共查询到20条相似文献,搜索用时 15 毫秒
1.
Li-Di Xu Susanne Muller Srinivasan R. Thoppe Fredrik Hellborg Lena Kanter Mikael Lerner Biying Zheng Svetlana Bajalica Lagercrantz Dan Grandér Keng Ling Wallin Klas G. Wiman Catharina Larsson Sonia Andersson 《PloS one》2014,9(11)
The p53 target gene WIG-1 (ZMAT3) is located in chromosomal region 3q26, that is frequently amplified in human tumors, including cervical cancer. We have examined the status of WIG-1 and the encoded Wig-1 protein in cervical carcinoma cell lines and tumor tissue samples. Our analysis of eight cervical cancer lines (Ca Ski, ME-180, MS751, SiHa, SW756, C-4I, C-33A, and HT-3) by spectral karyotype, comparative genomic hybridization and Southern blotting revealed WIG-1 is not the primary target for chromosome 3 gains. However, WIG-1/Wig-1 were readily expressed and WIG-1 mRNA expression was higher in the two HPV-negative cervical cell lines (C33-A, HT-3) than in HPV-positive lines. We then assessed Wig-1 expression by immunohistochemistry in 38 cervical tumor samples. We found higher nuclear Wig-1 expression levels in HPV-negative compared to HPV positive cases (p = 0.002) and in adenocarcinomas as compared to squamous cell lesions (p<0.0001). Cases with moderate nuclear Wig-1 staining and positive cytoplasmic Wig-1 staining showed longer survival than patients with strong nuclear and negative cytoplasmic staining (p = 0.042). Nuclear Wig-1 expression levels were positively associated with age at diagnosis (p = 0.023) and histologic grade (p = 0.034). These results are consistent with a growth-promoting and/or anti-cell death function of nuclear Wig-1 and suggest that Wig-1 expression can serve as a prognostic marker in cervical carcinoma. 相似文献
2.
Rawiah Alsiary Anke Brüning-Richardson Jacquelyn Bond Ewan E. Morrison Nafisa Wilkinson Sandra M. Bell 《PloS one》2014,9(5)
Mutations in the MCPH1 (Microcephalin) and ASPM (abnormal spindle-like microcephaly associated) genes cause primary microcephaly. Both are centrosomal associated proteins involved in mitosis. Microcephalin plays an important role in DNA damage response and ASPM is required for correct division of proliferative neuro-epithelial cells of the developing brain. Reduced MCPH1 mRNA expression and ASPM mRNA over-expression have been implicated in the development of human carcinomas. Epithelial ovarian cancer (EOC) is characterised by highly aneuploid tumours. Previously we have reported low Microcephalin and high ASPM protein levels and associations with clinico-pathological parameters in malignant cells from ascitic fluids. To confirm these previous findings on a larger scale Microcephalin and ASPM expression levels and localisations were evaluated by immunohistochemistry in two cohorts; a training set of 25 samples and a validation set of 322 EOC tissue samples. Results were correlated to the associated histopathological data. In normal ovarian tissues the Microcephalin nuclear staining pattern was consistently strong. In the cancer tissues, we identified low nuclear Microcephalin expression in high grade and advanced stage tumours (p<0.0001 and p = 0.0438 respectively). ASPM had moderate to high nuclear and low to moderate cytoplasmic expression in normal tissue. Cytoplasmic ASPM expression decreased with tumour grade and stage in the serous subtype of EOC (p = 0.023 and p = 0.011 respectively). Cytoplasmic ASPM increased with tumour stage in the endometrioid subtype (p = 0.023). Increasing tumour invasiveness (T3) and lymph node involvement (N1) also correlated with a decrease in cytoplasmic ASPM in EOC (p = 0.02 and p = 0.04 respectively). We have validated previous findings of deregulated expression of Microcephalin and ASPM in EOC by confirming associations for low nuclear Microcephalin levels and high cytoplasmic ASPM levels in a larger scale tumour tissue study. Microcephalin and ASPM may prove useful biomarkers in EOC. 相似文献
3.
Angel Chao Chyong-Huey Lai Chia-Lung Tsai Swei Hsueh Chuen Hsueh Chiao-Yun Lin Hung-Hsueh Chou Yu-Jr Lin Hsi-Wen Chen Ting-Chang Chang Tzu-Hao Wang 《PloS one》2013,8(2)
Stress-induced phosphoprotein 1 (STIP1) has been recently identified as a released biomarker in human ovarian cancer. In addition, STIP1 secreted by human ovarian cancer cells has been shown to promote tumor cell proliferation by binding to ALK2 (activin A receptor, type II-like kinase 2) and activating the SMAD-ID3 signaling pathways. In this study, a total of 330 ovarian cancer tumor samples were evaluated for STIP1 expression by immunohistochemistry and analyzed for a possible correlation with patient characteristics and survival. The quantification of immunoreactivity was accomplished by applying an immunohistochemical scoring system (histoscore). Patients with high-level STIP1 expression (histoscore ≥169) had a significantly worse survival (high STIP1, mean survival time = 76 months; low STIP1, mean survival time = 112 months; P<0.0001). Moreover, STIP1 histoscores were significantly higher in high-grade tumors (grade 3) than in low-grade (grade 1–2) malignancies (P<0.0001), suggesting that STIP1 may be a proxy for tumor aggressiveness. The results of multivariable analysis revealed that high STIP1 histoscores, advanced stages, histologic types, and the presence of residual disease (≥2 cm) were independent predictors of poor prognosis. The addition of STIP1 histoscores improved the prediction of overall and progression-free survival rates in the multivariable Cox proportional hazard model. The treatment of ovarian cancer cells with recombinant STIP1 stimulated cell proliferation and migration, but co-treatment with anti-STIP1 antibodies abrogated this effect. Our findings suggest that STIP1 expression may be related to prognosis and that the STIP1 pathway may represent a novel therapeutic target for human ovarian cancer. 相似文献
4.
Margaret Urban Emily Banks Sam Egger Karen Canfell Dianne O'Connell Valerie Beral Freddy Sitas 《PLoS medicine》2012,9(3)
Background
Oral contraceptives are known to influence the risk of cancers of the female reproductive system. Evidence regarding the relationship between injectable contraceptives and these cancers is limited, especially in black South Africans, among whom injectable contraceptives are used more commonly than oral contraceptives.Methods and Findings
We analysed data from a South African hospital-based case–control study of black females aged 18–79 y, comparing self-reported contraceptive use in patients with breast (n = 1,664), cervical (n = 2,182), ovarian (n = 182), and endometrial (n = 182) cancer, with self-reported contraceptive use in 1,492 control patients diagnosed with cancers with no known relationship to hormonal contraceptive use. We adjusted for potential confounding factors, including age, calendar year of diagnosis, education, smoking, alcohol, parity/age at first birth, and number of sexual partners. Among controls, 26% had used injectable and 20% had used oral contraceptives. For current and more recent users versus never users of oral or injectable contraceptives, the odds ratios (ORs) for breast cancer were significantly increased in users of oral and/or injectable contraceptives (OR 1.66, 95% CI 1.28–2.16, p<0.001) and separately among those exclusively using oral (1.57, 1.03–2.40, p = 0.04) and exclusively using injectable (OR 1.83, 1.31–2.55, p<0.001) contraceptives; corresponding ORs for cervical cancer were 1.38 (1.08–1.77, p = 0.01), 1.01 (0.66–1.56, p = 0.96), and 1.58 (1.16–2.15, p = 0.004). There was no significant increase in breast or cervical cancer risk among women ceasing hormonal contraceptive use ≥10 y previously (p = 0.3 and p = 0.9, respectively). For durations of use ≥5 y versus never use, the ORs of ovarian cancer were 0.60 (0.36–0.99, p = 0.04) for oral and/or injectable contraceptive use and 0.07 (0.01–0.49, p = 0.008) for injectable use exclusively; corresponding ORs for endometrial cancer were 0.44 (0.22–0.86, p = 0.02) and 0.36 (0.11–1.26, p = 0.1).Conclusions
In this study, use of oral and of injectable hormonal contraceptives was associated with a transiently increased risk of breast and cervical cancer and, for long durations of use, with a reduced risk of ovarian and endometrial cancer. The observed effects of injectable and of oral contraceptives on cancer risk in this study did not appear to differ substantially. Please see later in the article for the Editors'' Summary 相似文献5.
Corine M. Beaufort Jean C. A. Helmijr Anna M. Piskorz Marlous Hoogstraat Kirsten Ruigrok-Ritstier Nicolle Besselink Muhammed Murtaza Wilfred F. J. van IJcken Anouk A. J. Heine Marcel Smid Marco J. Koudijs James D. Brenton Els M. J. J. Berns Jozien Helleman 《PloS one》2014,9(9)
Epithelial ovarian cancer is a highly heterogeneous disease and remains the most lethal gynaecological malignancy in the Western world. Therapeutic approaches need to account for inter-patient and intra-tumoural heterogeneity and detailed characterization of in vitro models representing the different histological and molecular ovarian cancer subtypes is critical to enable reliable preclinical testing. There are approximately 100 publicly available ovarian cancer cell lines but their cellular and molecular characteristics are largely undescribed. We have characterized 39 ovarian cancer cell lines under uniform conditions for growth characteristics, mRNA/microRNA expression, exon sequencing, drug response for clinically-relevant therapeutics and collated all available information on the original clinical features and site of origin. We tested for statistical associations between the cellular and molecular features of the lines and clinical features. Of the 39 ovarian cancer cell lines, 14 were assigned as high-grade serous, four serous-type, one low-grade serous and 20 non-serous type. Three morphological subtypes: Epithelial (n = 21), Round (n = 7) and Spindle (n = 12) were identified that showed distinct biological and molecular characteristics, including overexpression of cell movement and migration-associated genes in the Spindle subtype. Comparison with the original clinical data showed association of the spindle-like tumours with metastasis, advanced stage, suboptimal debulking and poor prognosis. In addition, the expression profiles of Spindle, Round and Epithelial morphologies clustered with the previously described C1-stromal, C5-mesenchymal and C4 ovarian subtype expression profiles respectively. Comprehensive profiling of 39 ovarian cancer cell lines under controlled, uniform conditions demonstrates clinically relevant cellular and genomic characteristics. This data provides a rational basis for selecting models to develop specific treatment approaches for histological and molecular subtypes of ovarian cancer. 相似文献
6.
Background
Recently, evidence from several studies has revealed that air pollution is associated with the increased morbidity and mortality of breast cancer patients. However, to date, the underlying mechanism remains largely unclear. Considering the high prevalence of air pollution and breast cancer in China, it is necessary to understand how air pollution may affect breast cancer.Methods
We analyzed 1,832 female patients who had resided in the same cities for at least 10 years prior to their diagnosis. Variables including demographic data as well as clinical and tumor characteristics, including the patient’s age at menarche, family history of breast cancer, tumor histopathological type, tumor size, lymph node metastasis, distant metastasis, histological grade, estrogen receptor (ER) status, progesterone receptor (PR) status and human epidermal growth factor receptor 2 (HER-2) status at the time of diagnosis were analyzed.Results
Compared to patients residing in low-pollution areas, patients living in high-pollution areas demonstrated a younger age at menarche (p<0.001), a greater family history of breast cancer (p = 0.034) and more invasive cancers (p = 0.028) with higher tumor grades (p = 0.028) and estrogen receptor (ER)-positive status (p = 0.022). Differences in tumor grade were only found in ER-positive cases.Conclusions
Our findings and clinical data indicate that long-term air pollution exposure may contribute to the development of breast cancer by playing the role of a xenoestrogen, and also provides new insight into the association between air pollution and the morbidity and mortality of breast cancer patients. Furthermore, it is urgently necessary to study the association between air pollution and breast cancer to improve the living quality and health of females, and applicable public health strategies may need to be established or modified as soon as possible. 相似文献7.
8.
Sayeema Daudi Kevin H. Eng Paulette Mhawech-Fauceglia Carl Morrison Anthony Miliotto Amy Beck Junko Matsuzaki Takemasa Tsuji Adrienne Groman Sacha Gnjatic Guillo Spagnoli Shashikant Lele Kunle Odunsi 《PloS one》2014,9(8)
The MAGE cancer-testis antigens (CTA) are attractive candidates for immunotherapy. The aim of this study was to determine the frequency of expression, humoral immunity and prognostic significance of MAGE CTA in human epithelial ovarian cancer (EOC). mRNA or protein expression frequencies were determined for MAGE-A1, -A3, -A4, -A10 and -C1 (CT7) in tissue samples obtained from 400 patients with EOC. The presence of autologous antibodies against the MAGE antigens was determined from 285 serum samples. The relationships between MAGE expression, humoral immunity to MAGE antigens, and clinico-pathologic characteristics were studied. The individual frequencies of expression were as follows: A1: 15% (42/281), A3: 36% (131/390), A4: 47% (186/399), A10: 52% (204/395), C1: 16% (42/267). Strong concordant expression was noted with MAGE-A1:–A4, MAGE-A1:–C1 and MAGE-A4:–A10 (p<0.0005). Expression of MAGE-A1 or -A10 antigens resulted in poor progression free survival (PFS) (OR 1.44, CI 1.01–2.04, p = 0.044 and OR 1.3, CI 1.03–1.64, p = 0.03, respectively); whereas, MAGE-C1 expression was associated with improved PFS (OR 0.62, CI 0.42–0.92, p = 0.016). The improved PFS observed for MAGE-C1 expression, was diminished by co-expression of MAGE-A1 or -A10. Spontaneous humoral immunity to the MAGE antigens was present in 9% (27/285) of patients, and this predicted poor overall survival (log-rank test p = 0.0137). These findings indicate that MAGE-A1, MAGE-A4, MAGE-A3, and MAGE-A10 are priority attractive targets for polyvalent immunotherapy in ovarian cancer patients. 相似文献
9.
Yu-Li Chen Ming-Cheng Chang Chi-An Chen Han-Wei Lin Wen-Fang Cheng Chung-Liang Chien 《PloS one》2012,7(10)
Background
The regulatory T cells (Tregs) can actively suppress the immune responses. However, literature about detailed changes of host effective and suppressive immunities before and after depletion of Tregs in ovarian carcinomas, is rare.Materials and Methods
Ovarian cancer patients and the ascitogenic animal model were employed. Immunologic profiles with flow cytometric analyses, immunohistochemistric staining, RT-PCR, ELISA, and ELISPOT assays were performed. In vivo depletion of Treg cells with the mAb PC61was also performed in the animal model.Results
The cytokines, including IL-4 (p = 0.017) and TNF-α (p = 0.046), significantly decreased while others such as TGF-β (p = 0.013), IL-6 (p = 0.016), and IL-10 (p = 0.018) were elevated in ascites of ovarian cancer patients, when the disease progressed to advanced stages. The ratio of CD8+ T cell/Treg cell in ascites was also lower in advanced diseases than in early diseases (advanced 7.37±0.64 vs. early 14.25±3.11, p = 0.037). The kinetic low-dose CD25 Ab depletion group had significantly lower intra-peritoneal tumor weight (0.20±0.03 g) than the sequential high-dose (0.69±0.06 g) and sequential low-dose (0.67±0.07 g) CD25 Ab deletion groups (p = 0.001) after 49 days of tumor challenge in the animal. The kinetic low-dose CD25 Ab depletion group generated the highest number of IFN-γ-secreting, mesothelin-specific T lymphocytes compared to the other groups (p<0.001).Conclusions
The imbalance between effective and suppressive immunities becomes more severe as a tumor progresses. The depletion of Treg cells can correct the imbalance of immunologic profiles and generate potent anti-tumor effects. Targeting Treg cells can be a new strategy for the immunotherapy of ovarian carcinoma. 相似文献10.
Cheng-Cheng Hwang Shin Nieh Chien-Hong Lai Chien-Sheng Tsai Liang-Che Chang Chung-Ching Hua Wen-Ying Chi Hui-Ping Chien Chih-Wei Wang Siu-Cheung Chan Tsan-Yu Hsieh Jim-Ray Chen 《PloS one》2014,9(8)
Stem cell markers are upregulated in various cancers and have potential as prognostic indicators. The objective of this study was to determine the expression of three stem cell markers, aldehyde dehydrogenase 1 (ALDH-1), B cell-specific Moloney murine leukemia virus integration site 1 (Bmi-1), and Nanog, in esophageal squamous cell carcinoma (ESCC) tissues. Immunohistochemistry was used to measure the expression of ALDH-1, Bmi-1, and Nanog in ESCC tissues from 41 patients who received pre-operative chemoradiation. We evaluated the relationship between expression of these markers, and clinicopathological features, tumor regression grade (TRG), and 5-year overall survival (OS). There were no significant associations of ALDH-1 or Bmi-1 expression with age, gender, clinical stage, and treatments (p>0.05). However, patients with Nanog-positive tumors were significantly older than those whose tumors were Nanog-negative (p = 0.033). TRG after treatment was significantly associated with expression of ALDH-1 (p = 0.001), Bmi-1 (p = 0.004), and Nanog (p<0.001). Although OS was significantly better in patients with low TRGs (p = 0.001), there were no significant correlations between ALDH-1, Bmi-1, or Nanog with OS. Expression of ALDH-1, Bmi-1, and Nanog correlated with TRG, but not OS. Further large studies are necessary to fully elucidate the prognostic value of these stem cell markers for ESCC patients. 相似文献
11.
Marie Tuomarila Kaisa Luostari Ylermi Soini Vesa Kataja Veli-Matti Kosma Arto Mannermaa 《PloS one》2014,9(10)
Micro-RNAs are small, noncoding RNAs that act as tumor suppressors or oncogenes. MiR-200c is a member of the miR-200 family; it is known to be dysregulated in invasive breast carcinoma. MiR-200c maintains the epithelial-mesenchymal transition and inhibits cell migration and invasion. Recent studies showed that miR-200c regulated steroid hormone receptors, estrogen receptors (ER), and progesterone receptors (PR). The present study aimed to detect miR-200c in 172 invasive breast carcinoma cases selected from a prospective cohort enrolled in Kuopio, Eastern Finland, between 1990 and 1995. MiR-200c expression was determined with relative q-PCR, and results were compared to clinicopathological variables and patient outcome. We found that PR status combined with miR-200c expression was a significant marker of outcome. High miR-200c expression was associated with reduced survival in PR-negative cases (n = 68); low miR-200c expression indicated reduced survival in PR-positive cases (n = 86) (Cox regression: P = 0.002, OR = 3.433; and P = 0.004, OR = 4.176, respectively). In PR-negative cases, high miR-200c expression was associated with shortened relapse-free survival (Cox regression: P = 0.001, OR = 3.613); increased local/distant recurrence (Logistic regression: P = 0.006, OR = 3.965); and more frequent distant metastasis (Logistic regression: P = 0.015, OR = 3.390). We also found that high grade and low stage tumors were positively correlated with high miR-200c expression (Logistic regression for high grade tumors: P = 0.002, OR = 2.791 and for high stage tumors: P = 0.035, OR = 0.285). Our results indicated that miR-200c may play a role in invasive breast carcinoma. Furthermore, miR-200c combined with PR status provided a refined predictor of outcome. In future, a larger study is required to confirm our results. This data may provide a basis for new research target–progesterone receptor–regulated microRNAs in breast cancer. 相似文献
12.
MTDH(metadherin), an important oncogene that is widely overexpressed in various cancers, is a potential biomarker of tumor malignancy. Variants in MTDH have been associated with susceptibility to breast cancer. However, no studies assessing MTDH gene polymorphisms and their potential relationship to ovarian cancer susceptibility have been reported. Thus, we investigated the association of MTDH (−470G>A) polymorphism with ovarian cancer development in 145 ovarian cancer patients and 254 matched control subjects, using sequence analysis. We found that the MTDH (−470G>A) polymorphism was statistically correlated with ovarian cancer risk (under the additive genetic model, GG vs. GA vs AA, P = 0.042). Compared with genotypes containing the G allele (GG and GA), the AA genotype may decrease the risk of ovarian cancer (P = 0.0198, OR = 0.33, 95% CI [0.12∼0.78]). Compared with the G allele, the A allele is protective against ovarian cancer risk (P = 0.01756, OR = 0.66, 95% CI [0.46∼0.93]). Furthermore, a statistically significant association between the GG and GA+AA genotypes and the clinical stage was observed (P = 0.038). These data suggest that MTDH (−470G>A) could be a useful molecular marker for assessing ovarian cancer risk and for predicting ovarian cancer patient prognosis. 相似文献
13.
Objective
To evaluate the efficacy of continuous positive airway pressure (CPAP) on serum testosterone in men with obstructive sleep apnea (OSA).Methods
Two reviewers independently searched PubMed, Cochrane library, Embase and Web of Science before June 2014. Information on characteristics of subjects, study design, pre- and post-CPAP treatment of serum total testosterone, free testosterone and sexual hormone blinding protein (SHBG) was extracted for analysis.Results
A total of 7 studies with 9 cohorts that included 232 men were pooled into meta-analysis. There was no change of total testosterone levels before and after CPAP treatment in OSA men (standardized mean difference (SMD) = −0.14, 95%CI: −0.63 to 0.34, z = 0.59, p = 0.558), even subdivided by CPAP therapeutic duration (>3 months). Meanwhile, no significant differences in free testosterone and SHBG were detected after CPAP treatment (SMD = 0.16, 95%CI: −0.09 to 0.40, z = 1.25, p = 0.211 and SMD = −0.58, 95%CI: −1.30 to 0.14, z = 1.59, p = 0.112, respectively).Conclusion
CPAP has no influence on testosterone levels in men with OSA, further large-scale, well-design interventional investigation is needed. 相似文献14.
Huan-Xin Lin Hui-Juan Qiu Fei Zeng Hui-Lan Rao Guo-Fen Yang Hsiang-Fu Kung Xiao-Feng Zhu Yi-Xin Zeng Mu-Yan Cai Dan Xie 《PloS one》2013,8(4)
Background
It has been suggested that autophagy-related Beclin 1 plays a critical role in the regulation of tumor development and/or progression, but its prognostic significance and relationship with Bcl-xL expression in ovarian carcinoma are unclear.Methodology/Principal Findings
In the present study, the methods of Western blotting and immunohistochemistry (IHC) were utilized to investigate the expression status of Beclin 1 and Bcl-xL in fresh ovarian tissues and paraffin-embedded epithelial ovarian tumor tissues. Decreased expression of Beclin 1 was examined by IHC in 8.3% of normal ovaries, in 15.4% of cystadenomas, in 20.0% of borderline tumors, and in 55.6% of ovarian carcinomas, respectively. In ovarian carcinomas, decreased expression of Beclin 1 was correlated closely with ascending histological grade, later pT/pN/pM status and/or advanced clinical stage (P<0.05). In univariate survival analysis, a highly significant association between low-expressed Beclin 1 and shortened patient survival was evaluated in ovarian carcinoma patients (P<0.01), and Beclin 1 expression was an independent prognostic factor as evidenced by multivariate analysis (P = 0.013). In addition, decreased expression of Beclin 1 was inversely correlated with altered expression of Bcl-xL in ovarian carcinoma cohort, and combined analysis further showed that the low Beclin 1/high Bcl-xL group had the lowest survival rate.Conclusions/Significance
Our findings suggest that Beclin 1 expression, as examined by IHC, could be served as an additional tool in identifying ovarian carcinoma patients at risk of tumor progression, and predicting patient survival in ovarian carcinomas with increased expression of Bcl-xL. 相似文献15.
Zacharenia Saridaki Maria Tzardi Chara Papadaki Maria Sfakianaki Fraga Pega Aristea Kalikaki Eleftheria Tsakalaki Maria Trypaki Ippokratis Messaritakis Efstathios Stathopoulos Dimitris Mavroudis Vassilis Georgoulias John Souglakos 《PloS one》2011,6(1)
Background
To investigate the predictive significance of KRAS, BRAF, PIK3CA mutational status, AREG- EREG mRNA expression, PTEN protein expression and skin rash in metastatic colorectal cancer (mCRC) patients treated with cetuximab containing salvage chemotherapy.Methods
Primary tumors from 112 mCRC patients were analyzed. The worst skin toxicity during treatment was recorded.Results
KRAS, BRAF and PIK3CA mutations were present in 37 (33%), 8 (7.2%) and 11 (9.8%) cases, respectively, PTEN was lost in 21 (19.8%) cases, AREG and EREG were overexpressed in 48 (45%) and 51 (49%) cases. In the whole study population, time to tumor progression (TTP) and overall survival (OS) was significantly lower in patients with KRAS (p = 0.001 and p = 0.026, respectively) or BRAF (p = 0.001 and p<0.0001, respectively) mutant tumors, downregulation of AREG (p = 0.018 and p = 0.013, respectively) or EREG (p = 0.002 and p = 0.004, respectively) and grade 0-1 skin rash (p<0.0001 and p<0.0001, respectively). In KRAS wt patients TTP and OS was significantly lower in patients with BRAF (p = 0.0001 and p<0.0001, respectively) mutant tumors, downregulation of AREG (p = 0.021 and p = 0.004, respectively) or EREG (p = 0.0001 and p<0.0001, respectively) and grade 0-1 skin rash (p<0.0001 and p<0.0001, respectively). TTP was significantly lower in patients with PIK3CA mutations (p = 0.01) or lost PTEN (p = 0.002). Multivariate analysis revealed KRAS (Hazard Ratio [HR] 4.3, p<0.0001), BRAF mutation (HR: 5.1, p<0.0001), EREG low expression (HR: 1.6, p = 0.021) and absence of severe/moderate skin rash (HR: 4.0, p<0.0001) as independent prognostic factors for decreased TTP. Similarly, KRAS (HR 2.9, p = 0.01), BRAF mutation (HR: 3.0, p = 0.001), EREG low expression (HR: 1.7, p = 0.021), absecence of severe/moderate skin rash (HR: 3.7, p<0.0001) and the presence of undifferantited tumours (HR: 2.2, p = 0.001) were revealed as independent prognostic factors for decreased OS.Conclusions
These results underscore that KRAS-BRAF mutations and EREG expression can be used as biomarkers to further select patients undergoing anti-EGFR treatment. 相似文献16.
17.
Childhood diarrhea is a significant problem in many developing countries and E. coli is a main causative agent of diarrhea in young children. Lysozyme is an antimicrobial protein highly expressed in human milk, but not ruminant milk, and is thought to help protect breastfeeding children against diarrheal diseases. We hypothesized that consumption of milk from transgenic goats which produce human lysozyme (hLZ-milk) in their milk would accelerate recovery from bacterial-induced diarrhea. Young pigs were used as a model for children and infected with enterotoxigenic E. coli. Once clinical signs of diarrhea developed, pigs were fed hLZ-milk or non-transgenic control goat milk three times a day for two days. Clinical observations and complete blood counts (CBC) were performed. Animals were euthanized and samples collected to assess differences in histology, cytokine expression and bacterial translocation into the mesenteric lymph node. Pigs consuming hLZ-milk recovered from clinical signs of infection faster than pigs consuming control milk, with significantly improved fecal consistency (p = 0.0190) and activity level (p = 0.0350). The CBC analysis showed circulating monocytes (p = 0.0413), neutrophils (p = 0.0219), and lymphocytes (p = 0.0222) returned faster to pre-infection proportions in hLZ-milk fed pigs, while control-fed pigs had significantly higher hematocrit (p = 0.027), indicating continuing dehydration. In the ileum, pigs fed hLZ-milk had significantly lower expression of pro-inflammatory cytokine IL-8 (p = 0.0271), longer intestinal villi (p<0.0001), deeper crypts (p = 0.0053), and a thinner lamina propria (p = 0.0004). These data demonstrate that consumption of hLZ-milk helped pigs recover from infection faster, making hLZ-milk an effective treatment of E. coli-induced diarrhea. 相似文献
18.
Pengchao Li Jinbao Gu Xiao Yang Hongzhou Cai Jun Tao Xuejian Yang Qiang Lu Zengjun Wang Changjun Yin Min Gu 《PloS one》2013,8(8)
Background
A functional -94 insertion/deletion polymorphism (rs28362491) in the promoter of the NFKB1 gene was reported to influence NFKB1 expression and confer susceptibility to different types of cancer. This study aims to determine whether the polymorphism is associated with risk of bladder cancer.Materials and methods
TaqMan assay was used to determine genotype among 609 cases and 640 controls in a Chinese population. Logistic regression was used to assess the association between the polymorphism and bladder cancer risk, and quantitative real-time polymerase chain reaction was used to determine NFKB1 mRNA expression.Results
Compared with the ins/ins/ins/del genotypes, the del/del genotype was associated with a significantly increased risk of bladder cancer [adjusted odd ratio (OR) = 1.92, 95% confidence interval (CI) = 1.42–2.59]. The increased risk was more prominent among subjects over 65 years old (OR = 2.37, 95% CI = 1.52–3.70), male subjects (OR = 1.97, 95% CI = 1.40–2.79) and subjects with self-reported family history of cancer (OR = 3.59, 95% CI = 1.19–10.9). Furthermore, the polymorphism was associated with a higher risk of developing non-muscle invasive bladder cancer (OR = 2.07, 95% CI = 1.51–2.85), grade 1 bladder cancer (OR = 2.40, 95% CI = 1.68–3.43), single tumor bladder cancer (OR = 2.04, 95% CI = 1.48–2.82) and smaller tumor size bladder cancer (OR = 2.10, 95% CI = 1.51–2.92). The expression of NFKB1 mRNA in bladder cancer tissues with homozygous insertion genotype was higher than that with deletion allele.Conclusions
In conclusion, the -94 ins/del ATTG polymorphism in NFKB1 promoter may contribute to the etiology of bladder cancer in the Chinese population. 相似文献19.
Dong Shen Weidong Mao Tao Liu Qingfeng Lin Xiangdong Lu Qiong Wang Feng Lin Ulf Ekelund Katrien Wijndaele 《PloS one》2014,9(8)
Background
Sedentary behavior is ubiquitous in modern adults'' daily lives and it has been suggested to be associated with incident cancer. However, the results have been inconsistent. In this study, we performed a systematic review and meta-analysis of prospective cohort studies to clarify the association between sedentary behavior and incident cancer.Method
PubMed and Embase databases were searched up to March 2014. All prospective cohort studies on the association between sedentary behavior and incident cancer were included. The summary relative risks (RRs) with 95% confidence intervals (CIs) were estimated using random effect model.Results
A total of 17 prospective studies from 14 articles, including a total of 857,581 participants and 18,553 cases, were included in the analysis for sedentary behavior and risk of incident cancer. The overall meta-analysis suggested that sedentary behavior increased risk of cancer (RR = 1.20, 95%CI = 1.12–1.28), with no evidence of heterogeneity between studies (I 2 = 7.3%, P = 0.368). Subgroup analyses demonstrated that there were statistical associations between sedentary behavior and some cancer types (endometrial cancer: RR = 1.28, 95% CI = 1.08–1.53; colorectal cancer: RR = 1.30, 95%CI = 1.12–1.49; breast cancer: RR = 1.17, 95%CI = 1.03–1.33; lung cancer: RR = 1.27, 95%CI = 1.06–1.52). However, there was no association of sedentary behavior with ovarian cancer (RR = 1.26, 95%CI = 0.87–1.82), renal cell carcinoma (RR = 1.11, 95%CI = 0.87–1.41) or non-Hodgkin lymphoid neoplasms (RR = 1.09, 95%CI = 0.82–1.43).Conclusion
The present meta-analysis suggested that prolonged sedentary behavior was independently associated with an increased risk of incident endometrial, colorectal, breast, and lung cancers, but not with ovarian cancer, renal cell carcinoma or non-Hodgkin lymphoid neoplasms. 相似文献20.