Exploring the molecular characteristics of the malignant potential of gastric adenocarcinoma with enteroblastic differentiation.

AIMS: Gastric adenocarcinoma with enteroblastic differentiation (GAED) is a rare subset of alpha-fetoprotein (AFP)-producing carcinomas with poor prognosis. However, the molecular features associated with the malignant potential of GEAD remain partially elucidated. METHODS AND RESULTS: In this study, the relationship between clinicopathological parameters and aggressive biological behaviour was analysed in 37 patients with GAED. The results showed that GAED tended to infiltrate the deep layer of the gastric wall and possessed more frequent vascular invasion than conventional gastric adenocarcinoma (CGA) (P < 0.001). All distant metastases were observed in the GAED group, not the CGA group (P < 0.001). High HER2 expression was found in nearly 24.32% of the informative cases, and none showed EBV-encoded RNA positivity or deficient mismatch repair. The most frequently mutated gene in GAED was p53. Programmed cell death-ligand 1 (PD-L1) immunostaining revealed 13 patients with a combined positive score (CPS) ≥ 5 (65%, 13 of 20). Thus, based on these molecular markers (immunostaining, in situ hybridisation and mutation analysis), GAED may be classified as a unique subgroup of the chromosomal instability subtype with HER2+ /EBV- /MSS/TP53+ /PD-L1+ . Next-generation sequencing analyses showed that mutations in the TOPI, ELOA and NOTCH3 genes were found only in GAED, and abnormally expressed genes in GAED were significantly enriched in hepatocellular carcinoma-, gland development-, and gastric cancer-related pathways. CONCLUSION: The HER2+ /EBV- /MSS/TP53+ /PD-L1+ profile and hepatocellular carcinoma-related pathways may be significant in the malignant potential of GAED. In addition to anti-HER2 therapy, immune check-point inhibitors may be an effective treatment option for patients with GAED.

Sustainable nano-pesticide platform based on Pyrethrins II for prevention and control Monochamus alternatus.

BACKGROUND: Pine wilt disease as a devastating forest disaster result from Bursaphelenchus xylophilus that spread by stem-borers Monochamus alternatus feeding on pine leaves, which has brought inestimable economic losses to the world's forestry due to lack of effective prevention and control measures. In this paper, we put forward a proposal for utilizing nanoHKUST-1 to encapusulate the Pyrethrins II that a nerve agent extracted from plant to control M. alternatus, including toxicity mechanism research, traceable biopesticide monitoring, and environment assessment for the first time. The highly biocompatible nanoHKUST-1 can solve the problems of poor water solubility, easy degradation and low control efficiency of Pyrethrins II. RESULTS: The results illustrated the biopesticide loading efficiency of PthII@HKUST-1 reached 85% and the cumulative release of pH-dependent PthII@HKUST-1 was up to 15 days (90%), and also effectively avoid photodegradation (pH 7.0, retention 60.9%). 50 nm PthII@HKUST-1 made it easily penetrate the body wall of MA larvae and transmit to tissue cells through contact and diffusion. Moreover, PthII@HKUST-1 can effectively enhance the cytotoxicity and utilization of Pyrethrins II, which will provide valuable research value for the application of typical plant-derived nerve agents in the prevention and control of forestry pests. PthII@HKUST-1 as an environmentally friendly nano-pesticide can efficiently deliver Pyrethrins II to the larval intestines and absorbed by the larvae. PthII@HKUST-1 could also be transmitted to the epidemic wood and dead wood at a low concentration (10 mg/L). CONCLUSION: Here we speculate that nanoHKUST-1 will bring new opportunity to research biopesticide inhibition mechanism of different agricultural and forestry pests, which will break through the existing research limitations on development, utilization and traceable monitoring of biopesticide, especially for the study of targeting specific proteins.

Chromosomal and molecular pathway alterations in the neuroendocrine carcinoma and adenocarcinoma components of gastric mixed neuroendocrine-nonneuroendocrine neoplasm.

Gastric mixed adenoneuroendocrine carcinoma (MANEC) is a clinically aggressive subtype of mixed neuroendocrine-nonneuroendocrine neoplasm (MiNEN) with unclear clonal origin. In this study, we analyzed high-resolution copy number (CN) profiling data using the OncoScan CNV Assay in the neuroendocrine carcinoma (NEC) and adenocarcinoma components of eight MANECs. Some common CNVs, including the gain of CCNE1 (19q12) and the loss of FAT1 (4q35.2), were frequently detected in both components; these CNVs were verified by FISH, qPCR and immunohistochemistry staining assays in samples with sufficient material. The identification of common CNVs in both components supports the likelihood of single clonal origin of morphologically heterogeneous tumor cells and suggests several novel genetic events potentially involved in the development of gastric MANEC. We also detected and validated some CNVs and alterations specific for the NEC component, such as MAPK1 loss and MAPK signaling pathway alterations, which could contribute to the neuroendocrine differentiation of gastric MANEC. In addition, we found that the NEC component presented more CNVs and greater CN loss than the adenocarcinoma component (P = 0.007 and P = 0.004, respectively); the NEC components from different cases were not clustered in the hierarchical clustering analysis, indicating the marked genetic heterogenicity of the NEC component in gastric MANEC. In summary, this study describes the cytogenetic characteristics of each component of gastric MANEC, providing some clues for further studies on the development and progression of gastric MANEC as well as providing some potential therapeutic targets.

Self-assembled bovine serum albumin nanoparticles as pesticide delivery vectors for controlling trunk-boring pests.

BACKGROUND: Trunk-boring pests (TBPs) are an important type of forest pest, TBPs not only feed on the branches and trunks of trees, but also spread quarantine diseases in forests. However, because the larvae of TBPs live inside the trunk and are well concealed, prevention and control are difficult. The lack of effective control methods leads to the death of many trees in forests. In this study, a novel nanopesticide featuring high bioactivity and slow-release properties was developed to control TBPs. Thiacloprid (THI), which is commonly used to control Coleoptera species, was used as a model pesticide. RESULTS: The oleophobic properties of bovine serum albumin (BSA) were exploited to encapsulate the hydrophobic pesticide THI by self-assembly, and the size of the obtained nanoparticles, THI@BSA·NPs, was approximately 23 nm. The loading efficiency reached 70.4%, and THI@BSA·NPs could be released continuously for over 15 days, with the cumulative release reaching 93.5%. The fluorescein isothiocyanate (FITC)-labeled nanoparticles were evenly distributed in the digestive tract and body surface of a typical TBPs, M. alternatus, and the stomach and contact toxicities increased by 33.7% and 25.9%, respectively, compared with those of free THI. Furthermore, the results showed that the transport efficiency of THI@BSA·NPs was highest at a concentration of 50 µg/mL, and the THI@BSA·NPs content in the trunk, from to lower to higher layers, was 8.8, 8.2, 7.6, and 5.8 µg/g. At the same time, THI@BSA·NPs also exhibited high transport efficiency in dead trees. CONCLUSION: The transport efficiency and toxicity of the active ingredients are the key factors for the control of TBPs. This work provided idea for the application of biological delivery system encapsulated hydrophobic pesticides. The novel self-assembled THI@BSA·NPs have promising potential for sustainable control of TBPs.

Xp11 translocation renal cell carcinoma and clear cell renal cell carcinoma with TFE3 strong positive immunostaining: morphology, immunohistochemistry, and FISH analysis.

TFE3 is accepted as a good marker for the diagnosis of Xp11 translocation renal cell carcinoma. However, the significance of TFE3 in other types of renal cell carcinomas remains unclear. We examined the expression of TFE3 using immunohistochemistry by automated Ventana BenchMark XT system in 1818 consecutive renal cell carcinomas and verified the strong positive cases with TFE3 break-apart fluorescence in situ hybridization and RNA sequencing. Among the 27 renal cell carcinomas with TFE3 strong positive immunostaining, 20 cases were diagnosed as Xp11 translocation renal cell carcinoma, and seven cases were diagnosed as clear cell renal cell carcinoma. We further analyzed the morphology, clinicopathological features, and immunohistochemistry markers (CK7, CD117, CD10, P504s, vimentin, CA-IX, AE1/AE3, EMA, HMB45, Melan-A, and cathepsin K) of them. Pale to eosinophilic flocculent cytoplasm and psammomatous calcification were seen only in Xp11 translocation renal cell carcinomas (P < 0.05). Tumor necrosis occurred in all four cases of Xp11 translocation renal cell carcinomas with pT3a stage, which had local recurrence and distant metastasis (two of them died) within 3 years. The expressions of Vimentin, CA-IX, AE1/AE3, and EMA were significantly different between them (P < 0.05). CA-IX was diffusely strong positive in clear cell renal cell carcinomas but negative or focally mild positive in Xp11 translocation renal cell carcinomas. Our study first demonstrates that a very small minority (0.4%) of clear cell renal cell carcinomas with TFE3 strong positive immunostaining, which points out a potential pitfall in diagnosis of Xp11 translocation renal cell carcinomas by TFE3 immunohistochemistry. CA-IX is a good marker to distinguish clear cell renal cell carcinoma with TFE3 strong positive immunostaining from Xp11 translocation renal cell carcinoma. Tumor necrosis could be a potential factor relevant to pT3a stage, which may be a high-risk factor for the patients with Xp11 translocation renal cell carcinomas.

MIIP haploinsufficiency induces chromosomal instability and promotes tumour progression in colorectal cancer.

The gene encoding migration and invasion inhibitory protein (MIIP), located on 1p36.22, is a potential tumour suppressor gene in glioma. In this study, we aimed to explore the role and mechanism of action of MIIP in colorectal cancer (CRC). MIIP protein expression gradually decreased along the colorectal adenoma-carcinoma sequence and was negatively correlated with lymph node and distant metastasis in 526 colorectal tissue samples (p < 0.05 for all). Analysis of The Cancer Genome Atlas (TCGA) data showed that decreased MIIP expression was significantly associated with MIIP hemizygous deletion (p = 0.0005), which was detected in 27.7% (52/188) of CRC cases, and associated with lymph node and distant metastasis (p < 0.05 for both). We deleted one copy of the MIIP gene in HCT116 CRC cells using zinc finger nuclease technology and demonstrated that MIIP haploinsufficiency resulted in increased colony formation and cell migration and invasion, which was consistent with the results from siRNA-mediated MIIP knockdown in two CRC cell lines (p < 0.05 for all). Moreover, MIIP haploinsufficiency promoted CRC progression in vivo (p < 0.05). Genomic instability and spectral karyotyping assays demonstrated that MIIP haploinsufficiency induced chromosomal instability (CIN). Besides modulating the downstream proteins of APC/CCdc20 , securin and cyclin B1, MIIP haploinsufficiency inhibited topoisomerase II (Topo II) activity and induced chromosomal missegregation. Therefore, we report that MIIP is a novel potential tumour suppressor gene in CRC. Moreover, we characterized the MIIP gene as a novel CIN suppressor gene, through altering the stability of mitotic checkpoint proteins and disturbing Topo II activity. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

"One-Pot" Method Preparation of Dendritic Mesoporous Silica-Loaded Matrine Nanopesticide for Noninvasive Administration Control of Monochamus alternatus: The Vector Insect of Bursapherenchus xylophophilus.

Monochamus alternatus is an important stem-boring pest in forestry. However, the complex living environment of Monochamus alternatus creates a natural barrier to chemical control, resulting in a very limited control effect by traditional insecticidal pesticides. In this study, a stable pesticide dendritic mesoporous silica-loaded matrine nanopesticide (MAT@DMSNs) was designed by encapsulating the plant-derived pesticide matrine (MAT) in dendritic mesoporous silica nanoparticles (DMSNs). The results showed that MAT@DMSNs, sustainable nanobiopesticides with high drug loading capacity (80%) were successfully constructed. The release efficiency of DMSNs at alkaline pH was slightly higher than that at acidic pH, and the cumulative release rate of MAT was about 60% within 25 days. In addition, the study on the toxicity mechanism of MAT@DMSNs showed MAT@DMSNs were more effective than MAT and MAT (0.3% aqueous solutions) in touch and stomach toxicity, which might be closely related to their good dispersibility and permeability. Furthermore, MAT@DMSNs are also involved in water transport in trees, which can further transport the plant-derived insecticides to the target site and improve its insecticidal effect. Meanwhile, in addition, the use of essential oil bark penetrants in combination with MAT@DMSNs effectively avoids the physical damage to pines caused by traditional trunk injections and the development of new pests and diseases induced by the traditional trunk injection method, which provides a new idea for the application of biopesticides in the control of stem-boring pests in forestry.

Eosinophilic Solid and Cystic Renal Cell Carcinoma: Morphologic and Immunohistochemical Study of 18 Cases and Review of the Literature.

CONTEXT.­: Eosinophilic solid and cystic renal cell carcinoma is now defined in the 5th edition of the 2022 World Health Organization classification of urogenital tumors. OBJECTIVE.­: To perform morphologic, immunohistochemical, and preliminary genetic studies about this new entity in China for the purpose of understanding it better. DESIGN.­: The study includes 18 patients from a regional tertiary oncology center in northern China (Tianjin, China). We investigated the clinical and immunohistochemical features of these cases. RESULTS.­: The mean age of patients was 49.6 years and the male to female ratio was 11:7. Macroscopically, 1 case had the classic cystic and solid appearance whereas the others appeared purely solid. Microscopically, all 18 tumors shared similar solid and focal macrocystic or microcystic growth pattern, and the cells were characterized by voluminous and eosinophilic cytoplasm, along with coarse amphophilic stippling. Immunohistochemically, most of the tumors had a predominant cytokeratin (CK) 20-positive feature, ranging from focal cytoplasmic staining to diffuse membranous accentuation. Initially, we separated these cases into different immunohistochemical phenotypes. Group 1 (7 of 18; 38.5%) was characterized by positive phospho-4EBP1 and phospho-S6, which can imply hyperactive mechanistic target of rapamycin complex 1 (mTORC1) signaling. Group 2 (4 of 18; 23%) was negative for NF2, probably implying a germline mutation of NF2. Group 3 (7 of 18; 38.5%) consisted of the remaining cases. One case had metastatic spread and exhibited an aggressive clinical course, and we detected cyclin-dependent kinase inhibitor 2A (CDKN2A) mutation in this case; other patients were alive and without disease progression. CONCLUSIONS.­: Our research proposes that eosinophilic solid and cystic renal cell carcinoma exhibits prototypical pathologic features with CK20 positivity and has aggressive potential.

Design and Preparation of Avermectin Nanopesticide for Control and Prevention of Pine Wilt Disease.

Pine wilt disease is a devastating forest disaster caused by Bursaphelenchus xylophilus, which has brought inestimable economic losses to the world's forestry due to lack of effective prevention and control measures. In this paper, a porous structure CuBTC was designed to deliver avermectin (AM) and a control vector insect Japanese pine sawyer (JPS) of B. xylophilus, which can improve the biocompatibility, anti-photolysis and delivery efficacy of AM. The results illustrated the cumulative release of pH-dependent AM@CuBTC was up to 12 days (91.9%), and also effectively avoided photodegradation (pH 9.0, 120 h, retention 69.4%). From the traceable monitoring experiment, the AM@CuBTC easily penetrated the body wall of the JPS larvae and was transmitted to tissue cells though contact and diffusion. Furthermore, AM@CuBTC can effectively enhance the cytotoxicity and utilization of AM, which provides valuable research value for the application of typical plant-derived nerve agents in the prevention and control of forestry pests. AM@CuBTC as an environmentally friendly nanopesticide can efficiently deliver AM to the larval intestines where it is absorbed by the larvae. AM@CuBTC can be transmitted to the epidemic wood and dead wood at a low concentration (10 mg/L).

Self-Assembled Folic Acid-Targeted Pectin-Multi-Arm Polyethylene Glycol Nanoparticles for Tumor Intracellular Chemotherapy.

Ursolic acid is widely used as an effective anticancer drug for the treatment of various cancers. However, its poor water solubility, short circulation time in vivo, and lack of targeting have made it a burden for clinical applications. We report a self-assembled folate-modified pectin nanoparticle for loading ursolic acid (HCPT@F-Pt-PU NPs) and embed the anticancer drug hydroxycamptothecin to achieve synergistic treatment with ursolic acid. In addition, the galactose residue of the pectin molecule can be recognized by the asialoglycoprotein receptor on the surface of the liver cancer cell, promoting the rapid penetration and release of HCPT@F-Pt-PU NPs intracellularly. In particular, the introduction of multiarm polyethylene glycol can improve the uniformity (106 nm) and concealment of the nanoparticles and avoid the early release of the drug or the toxicity to normal cells. HCPT@F-Pt-PU NPs have a high drug loading (7.27 wt %) and embedding efficiency (19.84 wt %) and continuous circulation up to 80 h, leading to more apoptosis (91.61%). HCPT@F-Pt-PU NP intracellular drug delivery will be a promising strategy.

Enhanced Antiviral Ability by a Combination of Zidovudine and Short Hairpin RNA Targeting Avian Leukosis Virus.

Avian leukosis virus (ALV) causes tumor diseases in poultry and is circulating all over the world, leading to significant economic losses. In addition, mixed infection of ALV with other viruses is very common and is often reported to contaminate live vaccines. At present, there is no effective method to suppress the replication of ALV in vitro, so it is very difficult to remove it in mixed infection. As a retrovirus, the replication of ALV can be limited by reverse transcriptase (RT) inhibitors like zidovudine (AZT), but it also causes nontargeted cytotoxicity. To find the optimal solution in cytotoxicity and inhibition efficiency in vitro culture system, we firstly designed a combination therapy of AZT and short hairpin RNA (shRNA) targeting ALV and then verified its efficiency by multiple biological methods. Results showed that shRNA can effectively inhibit the expression of RT and then limit the replication of ALV. The combination of AZT and shRNA can significantly improve the antiviral efficiency in viral replication, shedding, and provirus assembly under the condition of low cytotoxicity. Overall, in this study, the combination therapy of AZT and shRNA targeting ALV showed excellent antiviral performance against ALV in vitro culture system. This method can be applied to multiple scenarios, such as the removal of ALV in mixed infection or the purification of contaminated vaccine strains.

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.

[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.

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.

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.

Amphiphilic carboxylated cellulose-g-poly(l-lactide) copolymer nanoparticles for oleanolic acid delivery.

Carboxylated cellulose nanocrystals (CCNs), as one of nanocellulose are promising hydrophilic biomass materials for drug delivery. In this work, a series of amphiphilic carboxylated cellulose-graft-Poly(L-lactide) (CC-g-PLLA) copolymers were synthesized via ring-opening polymerization (ROP) method. The copolymers were characterized by 1H-NMR, FT-IR, WXRD and TGA, and their solubility in organic solvents was improved. Then, these amphiphilic copolymers were self-assembled into nanoparticles for delivery of anticancer drug oleanolic acid (OA). The copolymer (DSPLLA 2.03) nanoparticles displayed the smallest size (196.82 ± 9.14 nm) and the highest drug loading efficiency (24.76 ± 0.58%). The nanoparticles exhibited a spherical shape, well water solubility of OA (16.9 mg/mL) and a prolonged drug release (120 h). In vitro and In vivo study indicated that the nanoparticles maintained cytotoxicity to 4T1 cells and MCF-7 cells and displayed high antitumor efficiency. The amphiphilic CC-g-PLLA copolymer nanoparticles provide a novel platform for drug delivery.

The diagnostic value of SYT-SSX detected by reverse transcriptase-polymerase chain reaction (RT-PCR) and fluorescence in situ hybridization (FISH) for synovial sarcoma: a review and prospective study of 255 cases.

This study aimed to evaluate the diagnostic value of SYT-SSX detected by reverse transcriptase-polymerase chain reaction (RT-PCR) and fluorescence in situ hybridization (FISH) for synovial sarcoma (SS) in known and potential cases. SYT-SSX was analyzed in formalin-fixed, paraffin-embedded tissues of 62 known SS, 60 non-SS and 133 potential SS by RT-PCR and FISH. FISH was mainly performed on a tissue microarray with some modifications. SYT-SSX was detected in 94.7% (54/57) of known SS and 70.5% (86/122) of potential SS by RT-PCR and in 96.7% (58/60) of known SS and 78.1% (100/128) of potential SS by FISH. Moreover, SYT-SSX was negative in 100% (58/58) of non-SS by RT-PCR and in 100% (59/59) of non-SS by FISH. Accordingly, SYT-SSX was detected in 106 potential SS by RT-PCR or FISH, including 80 cases manifested by both methods, 20 specimens verified only by FISH and 6 samples confirmed only by RT-PCR. Clinical findings and immunohistochemistry data were analyzed in potential SS with final molecular diagnosis. The positive ratio of cytokeratin (CK) and epithelial membrane antigen (EMA) in finally diagnosed SS was 51.9% (55/106) and 61.3% (65/106), respectively. Except EMA, clinical parameters (age, sex, tumor size, tumor sites) and other immunohistochemistry indexes (CK, S-100, neurone specific enolase (NSE), CD99, myoglobin, smooth muscle actin (SMA), cluster of differentiation (CD) 68 and mesothelial cell) had no significant difference between finally diagnosed SS and non-SS. It is indicated that the efficiency of FISH is comparable to or even higher than that of RT-PCR for SYT-SSX detection. The detection of SYT-SSX by RT-PCR or FISH is very useful for the final diagnosis of potential synovial sarcomas.

Role and mechanism of vasculogenic mimicry in gastrointestinal stromal tumors.

Vasculogenic mimicry (VM) is the formation of fluid-conducting channels by highly invasive and genetically dysregulated tumor cells. In this study, we collected specimens of 84 human gastrointestinal stromal tumors (GISTs) along with clinicopathologic data and another 42 GISTs with fresh tissue that was used for gelatin zymography. VM was found in 21 of the 84 GISTs using CD31/periodic acid-Schiff double staining and CD117 and CD31 immunohistochemical staining. There was a significant difference in the VM-positive rate between the lesions with a mitotic rate > or =5/50 high-power fields and those with a lower mitotic rate (P = .000) and between the cases with and without liver metastasis (P = .008). There was a significant difference in the VM-positive rate between the high-risk group (5.9%) and the very low/low-risk group (12.5%) (P = .010) or the intermediate-risk group (39.5%) (P = .020). Kaplan-Meier survival analysis showed VM indicated a poor prognosis (P = .0000). Cox proportional hazards model indicated that the presence of VM, tumor size 10 cm or greater, and hemorrhage were independent predictors of a poor prognosis (P = .000, .005, .032, respectively). The staining indexes of matrix metalloproteinase (MMP)-2 and MMP-9 were higher in the VM-positive than in the VM-negative group (P = .024 and .037, respectively). Gelatin zymography showed that the activity of MMP-2 and MMP-9 was significantly higher in the VM-positive lesions (P = .013 and .033, respectively). We conclude that VM in GISTs is an unfavorable prognostic sign and that patients with VM-positive tumors are prone to suffer liver metastasis. Both MMP-2 and MMP-9 play an important role in VM formation in GISTs.