be a tumor-associated factor involved in the pathogenesis and its clinical manifestations of MFH. In the local microenvironment, tumor-induced inflammatory reaction may play a role favoring tumor progression. To clarify the biological relevance of IL-6 in MFH, we established a human MFH cell line, named MIPS-2, derived from a resected specimen of a patient presenting with PNS. In this patient, the serum IL-6 level ran parallel to the disease course: elevated serum IL-6 concentration normalized immediately after radical surgery, and re-elevation occurred on tumor recurrence. MIPS-2 presented pleomorphic appearance, severe nuclear abnormalities with prominent nucleoli, and tumorigenesis in nude mice. MIPS-2 expressed IL-6, IL-6 receptor (IL-6R), and glycoprotein 130 (gp130) but lacked the soluble form of IL-6R (sIL-6R), as determined by flow cytometry and reverse transcriptase-polymerase chain reaction analyses. Stimulation of MIPS-2 with IL-6 combined with exogenous sIL-6R induced phosphorylation of both signal transducer and activator of transcription 3 (STAT3) and mitogen-activated protein kinase (MAPK), decreased cell proliferation, attenuated invasion, and induced morphological changes. Collectively, these data suggested that the IL-6/sIL-6R signaling pathway plays a pivotal role for proliferation, invasion, and morphology of MFH via STAT3 and MAPK pathway as autocrine and/or paracrine manner, and proposed the therapeutic potential for the use of both anti-growth factor and proinflammatory cytokine-targeting strategies to combat devastating MFH.