体格检查、超声及磁共振在乳腺癌新辅助化疗疗效评估中的价值

Background  Accurate evaluation of response following chemotherapy treatment is essential for surgical decision making in patients with breast cancer. Modalities that have been used to monitor response to neo-adjuvant chemotherapy (NAC) include physical examination (PE), ultrasound (US), and magnetic resonance imaging (MRI). The purpose of this study was to evaluate the accuracy of PE, US, and MRI in predicting the response to NAC in patients with breast cancer.

Methods  According to the response evaluation criteria in solid tumors guidelines, the largest unidimensional measurement of the tumor diameter evaluated by PE, US, and MRI before and after NAC was classified into four grades, including clinical complete response, clinical partial response, clinical progressive disease, clinical stable disease, and compared with the final histopathological examination.

Results  Of the 64 patients who received NAC, the pathologic complete response (pCR) was shown in 13 of 64 patients (20%). The sensitivity of PE, US, and MRI in predicting the major pathologic response was 73%, 75%, and 80%, respectively, and the specificity was 45%, 50%, and 50% respectively. For predicting a pCR, the sensitivity of PE, US, and MRI was 46%, 46%, and 39%, respectively, and the specificity was 65%, 98%, and 92% respectively.

Conclusions  Compared with final pathologic findings, all these three clinical and imaging modalities tended to obviously underestimate the pCR rate. A more appropriate, universal, and practical standard by clinical and imaging modalities in predicting the response to neo-adjuvant chemotherapy in vivo is essential.

     

Inhibition of Bcl-2 enhances the efficacy of epirubicin chemotherapy in PC-3 prostate cancer cells

Background  Overexpression of Bcl-2 protein in cancer cells can inhibit programmed cell death and engender chemoresistance. Bcl-2 antisense oligonucleotide (G3139) has shown its antitumor effects enhanced in preclinical models when combined with taxol-based chemotherapy. This study aimed to investigate the efficacy of G3139 combined with epirubicin in the androgen-independent prostate cancer.

Methods  PC3 prostate cancer cell line was cultured and treated with epirubicin and Bcl-2 antisense oligonucleotide alone or in combination. The effects of therapeutic agents on cells were determined by the MTT assay. Expression of Bcl-2 mRNA and protein was documented by RT-PCR and Western blotting. Apoptosis induction was confirmed by flow cytometric analysis.

Results  Bcl-2 antisense oligonucleotide alone produced no cytotoxic effects and the combination of Bcl-2 antisense oligonucleotide with epirubicin sensitized PC-3 cells to the killing effects of chemotherapy. A marked down-regulation of Bcl-2 mRNA and protein was observed after antisense and epirubicin cotreatment. A statistically significantly higher fraction of apoptotic cells was detected by flow-cytometric analysis after epirubicin treatment with prior antisense Bcl-2 transfenction, as compared with mono antisense Bcl-2 or epirubicin treatment.

Conclusion  These data suggested that inhibition of Bcl-2 expression combined with epirubicin may be an attractive therapeutic strategy in hormone-refractory prostate cancer.

     

Transitional cell carcinoma associated with aristolochic acid nephropathy: most common cancer in chronic hemodialysis patients in China

Background  The research of cancer in patients on hemodialysis (HD) in China has not been reported. The aim of this study was to investigate the clinical and histological features and outcomes of cancer in Chinese HD patients.

Methods  The study subjects were 49 cancer patients (1.4%) out of 3448 end stage renal disease (ESRD) patients maintained on HD at China-Japan Friendship Hospital from October 1997 to July 2011.

Results  Urinary tract cancer (74%) was the most common followed by gastrointestinal tract cancer (12%), breast cancer (6%), lung cancer (4%), thyroid cancer (2%), and hematologic cancer (2%). Thirty-three patients (67%) had urinary tract transitional cell carcinoma (TCC) and 29 of them had aristolochic acid nephropathy (AAN) as underlying disease. Death occurred in eight patients out of 49, and the survival rate of HD patients with cancer was similar to those without cancer (P=0.120).

Conclusion  The urinary tract TCC is the most common cancer in HD patients with AAN in one of the centers of northern China.

     

Primary stromal cells isolated from human various histological/pathological prostate have different phenotypes and tumor promotion role

Background  Prostate stromal cells are known to regulate epithelial growth as well as support and maintain epithelial function. However, how stromal cells regulate epithelial cells and what differences among various histological/pathological prostate stromal cells in prostate cancer progression still remain unclear. This study aimed to investigate the different phenotypes of human various histological/pathological prostate stromal cells, and their role in tumor promotion.

Methods  The different phenotypes of the human normal prostatic peripheral zonal primary stromal cells (NPPF), transitional zonal primary stromal cells (NPTF), and prostate cancer associated primary stromal cells (CAF) were examined with growth curves and Annexin V-fluorescein isothiocyanate (FITC) assay. The different effects on prostate cancer cell line C4-2B by NPPF, NPTF, and CAF were examined with MTT assay and Annexin V-FITC assay. The gene expression of different histological/pathological prostate stromal cells was profiled by microarray and hierarchical cluster analysis.

Results  The growth rate of NPPF, NPTF and CAF gradually increased, followed by decreasing apoptosis. In vitro stromal-C4-2B cell line co-culture models, the proliferation and apoptosis of C4-2B cell line were differently affected by human various histological/pathological prostate stromal cells. CAF showed the most powerful effect to C4-2B cell line, as opposed to a weakest effect of NPTF. Microarray and hierarchical cluster analysis showed that the differentially expressed genes of CAF and NPPF were less than NPPF and NPTF, or CAF and NPTF. This was consistent with clinical observations that prostate cancer mostly derived from the peripheral zone and does not usually occur in the transitional zone.

Conclusion  NPPF, NPTF and CAF possess extremely different biological characteristics and gene expression, which may play an important role in genesis and development of prostate cancer.

     

Roles of eEF-2 kinase in cancer

Objective  To provide a summary of the relationship between the eEF-2/eEF-2 kinase pathway and each phase of malignant neoplasms. The specific importance of this relationship in understanding and treating cancer was also explored.

Data sources  The data used in this review were mainly obtained from the articles listed in HighWire and PubMed in English. The search terms were “eEF-2 kinase”, “oncogenesis”, and “tumor progression”. 

Study selection  This review relates the observation that the overexpression of eEF-2 kinase is seen in cancer, and highlights that it has emerged as promoting the development of many malignant phenotypes when unregulated. This includes increasing the replicative potential of cells, angiogenesis, invasion and metastasis, and evasion of apoptosis. 

Results  eEF-2 kinase is a structurally and functionally unique protein kinase. The increased activity of this protein in cancer cells is a protective mechanism to allow tumor growth and evolution, and resist cell death through the eEF-2/eEF-2 kinase pathway, but it also makes a potential target for therapy.

Conclusion  eEF-2 kinase fills critical niches in the life of a cancer cell and the eEF-2/eEF-2 kinase pathway is a key biochemical sensor.

     

Differential proteome analysis of conditioned medium of BPH-1 and LNCaP cells

Background  Although the introduction of serum prostate-specific antigen (PSA) measurements into clinical practice has revolutionized the care of patients with prostate cancer, there are well-recognized limitations of PSA, and there is a critical need to identify additional prostate cancer biomarkers to assist in early detection and prognosis. In this regard, high resolution proteomic technology has the unexceptionable superiority to find those high abundance biomarkers. The purpose of this study was to search new tumor markers by proteomic technology.

Methods  The proteins in conditioned medium (CM) of BPH-1 and LNCaP cells were profiled by two-dimensional electrophoresis and identified by matrix-assisted laser desorption ionization mass spectrometry (MALDI-TOF-MS). The corresponding mRNA levels of some identified proteins were analyzed by RT-PCR.

Results  Totally 11 differentially expressed proteins (6 up-regulated including creatine kinase, brain (CKB), triosephosphate isomerase 1 (TPI1), isocitrate dehydrogenase 2 (IDH2) and 5 down-regulated including glutathione S-transferase pi (GST-pi)) in the CM were identified using MALDI-TOF-MS and database search. The expression pattern between mRNA and CM protein levels of CKB, IDH2, TPI1 and GST-pi in BPH-1 and LNCaP was similar.

Conclusion  We proved a feasible and effective way to search new tumor markers by a proteomics-based strategy and identified 11 potentially useful proteins in CM of BPH-1 and LNCaP cells to distinguish prostate cancer from benign prostatic hypertrophy.

     

Does urothelial cancer of bladder behave differently in young patients?

Background  Bladder urothelial cancer has been diagnosed at an increasing rate among young adults in China while the clinical outcomes remain highly controversial. To optimize the management of young patients with bladder cancer, we examined whether bladder urothelial cancer in young patients behaved differently from that in the elder patients.

Methods  From 1994 to 2008, a database of bladder urothelial cancer patients at a major tertiary medical center was retrospectively reviewed. The clinical and pathological parameters of patients who were less than 40 years of age and a series of patients older than 40 years of age as the control group during the same period were compared. A survival analysis was performed using the Kaplan–Meier method and log-rank test, and Cox regression was performed to identify clinical parameters that affected the clinic outcomes.

Results  Young bladder cancer patients had a lower male-to-female ratio and were less likely to have advanced stages and high-grade cancers at the initial diagnosis. Tumors in young bladder cancer patients tended to be less multifocal at diagnosis. In addition, young patients had a lower recurrence rate and longer recurrence interval than older patients. The Kaplan-Meier curve and Log-rank test showed that young patients had significantly better cancer specific survival than old patients. The univariate and multivariate Cox regression analysis revealed that tumor grade is the sole predictor for tumor recurrence in young patients.

Conclusions  Young patients with bladder cancer have favorable pathological features and clinical outcomes than older patients. These findings argue for more conservative management approaches for young patients with bladder cancer.

     

Resveratrol Induces Apoptosis in Pancreatic cancer cells

Background  Pancreatic cancer is one of the most lethal human cancers with a very low survival rate of 5 years. Conventional cancer treatments including surgery, radiation, chemotherapy or combinations of these show little effect on this disease. Several proteins have been proved critical to the development and the progression of pancreatic cancer. The aim of this study was to investigate the effect of resveratrol on apoptosis in pancreatic cancer cells.

Methods  Several pancreatic cancer cell lines were screened by resveratrol, and its toxicity was tested by normal pancreatic cells. Western blotting was then performed to analyze the molecular mechanism of resveratrol induced apoptosis of pancreatic cancer cell lines.

Results  In the screened pancreatic cancer cell lines, capan-2 and colo357 showed high sensitivity to resveratrol induced apoptosis. Resveratrol exhibited insignificant toxicity to normal pancreatic cells. In resveratrol sensitive cells, capan-2 and colo357, the activation of caspase-3 was detected and showed significant caspase-3 activation upon resveratrol treatment; p53 and p21 were also detected up-regulated upon resveratrol treatment.

Conclusion  Resveratrol provides a promising anti-tumor stratagy to fight against pancreatic cancer.

     

Distribution of wall shear stress in carotid plaques using

Background  Wall shear stress is an important factor in the destabilization of atherosclerotic plaques. The purpose of this study was to assess the distribution of wall shear stress in advanced carotid plaques using high resolution magnetic resonance imaging and computational fluid dynamics.

Methods  Eight diseased internal carotid arteries in seven patients were evaluated. High resolution magnetic resonance imaging was used to visualize the plaque structures, and the mechanic stress in the plaque was obtained by combining vascular imaging post-processing with computational fluid dynamics.

Results  Wall shear stresses in the plaques in all cases were higher than those in control group. Maximal shear stresses in the plaques were observed at the top of plaque hills, as well as the shoulders of the plaques. Among them, the maximal shear stress in the ruptured plaque was observed in the rupture location in three cases and at the shoulder of fibrous cap in two cases. The maximal shear stress was also seen at the region of calcification, in thrombus region and in the thickest region of plaque in the other three cases, respectively.

Conclusion  Determination of maximal shear stress at the plaque may be useful for predicting the rupture location of the plaque and may play an important role in assessing plaque vulnerability.

     

Role of co-expression of c-Myc, EZH2 and p27 in prognosis of prostate cancer patients after surgery

Background  c-Myc, EZH2 and p27 were defined to modulate the behavior of prostate cancer with pro-tumoral or anti-tumoral effects and had ability in predicting prostate cancer progression, but the research of their co-expression value of prognosis is rarely. This study aimed to investigate the prognostic value of combining tri-marker together in patients with intermediate-risk prostate cancer after surgery.

Methods  Expression levels of c-Myc, EZH2 and p27 in 129 patients with intermediate-risk prostate cancer were assessed using immunohistochemistry in a semi-quantitative manner. The expression profiles of these three markers were analyzed and investigated for association with biochemical recurrence.

Results  In all, fifty of 129 cases experienced biochemical recurrence during a median follow-up time of 31 months (range, 6–60 months). Of these relapse patients, one case without and 10 cases with any single positive marker were observed; 39 cases were detected with any two or all three positive markers (22 cases with any two and 17 cases with all three positive markers). Survival analysis showed that patients with over-expression of c-Myc or EZH2, and lower expression of p27 manifested significantly higher biochemical recurrence rates. Subsequent multivariate analysis revealed that c-Myc, EZH2 and p27 expression statuses showed potential in predicting relapse, respectively. Notably, combining three markers together as a ‘‘composite index’’ (0 or 1, vs. 2 or 3 positive markers) provided powerful prognostic value (HR 6.57, 95% CI 3.02–14.31, P <0.001). There was a significant difference between the patient subgroups with 0 or 1 and those with 2 or 3 positive markers expression statuses, and tri-marker composite index was an independent risk factor for predicting relapse in patients with intermediate-risk prostate cancer after surgery.

Conclusion  Composite index of c-Myc, EZH2, and p27 can be valued as powerful prognosis parameter for intermediate-risk prostate cancer patients after the surgery, and postoperative adjuvant therapy can be adopted accordingly.

     

Influence of dental restorative material properties on bond interface reliability: a finite element analysis

 

Background  Varieties of restorative materials are widely used in dentistry. The aim of this study is to explore the influence of different dental restorative materials on bond interface reliability.

Methods  A two-dimensional finite element analysis method was adopted to simulate the shear-bond efficacy test. The influence of elastic modulus and Poisson’s ratio were investigated separately. Several dental restorative materials including resins, metals, and ceramics were analyzed in this study.

Results  The deformation and peak equivalent stress level of the dentin-adhesive interface rose sharply following a decrease in the elasticity of restorative materials, especially those with a low elastic modulus range. The influence of the Poisson’s coefficient was not significant. Ceramics and gold alloy were preferred to resin composite in restorations bearing extensive shear load during service.

Conclusions  Restorative materials with an elastic modulus similar to that of teeth are not always the best clinical choice. This research provides a helpful guide for the application of different restorative materials in clinical practice.

     

Expression of nucleophosmin in glandular epithelium of non-pregnant human endometrium during the menstrual cycle

Background  Nucleophosmin plays a critical role in embryonic development. This study aimed to examine the expression pattern of nucleophosmin in glandular epithelium of human endometrium during the menstrual cycle.

Methods  Endometrial tissues used for this study were obtained from 46 non-pregnant patients who underwent hysterectomy which had been performed to treat benign diseases. Nucleophosmin expression was assessed by in situ hybridization and immunohistochemistry.

Results  At the early-, mid- and late-proliferative phase, nucleophosmin mRNA was highly expressed in glandular epithelium of human endometrium. At the secretory phase, the expression of nucleophosmin mRNA was reduced in glandular epithelium in early-secretory phase, and the expression in mid- and late-secretory phases was not detected. Similarly, nucleophosmin protein was strongly expressed in endometrial glands throughout the proliferative phase, but was gradually reduced during secretory phase.

Conclusion  Nucleophosmin mRNA and protein are expressed in glandular epithelium of human endometrium throughout the menstrual cycle.

     

Inhibitory effect of 2′-o-methoxyethyl-modified antisense oligonucleotides targeting vascular endothelial growth factor A on SKOV3 human ovarian cancer cells

Background  Ovarian cancers are often at an advanced stage at diagnosis because early detection is difficult. The poor prognosis of ovarian cancers highlights the crucial need to develop better therapeutic agents and strategies. The objective of this study was to investigate the inhibitory effects of a new modified antisense oligonucleotides targeting vascular endothelial growth factor A (VEGF-A) in SKOV3 ovarian cancer cells.

Methods  Antisense oligonucleotides targeting VEGF-A was designed, synthesized and transfected into SKOV3 ovarian cancer cells. Western blotting and real-time RT-PCR were used to analyze the inhibitory effects of antisense oligonucleotides on VEGF-A protein and mRNA expression. Transwell matrix assay was used to detect cell migration inhibition.

Results  The antisense oligonucleotides targeting VEGF-A significantly decreased VEGF-A protein and mRNA expression and inhibited cell migration in SKOV3 ovarian cancer cells.

Conclusions  This new modified antisense oligonucleotides targeting VEGF-A can decrease VEGF-A expression and inhibit cell migration in SKOV3 ovarian cancer cells. This new oligonucleotides may be a promising therapeutic agent for ovarian cancers.

     

Is the European System for Cardiac Operative Risk Evaluation useful in Chinese patients undergoing heart valve surgery?

Background  The European System for Cardiac Operative Risk Evaluation (EuroSCORE) is one of the most widely used risk models for the predicting mortality after cardiac surgery. The aim of this study was to validate the EuroSCORE model for predicting operative mortality in heart valve surgery on a Chinese multicenter database and comparing the performance of EuroSCORE with our new risk stratification system, the Sino System for Coronary Operative Risk Evaluation (SinoSCORE).

Methods  Data from patients undergoing heart valve surgery between January 2007 and December 2008 were retrospectively collected, from 43 hospitals in China. The EuroSCORE and the SinoSCORE were calculated for each patient. Mortality was defined as any in-hospital death. Area under the receiver operating characteristics curve (AUC) was used to study the discriminatory abilities of the models. The Hosmer-Lemeshow (H-L) goodness-of-fit test was used to study the calibration of the predictive models.

Results  A total of 15 367 patients were analyzed. For the entire cohort, the observed mortality was 2.34%, the predicted mortality was 3.71% (additive), 3.19% (logistic) and 3.66% (SinoSCORE). AUC was 0.747 for SinoSCORE, 0.699 additive and 0.696 for logistic EuroSCORE. Calibration of SinoSCORE and additive EuroSCORE was good (H-L: P=0.250 and P=0.051, respectively), but the logistic EuroSCORE model had a poor calibration (H-L: P<0.05). The discriminatory ability and calibration of the SinoSCORE were good in low- and high-risk patients. However, the discriminatory ability of the EuroSCORE model was poor in all risk deciles.

Conclusions  The EuroSCORE does not accurately predict mortality in Chinese patients with heart valve surgery, and the SinoSCORE is superior to the EuroSCORE at predicting in-hospital mortality in Chinese heart valve surgery patients.

     

Specific regulator of eosinophil apoptosis: Siglec-8—new hope for bronchial asthma treatment

Objective  It is known that Siglec-8 is selectively expressed on human eosinophils at a high level and mediates eosinophil apoptosis when crosslinked with its antibody. The aim of our review is to elucidate the molecular and biological characteristic of Siglec-8 and then discuss the function and possible mechanisms of Siglec-8 in eosinophils. Thereby, we will expand our understanding to the regulation of eosinophil apoptosis, and provide important clues to the treatment of asthma and other hyper-eosinophilic diseases.

Data sources  Most articles were identified by searching of PubMed online resources using the key term Siglecs.

Study selection  Mainly original milestone articles and critical reviews written by major pioneer investigators in the field were selected.

Results  Siglec-8 is selectively expressed on human eosinophil and can specifically induce eosinophil apoptosis.

Conclusion  The restricted expression of Siglec-8 on human eosinophil and the rapid progress in understanding its role as cell signaling and activation of death receptors have made it an attractive target for treatment of asthma and other hyper-eosinophilic diseases.

     

Changes in serum levels of soluble osteoclast-associated receptor in human rheumatoid arthritis

Background  Osteoclast-associated receptor (OSCAR) is a member of the newly identified leukocyte receptor complex, and has recently been described as a key molecule in osteoclastogenesis. In this study, we measured the levels of soluble osteoclast-associated receptor (sOSCAR) in the serum of rheumatoid arthritis (RA) patients and healthy controls to examine whether sOSCAR may play a role in the process of inflammatory arthritis.

Methods  Enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of sOSCAR in the serum of 40 healthy controls and 40 RA patients.

Results  The serum levels of sOSCAR were significantly lower in RA patients than in healthy controls, and were inversely associated with inflammatory activity.

Conclusion  sOSCAR is decreased in patients with RA and reduced levels of the protein are associated with increased inflammatory response.

     

Astrocyte elevated gene-1 induces breast cancer proliferation and invasion through upregulating HER2/neu expression

Background  Astrocyte elevated gene-1 (AEG-1), primarily identified as a late response gene induced by HIV-1 infection, plays multiple roles in the process of oncogenesis. This novel gene has been demonstrated to be involved in the several potent carcinogenic pathways, including PI3K/Akt pathway, nuclear factor (NF)-κB pathway, and Wnt/β-catenin pathway. Although the function of AEG-1 has been intensively investigated in recent years, the molecular mechanism underlying its oncogenic role is largely unknown. The aim of this research was to explore the potential function of AEG-1 in breast cancer development and progression.

Methods  AEG-1 was ectopically overexpressed in breast cancer MCF-7 cells and its biological effects on the proliferation and invasion of MCF-7 cells were studied by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and invasion assays. The expression of HER2/neu, a crucial oncogene involving in breast cancer carcinogenesis, was also determined.

Results  Overexpression of the AEG-1 promoted the proliferation and invasion ability of breast cancer cells, and upregulated the expression of HER2/neu, a crucial oncogene involving in breast cancer carcinogenesis.

Conclusion  AEG-1 might facilitate the proliferation and invasion of breast cancer cells by upregulating HER2/neu expression, which provides a potential target for breast cancer therapy.