Pretreatment plasma fibrinogen level as a prognostic biomarker for patients with lung cancer

Many researchers have shown that pretreatment plasma fibrinogen levels are closely correlated with the prognosis of patients with lung cancer (LC). In this study, we thus performed a meta-analysis to systematically assess the prognostic value of pretreatment plasma fibrinogen levels in LC patients. A computerized systematic search in PubMed, EMBASE, Web of Science and China National Knowledge Infrastructure (CNKI) was performed up to March 15, 2018. Studies with available data on the prognostic value of plasma fibrinogen in LC patients were eligible for inclusion. The pooled hazard ratios (HRs) and odd ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the correlation between pretreatment plasma fibrinogen levels and prognosis as well as clinicopathological characteristics. A total of 17 studies with 6,460 LC patients were included in this meta-analysis. A higher pretreatment plasma fibrinogen level was significantly associated with worse overall survival (OS) (HR: 1.57; 95% CI: 1.39-1.77; p=0.001), disease-free survival (DFS) (HR: 1.53; 95% CI: 1.33-1.76; p=0.003), and progression-free survival (PFS) (HR: 3.14; 95% CI: 2.15-4.59; p<0.001). Furthermore, our subgroup and sensitivity analyses demonstrated that the pooled HR for OS was robust and reliable. In addition, we also found that a higher fibrinogen level predicted advanced TNM stage (III-IV) (OR=2.18, 95% CI: 1.79-2.66; p<0.001) and a higher incidence of lymph node metastasis (OR=1.74, 95% CI: 1.44-2.10; p=0.02). Our study suggested that higher pretreatment plasma fibrinogen levels predict worse prognoses in LC patients.

HIF-1α Levels in patients receiving chemoradiotherapy for locally advanced non-small cell lung carcinoma

SUMMARY AIM To examine the relationship between treatment response and hypoxia-inducible factor-1 alpha (HIF-1α) levels in patients with locally advanced non-small cell lung cancer (NSCLC) who received chemoradiotherapy (CRT). METHODS Eighty patients with NSCLC were included in the study and treated at Acibadem Mehmet Ali Aydınlar University Medical Faculty. HIF-1 α levels were measured before and after CRT by the enzyme-linked immunosorbent assay (ELISA) method. RESULTS Patients' stages were as follows; stage IIIA (65%) and stage IIIB (35%). Squamous histology was 45%, adenocarcinoma was 44%, and others were 11%. Chemotherapy and radiotherapy were given concurrently to 80 patients. Forty-five (56%) patients received cisplatin-based chemotherapy, and 35 (44%) received carboplatin-based chemotherapy. Serum HIF-1α levels (42.90 ± 10.55 pg/mL) after CRT were significantly lower than the pretreatment levels (63.10 ± 10.22 pg/mL, p<0.001) in patients with locally advanced NSCLC. CONCLUSION The results of this study revealed that serum HIF-1α levels decreased after CRT. Decrease of HIF-1α levels after the initiation of CRT may be useful for predicting the efficacy of CRT.

RESUMO OBJETIVO Examinar a relação entre a resposta ao tratamento e os níveis de fator 1 induzida por hipóxia (HIF-1α) em pacientes com câncer de pulmão de células não pequenas localmente avançado (NSCLC) que receberam quimiorradioterapia (CRT). MÉTODO Oitenta pacientes com NSCLC foram incluídos no estudo e foram tratados na Faculdade de Medicina da Acibadem Mehmet Ali Aydınlar University. O nível de HIF-1α foi medido antes e depois da TRC pelo método de ensaio imunoenzimático (ELISA). RESULTADOS Os estágios dos pacientes foram os seguintes; estágio IIIA (65%) e estágio IIIB (35%). A histologia escamosa foi de 45%, o adenocarcinoma de 44% e o outro de 11%. Quimioterapia e radioterapia foram dadas simultaneamente a 80 pacientes. Quarenta e cinco (56%) pacientes receberam quimioterapia à base de cisplatina e 35 (44%) receberam quimioterapia à base de carboplatina. Os níveis séricos de HIF-1α (42,90 ± 10,55 pg / mL) após a TRC foram significativamente menores do que os níveis pré-tratamento (63,10 ± 10,22 pg / mL, p <0,001) em pacientes com NSCLC localmente avançado. CONCLUSÃO Os resultados deste estudo revelaram que os níveis séricos de HIF-1α diminuíram após a TRC. A diminuição dos níveis de HIF-1α após o início da TRC pode ser útil para prever a eficácia da TRC.

Experimental study of peripheral-blood pro-surfactant protein B for screening non-small cell lung cancer

Abstract Purpose: To evaluate the possibility of using peripheral-blood presurfactant protein B (Pro-SFTPB) for screening non-small cell lung cancer (NSCLC). Methods: A total of 873 healthy volunteers and 165 lung cancer patients hospitalized in the Fifth People's Hospital of Dalian were tested Pro-SFTPB once every half year from January 2014 to September 2015. The healthy volunteers were also conducted spiral computed tomography (CT) examination once every year. The data were then com-pared and statistically analyzed. Results: The positive expression rate of Pro-SFTPB in NSCLC was significantly higher than that in healthy volunteers, and significantly higher in lung adenocarcinoma than in squamous cell carcinoma; additionally, the expression rate was increased with the in-crease of smoking index, and the intergroup differences showed statistical signifi-cance (p≤0.05). The positive rate of newly diagnosed lung cancer was 29.55%, higher than healthy volunteers (22.34%), but there was no significant difference (p>0.05). Conclusion: Pro-SFTPB is over expressed in non-small cell lung cancer, especially in lung adeno-carcinoma, but it can't be used as a clinical screening tool for lung cancer.

miR-638 is a new biomarker for outcome prediction of non-small cell lung cancer patients receiving chemotherapy

MicroRNAs (miRNAs), a class of small non-coding RNAs, mediate gene expression by either cleaving target mRNAs or inhibiting their translation. They have key roles in the tumorigenesis of several cancers, including non-small cell lung cancer (NSCLC). The aim of this study was to investigate the clinical significance of miR-638 in the evaluation of NSCLC patient prognosis in response to chemotherapy. First, we detected miR-638 expression levels in vitro in the culture supernatants of the NSCLC cell line SPC-A1 treated with cisplatin, as well as the apoptosis rates of SPC-A1. Second, serum miR-638 expression levels were detected in vivo by using nude mice xenograft models bearing SPC-A1 with and without cisplatin treatment. In the clinic, the serum miR-638 levels of 200 cases of NSCLC patients before and after chemotherapy were determined by quantitative real-time PCR, and the associations of clinicopathological features with miR-638 expression patterns after chemotherapy were analyzed. Our data helped in demonstrating that cisplatin induced apoptosis of the SPC-A1 cells in a dose- and time-dependent manner accompanied by increased miR-638 expression levels in the culture supernatants. In vivo data further revealed that cisplatin induced miR-638 upregulation in the serum derived from mice xenograft models, and in NSCLC patient sera, miR-638 expression patterns after chemotherapy significantly correlated with lymph node metastasis. Moreover, survival analyses revealed that patients who had increased miR-638 levels after chemotherapy showed significantly longer survival time than those who had decreased miR-638 levels. Our findings suggest that serum miR-638 levels are associated with the survival of NSCLC patients and may be considered a potential independent predictor for NSCLC prognosis.

miR-638 is a new biomarker for outcome prediction of non-small cell lung cancer patients receiving chemotherapy

MicroRNAs (miRNAs), a class of small non-coding RNAs, mediate gene expression by either cleaving target mRNAs or inhibiting their translation. They have key roles in the tumorigenesis of several cancers, including non-small cell lung cancer (NSCLC). The aim of this study was to investigate the clinical significance of miR-638 in the evaluation of NSCLC patient prognosis in response to chemotherapy. First, we detected miR-638 expression levels in vitro in the culture supernatants of the NSCLC cell line SPC-A1 treated with cisplatin, as well as the apoptosis rates of SPC-A1. Second, serum miR-638 expression levels were detected in vivo by using nude mice xenograft models bearing SPC-A1 with and without cisplatin treatment. In the clinic, the serum miR-638 levels of 200 cases of NSCLC patients before and after chemotherapy were determined by quantitative real-time PCR, and the associations of clinicopathological features with miR-638 expression patterns after chemotherapy were analyzed. Our data helped in demonstrating that cisplatin induced apoptosis of the SPC-A1 cells in a dose- and time-dependent manner accompanied by increased miR-638 expression levels in the culture supernatants. In vivo data further revealed that cisplatin induced miR-638 upregulation in the serum derived from mice xenograft models, and in NSCLC patient sera, miR-638 expression patterns after chemotherapy significantly correlated with lymph node metastasis. Moreover, survival analyses revealed that patients who had increased miR-638 levels after chemotherapy showed significantly longer survival time than those who had decreased miR-638 levels. Our findings suggest that serum miR-638 levels are associated with the survival of NSCLC patients and may be considered a potential independent predictor for NSCLC prognosis.

Predictive factors of alcohol and tobacco use in adolescents / Fatores preditivos do uso de álcool e tabaco em adolescentes / Factores predictivos del uso de alcohol y tabaco en los adolescentes

OBJECTIVES: to analyze the effect of self-esteem, assertiveness, self-efficacy and resiliency on alcohol and tobacco consumption in adolescents. METHOD: a descriptive and correlational study was undertaken with 575 adolescents in 2010. The Self-Esteem Scale, the Situational Confidence Scale, the Assertiveness Questionnaire and the Resiliency Scale were used. RESULTS: the adjustment of the logistic regression model, considering age, sex, self-esteem, assertiveness, self-efficacy and resiliency, demonstrates significance in the consumption of alcohol and tobacco. Age, resiliency and assertiveness predict alcohol consumption in the lifetime and assertiveness predicts alcohol consumption in the last year. Similarly, age and sex predict tobacco consumption in the lifetime and age in the last year. CONCLUSION: this study can offer important information to plan nursing interventions involving adolescent alcohol and tobacco users. .

OBJETIVOS: analisar o efeito da autoestima, assertividade, autoeficácia e resiliência sobre o consumo de álcool e tabaco em adolescentes. MÉTODO: estudo descritivo correlacional com 575 adolescentes, realizado no ano 2010. Foram utilizadas a Escala de Autoestima, o Questionário de Confiança Situacional, o Questionário de Assertividade e a Escala de Resiliência. RESULTADOS: o ajuste do modelo de regressão logística, considerando a idade, sexo, autoestima, assertividade, autoeficácia e resiliência foi significante em relação ao consumo de álcool e tabaco. A idade, resiliência e assertividade foram preditores do consumo de álcool em algum momento na vida e a idade e a assertividade foram preditores no último ano. Para o consumo de tabaco, a idade e o sexo foram preditores em algum momento na vida e a idade no último ano. CONCLUSÃO: este estudo pode proporcionar informações importantes para o planejamento de intervenções de enfermagem em adolescentes usuários de álcool e tabaco .

OBJETIVOS: analizar el efecto de la autoestima, asertividad, autoeficacia y resiliencia sobre el consumo de alcohol y tabaco en adolescentes. MÉTODO: descritivo correlacional con 575 adolescentes, en 2010. Se utilizaron la Escala de Autoestima, el Cuestionario de Confianza Situacional, el Cuestionario de Asertividad y la Escala de Resiliencia. RESULTADOS: el ajuste del modelo de regresión logística, considerando la edad, sexo, autoestima, asertividad, autoeficacia y resiliencia, muestra significancia en el consumo de alcohol y tabaco. La edad, resiliencia y asertividad predicen el consumo de alcohol alguna vez en la vida y la edad y asertividad en el último año. De la misma forma la edad y sexo predicen el consumo de tabaco alguna vez en la vida y la edad en el último año. CONCLUSIÓN: este estudio puede proporcionar información importante para la planificación de intervenciones en enfermería de los adolecentes usuarios de alcohol y tabaco. .

Prognostic impact of serum albumin levels on the recurrence of stage I non-small cell lung cancer

Objective: Patients with stage I non-small cell lung cancer who have undergone complete surgical resection harbor a 30% risk for tumor recurrence. Thus, the identification of factors that are predictive for tumor recurrence is urgently needed. The aim of this study was to test the prognostic value of serum albumin levels on tumor recurrence in patients with stage I non-small cell lung cancer. Methods: Stage I non-small cell lung cancer patients who underwent complete surgical resection of the primary tumor at Zhejiang Hospital were analyzed in this study. Serum albumin levels were measured before surgery and once again after surgery in 101 histologically diagnosed non-small cell lung cancer patients. Correlations between the pre- and post-operative serum albumin levels and various clinical demographics and recurrence-free survival rates were analyzed. Results: Patients with pre-operative hypoalbuminemia (<3.5 g/dl) had a significantly worse survival rate than patients with normal pre-operative serum albumin levels (≥3.5 g/dl) (p=0.008). Patients with post-operative hypoalbuminemia had a worse survival rate when compared with patients with normal post-operative serum albumin levels (p=0.001). Cox multivariate analysis identified pre-operative hypoalbuminemia, post-operative hypoalbuminemia and tumor size over 3 cm as independent negative prognostic factors for recurrence. Conclusion: Serum albumin levels appear to be a significant independent prognostic factor for tumor recurrence in patients with stage I non-small cell lung cancer who have undergone complete resection. Patient pre-treatment and post-treatment serum albumin levels provide an easy and early means of discrimination between patients with a higher risk for recurrence and patients with a low risk of recurrence. .

Elevated Serum C-Reactive Protein as a Prognostic Marker in Small Cell Lung Cancer

PURPOSE: Elevated C-reactive protein (CRP) is associated with poor prognosis in several tumor types. The purpose of this study was to investigate serum CRP as a prognostic marker in small cell lung cancer (SCLC). MATERIALS AND METHODS: The pretreatment serum CRP level was measured in 157 newly diagnosed SCLC patients, and correlation between serum CRP level and other clinical parameters was analyzed. Multivariate analyses were performed to find prognostic markers using Cox's proportional hazards model. RESULTS: The initial CRP concentration was within the normal range in 72 (45.9%) patients and elevated in 85 (54.1%) patients. There was a significant correlation between serum CRP level and the extent of disease (p<0.001), weight loss (p=0.029) and chest radiation (p=0.001). Median overall survival (OS) in the normal CRp group was significantly longer than with the high CRp group (22.5 months vs. 11.2 months, p<0.001). Extent of disease (p<0.001), age (p=0.025), and performance status (p<0.001) were additional prognostic factors on univariate analysis. On multivariate analysis, elevated serum CRp level was an independent prognostic factor for poor survival (HR=1.8; p=0.014), regardless of the extent of disease (HR=3.7; p<0.001) and performance status (HR=2.2; p<0.001). CONCLUSION: High level of CRP was an independent poor prognostic serum marker in addition to previously well-known prognosticators in patients with SCLC.

Doxiciclina em pacientes com linfangioleiomiomatose: segurança e eficácia no bloqueio de metaloproteinases / Doxycycline use in patients with lymphangioleiomyomatosis: safety and efficacy in metalloproteinase blockade

OBJETIVO: A linfangioleiomiomatose (LAM) é caracterizada pela presença de cistos pulmonares, cuja formação está associada à hiperreatividade de metaloproteinases de matriz (MMP), principalmente MMP-2 e MMP-9. Objetivamos comparar os níveis dessas MMPs entre pacientes com LAM e controles saudáveis, assim como avaliar, nas pacientes com LAM, a segurança e a eficácia do tratamento com doxiciclina, um potente inibidor de MMPs. MÉTODOS: Estudo clínico prospectivo no qual as pacientes com LAM receberam doxiciclina (100 mg/dia) por seis meses, coletando-se amostras de urina e sangue para a dosagem de MMP-2 e MMP-9 antes e ao final do período. Foram ainda obtidas amostras de 10 mulheres saudáveis. RESULTADOS: De 41 pacientes com LAM que iniciaram o tratamento, 34 concluíram o protocolo. Os níveis de MMP-9 sérica e urinária foram significativamente inferiores no grupo controle (p < 0,0001). Comparando-se os valores antes e após o tratamento, a mediana do nível sérico da MMP-9 reduziu de 919 ng/mL para 871 ng/mL (p = 0,05), enquanto a mediana da dosagem urinária de MMP-9 diminui de 11.558 pg/mL para 7.315 pg/mL (p = 0,10). A mediana da MMP-2 sérica apresentou um decréscimo significativo após o tratamento (p = 0,04). Não foram detectados níveis de MMP-2 urinária. Epigastralgia, náuseas e diarreia foram os efeitos adversos mais prevalentes, e geralmente autolimitados. Apenas 1 paciente interrompeu o tratamento devido a efeitos colaterais. CONCLUSÕES: Pela primeira vez, conseguiu-se evidenciar em pacientes com LAM a redução dos níveis séricos e urinários de MMPs após o uso de doxiciclina, que se mostrou uma medicação segura, com efeitos colaterais leves e toleráveis.

OBJECTIVE: Lymphangioleiomyomatosis (LAM) is characterized by lung cysts, whose development is associated with matrix metalloproteinase (MMP) hyperactivity, principally that of MMP-2 and MMP-9. Our objective was to compare LAM patients and controls in terms of the levels of these MMPs, as well as to determine the safety and efficacy of treatment with doxycycline, a potent MMP inhibitor. METHODS: Prospective clinical study involving female LAM patients who received doxycycline (100 mg/day) for six months. Urine and blood samples were collected for the quantification of MMP-2 and MMP-9 before and after the treatment period. Samples from 10 healthy women were also collected. RESULTS:Of the 41 LAM patients who started the treatment, 34 completed the protocol. Serum and urinary MMP-9 levels were significantly lower in the controls than in the LAM patients (p < 0.0001). Comparing pre- and post-treatment values, we found that the median level of MMP-9 in serum decreased from 919 ng/mL to 871 ng/mL (p = 0.05), whereas that of MMP-9 in urine decreased from 11,558 pg/mL to 7,315 pg/mL (p = 0.10). After treatment, the median level of MMP-2 in serum was significantly lower (p = 0.04) and urinary MMP-2 levels were undetectable. Nausea, diarrhea, and epigastric pain were the most prevalent adverse affects and were often self-limiting. There was only one case in which the patient discontinued the treatment because of side effects. CONCLUSIONS: We have demonstrated, for the first time, a decrease in serum and urine levels of MMPs in LAM patients treated with doxycycline, which proved to be a safe medication, with mild and well-tolerated side effects.

Plasma proGRP Concentration is Sensitive and Specific for Discriminating Small Cell Lung Cancer from Nonmalignant Conditions or Non-small Cell Lung Cancer

To date, most clinical data on pro-gastrin-releasing peptide (proGRP) have been based on serum concentrations. This study evaluated the agreement between proGRP levels in fresh serum and plasma in patients with various lung diseases. Pairs of serum and EDTA plasma were collected from 49 healthy individuals. At the same time, EDTA plasma of 118 lung cancer patients and 23 patients with benign pulmonary diseases were prospectively collected. Compared to serum, plasma proGRP concentrations were higher by an average of 103.3%. Plasma proGRP was higher in malignancy (336.4 +/- 925.4 pg/mL) than in benign conditions (40.1 +/- 11.5 pg/mL). Small cell lung cancer (SCLC) patients showed higher levels of proGRP (1,256.3 +/- 1,605.6 pg/mL) compared to other types of lung cancer. Based on the ROC curve analyses at a specificity of 95%, the diagnostic sensitivity of plasma proGRP was estimated to be 83.8% in distinguishing SCLC from all the other conditions, and 86.5% for discriminating SCLC from the nonmalignant cases. Among the SCLC cases, limited stage disease had lower levels of plasma proGRP than extensive disease. When measuring circulating levels of proGRP, the use of plasma is preferred over serum. Plasma proGRP has a potential marker for discriminating SCLC from nonmalignant conditions or non-small cell lung cancer.

Avaliação clínica e laboratorial da trombose venosa em pacientes com câncer de pulmão / Clinical and laboratory evaluation of venous thrombosis in patients with lung cancer

INTRODUÇÃO: A trombose é um fenômeno frequente nos pacientes portadores de neoplasias e está relacionada com o prognóstico dos mesmos. No entanto, até os dias de hoje, a real incidência de trombose e os mecanismos relacionados ainda não estão totalmente elucidados. MÉTODOS: O presente estudo acompanhou, de forma prospectiva e consecutiva, 120 pacientes portadores de adenocarcinoma de pulmão em diferentes estágios da doença. Nestes pacientes foram testados ao diagnóstico e a cada 6 meses, marcadores da coagulação (TAP, PTT, fibrinogênio, D-dímero, proteína C, antitrombina, fatores (VIII e IX) e plaquetas) além de parâmetros imunológicos (presença de anticorpos anticardiolipina, anticoagulante lúpico, anti B2 glicoproteína l, níveis de interleucinas (1 e 6) e fator de necrose tumoral). Os mesmos foram acompanhados a cada 3 meses (no caso de sintomas) com pesquisa de trombose em membros inferiores e superiores (e no caso de suspeita, pesquisa de embolia pumonar). Daqueles pacientes dos quais se obteve o bloco de diagnóstico, também foi feito estudo da expressão de fator tecidual e receptores PAR1. RESULTADOS: Trombose foi um evento frequente (24% dos pacientes) e esteve relacionada com uma pior sobrevida. Em análise univariável, a presença de altos níveis de interleucina-6, fatores VIII e IX, fibrinogênio, além de presença de anticorpo anticoagulante lúpico, estiveram relacionados com o aumento de eventos trombóticos. Porém, em análise multivariável, apenas o anticoagulante lúpico manteve-se como fator de risco. Por outro lado, a presença de anticorpos anti B2 glicoproteína l do tipo IgM não só reduziu o risco de eventos trombóticos como também aumentou a sobrevida dos pacientes. A presença da expressão de fator tecidual esteve mais frequente nas fases avançadas da doença, enquanto a expressão de PAR foi maior em estados iniciais. Ambos não mostraram influenciar de forma significativa o risco de trombose e mortalidade...

INTRODUCTION: Thrombosis is a frequent event on cancer patients and are related to their prognosis. However, until now the real incidence and their mechanism are still not fully elucidated. METHODS: We studied prospectively and consecutively 120 patients with lung adenocarcinoma in different disease stages. Those patients made blood evaluation at diagnosis and each 6 month each for clotting (TAP, TPP, fibrinogen, D-dimmer, Protein C, antithrombin, platelets and clotting factors VIII and IX) than immunologic markers (anticardiolipin antibodies, lupus anticoagulant, anti B2 glicoproteín I, interleukin 1 and 6 and Tumor Necrosing Factor Levels). The same patients were submitted to limb and arms Doppler scan each 3 month to screening for thrombosis and if suspected of pulmonary embolism it was screened). From those patients of witch paraffin block of tumor biopsy were obtained, immunohistochemical analysis were made to detect tissue factor and PAR1 expression. RESULTS: Thrombosis were a frequent event (24% of patients), and were related to survival (independently if symptomatic or not). Univariable analysis showed that high levels of interleukin 6, fibrinogen, factors VIII or XI and lupus anticoagulant detection increases thrombosis risk. However in multivariable analysis, only lupus anticoagulant antibodies maintain as risk factor of thrombosis. But, despite be from antiphospholipid family, IgM anti B2 glicoproteín l decreased thrombosis risk and increase patients' survival as compared for those patients without those antibodies. Tissue factor expression was more evident on advanced stage of disease and PAR expression in early stages. However neither tissue factor nor PAR changes in a significantly manner patient's survival (however, the number of patients samples studied is small). CONCLUSION: Venous thrombosis is very frequent in lung adenocarcinoma patients. In our study, we show interaction between both systems (clotting and immunologic)...

Fluctuation of circulating tumor cells in patients with lung cancer by real-time fluorescent quantitative-PCR approach before and after radiotherapy.

BACKGROUND AND AIMS: The failure to reduce the mortality of patients with solid tumours is mainly a result of the early dissemination of cancer cells to secondary site, which is usually missed by conventional diagnostic procedures used for tumour staging. The possibility to use easily accessible body fluids as a source for circulating tumour cells (CTCs) detection enables longitudinal observations of the disease. In the study, we evaluated the CTCs in lung cancer following locoregional radiation therapy. METHODS: Samples of 5 ml peripheral blood was taken from each lung cancer patients (n=15) both before and after the radiotherapy course. Meanwhile tumour size was determined by chest X-ray or computed tomography. Using cytokeratin 19(CK19) as marker, the blood samples were subjected to real time RT-PCR assay. All patients with lung cancer were treated with primary definitive and mediastinal radiotherapy. RESULTS: Compare to that of pre-treatment, the value of CK19 mRNA in peripheral blood after therapy decreased dramatically (5.0932+/-1.0628 vs. 4.2493+/-0.8323, t=3.192, P=0.007). The change of CK19 mRNA level before and after radiotherapy was closely related to the type (NSCLC vs. SCLC, 0.5389+/-0.9030 vs. 1.6826+/-0.9467, t=2.1465, P=0.051). Meanwhile, there appeared to be a close link between the grade (Well/Mod vs. Poor) and the change of CK19 mRNA (0.5024 vs. 1.5271, t=2.017, P=0.065). The change of CK19 mRNA level was related to variation of tumour burden during radiotherapy (r=0.0575, P=0.025). Of the 15 cases studied, 12 cases were positive before radiotherapy (12/15, 80%). The positive rate was 53% (8/15) after radiotherapy, meaning that four patients converted into negative after radiotherapy. CONCLUSIONS: The disseminated circulating cancer cells can be affected by radiotherapy; meanwhile further more systemic adjuvant treatment should be conducted. Due to concordance between molecular response and radiological remission, assessment of the therapeutic response might be possible by serial quantitative of CTCs.

The Relationship between the Serum Intercellular Adhesion Molecule-1 Level and the Prognosis of the Disease in Lung Cancer

BACKGROUND: Adhesion molecules are related to cell-to-cell interaction and inflammatory interaction. In addition, adhesive interactions between tumor cells and adjacent cells and/or extracellular matrix play important roles in the complex process of tumor growth and development. Among these adhesion molecules, expression of intercellular adhesion molecule-1 (ICAM-1) has been identified in colon cancer, bladder cancer, lung cancer, melanoma, pancreatic cancer and hepatocellular carcinoma. In the current study, we analyzed serum ICAM-1 concentrations to investigate the relationship between the serum ICAM-1 level and prognosis in patients with lung cancer METHODS: Serum ICAM-1 was measured in 84 patients with lung cancer according to the pathologic type and clinical stage using the ICAM-1 ELISA kit. The Kaplan-Meier method was used to analyse survival time. RESULTS: There was no difference in serum ICAM-1 concentration among the different stages of lung cancer. Furthermore, there was no difference observed between histologic tumor type with regard to serum ICAM-1 concentration. Although the difference was not significant, the overall survival times of patients with a low serum ICAM-1 concentration ( or=306 ng/mL) in non-small cell lung cancer patients. CONCLUSION: These results suggest that high levels of serum ICAM-1 reflect poor prognosis for patients with non-small cell lung cancer.

Triplex polymerase chain reactions with confronting two-pair primers (PCR-CTPP) for NQO1 C609T, GSTM1 and GSTT1 polymorphisms: a convenient genotyping method.

The polymerase chain reaction with confronting two-pair primers (PCR-CTPP) is a time-saving and inexpensive genotyping method, which is applicable for most single nucleotide polymorphisms (SNPs). To date, we have established PCR-CTPP conditions for tens of SNPs, including duplex genotyping. This paper introduces triplex PCR-CTPP to simultaneously genotype three functional polymorphisms of carcinogen-detoxifying enzymes, NQO1 C609T, GSTM1 null, and GSTT1 null, all of which are reported to have a significant association with smoking-related cancers. We applied this method for 241 non-cancer patients to demonstrate the performance. Among the subjects, the genotype frequency of NQO1 C609T was 35.7% for CC, 44.4% for CT and 19.9% for TT. The null type frequencies of GSTM1 and GSTT1 were 53.4% and 44.0%, respectively. Their distributions were similar to those reported for Japanese by other studies. This is the first paper reporting the success of triplex PCR-CTPP. The polymorphisms applied are useful examples, which could be adopted not only for research purposes, but also for risk assessment of individuals exposed to carcinogenic substances, such as smokers. This convenient genotyping approach has advantages for application in cancer prevention, especially in the Asian Pacific region.

The Relationship between Serum VEGF Concentration and Prognosis of Lung Cancer

BACKGROUND: VEGF is an important factor for angiogenesis. Although many previous studies have reported an increased serum VEGF concentration in various malignant tumors, there are few studies on the relationship between serum VEGF concentration and its prognosis. This study investigated whether serum VEGF concentration is a prognostic indicator for lung cancer. METHODS: Using the ELISA kit, we measured the serum VEGF concentrations of 86 patients diagnosed with lung cancer on histologic examination. With a cut-off value of 686 pg/mL, the patients were classified as low-concentration ( or=686 pg/mL, n=28) based on their mean serum VEGF concentration values to compare survival rates, and serum VEGF concentrations for different histologic types and stages. RESULTS: There was no significant difference in serum VEGF concentration based on stage and histologic type between the two groups. Moreover, there was no significant difference in survival rate between the high-concentration and low-concentration groups (p=0.86). CONCLUSION: This study demonstrates that serum VEGF concentration is not associated with the prognosis of lung cancer.

Aplicação clínica dos marcadores tumorais séricos em carcinoma não-pequenas células do pulmão / Clinical application of serum tumor markers in patients with non-small cell lung carcinoma

O valor clínico dos marcadores tumorais séricos em câncer de pulmão é incerto. Objetivos: Avaliar a associação da concentração sérica de marcadores tumorais com a extensão da neoplasia e seu valor prognóstico. Casuística e método: Entre fevereiro de 1995 e setembro de 1997 foram estudados 103 pacientes, no Departamento de Cirurgia Torácica do Hospital do Câncer. Antes do tratamento os pacientes foram submetidos à coleta de sangue para dosagem da concentração do CEA, CYFRA21.1, CA15.3, CA19.9, CA72.4 e NSE. Resultados: O CYFRA21.1 foi o marcador mais freqüentemente elevado (55 por cento). Os pacientes com neoplasia avançada tiveram concentração sérica média do CEA (90,82 ± 329,08ng/ml), CYFRA21.1 (20,34 ± 58,42ng/ml) e CA15.3 (56,54 ± 86,81U/ml) significativamente superior às observadas nos tumores localizados, respectivamente, 10,24 ± 35,96ng/ml, 12,67 ± 25,23ng/ml e 22,22 ± 15,86U/ml. Mesmo considerando todos os marcadores deste estudo, apenas os pacientes com CEA elevado tiveram chance 5,6 vezes maior de ser portadores de neoplasia avançada, quando comparados com aqueles com CEA normal. A sobrevida foi influenciada pelo performance status (p = 0,001), extensão anatômica (p = 0,006), concentração aumentada do CEA (p = 0,043), mais que dois marcadores aumentados (p < 0,001) e tipo de tratamento (p < 0,001). O valor prognóstico da extensão da neoplasia atingiu o limite da significância (p = 0,052); entretanto, a presença de mais do que dois marcadores aumentados e a modalidade terapêutica tiveram valor prognóstico independente (respectivamente, p = 0,035 e p = 0,005). Conclusões: Nenhum dos marcadores tumorais séricos avaliados apresenta utilidade clínica no manejo dos pacientes com CNPCP.

Utility of serum cytokeratin 19 fragment (CYFRA 21-1) and carcinoembryonic antigen (CEA) as tumour markers for non-small cell lung cancer.

Serum cytokeratin 19 fragment (CYFRA 21-1) and carcinoembryonic antigen (CEA) levels were determined with an enzyme immunoassay in 51 patients with non-small cell lung cancer (NSCLC), 26 patients with benign lung diseases and 26 normal individuals in order to evaluate their clinical utility in the diagnosis of NSCLC. Patients with NSCLC demonstrated higher serum CYFRA 21-1 and CEA levels than both patients with benign lung diseases and normal group. We used the cut off value which was derived from the 95th percentile value of CYFRA 21-1 and CEA levels in the group of patients with benign lung diseases; CYFRA 21-1 at 3.13 ng/ml and CEA at 7.7 ng/ml. The sensitivity and diagnostic accuracy of CYFRA 21-1 and CEA for the group of NSCLC patients were 66.7 per cent, 76.6 per cent and 35.3 per cent, 55.8 per cent, respectively. When combining CYFRA 21-1 with CEA, the sensitivity and diagnostic accuracy were 68.6 per cent and 66 per cent. These results suggest that CYFRA 21-1 and CEA are useful serum markers for the diagnosis of NSCLC; especially subtype squamous cell and adenocarcinoma, respectively. The usefulness is not enhanced by combining the assay of CYFRA 21-1 and CEA.

Serum insulin-like growth factor (IGF)-I and IGF-binding proteins in lung cancer patients

Many studies have shown that insulin-like growth factors (IGF-I & IGF-II) are implicated in the autocrine and paracrine growth of various tumors. Alterations in serum IGFs and IGF-binding proteins (IGFBPs) profiles have been reported in lung cancer. In this study, we measured serum levels of IGF-I and IGFBPs in 41 patients with lung cancer (small cell lung cancer, SCLC, 9; non-small cell lung cancer, NSCLC, 32) by radioimmunoassay and Western ligand blot (WLB). The serum IGF-I level in patients with lung cancer was significantly lower than in controls (207.9+/-62.6 vs 281.3+/-53.9 ng/mL, p0.05). The concentration of IGFBP-3 in lung cancer was 48% of that found in controls by WLB. The serum level of IGFBP-2 was markedly elevated in patients with lung cancer compared with controls (1303.7+/-618.0 vs 696.2+/-300.5, p<0.01). However, there was no significant difference between SCLC and NSCLC groups. This result showed that serum level of IGF-I/IGFBPs may be useful markers for diagnosing and identifying tumor types in lung cancer and further studies are needed.

Calcitonina monomérica plasmática e hipercalcemia em pacientes portadores de neoplasia pulmonar / Monomeric plasmatic calcitonin and hypercalcemia in lung cancer patients

A calcitonina (CT) é um hormonio peptídico relacionado ao metabolismo de calcio produzido pelas células C da tiróide. Encontra-se com níveis plasmaticos bastante elevados no carcinoma medular de tiróide e mostra-se como excelente marcador dessa doença. No entanto, existem relatos na literatura que demonstraram níveis elevados deste peptídio em pacientes portadores de outras neoplasias, principalmente no carcinoma de pulmao. Objetivo. Avaliar a validade da dosagem da CT sérica como possível marcador tumoral em pacientes portadores de tumor de pulmao de diferentes tipos histológicos. Métodos. Foram dosados CT plasmatica e calcio ionizado sanguíneo em 56 pacientes portadores de tumores malignos de pulmao. Para as dosagens de CT os autores utilizaram um método de radioimunoensaio específico, realizado após extraçao prévia do soro em coluna de sílica. Resultados. Observou-se prevalência de hipercalcemia de 21,4 por cento; apenas três (5,4 por cento) dos 56 pacientes investigados apresentaram níveis pouco elevados de calcitonina, e o restante manteve níveis normais ou identectaveis do peptídio. Conclusao. Os resultados demonstram que, com a utilizaçao de um método bastante específico para dosagem da calcitonina em sua forma monomérica, nao se encontram níveis elevados deste hormonio em pacientes portadores de neoplasia pulmonar, desestimulando sua utilizaçao como marcador tumoral nesta patologia.