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1.
Pawel Domagala Anna Jakubowska Katarzyna Jaworska-Bieniek Katarzyna Kaczmarek Katarzyna Durda Agnieszka Kurlapska Cezary Cybulski Jan Lubinski 《PloS one》2015,10(6)
Purpose
This study sought to assess the prevalence of common germline mutations in several genes engaged in the repair of DNA double-strand break by homologous recombination in patients with triple-negative breast cancers and hereditary non-triple-negative breast cancers. Tumors deficient in this type of DNA damage repair are known to be especially sensitive to DNA cross-linking agents (e.g., platinum drugs) and to poly(ADP-ribose) polymerase (PARP) inhibitors.Methods
Genetic testing was performed for 36 common germline mutations in genes engaged in the repair of DNA by homologous recombination, i.e., BRCA1, BRCA2, CHEK2, NBN, ATM, PALB2, BARD1, and RAD51D, in 202 consecutive patients with triple-negative breast cancers and hereditary non-triple-negative breast cancers.Results
Thirty five (22.2%) of 158 patients in the triple-negative group carried mutations in genes involved in DNA repair by homologous recombination, while 10 (22.7%) of the 44 patients in the hereditary non-triple-negative group carried such mutations. Mutations in BRCA1 were most frequent in patients with triple-negative breast cancer (18.4%), and mutations in CHEK2 were most frequent in patients with hereditary non-triple-negative breast cancers (15.9%). In addition, in the triple-negative group, mutations in CHEK2, NBN, and ATM (3.8% combined) were found, while mutations in BRCA1, NBN, and PALB2 (6.8% combined) were identified in the hereditary non-triple-negative group.Conclusions
Identifying mutations in genes engaged in DNA damage repair by homologous recombination other than BRCA1/2 can substantially increase the proportion of patients with triple-negative breast cancer and hereditary non-triple-negative breast cancer who may be eligible for therapy using PARP inhibitors and platinum drugs. 相似文献2.
Isabelle Bourdel-Marchasson Abou Diallo Carine Bellera Christelle Blanc-Bisson Jessica Durrieu Christine Germain Simone Mathoulin-Pélissier Pierre Soubeyran Muriel Rainfray Mariane Fonck Adela?de Doussau 《PloS one》2016,11(2)
Purpose
The MNA (Mini Nutritional Assessment) is known as a prognosis factor in older population. We analyzed the prognostic value for one-year mortality of MNA items in older patients with cancer treated with chemotherapy as the basis of a simplified prognostic score.Methods
The prospective derivation cohort included 606 patients older than 70 years with an indication of chemotherapy for cancers. The endpoint to predict was one-year mortality. The 18 items of the Full MNA, age, gender, weight loss, cancer origin, TNM, performance status and lymphocyte count were considered to construct the prognostic model. MNA items were analyzed with a backward step-by-step multivariate logistic regression and other items were added in a forward step-by-step regression. External validation was performed on an independent cohort of 229 patients.Results
At one year 266 deaths had occurred. Decreased dietary intake (p = 0.0002), decreased protein-rich food intake (p = 0.025), 3 or more prescribed drugs (p = 0.023), calf circumference <31cm (p = 0.0002), tumor origin (p<0.0001), metastatic status (p = 0.0007) and lymphocyte count <1500/mm3 (0.029) were found to be associated with 1-year mortality in the final model and were used to construct a prognostic score. The area under curve (AUC) of the score was 0.793, which was higher than the Full MNA AUC (0.706). The AUC of the score in validation cohort (229 subjects, 137 deaths) was 0.698.Conclusion
Key predictors of one-year mortality included cancer cachexia clinical features, comorbidities, the origin and the advanced status of the tumor. The prognostic value of this model combining a subset of MNA items and cancer related items was better than the full MNA, thus providing a simple score to predict 1-year mortality in older patients with an indication of chemotherapy. 相似文献3.
Purpose
Solid tumor vasculature is highly heterogeneous, which presents challenges to antiangiogenic intervention as well as the evaluation of its therapeutic efficacy. The aim of this study is to evaluate the spatial tumor vascular changes due to bevacizumab/paclitaxel therapy using a combination approach of MR angiography and DCE-MRI method.Experimental Design
Tumor vasculature of MCF-7 breast tumor mouse xenografts was studied by a combination of MR angiography and DCE-MRI with albumin-Gd-DTPA. Tumor macroscopic vasculature was extracted from the early enhanced images. Tumor microvascular parameters were obtained from the pharmacokinetic modeling of the DCE-MRI data. A spatial analysis of the microvascular parameters based on the macroscopic vasculature was used to evaluate the changes of the heterogeneous vasculature induced by a 12 day bevacizumab/paclitaxel treatment in mice bearing MCF-7 breast tumor.Results
Macroscopic vessels that feed the tumors were not affected by the bevacizumab/paclitaxel combination therapy. A higher portion of the tumors was within close proximity of these macroscopic vessels after the treatment, concomitant with tumor growth retardation. There was a significant decrease in microvascular permeability and vascular volume in the tumor regions near these vessels.Conclusion
Bevacizumab/paclitaxel combination therapy did not block the blood supply to the MCF-7 breast tumor. Such finding is consistent with the modest survival benefits of adding bevacizumab to current treatment regimens for some types of cancers. 相似文献4.
Hee Jin Lee In Ah Park In Hye Song Sung-Bae Kim Kyung Hae Jung Jin-Hee Ahn Sei-Hyun Ahn Hak Hee Kim Gyungyub Gong 《PloS one》2015,10(9)
Purpose
Several methods are used to assess the pathologic response of breast cancer after neoadjuvant chemotherapy (NAC) to predict clinical outcome. However, the clinical utility of these systems for each molecular subtype of breast cancer is unclear. Therefore, we applied six pathologic response assessment systems to specific subtypes of breast cancer and compared the results.Patients and Methods
Five hundred and eighty eight breast cancer patients treated with anthracycline with/without taxane-based NAC were retrospectively analyzed, and the ypTNM stage, residual cancer burden (RCB), residual disease in breast and nodes (RDBN), tumor response ratio, Sataloff’s classification, and Miller—Payne grading system were evaluated. The results obtained for each assessment system were analyzed in terms of patient survival.Results
In triple-negative tumors, all systems were significantly associated with disease-free survival and Kaplan-Meier survival curves for disease-free survival were clearly separated by all assessment methods. For HR+/HER2- tumors, systems assessing the residual tumor (ypTNM stage, RCB, and RDBN) had prognostic significance. However, for HER2+ tumors, the association between patient survival and the pathologic response assessment results varied according to the system used, and none resulted in distinct Kaplan—Meier curves.Conclusion
Most of the currently available pathologic assessment systems used after anthracycline with/without taxane-based NAC effectively classified triple-negative breast cancers into groups showing different prognoses. The pathologic assessment systems evaluating residual tumors only also had prognostic significance in HR+/HER2- tumors. However, new assessment methods are required to effectively evaluate the pathologic response of HR+/HER2+ and HR-/HER2+ tumors to anthracycline with/without taxane-based NAC. 相似文献5.
Ann D. King Steven Kwok Keung Chow Kwok-Hung Yu Frankie Kwok Fai Mo David K. W. Yeung Jing Yuan Benjamin King Hong Law Kunwar S. Bhatia Alexander C. Vlantis Anil T. Ahuja 《PloS one》2015,10(12)
Background and Purpose
It is important to identify patients with head and neck squamous cell carcinoma (SCC) who fail to respond to chemoradiotherapy so that they can undergo post-treatment salvage surgery while the disease is still operable. This study aimed to determine the diagnostic performance of dynamic contrast enhanced (DCE)-MRI using a pharmacokinetic model for pre-treatment predictive imaging, as well as post-treatment diagnosis, of residual SCC at primary and nodal sites in the head and neck.Material and Methods
Forty-nine patients with 83 SCC sites (primary and/or nodal) underwent pre-treatment DCE-MRI, and 43 patients underwent post-treatment DCE-MRI, of which 33 SCC sites had a residual mass amenable to analysis. Pre-treatment, post-treatment and % change in the mean Ktrans, kep, ve and AUGC were obtained from SCC sites. Logistic regression was used to correlate DCE parameters at each SCC site with treatment response at the same site, based on clinical outcome at that site at a minimum of two years.Results
None of the pre-treatment DCE-MRI parameters showed significant correlations with SCC site failure (SF) (29/83 sites) or site control (SC) (54/83 sites). Post-treatment residual masses with SF (14/33) had significantly higher kep (p = 0.05), higher AUGC (p = 0.02), and lower % reduction in AUGC (p = 0.02), than residual masses with SC (19/33), with the % change in AUGC remaining significant on multivariate analysis.Conclusion
Pre-treatment DCE-MRI did not predict which SCC sites would fail treatment, but post-treatment DCE-MRI showed potential for identifying residual masses that had failed treatment. 相似文献6.
Purpose
To investigate the utility of dynamic contrast-enhanced MRI (DCE-MRI) with Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) for detecting liver fibrosis induced by carbon tetrachloride (CCl4) in rats.Methods
This study was approved by the institutional animal care and use committee. Liver fibrosis in rats was induced by intraperitoneal injection of 1 mL/kg 50% CCl4 twice a week for 4-13 weeks. Control rats were injected with saline. Liver fibrosis was graded using the Metaviar score: no fibrosis (F0), mild fibrosis (F1-F2) and advanced fibrosis (F3-F4). DCE-MRI with Gd-EOB-DTPA was performed for all rats. Ktrans, Kep, Ve and iAUC of the liver parenchyma were measured. Relative enhancement (RE) value of the liver was calculated on T1-weighted images at 15, 20 and 25 min after Gd-EOB-DTPA administration.Results
Thirty-five rats were included: no fibrosis (n=13), mild fibrosis (n=11) and advanced fibrosis (n=11). Ktrans and iAUC values were highest in advanced fibrosis group and lowest in no fibrosis group (P<0.05). The area under the receiver operating characteristic curve (AUROC) for fibrosis (stages F1 and greater) were 0.773 and 0.882 for Ktrans and iAUC, respectively. AUROC for advanced fibrosis were 0.835 and 0.867 for Ktrans and iAUC, respectively. Kep and RE values were not able to differentiate fibrosis stages (all P>0.05).Conclusion
Ktrans and iAUC obtained from DCE-MRI with Gd-EOB-DTPA are useful for the detection and staging of rat liver fibrosis induced by CCl4. 相似文献7.
Objectives
Deficient microvascular blood flow control is thought to cause tumor hypoxia and increase resistance to therapy. In glioma patients, we tested whether perfusion-weighted MRI (PWI) based indices of microvascular flow control provide more information on tumor grade and patient outcome than does the established PWI angiogenesis marker, cerebral blood volume (CBV).Material and Methods
Seventy-two glioma patients (sixty high-grade, twelve low-grade gliomas) were included. Capillary transit time heterogeneity (CTH) and the coefficient of variation (COV), its ratio to blood mean transit time, provide indices of microvascular flow control and the extent to which oxygen can be extracted by tumor tissue. The ability of these parameters and CBV to differentiate tumor grade were assessed by receiver operating characteristic curves and logistic regression. Their ability to predict time to progression and overall survival was examined by the Cox proportional-hazards regression model, and by survival curves using log-rank tests.Results
The best prediction of grade (AUC = 0.876; p < 0.05) was achieved by combining knowledge of CBV and CTH in the enhancing tumor and peri-focal edema, and patients with glioblastoma multiforme were identified best by CTH (AUC = 0.763; p<0.001). CTH outperformed CBV and COV in predicting time to progression and survival in all gliomas and in a subgroup consisting of only high-grade gliomas.Conclusion
Our study confirms the importance of microvascular flow control in tumor growth by demonstrating that determining CTH improves tumor grading and outcome prediction in glioma patients compared to CBV alone. 相似文献8.
Seho Park Jung Hyun Yoon Joohyuk Sohn Hyung Seok Park Hee Jung Moon Min Jung Kim Eun-Kyung Kim Seung Il Kim Byeong-Woo Park 《PloS one》2016,11(2)
Background
The accurate evaluation of favorable response to neoadjuvant chemotherapy (NCT) is critical to determine the extent of surgery. We investigated independent clinicopathological and radiological predictors to discriminate no residual carcinoma (ypT0) from residual ductal carcinoma in situ (ypTis) in breast cancer patients who received NCT.Patients and Methods
Parameters of 117 patients attaining pathological complete response (CR) in the breast after NCT between January 2010 and December 2013 were retrospectively evaluated by univariate and multivariate analyses. All patients underwent mammography, ultrasound, and magnetic resonance imaging (MRI) before and after NCT.Results
There were 67 (57.3%) patients with ypT0. These patients were associated with hormone receptor-negative status, human epidermal growth factor receptor-2 (HER2)-negative tumors, and a higher likelihood of breast-conservation surgery. Baseline mammographic and MRI presentation of the main lesion, absence of associated microcalcifications, shape, posterior features, and absence of calcifications on ultrasound were significantly associated with ypT0. CR in mammography, ultrasound, or MRI after NCT was also related to ypT0. By multivariate analysis, independent predictors of ypT0 were the triple-negative subtype [Odds ratio (OR), 4.23; 95% confidence interval (CI), 1.11–16.09] and CR in MRI after NCT (OR, 5.23; 95% CI, 1.53–17.85). Stratified analysis by breast cancer subtype demonstrated that MRI well predicted ypT0 in all subtypes except the HER2-positive subtype. In particular, of 40 triple-negative subtypes, 22 showed CR in MRI and 21 (95.5%) were ypT0 after NCT.Conclusion
Among imaging modalities, breast MRI can potentially distinguish between ypT0 and ypTis after NCT, especially in patients with triple-negative breast cancer. This information can help clinicians evaluate tumor response to NCT and plan surgery for breast cancer patients of all subtypes except for those with HER2-enriched tumors after NCT. 相似文献9.
Florence Figeac Maylis Dagouassat Meriem Mahrouf-Yorgov Sabine Le Gouvello Céline Trébeau Angeliqua Sayed Jean-Baptiste Stern Pierre Validire Jean-Luc Dubois-Randé Jorge Boczkowski Isabelle Mus-Veteau Anne-Marie Rodriguez 《PloS one》2015,10(3)
Background
Alteration of functional regenerative properties of parenchymal lung fibroblasts is widely proposed as a pathogenic mechanism for chronic obstructive pulmonary disease (COPD). However, what these functions are and how they are impaired in COPD remain poorly understood. Apart from the role of fibroblasts in producing extracellular matrix, recent studies in organs different from the lung suggest that such cells might contribute to repair processes by acting like mesenchymal stem cells. In addition, several reports sustain that the Hedgehog pathway is altered in COPD patients thus aggravating the disease. Nevertheless, whether this pathway is dysregulated in COPD fibroblasts remains unknown.Objectives and Methods
We investigated the stem cell features and the expression of Hedgehog components in human lung fibroblasts isolated from histologically-normal parenchymal tissue from 25 patients—8 non-smokers/non-COPD, 8 smokers-non COPD and 9 smokers with COPD—who were undergoing surgery for lung tumor resection.Results
We found that lung fibroblasts resemble mesenchymal stem cells in terms of cell surface marker expression, differentiation ability and immunosuppressive potential and that these properties were altered in lung fibroblasts from smokers and even more in COPD patients. Furthermore, we showed that some of these phenotypic changes can be explained by an over activation of the Hedgehog signaling in smoker and COPD fibroblasts.Conclusions
Our study reveals that lung fibroblasts possess mesenchymal stem cell-features which are impaired in COPD via the contribution of an abnormal Hedgehog signaling. These processes should constitute a novel pathomechanism accounting for disease occurrence and progression. 相似文献10.
Stefan Vordenb?umen Christoph Schleich Tim L?gters Philipp Sewerin Ellen Bleck Thomas Pauly Anja Müller-Lutz Gerald Antoch Matthias Schneider Falk Miese Benedikt Ostendorf 《Arthritis research & therapy》2014,16(5)
Introduction
Synovial inflammation and joint destruction in rheumatoid arthritis (RA) may progress despite clinical remission. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is increasingly used to detect synovial inflammation in RA. Although small joints such as metacarpophalangeal (MCP) joints are mainly affected by RA, MRI findings have never been directly compared to histological synovitis in MCP synovial tissue. The objective of the current study was therefore to analyse if DCE-MRI relates to histological signs of synovitis small RA joints.Methods
In 9 RA patients, DCE-MRI (3 Tesla, dynamic 2D T1 weighted turbo-flash sequence) of the hand was performed prior to arthroscopically-guided synovial biopsies from the second MCP of the imaged hand. Maximum enhancement (ME), rate of early enhancement, and maximum rate of enhancement were assessed in the MCP. Synovial biopsies were stained for determination of sublining CD68 and the Synovitis Score. Correlations between MRI and histological data were calculated according to Spearman.Results
ME of the MCP significantly correlated to sublining CD68 staining (r = 0.750, P = 0.02), the Synovitis Score (r = 0.743, P = 0.02), and the subscores for lining layer hypertrophy (r = 0.789, P = 0.01) and cellular density (r = 0.842; P = 0.004).Conclusions
Perfusion imaging of synovial tissue in RA finger joints employing DCE-MRI reflects histological synovial inflammation. According to our study, ME is the most closely associated parameter amongst the measures considered. 相似文献11.
Hyun Jung Koo Myoungsun Lee Jin Kim Chul Woong Woo Seong-Yun Jeong Eun Kyung Choi Namkug Kim Jin Seong Lee 《PloS one》2016,11(2)
Purpose
We assessed the effects of anti-angiogenic therapy (AAT) on radiation therapy (RT), evaluating the tumor growth and perfusion patterns on dynamic contrast enhanced MR (DCE-MR) images.Methods
Thirteen nude mice with heterotopic xenograft cancer of human lung cancer cell line were used. To observe the interval change of the tumor size and demonstrate the time-signal intensity enhancement curve of the tumor, the mice were subdivided into four groups: control (n = 2), AAT (n = 2), RT (n = 5), and combined therapy (AART, n = 4). DCE-MR images were taken four weeks after treatment. Perfusion parameters were obtained based on the Brix model. To compare the interval size changes in the RT group with those in the AART group, repeated measures ANOVA was used. Perfusion parameters in both the RT and AART groups were compared using a Mann-Whitney U test.Results
Tumor growth was more suppressed in AART group than in the other groups. Control group showed the rapid wash-in and wash-out pattern on DCE-MR images. In contrast to RT group with delayed and prolonged enhancement, both AAT and AART groups showed the rapid wash-in and plateau pattern. The signal intensity in the plateau/time to peak enhancement (P<0.016) and the maximum enhancement ratio (P<0.016) of AART group were higher than those of RT group.Conclusions
AART showed synergistic effects in anticancer treatment. The pattern of the time-intensity curve on the DCE-MR images in each group implies that AAT might help maintain the perfusion in the cancer of AART group. 相似文献12.
Background
Modeling studies using hypothetical polygenic risk data can be an efficient tool for investigating the effectiveness of downstream applications such as targeting interventions to risk groups to justify whether empirical investigation is warranted. We investigated the assumptions underlying a method that simulates risk data for specific values of the area under the receiver operating characteristic curve (AUC).Methods
The simulation method constructs risk data for a hypothetical population based on the population disease risk, and the odds ratios and frequencies of genetic variants. By systematically varying the parameters, we investigated under what conditions AUC values represent unique ROC curves with unique risk distributions for patients and nonpatients, and to what extend risk data can be simulated for precise values of the AUC.Results
Using larger number of genetic variants each with a modest effect, we observed that the distributions of estimated risks of patients and nonpatients were similar for various combinations of the odds ratios and frequencies of the risk alleles. Simulated ROC curves overlapped empirical curves with the same AUC.Conclusions
Polygenic risk data can be effectively and efficiently created using a simulation method. This allows to further investigate the potential applications of stratifying interventions on the basis of polygenic risk. 相似文献13.
Ramesh Narayanan Sunjoo Ahn Misty D. Cheney Muralimohan Yepuru Duane D. Miller Mitchell S. Steiner James T. Dalton 《PloS one》2014,9(7)
Introduction
The androgen receptor (AR) is the most highly expressed steroid receptor in breast cancer with 75–95% of estrogen receptor (ER)-positive and 40–70% of ER-negative breast cancers expressing AR. Though historically breast cancers were treated with steroidal androgens, their use fell from favor because of their virilizing side effects and the emergence of tamoxifen. Nonsteroidal, tissue selective androgen receptor modulators (SARMs) may provide a novel targeted approach to exploit the therapeutic benefits of androgen therapy in breast cancer.Materials and Methods
Since MDA-MB-453 triple-negative breast cancer cells express mutated AR, PTEN, and p53, MDA-MB-231 triple-negative breast cancer cells stably expressing wildtype AR (MDA-MB-231-AR) were used to evaluate the in vitro and in vivo anti-proliferative effects of SARMs. Microarray analysis and epithelial:mesenchymal stem cell (MSC) co-culture signaling studies were performed to understand the mechanisms of action.Results
Dihydrotestosterone and SARMs, but not bicalutamide, inhibited the proliferation of MDA-MB-231-AR. The SARMs reduced the MDA-MB-231-AR tumor growth and tumor weight by greater than 90%, compared to vehicle-treated tumors. SARM treatment inhibited the intratumoral expression of genes and pathways that promote breast cancer development through its actions on the AR. SARM treatment also inhibited the metastasis-promoting paracrine factors, IL6 and MMP13, and subsequent migration and invasion of epithelial:MSC co-cultures.Conclusion
1. AR stimulation inhibits paracrine factors that are important for MSC interactions and breast cancer invasion and metastasis. 2. SARMs may provide promise as novel targeted therapies to treat AR-positive triple-negative breast cancer. 相似文献14.
Fang Liu Li Qi Bao Liu Jie Liu Hua Zhang DeHai Che JingYan Cao Jing Shen JianXiong Geng Yi Bi LieGuang Ye Bo Pan Yan Yu 《PloS one》2015,10(3)
Objective
Fibroblast activation protein (FAP) plays a vital role in tumor invasion and metastasis. Previous studies have reported its prognostic value in different tumors. However, the results of these reports remain controversial. In this study, a meta-analysis was performed to clarify this issue.Methods
A search of the PubMed, Embase and CNKI databases was conducted to analyze relevant articles. The outcomes included the relations between FAP expression and histological differentiation, tumor invasion, lymph node metastasis, distant metastasis and overall survival (OS). Sensitivity analysis by FAP expression in different cells and tumor types were further subjected to sensitivity analyses as subgroups. Pooled odds ratios (ORs) and hazard ratios (HRs) were evaluated using the random-effects model.Results
The global analysis included 15 studies concerning various solid tumors. For global analysis, FAP overexpression in tumor tissue displayed significant associations with poor OS and tumor progression (OS: HR = 2.18, P = 0.004; tumor invasion: OR = 4.48, P = 0.007; and lymph node metastasis: OR = 3.80, P = 0.004). The subgroup analyses yielded two notable results. First, the relation between FAP overexpression and poor OS and tumor lymph node metastasis was closer in the patients with FAP expression in tumor cells. Second, the pooled analyses of colorectal cancers or pancreatic cancers all indicated that FAP overexpression was associated with a detrimental OS (HR: 1.72, P = 0.009; HR: 3.18, P = 0.005, respectively). The magnitude of this effect was not statistically significant compared with that in patients with non-colorectal cancers or non-pancreatic cancers. These analyses did not display a statistically significant correlation between FAP expression and histological differentiation and distant metastasis in all of the groups.Conclusions
FAP expression is associated with worse prognosis in solid tumors, and this association is particularly pronounced if FAP overexpression is found in the tumor cells rather than the stroma. 相似文献15.
Da Wang Tingting Li Gengtai Ye Zhiyong Shen Yanfeng Hu Tingyu Mou Jiang Yu Sihao Li Hao Liu Guoxin Li 《PloS one》2015,10(4)
Background
The receptor for advanced glycation endproducts (RAGE) is an oncogenic multidisciplinary trans-membranous receptor, which is overexpressed in multiple human cancers. Recently, it has been shown that RAGE is also involved in carcinogenesis and tumor invasion. In this study, we investigated the expression levels and prognostic value of RAGE in primary gastric cancers (GC).Methods
We investigated RAGE expression in primary GC and paired normal gastric tissue by real-time quantitative RT-PCR (n = 30) and Western blotting analysis (n = 30). Additionally, we performed immunohistochemistry on 180 paraffin-embedded GC specimens, 69 matched normal specimens.Results
RAGE was overexpressed in GC compared with the adjacent noncancerous tissues (P<0.001), and higher RAGE expression significantly correlated with the histological grade (P = 0.002), nodal status(P = 0.025), metastasis status(P = 0.002), and American Joint Committee on Cancer stage (P = 0.020). Furthermore, upregulation of RAGE expression is an independent prognostic factor in multivariate analysis using the Cox regression model (P = 0.001).Conclusions
RAGE Overexpression may be a useful marker to predict GC progression and poor prognosis. 相似文献16.
Weiping Chen Qiken Li Yongtian Fan Dechuan Li Lai Jiang Pengnian Qiu Lilong Tang 《PloS one》2016,11(3)
Background
Laparoscopic sphincter-preserving low anterior resection for rectal cancer is a surgery demanding great skill. Immense efforts have been devoted to identifying factors that can predict operative difficulty, but the results are inconsistent.Objective
Our study was conducted to screen patients’ factors to build models for predicting the operative difficulty using well controlled data.Method
We retrospectively reviewed records of 199 consecutive patients who had rectal cancers 5–8 cm from the anal verge. All underwent laparoscopic sphincter-preserving low anterior resections with total mesorectal excision (TME) and double stapling technique (DST). Data of 155 patients from one surgeon were utilized to build models to predict standardized endpoints (operative time, blood loss) and postoperative morbidity. Data of 44 patients from other surgeons were used to test the predictability of the built models.Results
Our results showed prior abdominal surgery, preoperative chemoradiotherapy, tumor distance to anal verge, interspinous distance, and BMI were predictors for the standardized operative times. Gender and tumor maximum diameter were related to the standardized blood loss. Temporary diversion and tumor diameter were predictors for postoperative morbidity. The model constructed for the operative time demonstrated excellent predictability for patients from different surgeons.Conclusions
With a well-controlled patient population, we have built a predictable model to estimate operative difficulty. The standardized operative time will make it possible to significantly increase sample size and build more reliable models to predict operative difficulty for clinical use. 相似文献17.
Jing Ping Yuan Lin Wei Wang Ai Ping Qu Jia Mei Chen Qing Ming Xiang Chuang Chen Sheng-Rong Sun Dai-Wen Pang Juan Liu Yan Li 《PloS one》2015,10(4)
Background
As a marker for tumor cell proliferation, Ki67 has important impacts on breast cancer (BC) prognosis. Although immunohistochemical staining is the current standard method, variations in analytical practice make it difficult for pathologists to manually measure Ki67 index. This study was to develop a fluorescent spectrum-based quantitative analysis of Ki67 expression by quantum-dots (QDs) multiple imaging technique.Methods
A QDs-based in situ multiple fluorescent imaging method was developed, which stained nuclear Ki67 as red signal and cytoplasmic cytokeratin (CK) as green signal. Both Ki67 and CK signals were automatically separated and quantified by professional spectrum analysis software. This technique was applied to tissue microarrays from 240 BC patients. Both Ki67 and CK values, and Ki67/CK ratio were obtained for each patient, and their prognostic value on 5-year disease free survival was assessed.Results
This method simultaneously stains nuclear Ki67 and cytoplasmic CK with clear signal contrast, making it easy for signal separation and quantification. The total fluorescent signal intensities of both Ki67 sum and CK sum were obtained, and Ki67/CK ratio calculated. Ki67 sum and Ki67/CK ratio were each attributed into two grades by X-tile software based on the best P value principle. Multivariate analysis showed Ki67 grade (P = 0.047) and Ki67/CK grade (P = 0.004) were independent prognostic factors. Furthermore, area under curve (AUC) of ROC analysis for Ki67/CK grade (AUC: 0.683, 95%CI: 0.613–0.752) was higher than Ki67 grade (AUC: 0.665, 95%CI: 0.596–0.734) and HER-2 gene (AUC: 0.586, 95%CI: 0.510–0.661), but lower than N stage (AUC: 0.760, 95%CI: 0.696–0.823) and histological grade (AUC: 0.756, 95%CI: 0.692–0.820) on predicting the risk for recurrence.Conclusions
A QDs-based quantitative and in situ multiple imaging on Ki67 and CK was developed to improve Ki67 assessment in BC, and Ki67/CK grade had better performance than Ki67 grade in predicting prognosis. 相似文献18.
Ziyao Li Min Ren Jiawei Tian Shuangquan Jiang Yujie Liu Lei Zhang Zhenzhen Wang Qianqian Song Chong Liu Tong Wu 《PloS one》2015,10(3)
Purpose
The aim of this study was to identify the ultrasound features and clinicopathological characteristics of basal-like subtype of triple negative breast cancers (TNBCs).Materials and Methods
This study was approved by the ethical board of the Second Affiliated Hospital of Harbin Medical University. The patients’ clinicopathological information was available. The ultrasound features of 62 tumors from 62 TNBC patients were interpreted. The immunohistochemical results of cytokertain5/6 (CK5/6) and Epidermal Growth Factor Receptor (EGFR) were used to classify the tumor into basal-like and normal-like groups. The association of the ultrasound features interpreted by experienced ultrasound doctors with the immunohistochemical classification was studied.Results
Of the 62 TNBC cases, 42 (67.7%) exhibited the basal-like phenotype and 20 (32.3%) exhibited the normal-like phenotype based on the immunohistochemical CK5/6 and EGFR markers. Of all the tumors, 90.3% were invasive carcinomas. The basal-like tumors were significantly associated with a maximum diameter on ultrasound of more than 20 mm (36, 85.7%) (P = 0.0014). The normal-like tumors usually exhibited lateral shadows (15, 75%) (P = 0.0115) as well as microlobulated margins (12, 60%) (P = 0.0204) compared to the basal-like subtype. Other ultrasound features showed no significant differences between the two groups.Conclusions
Although ultrasound cannot yet be used to differentiate between the basal-like subtype and normal-like subtype of TNBC, ultrasound can be used to provide some useful information to the clinicians. 相似文献19.
Chan Hyuk Park Eun Hye Kim Jung Hyun Kang Hyunsoo Chung Jun Chul Park Sung Kwan Shin Sang Kil Lee Yong Chan Lee 《PloS one》2016,11(1)
Background
Gastric cancer with undifferentiated histology has different clinicopathologic characteristics compared to differentiated type gastric cancer. We aimed to compare the risk of synchronous or metachronous tumors after curative resection of early gastric cancer (EGC) via endoscopic submucosal dissection (ESD), according to the histologic differentiation of the primary lesion.Methods
Clinicopathological data of patients with initial-onset EGC curatively resected via ESD between January 2007 and November 2014 in a single institution were reviewed. We analyzed the incidence of synchronous or metachronous tumors after ESD with special reference to the differentiation status of the primary lesion.Results
Of 1,560 patients with EGC who underwent curative resection via ESD, 1,447 had differentiated type cancers, and 113 had undifferentiated type cancers. The cumulative incidence of metachronous or synchronous tumor after ESD was higher in the differentiated cancer group than in the undifferentiated cancer group (P = 0.008). Incidence of metachronous or synchronous tumor was 4.8% and 1.2% per person-year in the differentiated and undifferentiated cancer groups, respectively. The Cox proportional hazard model revealed that undifferentiated cancers were associated with a low risk of synchronous or metachronous tumors after adjusting for confounding variables (hazard ratio [95% confidence interval] = 0.287 [0.090–0.918]).Conclusions
The rate of synchronous or metachronous tumors after curative ESD was significantly lower for undifferentiated cancers compare to differentiated cancers. These findings suggest that ESD should be actively considered as a possible treatment for undifferentiated type EGCs. 相似文献20.