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1.
Salma Khan Jessica M. S. Jutzy Malyn May A. Valenzuela David Turay Jonathan R. Aspe Arjun Ashok Saied Mirshahidi Dan Mercola Michael B. Lilly Nathan R. Wall 《PloS one》2012,7(10)
Background
Survivin is expressed in prostate cancer (PCa), and its downregulation sensitizes PCa cells to chemotherapeutic agents in vitro and in vivo. Small membrane-bound vesicles called exosomes, secreted from the endosomal membrane compartment, contain RNA and protein that they readily transport via exosome internalization into recipient cells. Recent progress has shown that tumor-derived exosomes play multiple roles in tumor growth and metastasis and may produce these functions via immune escape, tumor invasion and angiogenesis. Furthermore, exosome analysis may provide novel biomarkers to diagnose or monitor PCa treatment.Methods
Exosomes were purified from the plasma and serum from 39 PCa patients, 20 BPH patients, 8 prostate cancer recurrent and 16 healthy controls using ultracentrifugation and their quantities and qualities were quantified and visualized from both the plasma and the purified exosomes using ELISA and Western blotting, respectively.Results
Survivin was significantly increased in the tumor-derived samples, compared to those from BPH and controls with virtually no difference in the quantity of Survivin detected in exosomes collected from newly diagnosed patients exhibiting low (six) or high (nine) Gleason scores. Exosome Survivin levels were also higher in patients that had relapsed on chemotherapy compared to controls.Conclusions
These studies demonstrate that Survivin exists in plasma exosomes from both normal, BPH and PCa subjects. The relative amounts of exosomal Survivin in PCa plasma was significantly higher than in those with pre-inflammatory BPH and control plasma. This differential expression of exosomal Survivin was seen with both newly diagnosed and advanced PCa subjects with high or low-grade cancers. Analysis of plasma exosomal Survivin levels may offer a convenient tool for diagnosing or monitoring PCa and may, as it is elevated in low as well as high Gleason scored samples, be used for early detection. 相似文献2.
Jung EM Friedrich C Hoffstetter P Dendl LM Klebl F Agha A Wiggermann P Stroszcynski C Schreyer AG 《PloS one》2012,7(3):e33956
Objective
Assessing the feasibility and efficiency of interventions using ultrasound (US) volume navigation (V Nav) with real time needle tracking and image fusion with contrast enhanced (ce) CT, MRI or US.Methods
First an in vitro study on a liver phantom with CT data image fusion was performed, involving the puncture of a 10 mm lesion in a depth of 5 cm performed by 15 examiners with US guided freehand technique vs. V Nav for the purpose of time optimization. Then 23 patients underwent ultrasound-navigated biopsies or interventions using V Nav image fusion of live ultrasound with ceCT, ceMRI or CEUS, which were acquired before the intervention. A CEUS data set was acquired in all patients. Image fusion was established for CEUS and CT or CEUS and MRI using anatomical landmarks in the area of the targeted lesion. The definition of a virtual biopsy line with navigational axes targeting the lesion was achieved by the usage of sterile trocar with a magnetic sensor embedded in its distal tip employing a dedicated navigation software for real time needle tracking.Results
The in vitro study showed significantly less time needed for the simulated interventions in all examiners when V Nav was used (p<0.05). In the study involving patients, in all 10 biopsies of suspect lesions of the liver a histological confirmation was achieved. We also used V Nav for a breast biopsy (intraductal carcinoma), for a biopsy of the abdominal wall (metastasis of ovarial carcinoma) and for radiofrequency ablations (4 ablations). In 8 cases of inflammatory abdominal lesions 9 percutaneous drainages were successfully inserted.Conclusion
Percutaneous biopsies and drainages, even of small lesions involving complex access pathways, can be accomplished with a high success rate by using 3D real time image fusion together with real time needle tracking. 相似文献3.
Usha Malhotra Ali H. Zaidi Juliann E. Kosovec Pashtoon M. Kasi Yoshihiro Komatsu Christina L. Rotoloni Jon M. Davison Clint R Irvin Toshitaka Hoppo Katie S. Nason Lori A. Kelly Michael K. Gibson Blair A. Jobe 《PloS one》2013,8(11)
Background
Survivin is an inhibitor of apoptosis and its over expression is associated with poor prognosis in several malignancies. While several studies have analyzed survivin expression in esophageal squamous cell carcinoma, few have focused on esophageal adenocarcinoma (EAC) and/or cancer-adjacent squamous epithelium (CASE). The purpose of this study was 1) to determine the degree of survivin up regulation in samples of EAC and CASE, 2) to evaluate if survivin expression in EAC and CASE correlates with recurrence and/or death, and 3) to examine the effect of survivin inhibition on apoptosis in EAC cells.Methods
Fresh frozen samples of EAC and CASE from the same patient were used for qRT-PCR and Western blot analysis, and formalin-fixed, paraffin-embedded tissue was used for immunohistochemistry. EAC cell lines, OE19 and OE33, were transfected with small interfering RNAs (siRNAs) to knockdown survivin expression. This was confirmed by qRT-PCR for survivin expression and Western blot analysis of cleaved PARP, cleaved caspase 3 and survivin. Survivin expression data was correlated with clinical outcome.Results
Survivin expression was significantly higher in EAC tumor samples compared to the CASE from the same patient. Patients with high expression of survivin in EAC tumor had an increased risk of death. Survivin expression was also noted in CASE and correlated with increased risk of distant recurrence. Cell line evaluation demonstrated that inhibition of survivin resulted in an increase in apoptosis.Conclusion
Higher expression of survivin in tumor tissue was associated with increased risk of death; while survivin expression in CASE was a superior predictor of recurrence. Inhibition of survivin in EAC cell lines further showed increased apoptosis, supporting the potential benefits of therapeutic strategies targeted to this marker. 相似文献4.
Background
The use of both upper extremities (UE) is necessary for the completion of many everyday tasks. Few clinical assessments measure the abilities of the UEs to work together; rather, they assess unilateral function and compare it between affected and unaffected UEs. Furthermore, clinical assessments are unable to measure function that occurs in the real-world, outside the clinic. This study examines the validity of an innovative approach to assess real-world bilateral UE activity using accelerometry.Methods
Seventy-four neurologically intact adults completed ten tasks (donning/doffing shoes, grooming, stacking boxes, cutting playdough, folding towels, writing, unilateral sorting, bilateral sorting, unilateral typing, and bilateral typing) while wearing accelerometers on both wrists. Two variables, the Bilateral Magnitude and Magnitude Ratio, were derived from accelerometry data to distinguish between high- and low-intensity tasks, and between bilateral and unilateral tasks. Estimated energy expenditure and time spent in simultaneous UE activity for each task were also calculated.Results
The Bilateral Magnitude distinguished between high- and low-intensity tasks, and the Magnitude Ratio distinguished between unilateral and bilateral UE tasks. The Bilateral Magnitude was strongly correlated with estimated energy expenditure (ρ = 0.74, p<0.02), and the Magnitude Ratio was strongly correlated with time spent in simultaneous UE activity (ρ = 0.93, p<0.01) across tasks.Conclusions
These results demonstrate face validity and construct validity of this methodology to quantify bilateral UE activity during the performance of everyday tasks performed in a laboratory setting, and can now be used to assess bilateral UE activity in real-world environments. 相似文献5.
Ray Gervacio F. Blanco Joseph Califano Barbara Messing Jeremy Richmon Jia Liu Harry Quon Geoffrey Neuner John Saunders Patrick K. Ha Sheila Sheth Maura Gillison Carole Fakhry 《PloS one》2014,9(1)
Background
Base of tongue (BOT) is a difficult subsite to examine clinically and radiographically. Yet, anatomic delineation of the primary tumor site, its extension to adjacent sites or across midline, and endophytic vs. exophytic extent are important characteristics for staging and treatment planning. We hypothesized that ultrasound could be used to visualize and describe BOT tumors.Methods
Transcervical ultrasound was performed using a standardized protocol in cases and controls. Cases had suspected or confirmed BOT malignancy. Controls were healthy individuals without known malignancy.Results
100% of BOT tumors were visualized. On ultrasound BOT tumors were hypoechoic (90.9%) with irregular margins (95.5%). Ultrasound could be used to characterize adjacent site involvement, midline extent, and endophytic extent, and visualize the lingual artery. No tumors were suspected for controls.Conclusions
Ultrasonography can be used to transcervically visualize BOT tumors and provides clinically relevant characteristics that may not otherwise be appreciable. 相似文献6.
7.
Objectives
The aim of this feasibility study was to prospectively explore in a dog model of chronic ischemic renal disease (CIRD) the hypothesis that real-time contrast-enhanced ultrasonography (CEUS) can quantitatively evaluate the early perfusion changes of renal cortex.Materials and Methods
In this animal care and use committee-approved study, the model of CIRD was carried out in healthy dogs (10.0∼12.0 kg, n = 5), by placing the Ameroid ring constrictors on the distal portion of right renal artery through operation. CEUS monitoring of right kidney perfusion was performed by intravenous bolus injection of 0.6 ml Sulfur hexafluoride filled microbubbles (SonoVue; Bracco S.P.A., Milan, Italy) every week after operation. The slope rate of ascending curve (A) and descending curve (α), area under curve (AUC), derived peak intensity (DPI), and time to peak (TTP) were measured in renal cortex using commercial quantification software (Q-LAB version 6; Philips Medical Systems, Bothell,WA,USA). The sensitivity of CEUS was compared with blood serum urea nitrogen (BUN) and serum creatinine (SCr) level.Results
With the progression of CIRD, dogs showed delayed enhancement and perfusion in renal CEUS curve. Earliest significant changes happened 4 weeks after operation on DPI and TTP which changed from 13.04±2.71 to 15.58±4.75 dB and 9.03±2.01 to 10.62±6.04 sec, respectively (P<.05).Conclusions
CEUS can display the perfusion changes of CIRD in the early period. 相似文献8.
Chunguang Li Yan Yan Weidan Ji Longlong Bao Haihua Qian Lei Chen Mengchao Wu Hezhong Chen Zhigang Li Changqing Su 《PloS one》2012,7(11)
Background
OCT4 and Survivin are important factors for cancer cell proliferation, renewal and dedifferentiation, and correlate with resistance to radiotherapy and chemotherapy in most human cancers, but their regulatory mechanisms are not well known.Methodology/Principal Findings
In this study, 50 patients with esophageal squamous cell carcinoma (ESCC) were retrospectively analyzed. OCT4 was expressed in 13 cases (26%), and survivin was positively expressed in 31 cases (62%), examined by immunochemistry. OCT4 was found to be an independent predictive factor for median survival time, and the patients from the subgroup with both high expression of OCT4 and Survivin had the worst prognosis investigated by log-rank test. To further explore the molecular regulatory mechanism between OCT4 and Survivin, we constructed the specific small hairpin RNA (shRNA)-expressing vectors targeting OCT4 or/and Survivin and manipulated the expression of OCT4 and Survivin. By Western blotting and RT-PCR, we found that OCT4 could up-regulate Survivin expression in the esophageal cancer cell lines Eca109 and TE1. Simultaneously knockdown of OCT4 and Survivin expression induced cell apoptosis and G2-phase decrease of cell cycle by flow cytometry, and finally exerted an enhanced anti-proliferation potency in Eca109 and TE1 cell lines by MTT assay.Conclusions
This study shows that OCT4 and Survivin expression were correlated with poor survival in patients with ESCC. OCT4 and Survivin may be regarded as targets in ESCC biotherapy. 相似文献9.
Rui Li Meng-Xia Yuan Kuan-sheng Ma Xiao-Wu Li Chun-Lin Tang Xiao-Hang Zhang De-Yu Guo Xiao-Chu Yan 《PloS one》2014,9(5)
Aim
To verify if detailed analysis of temporal enhancement patterns on contrast enhanced ultrasound (CEUS) may help differentiate intrahepatic cholangiocarcinoma (ICC) from hepatocellular carcinoma (HCC) in cirrhosis.Methods
Thirty three ICC and fifty HCC in cirrhosis were enrolled in this study. The contrast kinetics of ICC and HCC was analyzed and compared.Results
Statistical analysis did not reveal significant difference between ICC and HCC in the time of contrast first appearance and arterial peak maximum time. ICC displayed much earlier washout than that of HCC (47.93±26.45 seconds vs 90.86±31.26 seconds) in the portal phase, and most ICC (87.9%) showed washout before 60 seconds than HCC (16.0%). Much more ICC (78.8%) revealed marked washout than HCC (12.0%) while most HCC (88.0%) showed mild washout or no washout in late part of the portal phase (90–120 seconds). Twenty six out of thirty three ICC (78.8%) demonstrated both early washout(<60seconds) and marked washout in late part of the portal phase, whereas, only six of fifty HCC (12.0%)showed these temporal enhancement features (p = 0.000).When both early washout and marked washout in the portal phase are taken as diagnostic criterion for ICC, the diagnostic sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 78.8%,88.0%,81.3%,86.3%,and 84.3% respectively by CEUS.Conclusions
Analysis of detailed temporal enhancement features on CEUS is helpful differentiate ICC from HCC in cirrhosis.If a nodule in cirrhotic liver displays hyper-enhancement in the arterial phase followed by early and marked washout in the portal phase, the nodule is highly suspicious of ICC rather than HCC. 相似文献10.
Thorsten Fuereder Volker Wacheck Sabine Strommer Peter Horak Marion Gerschpacher Wolfgang Lamm Danijel Kivaranovic Michael Krainer 《PloS one》2014,9(4)
Background
Endothelial progenitor cells (CEPs) and circulating endothelial cells (CECs) are potential biomarkers of response to anti-angiogenic treatment regimens. In the current study, we investigated the effect of docetaxel and sunitinib on CEP/CEC kinetics and clinical response in castration resistant prostate cancer (CRPC) patients.Patients and methods
Chemonaive patients with CRPC were enrolled in this study to receive either sunitinib (37.5 mg/d), in combination with docetaxel (75 mg/m2) or docetaxel alone. CEP and CEC kinetics were analyzed for every cycle. The primary objective was to compare CEP/CEC pharmacodynamics between both treatment arms. We also investigated if CEC/CEP spikes, induced by MTD docetaxel, are suppressed by sunitinib in patients treated with docetaxel/sunitinib relative to docetaxel monotherapy.Results
A total of 27 patients were enrolled. We observed a significant increase of CEP/CEC (total/viable) counts over time within each cycle (coefficients 0.29233, 0.22092 and 0.26089, respectively; p<0.001). However, no differences between the treatment groups, in terms of CEP and CEC kinetics, were detected. In the docetaxel monotherapy arm 4 (30%) patients responded to therapy with a 50% PSA decline, while 9 (64%) patients showed a PSA decline in the combination group (n.s.). The median PFS in the docetaxel monotherapy group was 3.1 months (2.6–3.6 months, 95% CI) and 6.2 months (4.9–7.4 months, 95% CI; p = 0.062) in the combination arm. Sunitinib/docetaxel was reasonably well tolerated and toxicity manageable.Conclusion
In summary, no significant differences in CEC and CEP kinetics between the treatment arms were observed, although a highly significant increase of CEPs/CECs within each cycle over time was detected. These results mirror the challenge we have to face when employing anti-angiogenic strategies in CRPC. Additional preclinical research is needed to elucidate the underlying molecular mechanisms. However, docetaxel/sunitinib therapy resulted in a better response in terms of PSA decline and a trend towards improved PFS.Trial Registery
clinicaltrialsregister.eu EudraCT 2007-003705-27 相似文献11.
Takashi Anayama Takahiro Nakajima Michael Dunne Jinzi Zheng Christine Allen Brandon Driscoll Douglass Vines Shaf Keshavjee David Jaffray Kazuhiro Yasufuku 《PloS one》2013,8(6)
Background
The rabbit VX2 lung cancer model is a large animal model useful for preclinical lung cancer imaging and interventional studies. However, previously reported models had issues in terms of invasiveness of tumor inoculation, control of tumor aggressiveness and incidence of complications.Purpose
We aimed to develop a minimally invasive rabbit VX2 lung cancer model suitable for imaging and transbronchial interventional studies.Methods
New Zealand white rabbits and VX2 tumors were used in the study. An ultra-thin bronchoscope was inserted through a miniature laryngeal mask airway into the bronchus. Different numbers of VX2 tumor cells were selectively inoculated into the lung parenchyma or subcarinal mediastinum to create a uniform tumor with low incidence of complications. The model was characterized by CT, FDG-PET, and endobronchial ultrasound (EBUS). Liposomal dual-modality contrast agent was used to evaluate liposome drug delivery system in this model.Results
Both peripheral and mediastinal lung tumor models were created. The tumor making success rate was 75.8% (25/33) in the peripheral lung tumor model and 60% (3/5) in the mediastinal tumor model. The group of 1.0×106 of VX2 tumor cells inoculation showed a linear growth curve with less incidence of complications. Radial probe EBUS visualized the internal structure of the tumor and the size measurement correlated well with CT measurements (r2 = 0.98). Over 7 days of continuous enhancement of the lung tumor by liposomal contrast in the lung tumor was confirmed both CT and fluorescence imaging.Conclusion
Our minimally invasive bronchoscopic rabbit VX2 lung cancer model is an ideal platform for lung cancer imaging and preclinical bronchoscopic interventional studies. 相似文献12.
Dong Ryul Jang Dae Chul Jung Young Taik Oh Songmi Noh Kyunghwa Han Kiwook Kim Koon-Ho Rha Young Deuk Choi Sung Joon Hong 《PloS one》2015,10(6)
Objectives
To prospectively determine whether multi-parametric MRI (mpMRI) - contrast-enhanced ultrasound (CEUS) correlated, imaging-guided target biopsy (TB) method could improve the detection of prostate cancer in re-biopsy setting of patients with prior negative biopsy.Methods
From 2012 to 2014, a total of 42 Korean men with a negative result from previous systematic biopsy (SB) and elevated prostate-specific antigen underwent 3T mpMRI and real-time CEUS guided TB. Target lesions were determined by fusion of mpMRI and CEUS. Subsequently, 12-core SB was performed by a different radiologist. We compared core-based cancer detection rates (CaDR) using the generalized linear mixed model (GLIMMIX) for each biopsy method.Results
Core-based CaDR was higher in TB (17.92%, 38 of 212 cores) than in SB (6.15%, 31 of 504 cores) (p < 0.0001; GLIMMIX). In the cancer-positive TB cores, CaDR with suspicious lesions by mpMRI was higher than that by CEUS (86.8% vs. 60.5%, p= 0.02; paired t-test) and concordant rate between mpMRI and CEUS was significantly different with discordant rate (48% vs. 52%, p=0.04; McNemar’s test).Conclusion
The mpMRI-CEUS correlated TB technique for the repeat prostate biopsy of patients with prior negative biopsy can improve CaDR based on the number of cores taken. 相似文献13.
Heba Bassiony Salwa Sabet Taher A. Salah El-Din Mona M. Mohamed Akmal A. El-Ghor 《PloS one》2014,9(11)
Background
Magnetite nanoparticles (MNPs) have been widely used as contrast agents and have promising approaches in cancer treatment. In the present study we used Ehrlich solid carcinoma (ESC) bearing mice as a model to investigate MNPs antitumor activity, their effect on expression of p53 and p16 genes as an indicator for apoptotic induction in tumor tissues.Method
MNPs coated with ascorbic acid (size: 25.0±5.0 nm) were synthesized by co-precipitation method and characterized. Ehrlich mice model were treated with MNPs using 60 mg/Kg day by day for 14 injections; intratumorally (IT) or intraperitoneally (IP). Tumor size, pathological changes and iron content in tumor and normal muscle tissues were assessed. We also assessed changes in expression levels of p53 and p16 genes in addition to p53 protein level by immunohistochemistry.Results
Our results revealed that tumor growth was significantly reduced by IT and IP MNPs injection compared to untreated tumor. A significant increase in p53 and p16 mRNA expression was detected in Ehrlich solid tumors of IT and IP treated groups compared to untreated Ehrlich solid tumor. This increase was accompanied with increase in p53 protein expression. It is worth mentioning that no significant difference in expression of p53 and p16 could be detected between IT ESC and control group.Conclusion
MNPs might be more effective in breast cancer treatment if injected intratumorally to be directed to the tumor tissues. 相似文献14.
Background
Wind turbine noise exposure and suspected health-related effects thereof have attracted substantial attention. Various symptoms such as sleep-related problems, headache, tinnitus and vertigo have been described by subjects suspected of having been exposed to wind turbine noise.Objective
This review was conducted systematically with the purpose of identifying any reported associations between wind turbine noise exposure and suspected health-related effects.Data Sources
A search of the scientific literature concerning the health-related effects of wind turbine noise was conducted on PubMed, Web of Science, Google Scholar and various other Internet sources.Study Eligibility Criteria
All studies investigating suspected health-related outcomes associated with wind turbine noise exposure were included.Results
Wind turbines emit noise, including low-frequency noise, which decreases incrementally with increases in distance from the wind turbines. Likewise, evidence of a dose-response relationship between wind turbine noise linked to noise annoyance, sleep disturbance and possibly even psychological distress was present in the literature. Currently, there is no further existing statistically-significant evidence indicating any association between wind turbine noise exposure and tinnitus, hearing loss, vertigo or headache.Limitations
Selection bias and information bias of differing magnitudes were found to be present in all current studies investigating wind turbine noise exposure and adverse health effects. Only articles published in English, German or Scandinavian languages were reviewed.Conclusions
Exposure to wind turbines does seem to increase the risk of annoyance and self-reported sleep disturbance in a dose-response relationship. There appears, though, to be a tolerable level of around LAeq of 35 dB. Of the many other claimed health effects of wind turbine noise exposure reported in the literature, however, no conclusive evidence could be found. Future studies should focus on investigations aimed at objectively demonstrating whether or not measureable health-related outcomes can be proven to fluctuate depending on exposure to wind turbines. 相似文献15.
Bj?rn Svensson Ingi?ld Hafstr?m Malin C Erlandsson Kristina Forslind Maria I Bokarewa 《Arthritis research & therapy》2014,16(1):R12
Introduction
High levels of the oncoprotein survivin may be detected in the majority of patients with early rheumatoid arthritis (RA). Survivin is a sensitive predictor of joint damage and persistent disease activity. Survivin-positive patients are often poor responders to antirheumatic and biological treatment. The aim of this study was to investigate the reproducibility of survivin status and its significance for clinical and immunological assessment of RA patients.Methods
Survivin levels were measured in 339 patients from the Better Anti-Rheumatic FarmacOTherapy (BARFOT) cohort of early RA at baseline and after 24 months. The association of survivin status with joint damage (total Sharp-van der Heijde score), disease activity (Disease Activity Score based on evaluation of 28 joints (DAS28)), functional disability (Health Assessment Questionnaire (HAQ)), and pain perception (Visual Analogue Scale (VAS)) was calculated in the groups positive and negative for survivin on both occasions, and for the positive-negative and negative-positive groups.Results
In 268 patients (79%) the levels of survivin were similar at baseline and after 24 months, 15% converted from survivin-positive to survivin-negative, and 5% from survivin-negative to survivin-positive. A combination of smoking and antibodies against cyclic citrullinated peptides (aCCP) predicted persistently (baseline and 24 months) high levels of survivin (odds ratio 4.36 (95% CI: 2.64 to 7.20), P < 0.001), positive predictive value 0.66 and specificity 0.83). The independent nature of survivin and aCCP was demonstrated by statistical and laboratory analysis. Survivin positivity on both test occasions was associated with the progression of joint damage, significantly higher DAS28 and lower rate of remission at 24 and 60 months compared to negative-negative patients. Survivin status was less associated with changes in HAQ and VAS.Conclusions
Survivin is a relevant and reproducible marker of severe RA. Persistently high levels of survivin were associated with smoking and the presence of aCCP and/or RF antibodies and predicted persistent disease activity and joint damage. 相似文献16.
Iwona Gisterek Ewelina Lata Agnieszka Halon Rafal Matkowski Jolanta Szelachowska Przemyslaw Biecek Jan Kornafel 《Reports of Practical Oncology and Radiotherapy》2011,16(5):173-177
Background
Hepatocyte growth factor plays an important role in tumor growth, metastasis and angiogenesis. C-met is HGF''s high affinity receptor.Aim
The aim of the study was to assess the correlations between c-met expression and clinic-pathological factors in breast cancer tissues. Furthermore, the purpose of the study was to evaluate the prognostic value of the hepatocyte growth factor receptor (HGFR, c-met) expressions in homogenous group of breast cancer patients.Materials and methods
Tumor samples were collected from 302 patients with breast carcinoma treated with primary surgery. We have assessed the percentage of tumor cells with c-met expression, the intensity of reaction and the ratio of these two factors—immunoreactivity according to the Remmele score.Results
We have observed no correlations between HGFR immunoreactivities and clinical parameters (tumor size, grade, axillary lymph node status, age). In 5-year observation we have found prognostic value of assessing c-met immunoreactivity in primary tumor.Conclusion
Our study has revealed prognostic value of c-met. Unlike in other authors’ studies, our patients’ group is very homogenous which might contribute to obtained results. 相似文献17.
Objective
Larger animal models provide relevant tumor burden in the development of advanced clinical imaging methods for non-invasive cancer detection and diagnosis, and are especially valuable for studying metastatic disease. Most available experimental models, however, are based on immune-compromised mice. To lay the foundation for studying spontaneous metastasis using non-invasive magnetic resonance imaging (MRI), this study aims to establish a highly metastatic breast cancer xenograft model in nude rats.Materials and Methods
A highly metastatic variant of human adenocarcinoma MDA-MB-231 known as LM2 was inoculated into nude rats. Orthotopic and subcutaneous (flank) sites were compared, with half of the orthotopic injections guided by ultrasound imaging. MRI with gadolinium contrast administration was performed weekly beginning on Day 6 and ending on Day 104. Excised tumors were assessed on histology using hematoxylin and eosin and CD34. Fisher''s exact test was used to compare successful tumor induction amongst different inoculation methods.Results
Primary LM2 tumors were established orthotopically in all cases under ultrasound-guided injection, and none otherwise (p = 0.0028). Contrast-enhanced MRI revealed rapidly progressing tumors that reached critical size (15 mm diameter) in 2 to 3 weeks after inoculation. MRI and histology findings were consistent: LM2 tumors were characterized by low vascularity confined to the tumor rim and large necrotic cores with increasing interstitial fluid pressure.Conclusions
The metastatic LM2 breast tumor model was successfully established in the mammary fat pads of nude rats, using ultrasound needle guidance as a non-invasive alternative to surgery. This platform lays the foundation for future development and application of MRI to study spontaneous metastasis and different stages throughout the metastatic cascade. 相似文献18.
Gerald B. Lee Eric B. Brandt Chang Xiao Aaron M. Gibson Timothy D. Le Cras Lou Ann S. Brown Anne M. Fitzpatrick Gurjit K. Khurana Hershey 《PloS one》2013,8(3)
Background
Diesel exhaust particle (DEP) exposure enhances allergic inflammation and has been linked to the incidence of asthma. Oxidative stress on the thiol molecules cysteine (Cys) and glutathione (GSH) can promote inflammatory host responses. The effect of DEP on the thiol oxidation/reduction (redox) state in the asthmatic lung is unknown.Objective
To determine if DEP exposure alters the Cys or GSH redox state in the asthmatic airway.Methods
Bronchoalveolar lavage fluid was obtained from a house dust mite (HDM) induced murine asthma model exposed to DEP. GSH, glutathione disulfide (GSSG), Cys, cystine (CySS), and s-glutathionylated cysteine (CySSG) were determined by high pressure liquid chromatography.Results
DEP co-administered with HDM, but not DEP or HDM alone, decreased total Cys, increased CySS, and increased CySSG without significantly altering GSH or GSSG.Conclusions
DEP exposure promotes oxidation and S-glutathionylation of cysteine amino acids in the asthmatic airway, suggesting a novel mechanism by which DEP may enhance allergic inflammatory responses. 相似文献19.
Objective
To evaluate the risk of cardiovascular disease in patients with rheumatoid arthritis exposed to glucocorticoids.Methods
Retrospective analysis of exposure to glucocorticoids in a prospective cohort of 353 patients with rheumatoid arthritis followed from June 2001 up to November 2011 for incident cardiovascular disease in a hospital-based outpatient cohort in the Netherlands. Hazard ratios with 95%-confidence intervals were calculated for the association between different types of exposure to glucocorticoids and incident cardiovascular disease. Associations were adjusted for demographics, cardiovascular risk factors and disease related parameters.Results
Recent and current exposure to glucocorticoids were associated with incident cardiovascular disease, as was a longer duration of exposure and cumulative exposure to glucocorticoids. Adjustment for disease activity and severity negated the association.Conclusion
In observational studies the finding of incident cardiovascular disease in patients with rheumatoid arthritis exposed to glucocorticoids is strongly confounded by indication due to high disease activity. The adverse cardiovascular effects of glucocorticoids might be balanced by positive effects working through inflammation control. 相似文献20.