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1.
Occup Med (Lond) ; 74(4): 323-327, 2024 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-38702919

RESUMO

A 38-year-old woman experienced a persistent dry cough and progressively worsening dyspnoea for 2 years. Spirometry testing revealed a moderate-to-severe restrictive abnormality. High-resolution chest computed tomography showed diffuse reticulonodular opacities. A lung biopsy disclosed alveolar parenchymal inflammation and fibrosis with bronchiolocentric features, prompting consideration of interstitial pneumonia. Following a thorough investigation of her occupational history and an on-site inspection, it was discovered that the patient had been grinding drill bits designed for printed circuit boards for 8 years, exposing her to hard metals. Mineralogical analyses confirmed excessive tungsten in urine, serum and hair, leading to a diagnosis of hard metal lung disease due to tungsten carbide-cobalt exposure. After discontinuing exposure and commencing corticosteroid therapy, her symptoms, pulmonary function and imaging showed modest improvement. This case highlights the significance of assessing occupational history in patients with interstitial pneumonia and understanding industrial hazards for accurate diagnosis and care.


Assuntos
Doenças Pulmonares Intersticiais , Doenças Profissionais , Exposição Ocupacional , Humanos , Feminino , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/induzido quimicamente , Adulto , Exposição Ocupacional/efeitos adversos , Doenças Profissionais/diagnóstico , Tomografia Computadorizada por Raios X , Tungstênio/efeitos adversos , Ligas/efeitos adversos , Cobalto/efeitos adversos , Pulmão/patologia , Pulmão/diagnóstico por imagem
2.
Hernia ; 28(1): 17-24, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37676569

RESUMO

PURPOSE: Unstructured data are an untapped source for surgical prediction. Modern image analysis and machine learning (ML) can harness unstructured data in medical imaging. Incisional hernia (IH) is a pervasive surgical disease, well-suited for prediction using image analysis. Our objective was to identify optimal biomarkers (OBMs) from preoperative abdominopelvic computed tomography (CT) imaging which are most predictive of IH development. METHODS: Two hundred and twelve rigorously matched colorectal surgery patients at our institution were included. Preoperative abdominopelvic CT scans were segmented to derive linear, volumetric, intensity-based, and textural features. These features were analyzed to find a small subset of OBMs, which are maximally predictive of IH. Three ML classifiers (Ensemble Boosting, Random Forest, SVM) trained on these OBMs were used for prediction of IH. RESULTS: Altogether, 279 features were extracted from each CT scan. The most predictive OBMs found were: (1) abdominopelvic visceral adipose tissue (VAT) volume, normalized for height; (2) abdominopelvic skeletal muscle tissue volume, normalized for height; and (3) pelvic VAT volume to pelvic outer aspect of body wall skeletal musculature (OAM) volume ratio. Among ML prediction models, Ensemble Boosting produced the best performance with an AUC of 0.85, accuracy of 0.83, sensitivity of 0.86, and specificity of 0.81. CONCLUSION: These OBMs suggest increased intra-abdominopelvic volume/pressure as the salient pathophysiologic driver and likely mechanism for IH formation. ML models using these OBMs are highly predictive for IH development. The next generation of surgical prediction will maximize the utility of unstructured data using advanced image analysis and ML.


Assuntos
Hérnia Incisional , Humanos , Hérnia Incisional/diagnóstico por imagem , Hérnia Incisional/etiologia , Hérnia Incisional/cirurgia , Herniorrafia/métodos , Tomografia Computadorizada por Raios X/métodos , Biomarcadores , Estudos Retrospectivos
3.
Hernia ; 26(5): 1355-1368, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36006563

RESUMO

PURPOSE: It is unknown whether the trend of rising incisional hernia (IH) repair (IHR) incidence and costs until 2011 currently persists. We aimed to evaluate how the IHR procedure incidence, cost and patient risk-profile have changed over the last decade relative to all abdominal surgeries (AS). METHODS: Repeated cross-sectional analysis of 38,512,737 patients undergoing inpatient 4AS including IHR within the 2008-2018 National Inpatient Sample. Yearly incidence (procedures/1,000,000 people [PMP]), hospital costs, surgical and patient characteristics were compared between IHR and AS using generalized linear and multinomial regression. RESULTS: Between 2008-2018, 3.1% of AS were IHR (1,200,568/38,512,737). There was a steeper decrease in the incidence of AS (356.5 PMP/year) compared to IHR procedures (12.0 PMP/year) which resulted in the IHR burden relative to AS (2008-2018: 12,576.3 to 9,113.4 PMP; trend difference P < 0.01). National costs averaged $47.9 and 1.7 billion/year for AS and IHR, respectively. From 2008-2018, procedure costs increased significantly for AS (68.2%) and IHR (74.6%; trends P < 0.01). Open IHR downtrended (42.2%), whereas laparoscopic (511.1%) and robotic (19,301%) uptrended significantly (trends P < 0.01). For both AS and IHR, the proportion of older (65-85y), Black and Hispanic, publicly-insured, and low-income patients, with higher comorbidity burden, undergoing elective procedures at small- and medium-sized hospitals uptrended significantly (all P < 0.01). CONCLUSION: IH persists as a healthcare burden as demonstrated by the increased proportion of IHR relative to all AS, disproportionate presence of high-risk patients that undergo these procedures, and increased costs. Targeted efforts for IH prevention have the potential of decreasing $17 M/year in costs for every 1% reduction.


Assuntos
Hérnia Ventral , Hérnia Incisional , Laparoscopia , Estudos Transversais , Gastos em Saúde , Hérnia Ventral/cirurgia , Herniorrafia/métodos , Humanos , Incidência , Hérnia Incisional/epidemiologia , Hérnia Incisional/cirurgia , Laparoscopia/métodos , Estudos Retrospectivos , Estados Unidos/epidemiologia
4.
Hernia ; 25(6): 1667-1675, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33835324

RESUMO

BACKGROUND: Incisional hernias (IH) following abdominal surgery persist as morbid, costly, and multi-disciplinary surgical challenges. Using longitudinal, multi-state, administrative claims data (HCUP State Inpatient Databases (SID)); (HCUP State Ambulatory Surgery and Services Databases (SASD)), we aimed to characterize the epidemiology, outcomes, recurrence, and costs of IH. STUDY DESIGN: 529,108 patients undergoing abdominal surgery in 2010 across six specialties (colorectal, general/bariatric, hepatobiliary, obstetrics/gynecology, urology, and vascular) were identified within inpatient and ambulatory databases for Florida (FL), Iowa (IA), Nebraska (NE), New York (NY), and Utah (UT). IH repairs, complications, and expenditures were assessed through 2014. Predictive regression modeling was validated using a training set of 1000 bootstrapped repetitions. RESULTS: 16,169 (3.1%) patients developed hernias requiring repair (4.3-year mean follow-up), 3176 (20%) underwent recurrent repair, and 731 (23%) underwent re-recurrent repair. Patients with IH had increased readmissions (6.6 vs. 2.4), morbidity (39 vs. 8% surgical and 22 vs. 7% medical), and costs ($46,000 vs. $25,000) when compared to patients without IH (p < 0.001). IH expenditures totaled $875 million: initial ($687 million), recurrent ($155 million), and re-recurrent hernias ($33 million). IH predominated in colorectal (10%), hepatobiliary (8%), and vascular (5%) procedures. Of 31 significant independent IH risk factors (p < 0.001), obesity, age, smoking, open surgery, and prior surgery were pervasive across surgical specialties. CONCLUSION: IH represents an unremitting surgical epidemic associated with considerable morbidity, costs, and features consistent with a chronic disease state. We define critical pervasive risk factors (obesity, age, smoking open surgery, and prior surgery) independently associated with IH across surgical disciplines. With failed repairs, subsequent success becomes less likely, increasing morbidity and costs-underscoring the critical importance of optimal treatment and prevention.


Assuntos
Neoplasias Colorretais , Hérnia Incisional , Neoplasias Colorretais/cirurgia , Custos de Cuidados de Saúde , Herniorrafia/métodos , Humanos , Hérnia Incisional/epidemiologia , Hérnia Incisional/etiologia , Hérnia Incisional/cirurgia , Obesidade/complicações , Obesidade/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Recidiva , Estudos Retrospectivos
5.
Ann Oncol ; 32(2): 197-207, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33186740

RESUMO

BACKGROUND: The phase III SANDPIPER study assessed taselisib (GDC-0032), a potent, selective PI3K inhibitor, plus fulvestrant in estrogen receptor-positive, HER2-negative, PIK3CA-mutant locally advanced or metastatic breast cancer. PATIENTS AND METHODS: Postmenopausal women with disease recurrence/progression during/after an aromatase inhibitor were randomized 2 : 1 to receive taselisib (4 mg; taselisib arm) or placebo (placebo arm) plus fulvestrant (500 mg). Stratification factors were visceral disease, endocrine sensitivity, and geographic region. Patients with PIK3CA-mutant tumors (central cobas® PIK3CA Mutation Test) were randomized separately from those without detectable mutations. The primary endpoint was investigator-assessed progression-free survival (INV-PFS) in patients with PIK3CA-mutant tumors. Secondary endpoints included objective response rate, overall survival, clinical benefit rate, duration of objective response, PFS by blinded independent central review (BICR-PFS), safety, and time to deterioration in health-related quality of life. RESULTS: The PIK3CA-mutant intention-to-treat population comprised 516 patients (placebo arm: n = 176; taselisib arm: n = 340). INV-PFS was significantly improved in the taselisib {7.4 months [95% confidence interval (CI), 7.26-9.07]} versus placebo arm (5.4 months [95% CI, 3.68-7.29]) (stratified hazard ratio [HR] 0.70; 95% CI, 0.56-0.89; P = 0.0037) and confirmed by BICR-PFS (HR 0.66). Secondary endpoints, including objective response rate, clinical benefit rate, and duration of objective response, showed consistent improvements in the taselisib arm. Safety was assessed in all randomized patients who received at least one dose of taselisib/placebo or fulvestrant regardless of PIK3CA-mutation status (n = 629). Serious adverse events were lower in the placebo versus taselisib arm (8.9% versus 32.0%). There were more discontinuations (placebo arm: 2.3%; taselisib arm: 16.8%) and dose reductions (placebo arm: 2.3%; taselisib arm: 36.5%) in the taselisib arm. CONCLUSION: SANDPIPER met its primary endpoint; however, the combination of taselisib plus fulvestrant has no clinical utility given its safety profile and modest clinical benefit.


Assuntos
Neoplasias da Mama , Receptores de Estrogênio , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Classe I de Fosfatidilinositol 3-Quinases/genética , Feminino , Fulvestranto , Humanos , Imidazóis , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Oxazepinas , Fosfatidilinositol 3-Quinases , Qualidade de Vida , Receptor ErbB-2/genética
6.
J Med Virol ; 81(8): 1444-9, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19551818

RESUMO

Cutaneous human papillomavirus (HPV) types are commonly found in normal skin, and some of them have been suspected to play a role in the development of non-melanoma skin cancer. This present study is divided into three sections, the aims of this study were to examine if certain HPV-types persist over time and if HPV-types are shared within families. From the first part of the study, swab samples from foreheads were collected for three longitudinal studies from one family with a newborn baby. Five specific HPV-types were isolated from the family with a newborn, with HPV-5 and FA67 being found at various time points and prevalence rates in all four members of the family. Part 2 consisted of a followed up study from two families with a 6 years interval. Six of the family members were found to have at least one of the HPV-types identified in the family 6 years earlier. Many of the HPV-types identified were shared within the families studied. Part 3 of this study involved weekly samples from four healthy females for 4 months. Among the four healthy individuals, 11%, 65%, and 56% of the weekly samples were HPV-DNA positive with one individual HPV-negative. All specimens were tested for HPV-DNA by PCR using the broad range HPV-type primer pair FAP59/64. The positive samples were HPV-type determined by cloning and sequencing. Specific cutaneous HPV-types persist over long periods of time in healthy skin in most individuals investigated and certain HPVs are shared between family members.


Assuntos
Papillomaviridae/classificação , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/virologia , Dermatopatias Virais/virologia , Pele/virologia , Adulto , Criança , Pré-Escolar , Saúde da Família , Feminino , Experimentação Humana , Humanos , Recém-Nascido , Masculino , Dados de Sequência Molecular , Papillomaviridae/genética , Adulto Jovem
7.
Cell ; 105(5): 645-55, 2001 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-11389834

RESUMO

We have discovered an early mitotic inhibitor, Emi1, which regulates mitosis by inhibiting the anaphase promoting complex/cyclosome (APC). Emi1 is a conserved F box protein containing a zinc binding region essential for APC inhibition. Emi1 accumulates before mitosis and is ubiquitylated and destroyed in mitosis, independent of the APC. Emi1 immunodepletion from cycling Xenopus extracts strongly delays cyclin B accumulation and mitotic entry, whereas nondestructible Emi1 stabilizes APC substrates and causes a mitotic block. Emi1 binds the APC activator Cdc20, and Cdc20 can rescue an Emi1-induced block to cyclin B destruction. Our results suggest that Emi1 regulates progression through early mitosis by preventing premature APC activation, and may help explain the well-known delay between cyclin B/Cdc2 activation and cyclin B destruction.


Assuntos
Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas de Drosophila , Ligases/metabolismo , Mitose/fisiologia , Proteínas/metabolismo , Complexos Ubiquitina-Proteína Ligase , Adenosina Trifosfatases/genética , Sequência de Aminoácidos , Ciclossomo-Complexo Promotor de Anáfase , Animais , Proteínas Cdc20 , Sequência Conservada , Ciclina A/metabolismo , Ciclina B/metabolismo , Drosophila , Técnicas In Vitro , Proteínas de Membrana/genética , Camundongos , Dados de Sequência Molecular , Oócitos/citologia , Oócitos/fisiologia , Coelhos , Ubiquitina-Proteína Ligases , Xenopus , Proteínas de Xenopus
8.
Cancer Res ; 61(7): 2852-6, 2001 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-11306457

RESUMO

Evidence from epidemiological, molecular, and genetic studies suggests a role for vitamin D in the development and/or progression of prostate cancer. In experimental models and clinical trials, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] was shown to exert antiproliferative, prodifferentiating, and antimetastatic/invasive effects on prostatic epithelial cells. Because the direct clinical application of 1,25(OH)2D3 is limited by the major side effect of hypercalcemia, we investigated the potential therapeutic utility of its less calcemic precursor, 25-hydroxyvitamin D3 [25(OH)D3], which is converted locally within the prostate to 1,25(OH)2D3 by 1alpha-hydroxylase. Quantification of 1alpha-hydroxylase activity in human prostatic epithelial cells by enzyme-substrate reaction analyses revealed a significantly decreased activity in cells derived from adenocarcinomas compared with cells derived from normal tissues or benign prostatic hyperplasia (BPH). In growth assays, we found that 25(OH)D3 inhibited growth of normal or BPH cells similarly to 1,25(OH)2D3. In contrast, in primary cultures of cancer cells and established cell lines, the antiproliferative action of 25(OH)D3 was significantly less pronounced than that of 1,25(OH)2D3. Our results indicate that growth inhibition by 25(OH)D3 depends on endogenous 1alpha-hydroxylase activity, and that this activity is deficient in prostate cancer cells. This finding has ramifications for both the prevention and therapy of prostate cancer with vitamin D compounds.


Assuntos
25-Hidroxivitamina D3 1-alfa-Hidroxilase/metabolismo , Calcifediol/farmacologia , Neoplasias da Próstata/enzimologia , Divisão Celular/efeitos dos fármacos , Células Epiteliais/enzimologia , Inibidores do Crescimento/farmacologia , Humanos , Masculino , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia
9.
Dig Surg ; 17(5): 528-31, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-11124564

RESUMO

BACKGROUND: Leiomyomas are rare esophagus neoplasms. They are usually solitary, and the diffuse lesion is extremely rare. CASE REPORT: A 19-year-old male presented with a 3-year history of occasional dysphagia and postprandial regurgitation. The chest radiographs showed a huge mass in the posterior mediastinum. Barium esophagograms showed narrowing of the middle third esophagus with proximal dilatation. The fibroesophagoscopy demonstrated multiple submucosal nodules below a level 22 cm from the incisor and covered with intact mucosa. CT scans of the chest showed a long segment of circumferential soft tissue in the posterior mediastinum which encircled and involved the upper two thirds of the esophagus. An intrathoracic esophagectomy with cervical esophagogastrostomy via the substernal route was performed. Grossly, multiple confluent myomatous nodules circumferentially involved the upper and middle third of the esophagus. Histologic findings showed diffuse leiomyomatosis of the esophagus. CONCLUSION: Esophageal leiomyomatosis should be considered in a young patient with long-standing dysphagia in whom smooth, tapered esophageal narrowing on barium study and circumferential esophageal wall thickening on CT scan are seen. An esophagectomy combined with a reconstruction procedure is indicated.


Assuntos
Neoplasias Esofágicas/cirurgia , Esofagectomia , Leiomiomatose/cirurgia , Adulto , Neoplasias Esofágicas/diagnóstico por imagem , Esofagostomia , Gastrostomia , Humanos , Leiomiomatose/diagnóstico por imagem , Masculino , Tomografia Computadorizada por Raios X
10.
Cell ; 102(3): 279-91, 2000 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-10975519

RESUMO

Phosphorylation of histone H3 at serine 10 occurs during mitosis and meiosis in a wide range of eukaryotes and has been shown to be required for proper chromosome transmission in Tetrahymena. Here we report that Ipl1/aurora kinase and its genetically interacting phosphatase, Glc7/PP1, are responsible for the balance of H3 phosphorylation during mitosis in Saccharomyces cerevisiae and Caenorhabditis elegans. In these models, both enzymes are required for H3 phosphorylation and chromosome segregation, although a causal link between the two processes has not been demonstrated. Deregulation of human aurora kinases has been implicated in oncogenesis as a consequence of chromosome missegregation. Our findings reveal an enzyme system that regulates chromosome dynamics and controls histone phosphorylation that is conserved among diverse eukaryotes.


Assuntos
Caenorhabditis elegans/citologia , Proteínas Fúngicas/metabolismo , Histonas/metabolismo , Mitose , Fosfoproteínas Fosfatases/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Saccharomyces cerevisiae/citologia , Animais , Aurora Quinases , Caenorhabditis elegans/metabolismo , Genoma , Proteínas de Helminto/metabolismo , Fenótipo , Fosforilação , RNA Antissenso , RNA Interferente Pequeno , Saccharomyces cerevisiae/metabolismo , Serina/metabolismo , Especificidade da Espécie
11.
Am J Pathol ; 156(5): 1515-25, 2000 May.
Artigo em Inglês | MEDLINE | ID: mdl-10793063

RESUMO

In human epidermis, functional symbiosis requires homeostatic balance between keratinocytes and melanocytes. Compelling evidence from co-culture studies demonstrated a sophisticated, multileveled regulation of normal melanocytic phenotype orchestrated by undifferentiated, basal-type keratinocytes. Keratinocytes control cell growth and dendricity, as well as expression of melanoma-associated cell surface molecules of normal melanocytes. In contrast, melanoma cells are refractory to the keratinocyte-mediated regulation. The loss of regulatory dominance by keratinocytes occurs in concert with down-regulation of E-cadherin expression in melanoma cells. To investigate the potential role of E-cadherin in melanoma-keratinocyte interaction, we transduced E-cadherin-negative melanoma cells with full-length E-cadherin cDNA using an adenoviral vector. Our results show that functional E-cadherin expression in melanoma cells leads to cell adhesion to keratinocytes rendering them susceptible for keratinocyte-mediated control. In a skin reconstruction model, ectopic E-cadherin expression inhibits invasion of melanoma cells into dermis by down-regulating invasion-related adhesion receptors, MelCAM/MUC18 and beta3 integrin subunit, and by induction of apoptosis. Thus, disruption of the E-cadherin-mediated, normal regulatory control from keratinocytes may represent one of the mechanisms accounting for melanocyte transformation.


Assuntos
Antígenos CD/metabolismo , Antígenos de Superfície/metabolismo , Caderinas/metabolismo , Queratinócitos/citologia , Melanoma/metabolismo , Glicoproteínas de Membrana , Moléculas de Adesão de Célula Nervosa , Glicoproteínas da Membrana de Plaquetas/metabolismo , Adenoviridae/genética , Apoptose , Western Blotting , Antígeno CD146 , Caderinas/genética , Adesão Celular , Divisão Celular , Linhagem Celular , Técnicas de Cocultura , DNA Recombinante/genética , Regulação para Baixo , Humanos , Integrina beta3 , Melanoma/genética , Melanoma/patologia , Invasividade Neoplásica , Pele Artificial , Transfecção , Células Tumorais Cultivadas
12.
In Vitro Cell Dev Biol Anim ; 35(10): 647-54, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10614876

RESUMO

Vascular smooth muscle cells produce and respond to interleukin-1, a cytokine which modifies inflammation-associated vascular activities including the synthesis of extracellular matrix proteins. We have established vascular smooth muscle cells culture conditions in which heparin, in the presence of endothelial cell growth supplement, promotes cell proliferation and inhibits interleukin-1 and matrix protein expression. To test whether interleukin-1 mediates growth and matrix modulation by heparin/endothelial cell growth supplement, vascular smooth muscle cells were transfected with an Epstein-Barr virus-derived expression vector designed to express interleukin-1 antisense transcripts. RNase protection and ELISA assays demonstrated a complete block of interleukin-1 transcription and protein synthesis. Northern blot analysis also showed that interleukin-1 antisense decreased the expression of matrix genes such as type I collagen, fibronectin, and decorin similar to downregulation after heparin/endothelial cell growth supplement treatment. In contrast, the expression of versican was not affected, indicating a selective suppression of matrix proteins. In addition, interleukin-1 antisense significantly prolonged the life span of vascular smooth muscle cells in culture. Our data suggest that heparin/endothelial cell growth supplement induces matrix remodeling and controls growth and senescence of vascular smooth muscle cells through down-regulation of interleukin-1.


Assuntos
Fatores de Crescimento Endotelial/farmacologia , Proteínas da Matriz Extracelular/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Heparina/farmacologia , Interleucina-1/metabolismo , Músculo Liso Vascular/efeitos dos fármacos , Adulto , Sequência de Bases , Northern Blotting , Divisão Celular , Células Cultivadas , Primers do DNA , Regulação para Baixo , Humanos , Interleucina-1/genética , Masculino , Músculo Liso Vascular/citologia , Músculo Liso Vascular/metabolismo , RNA Antissenso/genética , Transfecção
13.
Ultrasound Med Biol ; 24(8): 1087-95, 1998 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-9833576

RESUMO

Color Doppler ultrasound (US) was performed in 153 patients (including 102 with lung cancer and 51 with benign lesions) to assess pulsatile flow signals in thoracic lesions. The values of resistive index (RI) and pulsatility index (PI) of color Doppler US pulsatile flow signals in lung cancers and benign lesions were measured, analyzed, and compared. In the enrolled 153 patients with thoracic lesions, 61 lung cancers and 34 benign lesions had detectable color Doppler US pulsatile flow signals, and lung cancers had lower RI and PI values than benign lesions (RI: 0.70+/-0.03 vs. 0.79+/-0.04, p < 0.05; PI: 1.61+/-0.15 vs. 2.44+/-0.25, p < 0.005). However, overlapping RI and PI values in lung cancers and benign lesions somewhat limited color Doppler US pulsatile flow signals to differentiate lung cancers from benign lesions. Further analysis of RI and PI values in subgroups of lung cancers [squamous cell carcinoma (SCC, n = 34), adenocarcinoma (AC, n = 18), and small-cell lung cancer (SCLC, n = 6)] and benign lesions [cavitary benign lesions (CBL, n = 8), and noncavitary benign lesions (NCBL, n = 26)] revealed that all different cell types of lung cancers (SCC, AC, and SCLC), indeed, had lower RI and PI values than NCBL (for RI, all p < 0.01; for PI, all p< or =0.001). Moreover, the mean RI and PI values showed a significant incremental decrease from NCBL (mean RI, PI = 0.88, 2.94) toward SCC and AC (for SCC, mean RI, PI = 0.71, 1.68; for AC, mean RI, PI = 0.68, 1.67) and, finally, to SCLC (mean RI, PI = 0.62, 1.05). In contrast, CBL had relatively lower RI and PI values than AC and SCLC (for CBL, mean RI, PI = 0.53, 0.80; both p > 0.05 for RI and PI), and even a significant difference from SCC (p < 0.05 for RI and PI). We conclude that color Doppler US pulsatile flow signal is somewhat limited to differentiate lung cancers from benign lesions, but provides a noninvasive in vivo model to assess the neovascularity intensity of lung cancers.


Assuntos
Adenocarcinoma/fisiopatologia , Carcinoma de Células Pequenas/fisiopatologia , Carcinoma de Células Escamosas/fisiopatologia , Pneumopatias/fisiopatologia , Neoplasias Pulmonares/fisiopatologia , Ultrassonografia Doppler em Cores , Adenocarcinoma/irrigação sanguínea , Adenocarcinoma/diagnóstico por imagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha , Velocidade do Fluxo Sanguíneo , Carcinoma de Células Pequenas/irrigação sanguínea , Carcinoma de Células Pequenas/diagnóstico por imagem , Carcinoma de Células Escamosas/irrigação sanguínea , Carcinoma de Células Escamosas/diagnóstico por imagem , Diagnóstico Diferencial , Feminino , Seguimentos , Humanos , Pneumopatias/diagnóstico por imagem , Neoplasias Pulmonares/irrigação sanguínea , Neoplasias Pulmonares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Fluxo Pulsátil , Estudos Retrospectivos
14.
Am J Pathol ; 153(5): 1435-42, 1998 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-9811334

RESUMO

Expression of the beta3 subunit of the alphavbeta3 vitronectin receptor on melanoma cells is associated with tumor thickness and the ability to invade and metastasize. To address the role of alphavbeta3 in the complex process of progression from the nontumorigenic radial to the tumorigenic vertical growth phase of primary melanoma, we examined the biological consequences of overexpressing alphavbeta3 in early-stage melanoma cells using an adenoviral vector for gene transfer. Overexpression of functional alphavbeta3 in radial growth phase primary melanoma cells 1) promotes both anchorage-dependent and -independent growth, 2) initiates invasive growth from the epidermis into the dermis in three-dimensional skin reconstructs, 3) prevents apoptosis of invading cells, and 4) increases tumor growth in vivo. Thus, alphavbeta3 serves diverse biological functions during the progression from the nontumorigenic radial growth phase to the tumorigenic and-invasive vertical growth phase primary melanoma.


Assuntos
Antígenos CD/genética , Transformação Celular Neoplásica/genética , Técnicas de Transferência de Genes , Melanoma/genética , Melanoma/patologia , Glicoproteínas da Membrana de Plaquetas/genética , Receptores de Vitronectina/genética , Adenoviridae , Animais , Antígenos CD/biossíntese , Apoptose , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Integrina beta3 , Camundongos , Camundongos SCID , Invasividade Neoplásica/genética , Fenótipo , Glicoproteínas da Membrana de Plaquetas/biossíntese , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Células Tumorais Cultivadas
15.
Cancer Res ; 58(21): 4817-22, 1998 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-9809984

RESUMO

Endothelin-1 (ET-1) is not only a potent vasoconstrictor but also serves as an important growth stimulator in various cancers, including breast, cervical, pancreatic, and prostate cancer. This suggests that blockage of ET-1 production may suppress tumor growth and possibly metastasis. We observed that certain synthetic retinoids, and all-trans-retinoic acid can repress LNCaP prostate cancer cell growth in vitro. In addition, these retinoid compounds counteracted exogenous ET-1-induced growth stimulation. Retinoid-dependent growth retardation of LNCaP cells coincided with suppression of ET-1 gene expression to a level undetectable by reverse transcription-PCR. Contrarily, the androgen-insensitive DU145 cells were refractory to retinoid treatment. To investigate the underlying mechanisms of the cell-specific response to retinoids, we transfected ET-1 promoter constructs containing wild-type or mutated AP-1 or GATA-2 site into prostate cancer cells. Distinct regulations of ET-1 promoter activity were found; in LNCaP cells, both binding sites are essential for optimal promoter activation, whereas in DU145 cells, additional promoter sequences and/or transcriptional factors seem to be involved. Furthermore, several anti-AP-1 selective retinoids failed to repress ET-1 promoter activity and to exhibit a cell growth-inhibitory effect on LNCaP cells, suggesting that different retinoid structural configurations are required for the inhibition of an AP-1 complex versus an AP-1/GATA-2 complex.


Assuntos
Endotelina-1/biossíntese , Neoplasias da Próstata/tratamento farmacológico , Retinoides/farmacologia , Proteínas de Ligação a DNA/fisiologia , Endotelina-1/genética , Fator de Transcrição GATA2 , Humanos , Masculino , Regiões Promotoras Genéticas , Neoplasias da Próstata/patologia , Fator de Transcrição AP-1/fisiologia , Fatores de Transcrição/fisiologia , Transcrição Gênica/efeitos dos fármacos , Células Tumorais Cultivadas
16.
Am J Clin Oncol ; 21(5): 487-90, 1998 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-9781606

RESUMO

This phase II study was designed to assess the response rate and toxicity of paclitaxel and cisplatin chemotherapy in Chinese patients with untreated advanced non-small-cell lung cancer (NSCLC). Eligibility requirements included histologically confirmed stage IIIb-IV NSCLC, Eastern Cooperative Oncology Group performance status less than 2, no previous chemotherapy, and adequate bone marrow, renal, and hepatic function. From April 1996 through March 1997, 32 patients were treated. The dose of paclitaxel was 135 mg/m2 as a 3-hour infusion on day 1 and cisplatin 75 mg/m2 on day 2. The regimen was repeated every 3 to 4 weeks for up to 6 to 8 cycles unless there was evidence of tumor progression. The median age was 57 years (range, 31-77 years). Sixty-five percent were men. Sixty-nine percent had adenocarcinoma, and 75% had stage IV disease. One hundred seventy-two cycles were administrated; 18 patients (56%) completed all six cycles. Peripheral neuropathy and myelosuppression were the principle toxicities. Neurotoxicity appeared to be dose limiting and manifested primarily as paresthesia. Grade 2 neurotoxicity was observed in 5% of courses, which was slowly reversible. However, the severity of myelosuppression was generally mild to moderate. No episode of neutropenic fever was noted. Thrombocytopenia remained infrequent throughout the study. Other nonhematologic toxicities were also generally mild. The objective response rate was 50%. In conclusion, this combination of paclitaxel and cisplatin is active in Chinese patients with advanced NSCLC. It merits further investigation in phase III trials.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/patologia , China , Cisplatino/administração & dosagem , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Paclitaxel/administração & dosagem , Resultado do Tratamento
17.
Jpn J Clin Oncol ; 28(3): 187-91, 1998 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-9614441

RESUMO

BACKGROUND: Traditional pleurodesis for malignant pleural effusion is performed by large-bore chest tube insertion with the instillation of sclerosing agents after the compressed lung re-expansion and pleural fluid drainage of 100-150 ml/day. This study was carried out to evaluate the possibility of rapid sclerotherapy for malignant pleural effusions by insertion of a small-bore Elecath tube (12-French) under ultrasound guidance and intrapleural injection of bleomycin 60 IU. METHODS: Twenty-six patients, with 28 cytopathologically proven malignant pleural effusions (two patients had bilateral pleural effusions) and receiving the insertion of the Elecath tube for drainage, were included in our series. This rapid and short-term sclerosing method was performed and completed by intrapleural injection of bleomycin when the pleural effusion had been clearly drained by the small-bore Elecath tube and the compressed lung had fully re-expanded on follow-up chest radiographs. RESULTS: Twenty patients with 22 pleural effusions underwent the intrapleural injection of bleomycin, with the results of pleurodesis being complete response 41% (9/22), partial response 36% (8/22) and failure 23% (5/22). Interestingly, among the 17 successful procedures of pleurodesis (complete response and partial response), 71% (12) procedures could be completed within 2 days (seven within one day and five within 2 days). The remaining unsuccessful procedures carried out on six patients without the injection of bleomycin were due to a non-re-expanded lung (n = 3) and inadequate drainage (n = 3); of these, four patients also received the large-bore chest tube insertion after the removal of the Elecath tube, but the compressed lung still could not re-expand. The complications of the bleomycin injection were fever [77% (17/22)], vomiting [14% (3/22)] and hiccup [5% (1/22)]. CONCLUSION: The method of rapid sclerotherapy for malignant pleural effusions by small-bore Elecath tube is promising, with a success rate achieving 77%, usually within 2 days.


Assuntos
Bleomicina/administração & dosagem , Drenagem/instrumentação , Derrame Pleural Maligno/terapia , Escleroterapia/instrumentação , Feminino , Humanos , Intubação , Neoplasias Pulmonares/complicações , Masculino , Derrame Pleural Maligno/diagnóstico por imagem , Soluções Esclerosantes/administração & dosagem , Ultrassonografia
18.
J Clin Ultrasound ; 25(3): 119-25, 1997.
Artigo em Inglês | MEDLINE | ID: mdl-9058260

RESUMO

Thirty-six patients with pleural masses underwent ultrasonically guided needle biopsy (UGNB), including ultrasonically guided aspiration biopsy (UGAB) in all 36 patients and ultrasonically guided cutting biopsy (UGCB) in 13 patients. Using UGAB alone, the diagnostic rate for pleural masses was 64% (23/36); carcinomatous pleural masses were more easily diagnosed than non-carcinomatous pleural masses (87% vs 23%, p < 0.01). If both UGAB and UGCB were used, the diagnostic rate was 89% (32/36); thus, selective UGCB was valuable in improving the diagnostic rate of non-carcinomatous pleural masses (from 23% to 69%). In patients with pleural effusions (n = 19), 11 underwent cytologic examinations of the pleural effusion (3 also undergoing pleural biopsy) without conclusive diagnosis; however, the diagnosis was made from pleural masses by UGAB (n = 7) or UGCB (n = 4). In patients without pleural effusions (n = 17), 12 had only pleural masses (3 also having multiple peripheral pulmonary nodules and 4 having mediastinal tumors) and could not be diagnosed by conventional bronchoscopic and sputum examinations. However, the diagnosis was rapidly confirmed by UGAB (n = 5) or UGCB (n = 3) from the pleural masses in 8 patients. We conclude that UGNB is a useful and valuable diagnostic tool, not only detecting the pleural masses hidden by pleural effusions but also for rapidly diagnosing the pleural masses.


Assuntos
Doenças Pleurais/diagnóstico por imagem , Doenças Pleurais/patologia , Adolescente , Adulto , Idoso , Biópsia por Agulha/métodos , Criança , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pleurais/diagnóstico por imagem , Neoplasias Pleurais/etiologia , Neoplasias Pleurais/patologia , Valor Preditivo dos Testes , Estudos Retrospectivos , Ultrassonografia
19.
Respiration ; 64(5): 319-25, 1997.
Artigo em Inglês | MEDLINE | ID: mdl-9311046

RESUMO

Fourteen patients, with abnormalities on their chest radiographs found over a period of > or = 4 weeks and diagnosed as chronic pulmonary infections in the follow-up, underwent ultrasound-guided fine-needle aspiration biopsy (US-guided FNAB). Six patients also underwent color Doppler ultrasound examination before needle aspiration biopsy. Nine patients had a confirmed diagnosis [tuberculosis (n = 1), cryptococcosis (n = 3), actinomycosis (n = 2), and aspergillosis (n = 1)] or a suggestive diagnosis [caseating granulomatous inflammation (n = 1) and caseous necrosis (n = 1)] made after US-guided FNAB. The remaining 5 patients were finally diagnosed by US-guided large-bore cutting biopsy (n = 1, tuberculosis) and surgical resection [aspergillosis and organized pneumonia (n = 1), mucormycosis and organized pneumonia (n = 1), penicillium infection and organized pneumonia (n = 1), and cryptococcosis (n = 1)]. In 8 patients receiving gray scale US examination only, complications developed in 2 patients after US-guided FNAB [minimal pneumothorax (n = 1) and hemoptysis (n = 1)]. Of the 6 patients who also underwent color Doppler US examination, 4 had detectable blood vessels within the lesion. Thus, the site for US-guided FNAB was changed in 2 patients to prevent injury to prominent blood vessels. There were no complications observed following color Doppler US examination. We conclude that US-guided FNAB is useful for diagnosing chronic pulmonary infections, and color Doppler US is valuable for preventing injury to blood vessels.


Assuntos
Biópsia por Agulha/métodos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Infecções Respiratórias/diagnóstico , Ultrassonografia Doppler em Cores/métodos , Adulto , Idoso , Biópsia por Agulha/instrumentação , Doença Crônica , Diagnóstico Diferencial , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Infecções Respiratórias/terapia , Sensibilidade e Especificidade , Resultado do Tratamento
20.
J Clin Ultrasound ; 24(5): 225-33, 1996 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-8723510

RESUMO

One hundred eighty-eight patients with 191 lung cancers were collected retrospectively to evaluate the diagnostic results and to determine the accuracy of cytologic diagnoses obtained from ultrasound-guided fine-needle aspiration biopsy (US-guided FNAB), and to discuss the necessity of large-bore tissue core needle biopsy. All 188 patients underwent US-guided FNAB, and 20 patients with 21 lung tumors also underwent US-guided tissue-core needle biopsy. Using US-guided FNAB alone, the positive cytologic results and correct cytologic diagnoses were 91% (174 of 191) and 71% (37 of 52). If both US-guided FNAB and selected US-guided tissue core needle biopsy (n = 21) were evaluated, the positive cytologic or histologic results and correct cytologic or histologic diagnoses were 94% (180 of 191) and 80% (45 of 57), respectively. Analyzing the disagreement between the cytologic results and histologic diagnoses (n = 15), we found that the disagreement usually occurred in the specimens with poorly differentiated carcinomas (nonspecific cell type) (53% [8 of 15]); of these, two patients (13% [2 of 15], small cell carcinoma) would have a change in treatment. The complications of US-guided FNAB were pneumothorax (n = 3), hemoptysis (n = 1), hemothorax (n = 1), and suspected tract metastasis (n = 1). We conclude that US-guided FNAB has a high diagnostic yield in lung cancers, and US-guided tissue core needle biopsy is only necessary in patients whose cytologic results are negative or who have poorly differentiated carcinomas.


Assuntos
Biópsia por Agulha/métodos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha/efeitos adversos , Hemoptise/etiologia , Hemotórax/etiologia , Humanos , Pulmão/diagnóstico por imagem , Pessoa de Meia-Idade , Pneumotórax/etiologia , Estudos Retrospectivos , Ultrassonografia
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