RESUMO
PURPOSE: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) and bevacizumab plus chemotherapy were effective for EGFR-mutant patients. However, the appropriated treatment orders remained controvertible. We investigated the efficacy of treatment orders between bevacizumab plus chemotherapy and EGFR-TKIs for EGFR-mutant patients with advanced pulmonary adenocarcinoma. PATIENTS AND METHODS: This study involved 40 EGFR-mutant patients with advanced pulmonary adenocarcinoma who were treated with bevacizumab plus carboplatin and paclitaxel (Bev + CP) and EGFR-TKIs in different treatment orders or gemcitabine plus cisplatin (GP) in first-line setting. Seventeen patients were treated with Bev + CP and 10 cases with GP in first-line treatment. Thirteen patients received EGFR-TKIs after first-line Bev + CP regimen, while 13 patients were treated with first-line EGFR-TKIs. Progression-free survival (PFS), the response rate (ORR) and overall survival (OS) were evaluated. RESULTS: Median PFS of Bev + CP treatment was significantly longer in first-line than non-first-line settings (11.7 vs. 5.6 months, P = 0.003). Median OS was 37.8 months for EGFR-mutant patients with first-line Bev + CP followed by second-line EGFR-TKIs and 31.0 months for those with first-line EGFR-TKIs and non-first-line Bev + CP, respectively (P = 0.509). Median PFS was 11.7 (95% CI 10.6-12.8) months for Bev + CP group and 4.7 (95% CI 4.4-5.0) months for GP group with the hazard ratio of 0.17 (P = 0.001). ORR was 70.6 and 50.0% in the two groups, respectively (P = 0.415). However, there was no significant difference in median OS (33.7 vs 27.8 months, P = 0.293). CONCLUSIONS: First-line Bev + CP followed by EGFR-TKIs might possibly provide favorable prognosis for EGFR-mutant patients. Bev + CP regimen significantly prolonged PFS in first-line than non-first-line settings. These findings warrant further investigations.
Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Receptores ErbB/genética , Neoplasias Pulmonares/tratamento farmacológico , Mutação , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adulto , Idoso , Bevacizumab/administração & dosagem , Carboplatina/administração & dosagem , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
The aim of this study was to detect the expression of transforming growth factor-ß1 (TGF-ß1) in neonatal rats with hyperoxia-induced bronchopulmonary dysplasia (BPD) and to explore its relationship with lung development. Forty-eight rats (2-3 days old) were randomly divided into a hyperoxia group and a control group (N = 24) which were then fed in ≥95% oxygen atmosphere and air, respectively. On the 1st, 3rd and 7th days of hyperoxia exposure, morphological changes of lung tissues were observed under an optical microscope. TGF-ß1 mRNA and protein levels in lung tissues were detected by real-time quantitative polymerase chain reaction and western blot, respectively. With increasing time of hyperoxia exposure, the hyperoxia group gradually suffered from pathological changes such as poor development of lung tissues, alveolar simplification, decrease in the number of alveoli, and hindered pulmonary microvascular development. On the 7th day of hyperoxia exposure, TGF-ß1 mRNA and protein levels (relative to b-actin) of the hyperoxia group (0.34 ± 0.19 and 0.21 ± 0.09, respectively) were significantly lower than those of the control group (0.83 ± 0.45 and 0.57 ± 0.45, respectively; P < 0.05). TGF-ß1 participates in the pathogenesis of BPD as an important regulatory factor during pulmonary vascular development.
Assuntos
Displasia Broncopulmonar/metabolismo , Hiperóxia/complicações , Pulmão/crescimento & desenvolvimento , Fator de Crescimento Transformador beta1/metabolismo , Animais , Displasia Broncopulmonar/etiologia , Displasia Broncopulmonar/genética , Displasia Broncopulmonar/patologia , Feminino , Pulmão/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Fator de Crescimento Transformador beta1/genéticaRESUMO
PURPOSE: ZFP36 ring finger protein (ZFP36) and the suppressor of cytokine signaling 3 (SOCS3) have been reported to, respectively, regulate NF-κB and STAT3 signaling pathways. To better understand the correlation of NF-κB and STAT3 negative regulates pathway, we have investigated the involvement of ZFP36 and SOCS3 expressions in human prostate cancer (PCa). METHODS: In the present study, paired patient tissue microarrays were analyzed by immunohistochemistry, and the ZFP36 protein expression was quantitated as immunoreactive scores in patients with PCa. Associations between ZFP36/SOCS3 expression and various clinicopathological features and prognosis of PCa patients were statistically analyzed based on the Taylor database. Then, the functions of ZFP36 and SOCS3 in cancerous inflammation were determined using qPCR and immunohistochemistry in vitro and in vivo. RESULTS: ZFP36 protein expression in PCa tissues was significantly lower than those in non-cancerous prostate tissues (P < 0.05). In mRNA level, ZFP36 and SOCS3 had a close correlation with each other (P < 0.01, Pearson r = 0.848), and its upregulation was both significantly associated with low Gleason score (P < 0.001 and P < 0.001, respectively), negative metastasis (P < 0.001 and P < 0.001, respectively), favorable overall survival (P < 0.001 and P < 0.05, respectively), and negative biochemical recurrence (P < 0.001 and P < 0.001, respectively). Functionally, LPS treatment could lead to the overexpression of ZFP36 and SOCS3 in vitro and vivo. CONCLUSIONS: Our data offer the convincing evidence for the first time that the aberrant expressions of ZFP36 and SOCS3 may be involved into the progression and patients' prognosis of PCa, implying their potentials as candidate markers of this cancer.
Assuntos
Biomarcadores Tumorais/análise , Neoplasias da Próstata/patologia , Proteína 3 Supressora da Sinalização de Citocinas/biossíntese , Tristetraprolina/biossíntese , Idoso , Idoso de 80 Anos ou mais , Animais , Intervalo Livre de Doença , Humanos , Imuno-Histoquímica , Inflamação/metabolismo , Inflamação/patologia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Prognóstico , Modelos de Riscos Proporcionais , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/mortalidade , Ratos , Ratos Sprague-Dawley , Proteína 3 Supressora da Sinalização de Citocinas/análise , Análise Serial de Tecidos , Tristetraprolina/análiseRESUMO
The aim of this study was to evaluate the control of blood glucose and glycosylated hemoglobin A1c (HbA1c) and its influencing factors, in elderly type 2 diabetic mellitus (T2DM) patients undergoing comprehensive management. After years of comprehensive prevention of and control measures for diabetes, elderly T2DM patients who were receiving long-term health care were comprehensively evaluated through an annual physical examination. In addition to routine health examination, the patients were required to undergo HbA1c measurement. Among 688 patients, 652 were men and 36 were women, with a mean age of 78.2 ± 9.1 years. The average HbA1c was 6.6 ± 0.9%. A total of 50.6% of the patients had HbA1c <6.5%, whereas 76.3% had HbA1c <7.0%. Among all patients, 77.1, 46.4, 66.1, 67.8, 36.3, and 57.4% achieved the target total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglyceride (TG), blood pressure, and body mass index (BMI) levels, respectively. The duration of disease and type of treatment, as well as the LDL, HDL, TG, BMI, and blood pressure levels, were significantly associated with HbA1c control. No patient was admitted because of ketoacidosis or hyperosmolar nonketotic diabetic coma in 10 years. Approximately half of the T2DM patients achieved the target HbA1c level. The more effective blood glucose control observed in our study compared with previous studies can be attributed to the effective monitoring of medical conditions and comprehensive management of patients.
Assuntos
Doença de Alzheimer/sangue , Doença de Alzheimer/terapia , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/terapia , Idoso , Idoso de 80 Anos ou mais , Colesterol/sangue , Diabetes Mellitus Tipo 2/psicologia , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , MasculinoRESUMO
PURPOSE: The role of interleukin-17 (IL-17) in the tumor microenvironment is controversial. We analyzed the in situ tumor expression of IL-17 in colorectal cancer (CRC), adenoma and non-tumor tissue to explore the possible correlation of IL-17 expression to clinicopathological characteristics, tumor-infiltrating neutrophils (TINs) and survival in CRC. METHODS: We reviewed the records of 78 consecutive patients diagnosed with CRC. Archival tissues were used. Thirty-six patients with colorectal adenoma were also included. From the 78 CRC patients, we randomly chose 40 cases and collected non-tumor tissue at 10 cm from the edge of the resected tumor. Immunohistochemistry was performed using anti-IL-17 and anti-CD15 (targeting neutrophils) antibody, respectively. Real-time PCR was used to detect IL-17 mRNA in different tissues. Associations between IL-17 expression, clinicopathological parameters and prognosis were evaluated. RESULTS: The level of IL-17 mRNA was higher in CRC than in adenoma and non-tumor tissue (P < 0.05). Positive IL-17 protein expression was observed more frequently in CRC as compared to colorectal adenoma and non-tumor tissue, respectively (P < 0.01). IL-17 expression correlated to well differentiation and early stage CRC. The number of CD15+ neutrophils significantly increased in CRC and positively correlated to the expression of IL-17 (P < 0.05). Both KaplanMeier analysis and multivariate Cox regression analysis indicated that patients with positive IL-17 expression showed better overall survival. CONCLUSIONS: The association between IL-17 expression and the clinicopathological parameters, as well as the clinical outcome suggests a significant role of IL-17 in CRC. IL-17 is a marker of favorable prognosis.
Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/metabolismo , Regulação Neoplásica da Expressão Gênica , Interleucina-17/metabolismo , Adenoma/metabolismo , Idoso , Neoplasias Colorretais/diagnóstico , Feminino , Perfilação da Expressão Gênica , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Antígenos CD15/metabolismo , Masculino , Pessoa de Meia-Idade , Neutrófilos/metabolismo , Prognóstico , Modelos de Riscos Proporcionais , Reação em Cadeia da Polimerase em Tempo Real , Resultado do Tratamento , Microambiente TumoralRESUMO
PURPOSE: Our previous study showed the upregulation of inosine 5'-monophosphate dehydrogenase type II (IMPDH2) protein in human prostate cancer (PCa) tissues and sera compared to non-cancerous controls by proteomics and ELISA analyses. However, the clinical significance of IMPDH2 in PCa has not been fully elucidated. Thus, the aim of the current study was to investigate the associations of IMPDH2 upregulation with tumor progression in patients with PCa. METHODS: IMPDH2 expression at mRNA and protein levels in human PCa and non-cancerous prostate tissues was respectively detected by qRT-PCR, Western blot and immunohistochemistry analyses, which was validated by microarray-based Taylor Data. Then, the association of IMPDH2 expression with clinicopathological features of PCa patients was statistically analyzed. RESULTS: Compared with non-cancerous prostate tissues, IMPDH2 mRNA and protein expression levels were both significantly upregulated (at mRNA level: 9.22 ± 2.49 vs 5.06 ± 1.45, P < 0.01; at protein level by Western blot: 0.674 ± 0.029 vs 0.418 ± 0.140, P < 0.001; at protein level by immunohistochemistry: 4.97 ± 0.760 vs 3.32 ± 1.66, P < 0.001) in PCa tissues, which were consistent with our previous data. In addition, the enhanced expression of IMPDH2 in PCa tissues was significantly correlated with the advanced clinical stage (for our cohort: P < 0.001; for Taylor data: P = 0.002), the presence of metastasis (for our cohort: P < 0.001; for Taylor data: P = 0.012) and the higher Gleason score (for our cohort: P = 0.002; for Taylor data: P = 0.028). CONCLUSIONS: These findings suggest for the first time that the enhanced expression of IMPDH2 may promote the tumor metastasis and the advanced tumor progression in patients with PCa.
Assuntos
Regulação Neoplásica da Expressão Gênica , IMP Desidrogenase/genética , Neoplasias da Próstata/genética , RNA Mensageiro/metabolismo , Idoso , Western Blotting , Humanos , IMP Desidrogenase/metabolismo , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Próstata/metabolismo , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Regulação para CimaRESUMO
OBJECTIVE: As a small heavily glycosylated mucin-like glycosyl-phosphatidylinositol-anchored cell surface protein, CD24 plays an important role in carcinogenesis of various human malignancies. However, its involvement in osteosarcoma is still unclear. The aim of this study was to investigate the expression pattern and the clinical significance of CD24 in human osteosarcoma. METHODS: CD24 mRNA and protein expression levels were, respectively, detected by RT-PCR and Western blot assays using 30 pairs of osteosarcoma and noncancerous bone tissues. Then, immunohistochemistry was performed to analyze the association of CD24 expression in 166 osteosarcoma tissues with clinicopathological factors or survival of patients. RESULTS: CD24 expression at mRNA and protein levels were both significantly higher in osteosarcoma tissues than those in corresponding noncancerous bone tissues (both P < 0.001). In addition, CD24 protein was positively expressed in 129 of 166 (77.7 %) osteosarcoma specimens with a cytoplasmic and membraneous staining, and also increased in the osteosarcoma specimens with advanced clinical stage (P = 0.01) and positive distant metastasis (P = 0.005). The univariate and multivariate analyses showed that osteosarcoma patients with high CD24 expression had poorer overall and disease-free survival, and high CD24 expression was an independent prognostic factor for both overall and disease-free survival. CONCLUSION: The aforementioned findings offer convincing evidence for the first time that the increased expression of CD24 is correlated with tumor aggressiveness and tumor metastasis of osteosarcoma, and this molecule is an independent prognostic marker for osteosarcoma patients.
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Neoplasias Ósseas/metabolismo , Antígeno CD24/genética , Osteossarcoma/metabolismo , Adulto , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/patologia , Antígeno CD24/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Osteossarcoma/diagnóstico , Osteossarcoma/patologia , Prognóstico , RNA Mensageiro/metabolismo , Análise de SobrevidaRESUMO
Preeclampsia affects 3-8% of pregnancies and is a major cause of maternal and perinatal morbidity and mortality worldwide. Inappropriate activation of the renin-angiotensin system may play a role in the development of preeclampsia. An insertion/deletion polymorphism in the angiotensin-converting enzyme gene (ACE-I/D) has been associated with differences in ACE activity. However, there are controversies in reports on the association of ACE-I/D with preeclampsia. Data were analyzed using Review Manager Version 5.0 and a random effects model was applied irrespective of between studies heterogeneity, which was evaluated via sensitivity and subgroup analyses. Publication bias was evaluated using the fail-safe number. A systematic search was performed based on published case control studies up to October 1, 2011, and 11 studies were included, involving 800 patients and 949 controls. Significant association of the ACE D allele with increase risk of preeclampsia was found (odds ratio = 1.93, 95% confidence interval = 1.19-3.12; P = 0.008). Sensitivity analysis showed that no individual study had an undue influence on the summary odds ratios for all contrasts. An analysis stratified by study size showed an attenuated odds ratio towards a null effect as study size increased. Based on our meta-analysis, we suggest that the D allele of the ACE gene is related with increased risk for preeclampsia in the Chinese population. Considering the potential existence of small study bias, further research should be performed with a larger dataset.
Assuntos
Povo Asiático/genética , Predisposição Genética para Doença , Mutação INDEL/genética , Peptidil Dipeptidase A/genética , Pré-Eclâmpsia/enzimologia , Pré-Eclâmpsia/genética , Adulto , Alelos , China , Feminino , Humanos , Razão de Chances , Gravidez , Viés de Publicação , Fatores de RiscoRESUMO
Human caliciviruses (HuCVs) contain two genera: "Norwalk-like viruses" (NLVs) and "Sapporo-like viruses" (SLVs). The importance of the two genera as a cause of acute gastroenteritis of infants and children remains unknown. Beginning in 1989, a birth cohort of children in Mexico was enrolled and monitored for acute gastroenteritis. A subset of 115 diarrhea stool specimens from 76 children and 66 non-diarrhea stool specimens from 64 children was examined for HuCVs by RT-PCR by using a primer pair (p289/290) that detects both NLVs and SLVs. Twenty-two (19%) of the 115 diarrhea stool specimens and 5 (7%) of 66 non-diarrhea stool specimens produced RT-PCR products of expected size (319 bp for NLVs and 331 bp for SLVs). Twenty of the twenty-seven strains were cloned and sequenced. Pairwise sequence analysis showed that 9 (60%) and 6 (40%) of the 15 strains from the diarrhea stools were NLVs and SLVs, respectively. The same proportions of NLVs (60%) and SLVs (40%) were observed in the non-diarrhea stools. Strains in the NLV genus could be further divided into four clusters: Lordsdale, MxV, and HV and one potentially new cluster. Strains in the SLV genus could be divided into three clusters: Sapporo/82, Lon/92, and a potentially new cluster. Strains from the Lordsdale cluster were the most common among these children. The findings of both genera and multiple clusters of HuCVs co-circulating and the identification of new strains of HuCVs in the population justify the need for future studies of HuCVs in infants and children.
Assuntos
Infecções por Caliciviridae/epidemiologia , Caliciviridae/genética , Gastroenterite/epidemiologia , Variação Genética , Vírus Norwalk/genética , Caliciviridae/isolamento & purificação , Infecções por Caliciviridae/virologia , Pré-Escolar , Gastroenterite/virologia , Humanos , Lactente , México/epidemiologia , Vírus Norwalk/isolamento & purificação , Prevalência , RNA Viral , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Two-hundred Mexican children monitored from birth to 2 years of age in a cohort study of diarrhea were tested for Norwalk virus (NV) and Norwalk-related virus infection. Blood was collected quarterly and tested by an enzyme immunoassay (EIA) using the recombinant NV (rNV) particles as antigen. Stool was collected weekly and tested by an EIA using hyperimmune anti-sera from animals immunized with rNV and a reverse transcription-polymerase chain reaction (RT-PCR) with primers in the RNA polymerase region of NV. A high prevalence of serum antibody to NV (85% at age 2 years) was found by the antibody EIA. In 54 stool specimens selected from children who developed a high titer of serum antibody to rNV, none was positive for NV by the antigen EIA, but 6 yielded products by the RT-PCR. One stool specimen (MX virus) yielded a 3.3 kb RT-PCR product from the 3' end of the viral genome. The MX virus cDNA has a genomic organization like other caliciviruses. Sequence comparison showed that MX virus shares 80% nucleic acid and 91% amino acid sequence identity with Snow Mountain agent (SMA), but only 62% and 60% identity, respectively, with NV in the RNA polymerase region, suggesting that MX virus is a SMA-like virus.