Evaluation of whether serum tumor markers in patients with epithelial ovarian carcinoma change following chemotherapy

Background  Phenotypic and genotypic heterogeneity is a known feature of many cancers. Whether serum tumor marker kinds vary and change following chemotherapy is still unclear. The aim of this study was to investigate whether there is a change in the expression of serum tumor markers following chemotherapy, and the potential clinical significance in patients with epithelial ovarian carcinoma (EOC) or primary serous peritoneal carcinoma (PSPC).

Methods  Samples were collected before surgery, during chemotherapy and during follow-up for enzyme-linked immunosorbent assay (ELISA)-based evaluation of serum CA-125, CA19-9 and CP2 levels in patients with EOC or PSPC who had received primary debulking surgery followed by adjuvant chemotherapy. In total, 72 patients were examined, including 37 patients with recurrent lesions and 35 patients receiving first-line chemotherapy.

Results  In 35 de novo patients, 20% (7/35) demonstrated a significant changed serum tumor marker kinds among whom the patients with mucinous carcinoma (57.1%, 4/7) showed resistance to chemotherapy. In the 37 recurrent patients, 51.4% (19/37) had changed serum tumor markers, of whom 57.9% (11/19) presented with serous carcinoma. There was no significant difference in median progression-free survival or overall survival in patients with drug-sensitive or drug-resistant recurrence in patients with changed tumor marker kinds relative to those with unchanged markers. However, for patients with changed serum tumor markers there was a trend towards prolonged survival compared with the unchanged serum tumor marker group. In the 17 patients with secondary recurrence, 37.5% (6/17) had changed tumor marker levels. The ratios of CA-125/CP2 and CA-125/CA19-9 were significantly different after either chemotherapy or recurrence.

Conclusions  Serum tumor marker expression in patients with EOC or PSPC may change after chemotherapy or recurrence, indicating that in addition to the markers that are abnormal before surgery, those markers that are normal should also be monitored during chemotherapy and follow-up.

     

HLA-DR expression on regulatory T cells is closely associated with the global immune activation in HIV-1 infected subjects naïve to antiretroviral therapy

Background  The frequencies of regulatory T cells (Tregs) increased over the HIV infection but its counts actually decreased. We proposed that the decrease of Treg counts may cause the reduction of inhibitory effect and thereby account for the over-activation of Tregs during HIV infection. However, it remains unknown whether Tregs are also over-activated and thereafter the activation induced death may lead to the decrease of Tregs.

Methods  Tregs were defined as CD4⁺CD25⁺CD127^lo/- T cells. Eighty-one HIV-1 infected patients were enrolled in our study, and twenty-two HIV-1 seronegative donors were recruited as the control. The levels of HLA-DR on Tregs were determined by FACSAria flow cytometer.

Results  Compared to HIV-1 seronegative donors, the levels of HLA-DR on CD4⁺CD25⁺CD127^lo/- Tregs were significantly increased in HIV-1 infected patients, and its increase was positively associated with viral loads (r=0.3163, P=0.004) and negatively with CD4 T-cell counts (r=−0.4153, P <0.0001). In addition, significant associations between HLA-DR expression on CD4⁺CD25⁺CD127^lo/- Tregs and the percentages of HLA-DR, CD38, Ki67 expressing CD4⁺ and CD8⁺ T cells were also identified.

Conclusion  HLA-DR on Tregs is a good marker for viral replication and disease progression. The over-activation of Tregs might result in the decrease of Tregs.

     

Perioperative and late outcomes of laparoscopic fundoplication for neurologically impaired children with gastro-esophageal

Background  Persistent gastro-esophageal reflux (GER) due to various pathological factors often results in overt clinical symptoms and signs, which is termed as gastro-esophageal reflux disease (GERD). Affected children usually present with failure to thrive, recurrent pneumonia or apnea. Many neurologically impaired children have symptoms related to GERD. Although laparoscopic fundoplication has been established to be an effective treatment modality for children with GERD, data on its role and long-term efficacy for neurologically impaired patients remain sparse. The aim of this study was to review the results of such patients who underwent laparoscopic fundoplication.

Methods  A retrospective review was performed from 1998 to 2009. All children with neurological impairment who had laparoscopic fundoplication were included.

Results  Fifty-nine GERD patients (male=32, female=27; mean age 6 years) were identified. All subjects showed symptoms of frequent emesis; 32 of them had history of hematemesis (54.2%); 54 had feeding difficulty; 35 (59.3%) had associated respiratory symptoms, including recurrent pneumonia. Gastrostomy was performed concurrently in 39 cases. There was no conversion to open procedure nor was there intra-operative complications and operative mortality. Emesis or hematemesis was controlled adequately in all. However, respiratory symptoms were not controlled in 10 patients (16.9%), and five of them required further respiratory assistance including nasal airway tube and tracheostomy. Clinical recurrence of GERD was not observed in any subject. Twelve patients died during follow-up (range from 3 months to 9 years) due to severe respiratory complications, cardiac arrest, and brain tumor.

Conclusions  Laparoscopic fundoplication is an excellent procedure for controlling clinically significant symptoms in neurological impaired patients with GERD. Further studies are required to assess the improvement of the quality of life in such patients.

     

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.

     

Impact of multidisciplinary team working on the management of colorectal cancer

Background  The continual and rapid development of techniques which are used for diagnosis and treatment makes management of colorectal cancer more difficult depending on single discipline. Colorectal cancer multidisciplinary team (MDT) working model is recommended by UK and other countries, but there is little information on the impact of MDT working on management of colorectal cancer in China. The aim of this study was to assess the effect on management of colorectal cancer after the inception of an MDT.

Methods  A total of 595 consecutive colorectal cancer patients were referred to the Department of Gastroenterological Surgery, the pre-MDT cohort include 297 patients, recruited from January 1999 to November 2002, and the MDT cohort had 298 patients enrolled from December 2002 to September 2006. Information recorded included: TNM stage from histological reports, degree of differentiation, the number of examined lymph nodes and CT TNM staging performed or not, and its accuracy, including local and distant recurrence.

Results  The number of examined lymph nodes and the accuracy of TNM staging by CT in the MDT group were significantly more than those in pre-MDT group. CT TNM staging was more accurate in the MDT group compared to the pre-MDT group (P=0.044). The rate of tumor recurrence in the MDT group was lower than pre-MDT group (log-rank test, P <0.001). Multivariate analysis revealed that age (P=0.001), management after inception of the MDT (P=0.002), degree of differentiation (P=0.003), number of examined lymph nodes (P=0.002), and TNM stage (P=0.000) were important factors that independently influence overall survival.

Conclusions  The inception of MDT working improved the diagnostic accuracy and overall survival of colorectal cancer patients. MDT working promoted communication and cooperation between disciplines and ensured high-quality diagnosis, evidence-based decision making, and optimal treatment planning.

     

Proteomic analysis for detecting serum biomarkers related to smoking in humans

Background  Smoking is the leading cause of death in the world. This study focused on the difference of the serum proteomic profiling between healthy smokers and nonsmokers in order to find smoking-specific serum biomarkers.

Methods  Pattern-based proteomic profiling of 100 serum samples (from 50 Chinese male smokers and 50 matched nonsmokers) was performed through magnetic bead fractionation coupled with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis (MALDI-TOF-MS) and resulting data were statistically analyzed by Ciphergen ProteinChip software 3.0.2.

Results  We found 72 serum peaks were significantly different between smokers and nonsmokers (P <0.05). Marker peaks of mass-to-charge ratio (m/z) 3159.13, 7561.03 and 9407.32 were smoking-specific.

Conclusion  The preliminary data suggested that smoking-specific serum biomarkers could be detected in humans.

     

Immature CD4+ dendritic cells conditioned with donor kidney antigen prolong renal allograft survival in rats

Background  Allogeneic transplant rejection is currently a major problem encountered during organ transplantation. The dendritic cell (DC) is the most effective powerful known professional antigen-presenting cell, and recent studies have found that DCs can also induce immune tolerance, and avoid or reduce the degree of transplant rejection. The aim of this study was to evaluate the effect of transfused immature CD4⁺ DCs on renal allografts in the rat model.

Methods  In this study, we induced CD4⁺ immature DCs from rat bone marrow cells by a cytokine cocktail. The immature CD4⁺ DCs were identified by morphological analysis and then the suppressive activity of these cells conditioned with donor kidney antigen was evaluated in vitro and in vivo.

Results  Immature CD4⁺ DCs conditioned with donor kidney antigen possessed immunosuppressive activity in vitro and they were able to prolong renal transplant survival in an allograft rat model in vivo.

Conclusions  Our study provides new information on efficacious renal transplantation, which might be useful for understanding the function of immature CD4⁺ DCs in modulating renal transplant rejection and improving clinical outcome in future studies.

     

Effect of peritumoral injection of boanmycin hydrochloride within temperature-sensitive in situ gel using Hep-G2 hepatoma nude mice model

Background  Boanmycin hydrochloride, a new antitumor agent, has a short half-life and fast clearance speed in vivo. The aim of this research was to investigate the effectiveness of peritumor injection of boanmycin hydrochloride within temperature-sensitive gel in situ using Hep-G2 hepatoma nude mice model.

Methods  Nude mice with human Hep-G2 tumor in right flank were randomly divided into four groups: normal saline group, in situ gel only group, boanmycin hydrochloride in situ saline group, and boanmycin hydrochloride in situ gel group, and were treated with injection of corresponding agents into peripheral tissue of the tumor. The volume of the tumor and the body weight of the mice were regularly measured, and tumor growth curve was generated. The size, internal echo, and blood flow of the tumors were observed by color Doppler ultrasonography. Histopathologic changes of the tumor after treatment were observed under both optical and transmission electron microscopy.

Results  The tumor growth was significantly inhibited by peritumoral therapy in boanmycin hydrochloride in situ gel group with the tumor inhibitory rate of 86.76%. The blood flow of the tumor was still seen in both normal saline group and in situ gel only group on color Doppler ultrasound. Punctate calcification and dotted blood flow were seen in boanmycin hydrochloride group; however, there was massive calcification and no blood flow in the tumor in the boanmycin hydrochloride in situ gel group. Large areas of necrosis and apoptotic cells were shown by microscopic observation in boanmycin hydrochloride in situ gel group.

Conclusion  Temperature-sensitive boanmycin hydrochloride in situ gel can effectively delay the release of boanmycin hydrochloride and increase its anticancer effects for liver cancer in animal model.

     

Correlation between dynamic contrast-enhanced MRI and histopathology in the measurement of tumor and breast volume and their ratio in breast cancer patients: a prospective study

Background  Earlier studies have examined the association between the diameter of primary tumors measured by magnetic resonance imaging (MRI) and histopathology in breast cancer patients. However, the diameter does not completely describe the dimensions of the breast tumor or its volumetric proportion relative to the whole breast. The association between breast tumor volume/breast volume ratios measured by these two techniques has not been reported.

Methods  Seventy-three patients were recruited from female patients with primary breast tumors admitted to our center between January and December 2010. They were divided into two groups. Group A (n=46) underwent modified radical mastectomy (MRM), and Group B (n=27) underwent preoperative neoadjuvant chemotherapy before MRM. They were examined by dynamic-contrast enhanced MRI (DCE-MRI) to measure breast volumes (BVs), tumor volumes (TVs), and tumor volume/breast volume ratios (TV/BV). These measurements were compared with histopathology results after MRM, and the associations between MRI and pathology were analyzed by linear regression and Bland-Altman analysis.

Results   For Group A, the correlation coefficients for BVs, TVs, and TV/BV ratios measured by the two techniques were 0.938, 0.921, and 0.897 (all P <0.001), respectively. For Group B, the correlation coefficients for BVs, TVs, and TV/BV ratios were 0.936, 0.902, and 0.869 (all P <0.01), respectively. The results suggest statistically significant correlations between these parameters measured by the two techniques for both groups.

Conclusion  For these patients, BVs, TVs, and TV/BV ratios measured by DCE-MRI significantly correlated with those determined by histopathology.

     

An Asian population-based survival analysis of patients with distal esophageal and gastric cardia adenocarcinomas

Background  Gastroesophageal junction adenocarcinomas include adenocarcinomas of the distal esophagus (DE) and gastric cardia (GC). It is controversial whether these tumors are the same entity and whether they have the same survival rates. Patients with DE and GC adenocarcinomas have a similar survival rate in the US; however, data are lacking in Asian countries. Therefore, we conducted a retrospective study to understand the implications of the tumor location in the survival of Asian patients.

Methods  A total of 209 patients with pathologically confirmed DE and GC adenocarcinomas, from 2005 to 2007, were included in the study. We identified patients with adenocarcinomas of the DE (DE group, n=91) and GC (GC group) (n=118). We performed an unadjusted survival analysis using the Kaplan-Meier method, and used a Cox proportional hazards regression model to adjust for potential confounding covariates.

Results  We found no significant difference between the overall survival of the DE and GC groups. The 3-year survival rates were 44.8% and 53.0%, respectively, and the 5-year survival rates were 27.9% and 30.2%, respectively (P=0.162). We found no significant difference in early staging, advanced staging, different T staging, and different N staging, between the groups. Both advanced post-operative N staging and advanced AJCC staging had a significant adverse effect on survival.

Conclusions  Patients with DE and GC adenocarcinomas have similar survival rates in the Asian population. Both post-operative N staging and AJCC staging are prognostic factors.

     

创伤骨科患者创伤严重程度和血浆D二聚体水平的相关分析

Background  The correlation between the plasma D-dimer level and deep vein thrombosis has not been conclusive in various studies. The aim of this research was to study the relationship between plasma D-dimer levels and the severity of orthopedic trauma by retrospective examination of orthopedic trauma cases.

Methods  Clinically acute trauma and non-acute trauma patients were selected and their plasma D-dimer levels were measured. Plasma D-dimer levels in patients of these two groups were compared. The relationship between the plasma D-dimer level and the severity of the trauma was also studied.

Results  There were 548 cases in the acute trauma group and 501 cases in the non-acute trauma group. The levels of plasma D-dimer were significantly higher in the acute trauma group than in the non-acute trauma group (P <0.01). In the acute trauma group, the correlation between the D-dimer level and the number of fractures was a positive linear correlation (r=0.9532).

Conclusions  Elevated plasma D-dimer is common in trauma patients. The D-dimer level and the number of fractures in the trauma patients are closely correlated. D-dimer is not only an indicator for the diagnosis of deep vein thrombosis and pulmonary embolus, but also an indicator of the severity of trauma in acute trauma patients.

     

Endothelial progenitor cell down-regulation in a mouse model of Kawasaki disease

Background  Cardiovascular complications of Kawasaki disease (KD) are a common cause of heart disease in pediatric populations. Previous studies have suggested a role for endothelial progenitor cells (EPCs) in coronary artery lesions associated with KD. However, long-term observations of EPCs during the natural progression of this disorder are lacking. Using an experimental model of KD, we aimed to determine whether the coronary artery lesions are associated with down-regulation of EPCs.

Methods  To induce KD, C57BL/6 mice were administered an intraperitoneal injection of Lactobacillus casei cell wall extract (LCWE; phosphate buffered saline used as control vehicle). Study groups included: group A (14 days following LCWE injection), group B (56 days following LCWE injection) and group C (controls). Numbers of circulating EPCs (positively staining for both CD34 and Flk-1 while staining negative for CD45) were evaluated using flow cytometry. Bone marrow mononuclear cells were cultured in vitro to expand EPCs for functional analysis. In vitro EPC proliferation, adhesion and migration were assessed.

Results  The model was shown to exhibit similar coronary artery lesions to KD patients with coronary aneurysms. Numbers of circulating EPCs decreased significantly in the KD models (groups A and B) compared to controls ((0.017±0.008)% vs. (0.028±0.007)%, P <0.05 and (0.016±0.007)% vs. (0.028±0.007)%, P <0.05). Proliferative, adhesive and migratory properties of EPCs were markedly impaired in groups A and B.

Conclusion  Coronary artery lesions in KD occur as a consequence of impaired vascular injury repair, resulting from excess consumption of EPCs together with a functional impairment of bone marrow EPCs and their precursors.

     

Increased expression of serum gelsolin in patients with osteosarcoma.

Background  Identification of potential serum biomarkers of osteosarcoma to aid in its early diagnosis and in the discovery of possible therapeutic targets is an area of increasing interest.

Methods  Two-dimensional difference-in-gel electrophoresis was used to assess multiple serum samples in patients with osteosarcoma. In addition, differential expression of protein biomarkers was characterized in osteosarcoma serum by using matrix-assisted desorption/ionization time-of-flight mass spectrometry coupled with database interrogation. Serum samples from four individuals with osteosarcoma and four age- and sex-matched healthy control subjects were compared.

Results  Fifty-eight significant protein spot features in the osteosarcoma sera were found. These spot features were excised, digested with trypsin, and analyzed with mass spectrometry. Gelsolin was down-regulated only in osteosarcoma. Furthermore, Western blotting and enzyme linked immunosorbent assay (ELISA) confirmed decreased levels of gelsolin in the osteosarcoma serum samples.

Conclusions  These results indicated that gelsolin might have great potential as a biomarker of osteosarcoma and as a potential target for gene therapy.

     

Epicardial radiofrequency ablation for left ventricular aneurysm related ventricular arrhythmias during off-pump coronary artery bypass surgery

Background  Left ventricular aneurysm (LVA) is one of the serious complications after acute myocardial infarction. We attempted to evaluate the preliminary efficacy of LVA repair combined with epicardial radiofrequency ablation for ventricular arrhythmia during off-pump coronary artery bypass grafting (OPCAB).

Methods  From June 2009 to April 2011, 31 patients with LVA had angina symptoms and ventricular arrhythmia. In all patients, circular and cross-shaped radiofrequency epicardial ablations were performed using unipolar ablation pen along the border between the aneurysm wall and normal cardiac tissue and in the central zone of the aneurysms, followed by a linear placation of ventricular aneurysms on beating heart.

Results  All the patients showed complete recovery. The average number of grafted vessels was 2.7±1.3. Intraoperative examinations revealed that the ventricular arrhythmia was effectively controlled by radiofrequency ablation. All cases had been followed up for one year. Holter monitoring revealed a significant reduction in ventricular arrhythmias (P <0.05). Echocardiography showed significant increase in left ventricular ejection fraction (P <0.05) and decrease in left ventricular end-diastolic diameter (P <0.05).

Conclusions  For patients with ventricular aneurysm and preoperative malignant arrhythmia, aneurysm repair plus epicardial radiofrequency ablation in OPCAB was found to be an effective and feasible therapeutic technique. However, medium- to long-term therapeutic efficacy of this method remains to be determined by future studies and observations.

     

非肿瘤细胞凋亡引起肿瘤机体血清细胞色素C增高

Background  Neuroblastoma (NB) is one of the most common malignant solid tumors of childhood. It is still not clear whether the apoptosis of tumor cells or the non-tumor cells contributes to the increase of concentration of cytochrome c (Cyt c) in the serum of the cancer patients. The aim of this research was to identify the source of the Cyt c in the serum when the tumor grows up by subcutaneous inoculation of human NB cells into nude mice.

Methods  We subcutaneously inoculated human NB cells (KP-N-NS) into nude mice and collected the sera of tumor-bearing mice (n=14) and control mice (n=25) 4 weeks later in order to screen for and identify differentially expressed proteins in the serum. Differentially expressed proteins in the serum were screened by surface-enhanced laser desorption/ionization-time-of-flight (SELDI-TOF) mass spectrometry.

Results  The relative intensity of a protein having a mass-to-charge ratio (m/z) of 11 609 was 3338.37±3410.85 in the tumor group and 59.84±40.74 in the control group, indicating that the expression level of this protein in the tumor group was 55.8 times higher than that in the control group. Serum proteins were separated and purified by high-performance liquid chromatography (HPLC). Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) was performed to produce peptide mass fingerprints (PMFs). Spectrum analysis and a database search revealed that the highly expressed protein (m/z=11 605.4) from the serum of tumor-bearing mice was the mouse Cyt c.

Conclusions  Increased concentration of Cyt c in the serum of tumor-bearing nude mice might be partially attributed to the secretion of this protein by non-tumor cells.

     

Reversal of multidrug resistance in renal cell carcinoma by short hairpin RNA targeting MDR1 gene

Background  Over-expression of P-glycoprotein (P-gp), encoded by the MDR1 gene, confers multidrug resistance (MDR) in renal cell carcinoma (RCC) and is a major reason for unsuccessful chemotherapy. This study aimed to determine the effct of RNA interference (RNAi) on the reversal of MDR in human RCC.

Methods  We designed and selected one short hairpin RNA (shRNA) targeting MDR1 gene, which is stably expressed from integrated plasmid and transfected by lentivirus fluid in human RCC A498 cell.

Results  The MDR1-targeted RNAi resulted in decreased MDR1 gene mRNA level (P <0.001), almost abolished P-gp expression and reversed MDR to different chemotherapy drugs in the RCC A498 cell line.

Conclusion  MDR could be reversed by RNAi in human RCC A498 cell line, which may be used for clinical application in future.

     

Gene delivery in peritoneal dialysis related peritoneal fibrosis research

Objective  To summarize the development of gene delivery vectors in peritoneal fibrosis research and discuss the feasibility and superiority of lentiviral vectors.

Data sources  The data in this article were collected from PubMed database with relevant English articles published from 1995 to 2011.

Study selection  Articles regarding the gene therapy in peritoneal fibrosis research using non-viral vectors, adenoviral vectors, retroviral vectors, and lentiviral vectors were selected. Data were mainly extracted from 60 articles, which are listed in the reference section of this review.

Results  Non-viral vector-mediated gene delivery (including naked DNA for ex vivo, oligonucleotides, ultrasound- contrast agent mediated naked gene delivery, etc.) and viral vector-mediated gene delivery (including adenovirus, helper-dependant adenovirus, and retrovirus vectors) have been successfully applied both in the mechanistic investigation and the potential prevention and treatment of peritoneal fibrosis.

Conclusions  Peritoneal fibrosis is a major complication of peritoneal dialysis (PD). Recently, the wide use of the gene delivery technique made it possible to access and further research peritoneal fibrosis. The use of lentiviral vector is expected to be widely used in PD research in the future due to its advantages in gene delivery.

     

Association of NFATc1 gene polymorphism with ventricular septal defect in the Chinese Han population

Background Congenital heart disease (CHD) is a diverse group of diseases determined by genetic and environmental factors.Considerable research has been done on genes associated with the development of ...     

Long-pulse Nd:YAG 1064-nm laser treatment for onychomycosis

Background  Recent research shows that lasers can inhibit fungal growth and that Nd:YAG 1064-nm lasers can penetrate as deep as the lower nail plate. The aim of this study was to observe the effect of a long-pulse Nd:YAG 1064-nm laser on 154 nails of 33 patients with clinically and mycologically proven onychomycosis.

Methods  Thirty-three patients with 154 nails affected by onychomycosis were randomly assigned to two groups, with the 154 nails divided into three sub-groups (II degree, III degree, and IV degree) according to the Scoring Clinical Index of Onychomycosis. The 15 patients (78 nails) in group 1 were given eight sessions with a one-week interval, and the 18 patients (76 nails) in group 2 were given four sessions with a one-week interval.

Results  In group 1, the effective rates at 8 weeks, 16 weeks, and 24 weeks were 63%, 62%, and 51%, respectively, and the effective rates in group 2 were 68%, 67%, and 53% respectively. The treatment effect was not significantly different between any sub-group pair (P >0.05).

Conclusions  Long pulse Nd:YAG 1064-nm laser was effective for onychomycosis. It is a simple and effective method without significant complications or side effects and is expected to become an alternative or replacement therapy for onychomycosis.