Geological significance of new zircon U-Pb geochronology and geochemistry: Niuxinshan intrusive complex, northern North China Craton.

The Huajian gold deposit is one of the largest hydrothermal intrusion-related gold deposits in eastern Hebei Province, located in the northern margin of the North China Craton (NCC). The mineralization in this district displays a close spatial association with the shoshonitic Niuxinshan intrusive complex (NIC), which contributes to the characterization of the metallogeny associated with convergent margin magmatism. In the current study, new geochronological and geochemical data are combined with previously published isotopic data, obtained from the granitic rocks in the NIC, to constrain the timing of the district's tectonic setting transformation and determine its bearing on regional metallogeny. The new geochronological data constrain the timing of the tectonic transformation between 155 and 185 Ma. The NIC's granitic rocks can be geochemically subdivided into two groups. One group's geochemical signature exhibits steep rare earth element (REE) patterns with negligible Eu anomalies, lower Yb, higher Sr, and negative Nb-Ta-Ti (NTT) anomalies, which indicate a volcanic-arc environment with a thickened crust in a convergent setting. The other group exhibits flat REE patterns with obvious negative Eu anomalies, higher Yb, lower Sr, and weak NTT anomalies, which indicate an intra-plate extensional environment with a thinning crust. Combining geochronologic and isotopic data, the mineralization is Late Jurassic (~155 Ma). This is interpreted to be genetically related to the crystallization of the shallow crustal-sourced portions of this complex. Additionally, a tectonic model is presented that provides a plausible explanation for the abundant polymetallic mineralization that occurs in the northern margin of the NCC after 155 Ma.

A novel self-assembled pH-sensitive targeted nanoparticle platform based on antibody-4arm-polyethylene glycol-pterostilbene conjugates for co-delivery of anticancer drugs.

Recently, antibody-drug conjugates (ADC) have shown potential for cancer immunotherapy by tumor-targeted delivery of anticancer drugs. However, the development of ADC is subject to many restrictions, such as the payloads, stabilities and intracellular uptake of the drugs, which has greatly restricted their clinical application. To overcome these hurdles, in this study, a novel pH-sensitive targeted nanoparticle platform based on a newly synthesized amphipathic antibody-drug conjugate (antibody-4arm-polyethylene glycol-pterostilbene, mAb-4arm-PEG-PS) was fabricated for co-delivery of another anticancer drug (10-hydroxy camptothecin, HCPT). The prepared mAb-4arm-PEG-PS/HCPT nanoparticles (NPs) had a moderate particle size (∼120 nm), a high drug to antibody ratio (∼22.4) and relatively high binary drug loading capacity (∼24.2 wt% HCPT, ∼2.9 wt% PS). Moreover, the mAb-4arm-PEG-PS/HCPT NPs exhibited enhanced intracellular uptake (∼5 fold that of mAb-4arm-PEG-PS conjugates) and excellent cytotoxicity in vitro. In subsequent Daudi lymphoma xenograft assays, compared with free drugs and mAb-4arm-PEG-PS conjugates, the mAb-4arm-PEG-PS/HCPT NPs inhibited tumor growth more efficiently. Our results indicated the great potential of mAb-4arm-PEG-PS/HCPT NPs for targeted co-delivery of anticancer drugs to solid tumors.

Self-Assembled pH and Redox Dual Responsive Carboxymethylcellulose-Based Polymeric Nanoparticles for Efficient Anticancer Drug Codelivery.

To face the growing demand of polymeric nanoparticles with biocompatibility and a drug release profile, in this work, a novel carboxymethylcellulose-based pH and redox dual-responsive polymeric nanoparticle, carboxymethyl cellulose-dithiopropionate hydrazide-8arm-polyethylene glycol-pterostilbene/10-hydroxy camptothecin (CTPP/HCPT), was prepared for efficient drug codelivery. These well-dispersed CTPP/HCPT NPs were prepared with a dimension of around 144 nm and exhibited high binary drug loading capacity and good biocompatibility. The biggest advantage of this design is that these nanoparticles can rapidly release the drug payload responding to intracellular acidic or reductive stimuli, while maintaining sufficient stability under normal physiological conditions. The in vitro drug release study revealed that the HCPT payload released from nanoparticles in a weakly acidic environment with 10 mM reductive glutathione was about 74.8%, which was 3.8-fold higher than under normal physiological conditions (∼19.6%). Further in vitro and in vivo investigation demonstrated that such dual-responsive CTPP/HCPT NPs could potently kill cancer cells and suppress tumor growth with lower adverse effects. All these results suggested that CTPP/HCPT NPs were suitable as potential and effective candidates for cancer therapy.

[Expression of VEGFR-2 and VEGFR-3 in papillary renal cell carcinoma and their relationship with prognosis].

OBJECTIVE: To detect the expression of VEGF receptors in papillary renal cell carcinoma and to explore the correlation between their expression and clinical prognosis. METHODS: Expression of VEGF receptors and PCNA (proliferating cell nuclear antigen) were evaluated in 82 patients with papillary renal cell carcinoma using tissue microarray and SP immunohistochemical staining. RESULTS: The expression of VEGFR-1 in papillary renal cell carcinoma was 82.93%, VEGFR-2 63.41%, VEGFR-3 34.15% and PCNA 67.07%, respectively. Increased VEGFR-2 expression was significantly correlated with tumor size (P = 0.016), histological grade (P = 0.034) and distant metastasis (P = 0.002). VEGFR-3 expression was correlated with histological grade (P = 0.028), lymph node status (P = 0.010) and distant metastasis (P = 0.018), but not correlated with gender, age, location, tumor size and TNM staging. VEGFR-1 expression had no correlation with any clinic and pathologic factors. PCNA expression was correlated with histological grade (P = 0.011), but not correlated with other factors. The expression of VEGFR-2 and VEGFR-3 in death cases were higher than that in surviving patients. CONCLUSION: Both VEGFR-2 and VEGFR-3 can serve as markers for prognosis of papillary renal cell carcinoma. Differently, VEGFR-3 is a predictor of lymph node metastasis, increased VEGFR-2 expression could be used to predict a potential blood dissemination.

[Non-clear cell renal carcinoma: comparative analysis of the new and old histological classification in 79 cases].

OBJECTIVE: To compare the old classification and 2004 WHO histological classification of renal cell carcinoma, summarize the differences and possible reasons, and correct the traditional pathological concepts of kidney cancer. METHODS: Specimens of 79 cases histopathologically diagnosed as non-clear cell renal cell carcinomas after radical nephrectomy during 1998 to 2005 in Tianjin Medical University Cancer Hospital were reclassified according to the 2004 WHO renal cell carcinoma histological classification system. RESULTS: After reclassification, there were 14 cases of clear cell renal cell carcinoma (CCRCC), 23 cases of papillary renal cell carcinoma (PRCC), 34 cases of chromophobe renal cell carcinoma (ChRCC), one collecting duct renal cell carcinoma, one unclassified renal cell carcinoma, 5 cases of mixed cell renal cell carcinoma (CCRCC + PRCC 2 cases, CCRCC + ChRCC 2 cases, PRCC + ChRCC 1 case), and one oncocytoma diagnosed. CONCLUSIONS: Some chromophobe renal cell carcinomas and papillary renal cell carcinomas were easier to be diagnosed as granular cell renal cell carcinoma in the past. The eosinophilic cytoplasm similar to that in the granular cells, and some confusion between PRCC and ChRCC are the main reasons. The cellular characteristic features of granular renal cell carcinoma can be found in many types of renal tumors. Granular cell renal cell carcinoma is not an independent entity, therefore, it should be removed from the histological classification of renal cell carcinoma. The diagnosis standard of mixed renal cell carcinoma (MRCC) need to be determined and consummated.

[Correlation of microvascular density and clinicopathological factors in different subtypes of renal cell carcinoma].

OBJECTIVE: The aim of this study was to evaluate the expressions of CD34, CD31 and microvessel density (MVD) in different subtypes of renal cell carcinoma (RCC) as well as the relationship between MVD and clinicopathological factors. METHODS: Expressions of CD31 and CD34 were detected in 149 patients with RCC using SP immunohistochemical staining. The MVD was studied by Weidner's method. RESULTS: The expressions of CD31 and CD34 in the clear cell renal cell carcinoma (CCRCC) (98.35 +/- 55.05, 128.04 +/- 46.44) were significantly higher than those in chromophobe renal cell carcinoma (ChRCC) (30.70 +/- 17.72, 48.55 +/- 14.09) and papillary renal cell carcinoma (PRCC) (21.60 +/- 9.38, 38.12 +/- 10.98) (P < 0.01). The MVD value marked by CD31 (30.70 +/- 17.72, 21.60 +/- 9.38) was much lower than that marked by CD34 (48.55 +/- 14.09, 38.12 +/- 10.98) between ChRCC and PRCC (P < 0.01). Smaller and immatured microvessels and even single endothelial cells could be clearly seen. The MVD values marked by CD31 and CD34 were negatively correlated with the pathological grades (r(CD34) = -0.618, P < 0.01; r(CD31) = -0.442, P < 0.01) and clinical stages (r(CD34) = -0.283, P < 0.05; r(CD31) = -0.256, P < 0.05) in CCRCC. But no association was found in non-CCRCC (P > 0.05). CONCLUSION: MVD is significantly correlated with different types of endothelial labeling. The microvascular endothelial cells could be shown clearly by its related antigen labeling such as CD34 and CD31. CD34 is more sensitive than CD31. The MVD of CCRCC is significantly higher than that in non-CCRCC. The expressions of CD31 and CD34 are not correlated with tumor grade and stage in ChRCC and PRCC, while there is a negative correlation in CCRCC.

Different sites and prognoses of gastrointestinal stromal tumors of the stomach: report of 187 cases.

BACKGROUND: The stomach is the most common site of gastrointestinal stromal tumors (GISTs), but the clinical behavior of gastric GISTs at different sites is unclear. This study was designed to evaluate the clinicopathological (CP) parameters and influence of different gastric sites on outcome in patients with GIST. METHODS: The CP and follow-up records of 187 patients with GIST who were treated at TianJin Medical University Cancer Institute & Hospital between January 1985 and December 2006 were reviewed. There were 97 men and 90 women (aged 17-88 (median, 56.5) years). CP factors were assessed for overall survival (OS) by using univariate and multivariate analysis. RESULTS: The numbers of cases of upper, middle, and lower third gastric GISTs were 69 (36.9%), 103 (55.1%), and 15 (8%), respectively. Sites of GISTs in the middle or upper stomach, tumor size, intermediate- or high-risk groups, high mitotic count, and low resection status were associated with poor OS (p = 0.041, 0.046, 0.006, 0.000, 0.000, respectively) in a univariate analysis. In a multivariate analysis, tumor location in the upper and middle third of the stomach (p = 0.035), an intermediate or high risk (p = 0.01), and incomplete resection status (p = 0.006) were predictive of poor OS. CONCLUSIONS: Patients in intermediate- and high-risk groups had an unfavorable outcome. A complete resection is the most important treatment for survival. The location of GIST in the lower third of the stomach may be a favorable factor, and the significance of different tumor sites for prognosis of gastric GISTs needs to be further clarified.

Synchronous infiltrating ductal carcinoma and primary extramedullary plasmacytoma of the breast.

BACKGROUND: Extramedullary plasmacytomas are seldom solitary and usually progress to diffuse myelomatosis. Plasmacytomas of the breast are rare, especially when not associated multiple myeloma. Synchronous infiltrating ductal carcinoma and primary extramedullary plasmacytoma of the breast have not previously reported. CASE PRESENTATION: A 27-years-old woman with an untreated upper outer quadrant breast mass for 1-year was referred to our cancer hospital for surgical evaluation of increasing breast pain. Postoperatively, microscopic examination revealed an infiltrating ductal carcinoma complicated by an extramedullary plasmacytoma divided by fibrous tissue in one section. Following surgery, the patient received chemotherapy for the carcinoma and radiotherapy for the plasmacytoma. CONCLUSION: In this case, careful histopathology examination was essential to make the correct diagnosis and therapy for these synchronous lesions. The patient finished chemotherapy and radiotherapy without significant adverse effects.

[Diagnostic value of SYT-SSX fusion gene detection by fluorescence in-situ hybridization for synovial sarcoma].

OBJECTIVE: To establish a method of SYT-SSX fusion gene detection by FISH and to explore its diagnostic value for synovial sarcoma. METHODS: The presence of SYT-SSX fusion gene was determined by FISH using a tissue microarray containing 62 known synovial sarcomas, 60 non-synovial sarcomas and 133 equivocal synovial sarcomas. FISH results were compared with those of RT-PCR published previously. RESULTS: Overall, 96.9% (247/255) of the cases were successfully analyzed by FISH. The sensitivity of FISH for known synovial sarcomas was 96.7% (58/60), and the specificity for the non-synovial sarcoma was 100% (59/59). Moreover, SYT-SSX gene fusion was detected in 78.1% (100/128) of the equivocal synovial sarcomas. The concordance rate between FISH and RT-PCR was 83.6% (102/122) in those equivocal synovial sarcomas, and overall 79.7% (106/133) of these cases were confirmed as synovial sarcomas either by RT-PCR or by FISH. CONCLUSIONS: The sensitivity and specificity of FISH detection of SYT-SSX fusion gene are high. FISH and RT-PCR are complementary to each other in the confirmation of synovial sarcomas, particularly those questionable cases.

[Relationship between the expression of matrix metalloproteinase-13 protein and other biomarkers, prognosis in invasive breast cancer].

OBJECTIVE: The study was designed to investigate the expression patterns of metalloproteinase (MMP)-13 protein in invasive breast carcinoma and to determine the clinicopathological and prognostic values of its various localization and relation to the tumor phenotypes. METHODS: Immunohistochemistry was performed on paraffin-embedded tissue array from 263 invasive breast carcinomas to investigate the protein expressions of MMP-13, estrogen receptor, progesterone receptor, HER2, MMP-2, MMP-9 and tissue inhibitor of matrix metalloproteinases (TIMP)-1, TIMP-2. RESULTS: MMP-13 protein was detected in the cytoplasm of carcinoma cells and peritumoral fibroblasts. High level expression of MMP-13 protein in tumor cells was associated with more lymph node involvement and higher tumor grade (both P < 0.01), and positively correlated with HER2 (P = 0.015) and TIMP-1 protein (P < 0.01) expression in carcinoma cells. Moreover, high expression of MMP-13 was associated with shortened overall survival for the entire patient population and the patient group with positive lymph node. Tumor cell derived MMP-13 had different impact on patients with different HER2 status. Peritumoral fibroblasts derived MMP-13 protein, although correlated with tumor cell derived MMP-13 and associated with lymph node stage and HER2 expression, was found having less prognostic impact. Univariate survival analysis showed that the tumor size, grade, lymph node status, PR status, HER2 expression, tumors TIMP-1 and MMP-13 expression were prognostic factors. However, multivariate survival analysis showed that only tumor size, lymph node status, HER2 expression, tumors TIMP-1 and MMP-13 were independent prognostic factors. CONCLUSION: MMP-13 protein expressed by tumor cells correlates with the invasion and metastasis of breast carcinoma, and therefore, may serve as a poor prognostic marker for the patient.

[Correlation between matrix metalloproteinases-2 and tissue inhibitor of metalloproteinase-2 expression, metastatic potential and tumor angiogenesis in synovial sarcoma and its prognostic significance].

OBJECTIVE: To study the expression of matrix metalloproteinases (MMP)-2 and tissue inhibitor of metalloproteinase (TIMP)-2 in tumor cells of synovial sarcoma and its clinical significance. METHODS: Expression of MMP-2 and TIMP-2 in tumor cells of 72 cases of synovial sarcoma was studied by immunohistochemistry. The profile was correlated with clinicopathologic parameters, microvessel density (MVD) (analyzed by CD31 immunostaining) and survival rate. RESULTS: (1) There was a statistically significant negative correlation between expression of MMP-2 and TIMP-2 (r = -0.290 and P = 0.013). (2) The proportion of high MMP-2 expression to low TIMP-2 expression in patients with tumor metastasis was significantly higher than that in patients without metastasis (P = 0.010 and 0.002 respectively). (3) MVD of patients with high MMP-2 expression was higher than that in the low MMP-2 expression group (P = 0.005). MVD of patients with high TIMP-2 expression was lower than that in the low TIMP-2 expression group (P = 0.048). (4) Low TIMP-2 expression significantly correlated with poor prognosis of patients with synovial sarcoma, by univariate and multivariate survival analysis (P = 0.002 and 0.016 respectively). CONCLUSIONS: Expression of MMP-2 and TIMP-2 correlates with metastatic potential and tumor angiogenesis in synovial sarcoma. Low TIMP-2 expression often indicates poor prognosis and unfavorable clinical outcomes.

Preparation and analysis of cSNP chip on hepatocellular carcinoma-related genes.

BACKGROUND: The understanding of cSNPs of cancer-related genes harboring in high frequency loss regions of tumor chromosomes can advance the disclosure of genetic and variant mechanisms of tumorigenesis, and the investigation of cancer susceptibility. In preparing a gene chip for detecting polymorphisms on coding region of genes in hepatocellular carcinoma tissues, some cSNPs are of interest for their potential links with phenotype. METHODS: The genes harboring in loss regions with high frequency of hepatocellular carcinoma (HCC) were selected, the related information of cSNP sequences was obtained from the SNP database (dbSNP) of the National Center for Biotechnology Information (NCBI). Then appropriate primers and oligonucleotide probes were designed according to the SNP sites, and a gene chip for the detection of SNPs was constructed. The chip included 48 cSNPs of 25 hepatocellular carcinoma-related genes. The PCR products labeled by Dig-dUTP were hybridized with the cSNP chip. RESULTS: The sensitivity, influence by probe concentration, and reiteration of the chip were detected, with a high sensitivity of 6X10(-3) ng/mul. The signal of hybridization was reduced with a lower concentration of probe. Seven polymorphisms of caspase 9 (rs2308941)C-->T and DOK2(rs2242241) T-->G, 6 of polymorphisms of EGFL3 (rs947345)A -->G, caspase 9 ( rs2308938) C-->G and PHGDH(rs1801955)T-->A, 5 of polymorphisms of E2F2(rs3218170) G-->A,4 of polymorphisms of MUTYH(rs1140507)T-->C and BNIP3L(rs1055806)G-->T, and 1 of polymorphism of TNFRSF1B (rs1061622)T-->G were detected by the chip in the tissues of 10 HCC. Samples of caspase 9 (rs2308941G) and (rs2308941A) were verified by PCR-SSCP and sequencing. CONCLUSION: The cSNP chip of hepatocellular carcinoma-related genes can accelerate the discovery of polymorphic markers on hepatocellular carcinoma.

[Expressions and significance of E-cadherin and beta-catenin in synovial sarcoma].

OBJECTIVE: To explore the expression and significance of E-cadherin (E-cad) and beta-catenin (beta-cat) in synovial sarcoma. METHODS: Expression of E-cad and beta-cat in 72 cases of synovial sarcoma were detected by tissue microarray technique and immunohistochemistry. The relationships between E-cad and beta-cat expression and clinicopathological data and survival rate were analyzed. RESULTS: (1) 95.1% of dots on the tissue microarrays were observable morphologically. The background was clear and the contrast was vivid after immunohistochemistry. (2) The expression of E-cad was reduced in 56 patients (77.8%) and that of beta-cat was reduced in 51 patients (70.8%). (3) In patients with synovial sarcoma of monophasic fibrous type, grade III, and in patients with recurrence or metastasis, CK-negative and EMA-negative the rates of reduced expression of E-cad and beta-cat were significantly higher than those with primary sarcoma of biphasic type, grade II, CK-positive and EMA positive (P < 0.05 for all). (4) The survival of synovial sarcoma patients with E-cad and beta-cat expressions preserved was significantly better than those with reduced expressions (P = 0.012, P = 0.047). CONCLUSION: The expression of E-cad and beta-cat is correlated with cell differentiation. Reduced expression of E-cad and beta-cat may indicate a high potential of recurrence or metastasis and poor prognosis. Tissue microarray technique is applicable for retrospective studies of large sample size.

Expression of e-cadherin and beta-catenin in human esophageal squamous cell carcinoma: relationships with prognosis.

AIM: To elucidate the expression of E-cadherin and beta-catenin correlating with its clinical outcome in patients with esophageal squamous cell carcinoma (ESCC), by analyzing their interrelationship with clinicopathological variables and their effects on progress and prognosis. METHODS: Expression of E-cadherin and beta-catenin was determined by SP immunohistochemical technique in patients with ESCC consecutively, their correlation with clinical characteristics was evaluated and analyzed by multivariate analysis. RESULTS: The rate of expression of E-cadherin decreased to 66.03 % (70/106) in ESCC and the protein level was negative correlated with histologic grade, tumor size, clinical staging, lymph node metastasis and venous invasion. Whereas the expression rate of beta-catenin was reduced to 69.8 % (74/106) and the level of protein expression correlated only with histologic grade. There obviously existed inverse correlation between level of E-cadherin protein and survival, especially in stage I, IIa, IIb (P=0.0033), Patients with low-expressing tumors for beta-catenin and non-expressing tumors for E-cadherin/beta-catenin had lower survival period than those with normal-expressing ones (P=0.0501 and P=0.0080, respectively). Patients with diminished expression of E-cadherin as grade II or III had shorter survival period than those with normally expressing and grade I, no significance existed between grade I and grade II or III with respect to different status of E-cadherin expression. Furthermore, Correlation analysis showed level of E-cadherin correlated with that of beta-catenin (P=0.005). Cox proportional hazards model analysis suggested downregulation of E-cadherin was an important factor indicating poor prognosis. CONCLUSION: As a probable independent prognostic factor, it correlates with overall and disease free survival period, expression of E-cadherin but not beta-catenin may predict prognosis in patients with ESCC.