Discovery of SILA-123 as a Highly Potent FLT3 Inhibitor for the Treatment of Acute Myeloid Leukemia with Various FLT3 Mutations.

The FLT3-ITD (internal tandem duplication) mutant has been a promising target for acute myeloid leukemia (AML) drug discovery but is now facing the challenge of resistance due to point mutations. Herein, we have discovered a type II FLT3 inhibitor, SILA-123. This inhibitor has shown highly potent inhibitory effects against FLT3-WT (IC50 = 2.1 nM) and FLT3-ITD (IC50 = 1.0 nM), tumor cells with the FLT3-ITD mutant such as MOLM-13 (IC50 = 0.98 nM) and MV4-11 (IC50 = 0.19 nM), as well as BaF3 cells associated with the FLT3-ITD mutant and point mutations like BaF3-FLT3-ITD-G697R (IC50 = 3.0 nM). Moreover, SILA-123 exhibited promising kinome selectivity against 310 kinases (S score (10) = 0.06). In in vivo studies, SILA-123 significantly suppressed the tumor growth in MV4-11 (50 mg/kg/d, TGI = 87.3%) and BaF3-FLT3-ITD-G697R (50 mg/kg/d, TGI = 60.0%) cell-inoculated allograft models. Our data suggested that SILA-123 might be a promising drug candidate for FLT3-ITD-positive AML.

Effects of willow and Sedum alfredii Hance planting patterns on phytoremediation efficiency under AC electric field.

Heavy metal contamination to soil is tricky due to its difficult removal, long retention time, and biomagnified toxicity. The green and low-cost phytoremediation with electric field treatment and planting pattern selection is an emerging and more effective approach to remove heavy metals from soils. In this study, alternating current (AC) electric field-assisted phytoremediation was examined with different planting patterns, i.e., monoculture willow (Salix sp.), monoculture Sedum alfredii Hance, and interplanting of willow and S. alfredii. AC electric field greatly increased phytoremediation efficiency to soil cadmium (Cd) regardless of planting patterns, either single plant species of willow or S. alfredii. The Cd removal capacity of willow and S. alfredii raises apparently under 0.5 V cm-1 AC electric field. Under different planting patterns of AC electric field treatment, Cd accumulation in the whole plant by interplanting was 5.63 times higher than monoculture willow, but only 0.75 times as high as monoculture S. alfredii. The results showed that AC electric field-assisted interplanting of willow and S. alfredii is a promising remediation technique for efficiently clean-up Cd-contaminated soil.

Targeted passivation and optimized interfacial carrier dynamics improving the efficiency and stability of hole transport layer-free narrow-bandgap perovskite solar cells.

Narrow-bandgap mixed Sn-Pb perovskite solar cells (PSCs) have showcased great potential to approach the Shockley-Queisser limit. Nevertheless, the practical application and long-term deployment of mixed Sn-Pb PSCs are still largely impeded by the rapid oxidation of Sn2+ ions and under-optimized carrier transport layer (CTL)/perovskite interfaces that would inevitably incur serious interfacial charge recombination and device performance degradation. Herein, we successfully removed the hole transport layer (HTL) by incorporating a small amount of organic phosphonic acid molecules into perovskites, which could preferably interact with Sn2+ ions (relative to Pb2+ analogues) at the grain boundaries (GBs) throughout the perovskite film thickness via coordination bonding, thus effectively retarding the oxidation of Sn2+, passivating the defects and suppressing the non-radiative recombination. Targeted modification effectively reinforced built-in potential by ∼100 mV, and favorably induced energy level cascade, thus accelerating spatial charge separation and facilitating the hole extraction from perovskite layer to underlying conductive electrodes even in the absence of HTL. Consequently, enhanced power conversion efficiencies up to 20.21% have been achieved, which is the record efficiency for the HTL-free mixed Sn-Pb PSCs, accompanied by a decent photovoltage of 0.87 V and improved long-term stability over 2400 h.

Expansion of Cyclophyllidea Biodiversity in Rodents of Qinghai-Tibet Plateau and the "Out of Qinghai-Tibet Plateau" Hypothesis of Cyclophyllideans.

The Cyclophyllidea comprises the most species-rich order of tapeworms (Platyhelminthes, Cestoda) and includes species with some of the most severe health impact on wildlife, livestock, and humans. We collected seven Cyclophyllidea specimens from rodents in Qinghai-Tibet Plateau (QTP) and its surrounding mountain systems, of which four specimens in QTP were unsequenced, representing "putative new species." Their complete mitochondrial (mt) genomes were sequenced and annotated. Phylogenetic reconstruction of partial 28S rDNA, cox1 and nad1 datasets provided high bootstrap frequency support for the categorization of three "putative new species," assigning each, respectively, to the genera Mesocestoides, Paranoplocephala, and Mosgovoyia, and revealing that some species and families in these three datasets, which contain 291 species from nine families, may require taxonomic revision. The partial 18S rDNA phylogeny of 29 species from Taeniidae provided high bootstrap frequency support for the categorization of the "putative new species" in the genus Hydatigera. Combined with the current investigation, the other three known Taeniidae species found in this study were Taenia caixuepengi, T. crassiceps, and Versteria mustelae and may be widely distributed in western China. Estimates of divergence time based on cox1 + nad1 fragment and mt protein-coding genes (PCGs) showed that the differentiation rate of Cyclophyllidea species was strongly associated with the rate of change in the biogeographic scenarios, likely caused by the uplift of the QTP; i.e., species differentiation of Cyclophyllidea might be driven by host-parasite co-evolution caused by the uplift of QTP. We propose an "out of QTP" hypothesis for the radiation of these cyclophyllidean tapeworms.

On-surface synthesis of 2D COFs via molecular assembly directed photocycloadditions: a first-principles investigation.

Over the past decades, the rational synthesis of two-dimensional covalent organic framework (2D COFs) monolayer via on-surface chemistry has been widely explored. Herein, we propose the [2 + 2] photocycloaddition as a novel strategy for large-scale fabrication of COFs from theoretical perspective. Thanks to the symmetry forbidden of thermal [2 + 2] cycloaddition, the molecular precursors carrying vinyl groups will not chemically interact with each other during thermal annealing, which is essential to achieve molecular assembly. The subsequent photocycloaddition of these precursors may produce large-scale 2D COFs at low temperatures, in which the symmetry of molecular assembly remains unchanged. Our results show that 2D COFs can be produced via [2 + 2] photocycloadditions directed from self-assembled precursors, in which alkylbenzene molecules with vinyl groups on side chains exhibit appropriate intermolecular distances. By performing high-throughput calculations, several promising molecular precursors are proposed to achieve large-scale 2D COFs. This work provides an applicable strategy for the large-scale synthesis of 2D carbon materials.

Genetic Evolution and Implications of the Mitochondrial Genomes of Two Newly Identified Taenia spp. in Rodents From Qinghai-Tibet Plateau.

The larva of Taeniidae species can infect a wide range of mammals, causing major public health and food safety hazards worldwide. The Qinghai-Tibet Plateau (QTP), a biodiversity hotspot, is home to many species of rodents, which act as the critical intermediate hosts of many Taeniidae species. In this study, we identified two new larvae of Taenia spp., named T. caixuepengi and T. tianguangfui, collected from the plateau pika (Ochotona curzoniae) and the Qinghai vole (Neodon fuscus), respectively, in QTP, and their mitochondrial genomes were sequenced and annotated. Phylogenetic trees based on the mitochondrial genome showed that T. caixuepengi has the closest genetic relationship with T. pisiformis, while T. tianguangfui was contained in a monophyletic group with T. crassiceps, T. twitchelli, and T. martis. Biogeographic scenarios analysis based on split time speculated that the speciation of T. caixuepengi (∼5.49 Mya) is due to host switching caused by the evolution of its intermediate host. Although the reason for T. tianguangfui (∼13.11 Mya) speciation is not clear, the analysis suggests that it should be infective to a variety of other rodents following the evolutionary divergence time of its intermediate host and the range of intermediate hosts of its genetically close species. This study confirms the species diversity of Taeniidae in the QTP, and speculates that the uplift of the QTP has not only a profound impact on the biodiversity of plants and animals, but also that of parasites.

Effect of bamboo biochar on reducing grain cadmium content in two contrasting wheat genotypes.

Wheat is the second most important food crop worldwide, which is prone to accumulate cadmium (Cd). Accumulation of Cd in wheat grains depends not only on wheat genotype, but also largely on the availability of soil Cd and its internal distribution. In this study, several experiments were used to achieve low-grain Cd content: a field trial for wheat genotype screening, a soil incubation experiment to test passivation effect of bamboo biochar on soil Cd, and a soil pot experiment to examine bamboo biochar effect on wheat grain accumulation. The results showed that of the 243 wheat cultivars tested, the variation range of grain Cd content was 0.365-1.243 mg/kg, in a field with soil Cd of 3 mg/kg. The application of bamboo biochar reduced soil Cd availability, among which 5.0% bamboo biochar treatment had the greatest effect. The content of available Cd in soil treated with 5.0% bamboo biochar decreased by 0.32 mg/kg compared with the control in a 120-day incubation experiment. Effect of bamboo biochar (0, 0.1%, 1.0%, and 5.0%) on reducing grain Cd content in two wheat genotypes (Mianyou-1 and 1279-9) was investigated. The application of bamboo biochar decreased Cd uptake by plants, while distribution of Cd in different wheat plant parts was more controlled by the plant genetic characteristics. Compared with the control, Cd content in roots, straw, and grains was decreased by 34.06% (P < 0.05), 21.57%, and 23.33%, respectively, in low-grain Cd wheat cultivar 1279-9 by 5% bamboo biochar application. Overall, the combination of low-grain Cd accumulation wheat and bamboo biochar may be a feasible strategy to lessen grain Cd accumulation in Cd-contaminated soils.

Synthesis and separation of cucurbit[n]urils and their derivatives.

Cucurbit[n]uril chemistry has become an important part of contemporary supramolecular chemistry since cucurbit[n]urils (Q[n]s) are not only able to encapsulate various guests, but are also capable of coordinating to a wide range of metal ions, leading to the establishment of Q[n]-based host-guest chemistry and coordination chemistry. Each of these impressive developments can be attributed to the growth of protocols for obtaining Q[n]s. In this review, we survey synthetic procedures for obtaining cucurbit[n]urils and their substituted derivatives together with the separation and purification of these remarkable compounds. The coverage is aimed at both existing workers in the field as well as at those requiring an "entry" into Q[n]-based research.

A rare gastric neuroendocrine carcinoma coexisting with Brunner's gland adenoma: A case report.

Gastric neuroendocrine carcinoma (G-NEC) is a rare neoplasm known for its aggressive behavior and poor prognosis. Brunner's gland adenoma (BGA) is a rare benign proliferative lesion that develops most commonly in the duodenum. To the best of our knowledge, no cases of G-NEC coexisting with BGA have previously been reported. The present study therefore reports the first case of G-NEC combined with BGA. A 67-year-old female presented with upper abdominal discomfort. No distant metastases were detected upon pre-operative abdominal computed tomography imaging. The patient underwent a radical distal gastrectomy, D2 lymphadenectomy and Billroth I gastroenterostomy. The resected masses were histologically confirmed to be G-NEC and BGA, respectively. The patient did not receive neoadjuvant or adjuvant chemotherapy or radiotherapy, and remains alive with no evidence of metastasis or recurrence at four years post-surgery.

Fibroblast growth factor receptor 4 protein expression and clinicopathological features in gastric cancer.

AIM: To investigate fibroblast growth factor receptor 4 (FGFR4) protein expression in Chinese patients with resectable gastric cancer (GC) and the association with clinicopathological characteristics and survival. METHODS: One hundred and seventy-five GC patients who underwent curative surgical procedures were enrolled in this study. The protein expression of FGFR4 in formalin-fixed, paraffin-embedded (FFPE) GC tissues was determined by immunohistochemical (IHC) analysis. Patient clinicopathological data and survival information were also collected and χ(2) statistical analysis was performed to analyze FGFR4 protein expression in the subgroups with differing clinicopathological characteristics including; gender, age, tumor location, differentiation, tumor-node-metastasis stage, macroscopic type, depth of invasion, lymph node metastases, distant metastasis, neural invasion and vascular invasion. Furthermore, some common molecular markers of GC in our cancer center, including p53, p27, topoisomerase IIα (Topo IIα) were also determined by IHC and their association with FGFR4 protein expression evaluated. The probability of survival for different subgroups with different clinicopathological characteristics was calculated using the Kaplan-Meier method and survival curves plotted using the log rank test. RESULTS: Seventy seven cases (44%) were found to have high expression of FGFR4 protein. Significantly different FGFR4 expression was observed between gastric cancers with differing expression of Topo IIα (log rank χ(2) = 9.4760, P = 0.0236). No significant differences were observed between subgroups defined by any of the other clinicopathological characteristics. The median survival time of the FGFR4 high expression (77 cases) and low expression groups (98 cases) was 27 mo and 39 mo, respectively. The five-year survival rates and median survival times of gastric cancers with high FGFR4 expression were worse than those with low expression (30.8% vs 39.2%, 27 mo vs 39 mo), respectively, however, no significant difference was observed in survival time (log rank χ(2) = 1.0477, P = 0.3060). Survival analysis revealed that high expression of FGFR4 was a predictor of poor outcome in GC patients if the tumor was small (less than or equal to 3 cm in size) (log rank χ(2) = 5.5033, P = 0.0190), well differentiated (log rank χ(2) = 7.9757, P = 0.0047), and of T1 or T2 stage invasion depth (log rank χ(2) = 4.8827, P = 0.0271). CONCLUSION: Our results suggest that high tumor expression of FGFR4 protein is not an independent risk factor for GC cancer initiation, but is a useful prognostic marker for GC patients when the tumor is relatively small, well differentiated, or in the early stages of invasion.

Two cases of neuroendocrine carcinoma of the gallbladder.

Neuroendocrine carcinoma (NEC) of the gallbladder is a rare subtype of gallbladder tumor. Here, we report two cases of NEC in two patients initially suspected to have gallbladder carcinoma. No specific symptoms or abnormal blood test results were observed preoperatively. Abdominal computed tomography scans indicated intraluminal masses in the gallbladder and lymph node enlargement in the hepatic hilum. Radical cholecystectomy and regional lymphadenectomy were performed. The first patient also presented with liver invasion and therefore underwent resection of liver segment IV. A diagnosis of NEC was made upon postoperative pathological examination and immunohistochemical staining according to the WHO Classification of Tumors of the Digestive System (2010). One tumor was identified as poorly differentiated NEC and the other as poorly differentiated mixed adenoneuroendocrine carcinoma. Immunohistochemical staining data from both tumors showed positivity for chromogranin A and synaptophysin. The first patient received 4 cycles of chemotherapy consisting of cisplatin and etoposide. No metastases or recurrence were observed 12 mo following surgery. The second patient refused chemotherapy and presented with tumor recurrence 4 mo after surgery. In conclusion, NEC of the gallbladder is an aggressive tumor and the identification of a standardized optimal treatment still requires further research. Our experience together with published studies suggests that radical surgery and adjuvant chemotherapy may improve the prognosis.

A comparison of loop-mediated isothermal amplification (LAMP) with other surveillance tools for Echinococcus granulosus diagnosis in canine definitive hosts.

BACKGROUND: Cystic echinococcosis is highly prevalent in northwest China. A cost-effective, easy to operate diagnostic tool with high sensitivity and specificity would greatly facilitate the monitoring of Echinococcus infections in canine definitive hosts. METHODS: The primers used in the LAMP assay were based on the mitochondrial nad5 gene of E. granulosus sensu stricto (E. granulosus s.s., or E.g.s.s.) and were designed using Primer Explorer V4 software. The developed LAMP assay was compared with a conventional PCR method, copro-ELISA and microscopy, using the faeces of dogs experimentally infected with E.g.s.s., and field-collected faeces of domestic dogs including 190 from Qinghai province highly endemic for E.g.s.s. and 30 controls from an area in Gansu, where a domestic dog de-worming program was in operation. RESULTS: The positivity rates obtained for the field-collected faecal samples were 12.6%, 1.6% and 2.1% by the LAMP, PCR and copro-ELISA assays, respectively. All samples obtained from the control dogs were negative. Compared with the conventional PCR, the LAMP assay provided 88.8% specificity and 100% sensitivity. The higher sensitivity of the LAMP method was also shown by the fact that it could detect the presence of laboratory challenge dog infections of E. granulsous s.s. four days earlier than the PCR method. Three copro-samples shown positive by the commercial copro-ELISA were all negative by LAMP, PCR and microscopy, which suggests these samples may have originated from another infection rather than E. granulsous s.s., possibly E. shiquicus or E. Canadensis, which is also present in China. CONCLUSIONS: We have developed a potentially useful surveillance tool for determining the prevalence of canine E. granulosus s.s. infections in the field. The LAMP assay may lead to a more cost-effective and practicable way of tracking Echinococcus infections in canids, especially when combined with the copro-ELISA.

Fibroblast growth factor receptor 4 Gly388Arg polymorphism in Chinese gastric cancer patients.

AIM: To investigate the contribution of the fibroblast growth factor receptor 4 (FGFR4) Gly388Arg polymorphism as a genetic risk factor for gastric cancer (GC) and to investigate any associations between this polymorphism and clinicopathological parameters and survival. METHODS: Tumors and matched adjacent non-cancer tissues were collected from 304 GC patients, and 5 mL of venous blood was collected from 62 GC patients and 392 age- and sex-matched healthy controls without cancer history from the same ethnic population. DNA was extracted, and direct sequencing analyses were performed to genotype the FGFR4 Gly388Arg polymorphism in all the samples. Differences in the genotype frequencies of the FGFR4 Gly388Arg polymorphism between GC patients and healthy controls were estimated using the χ(2) test. Binary logistic regression was used for all analysis variables to estimate risk as the ORs with 95%CIs. The relationships between the FGFR4 genotype and clinicopathological parameters were tested with the χ(2) test. The Kaplan-Meier product-limit method, the log-rank test, and the Cox regression model were applied to evaluate the effect of the FGFR4 genotype on the overall survival of patients with GC. RESULTS: In the present GC cohort, 118 patients (38.8%) were homozygous for the Gly388 allele, 124 patients (40.8%) were heterozygous, and 62 patients (20.4%) were homozygous for the Arg388 allele. The frequencies of the Gly/Gly, Gly/Arg, and Arg/Arg genotypes in the healthy controls were 33.6%, 48.0%, and 18.4%, respectively. The distributions of genotypes (χ(2) = 3.589, P = 0.166) and alleles (χ(2) = 0.342, P = 0.559) of the FGFR4 Gly388Arg polymorphism were not different between the GC patients and the healthy controls. Although we observed no correlation between the FGFR4 Gly388Arg polymorphism and clinicopathological parameters or survival in the total cohort of GC patients, the presence of the Arg388 allele was associated with shorter survival time in patients with GC if the tumor was small (log rank χ(2) = 5.449, P = 0.020), well differentiated (log rank χ(2) = 12.798, P = 0.000), T1 or T2 stage (log rank χ(2) = 4.745, P = 0.029), without lymph node involvement (log rank χ(2) = 6.647, P= 0.010), and at an early clinical stage (log rank χ(2) = 4.615, P = 0.032). CONCLUSION: Our results suggest that the FGFR4 Gly388Arg polymorphism is not a risk factor for GC cancer initiation but that it is a useful prognostic marker for GC patients when the tumor is relatively small, well differentiated, or at an early clinical stage.

Loss of BRCA1 expression leads to worse survival in patients with gastric carcinoma.

AIM: To investigate the expression deficiency of key molecular markers in the homologous recombination pathway. METHODS: Expression loss of breast cancer type 1 susceptibility protein (BRCA1), ataxia telangiectasia mutated (ATM), ATM-Rad3-related (ATR), mediator of DNA damage checkpoint protein 1 (MDC1) and meiotic recombination 11 (Mre11) were correlated with their clinicopathological parameters in gastric cancer (GC). One hundred and twenty treatment-naive GC samples were formalin-fixed and paraffin-embedded into tissue blocks. Two representative cores from each block were extracted and constructed into tissue microarrays. Expression levels of BRCA1, ATM, ATR, MDC1 and Mre11 were determined using immunohistochemical analysis, and correlated with clinical parameters, including age, gender, Lauren subtype, tumor grades, clinical stage and overall survival. RESULTS: Expression loss of BRCA1, ATM, ATR, MDC1, and Mre11 was found in 21.4%, 20.2%, 21.0%, 11.1% and 4.6%, respectively, of interpretable cases. BRCA1 loss was significantly associated with patients of diffused subtype (intestinal vs diffused, 8.2% vs 31.7%, P = 0.001), higher tumor grade (I/II vs III, 10.7% vs 20.5; I/II vs IV, 10.7% vs 54.5%, P = 0.047) and advanced clinical stage (I/II vs III, 12.9% vs 16.9%; I/II vs IV, 12.9% vs 45.5%, P = 0.006). MDC1 loss was significantly associated with patients of diffused subtype (intestinal vs diffused, 0% vs 19.7%, P = 0.001) and higher tumor grade (I/II vs III, 0% vs 12%; I/II vs IV, 0% vs 30.8%, P = 0.012). In addition, the survival time of the patients with expression loss of BRCA1 was significantly shorter than those with positive expression of BRCA1 (2-year survival rate, 32.4% vs 62.8%, P = 0.015). No correlations were found between clinicopathological parameters and expression loss of ATM, ATR and Mre11. CONCLUSION: Our results support the hypothesis that homologous recombination deficiency plays an important role in the progression of gastric carcinoma. Loss of expression of BRCA1 and MDC1 may serve as predictive factors in tumor development or progression in GC patients.

Correlation of human epidermal growth factor receptor 2 expression with clinicopathological characteristics and prognosis in gastric cancer.

AIM: To investigate human epidermal growth factor receptor 2 (HER2) gene amplification and protein expression in Chinese patients with resectable gastric cancer and the association with clinicopathological characteristics and survival. METHODS: One hundred and ninety-seven gastric cancer patients who underwent curative surgery procedures were enrolled into this study. HER2 gene amplification and protein expression were examined using fluorescence in-situ hybridization (FISH) and immunohistochemistry (IHC) analysis on formalin-fixed paraffin-embedded gastric cancer samples from all patients. For scoring, Hofmann's HER2 gastric cancer scoring system was adopted. All cases showing IHC3+ or FISH positivity were defined as HER2 positive. Patient clinicopathological data and survival information were collected. Finally, χ² statistical analysis was performed to analyze the HER2 positivity rate amongst the subgroups with different clinicopathological characteristics including; gender, age, tumor location, Lauren classification, differentiation, TNM staging, depth of invasion, lymph node metastases and distant metastasis. The probability of survival for different subgroups with different clinicopathological characteristics was calculated using the Kaplan-Meier method and survival curves plotted using log rank inspection. RESULTS: According to Hofmann's HER2 gastric cancer scoring criteria, 31 cases (15.74%) were identified as HER2 gene amplified and 19 cases (9.64%) were scored as strongly positive for HER2 membrane staining (3+), 25 cases (12.69%) were moderately positive (2+) and 153 cases (77.66%) were HER2 negative (0/1+). The concordance rate between IHC and FISH analyses was 88.83% (175/197). Thirty-six cases were defined as positive for HER2 gene amplification and/or protein expression, with 24 of these cases being eligible for Herceptin treatment according to United States recommendations, and 29 of these cases eligible according to EU recommendations. Highly consistent results were detected between IHC3+, IHC0/1 and FISH (73.68% and 95.42%), but low consistency was observed between IHC2+ and FISH (40.00%). The positivity rates in intestinal type and well-differentiated gastric cancer were higher than those in diffuse/mixed type and poorly-differentiated gastric cancer respectively (28.57% vs 13.43%, P = 0.0103; 37.25% vs 11.64%, P < 0.0001), but were not correlated with gender, age, tumor location or TNM stage, depth of invasion, lymph node metastases and distant metastasis. In poorly-differentiated gastric cancer patients, those without lymph node metastasis showed a higher HER2 positivity rate than those with lymph node metastasis (26.47% vs 7.14%, P = 0.0021). This association was not present in those patients with well-differentiated gastric cancer (28.57% vs 43.33%, P = 0.2832). Within our patient cohort, 26 cases were lost to follow-up. The median survival time for the remaining 171 patients was 18 mo. The median survival times of the HER2 positive and negative groups were 17 and 18.5 mo respectively. Overall survival was not significantly different between HER2-positive and negative groups (χ(2) = 0.9157, P = 0.3386), but in patients presenting well-differentiated tumors, the overall survival of the HER2-positive group was significantly worse than that of the HER2-negative group (P = 0.0123). In contrast, patients with poorly differentiated and diffuse/mixed subtype gastric cancers showed no significant differences in overall survival associated with HER2. Furthermore, the median survival time of the HER2 positive group did not show any statistically significant differences when compared to the subgroups of gender, age, tumor location, TNM classification, lymph node metastases and distant metastasis. CONCLUSION: Patients with intestinal type gastric cancer (GC), well-differentiated GC and poorly-differentiated GC without lymph node metastasis, may all represent suitable candidates for targeted therapy using Herceptin.

[The signaling systems in Echinococcus multilocularis].

Signaling pathway is the way by which cells receive various stimulation signals, and produce a series of corresponding responses, such as cell proliferation, differentiation and apoptosis. During infection with Echinococcus multilocularis, both parasite and host cells may secrete many cytokines such as insulin, which make stimulating signals transmitted into the cells through their receptors on the surface of cells. As a result, the parasite can grow and proliferate in the host. Study on related signaling pathways and their blocking drugs will play a crucial role in the control of alveolar echinococcosis caused by the larvae of E. multilocularis.

[Clinicopathological features and prognostic analysis of esophageal sarcomatoid carcinoma].

OBJECTIVE: To analyze the clinicopathological characteristics and prognosis of a rare histological type of esophageal cancer-sarcomatoid carcinoma. METHODS: Clinicopathological data of 31 patients with esophageal sarcomatoid carcinoma who underwent surgery in the Department of Thoracic Surgery of Zhejiang Cancer Hospital from Jan 2000 to Dec 2009 were collected and analyzed. The survival analysis was performed using Kaplan-Meier method. RESULTS: All the patients underwent surgery. Of the 31 patients, one received preoperative chemoradiotherapy and postoperative chemotherapy, and 8 received postoperative chemotherapy. All the tumors were located in the middle or lower esophagus. Microscopically, the tumors were composed of both carcinomatous and sarcomatous components, and there was a transition between the two components, but no obvious heterogenous elements such as osteosarcoma, chondrosarcoma or rhabdomyosarcoma were found. In the carcinomatous components, positive expression of CK and EMA was found in all the 31 cases, and positive expression of vimentin in 5 of the 31 cases. In the sarcomatous components, positive expression of CK, EMA and vimentin was found in 29, 28 and 23 cases, respectively. The 1-, 3-, and 5-year survival rates were 80.6%, 55.9% and 33.4%, respectively, and the median survival time was 40 months. CONCLUSIONS: Esophageal sarcomatoid carcinoma is a particular type of esophageal malignancy with unique clinicopathological features. The diversity and complexity of the carcinomatous and sarcomatous components and their potential of transformation and differentiation lead to different prognosis from each other.

[Research advances in interplay of host immune mechanism and Echinococcus multilocularis metacestodes].

Through affecting on host innate and acquired immune responses, Echinococcus multilocularis orchestrates various interplays that are beneficial not only to facilitate its intrahepatic proliferation and maturation during life cycle, but also to limit pathological process in its intermediate host. This review reveals the role of the metacestode's immune-related molecules in modulating host responses and optimizing its own survival.

Genetic variation of the 8-kDa glycoprotein family from Echinococcus granulosus, Taenia multiceps and Taenia hydatigena.

BACKGROUND: Echinococcosis, coenurosis and cysticercosis are debilitating diseases which prevail in China. Immunological diagnosis of metacestodosis is important in disease control. The 8-kDa glycoproteins from taeniid cestodes have successfully been used for diagnosis of human cysticercosis in immunological assays. The aim of the present study was to investigate genetic variations and phylogenetic relationships of the 8-kDa proteins for evaluating the possibility of utilizing these proteins as diagnostic antigens for other metacestode infections. METHODS: The genes and complementary DNAs (cDNAs) encoding the 8-kDa proteins from Echinococcus (E.) granulosus, Taenia (T.) multiceps and T. hydatigena were amplified using PCR method. Their amplicons were cloned into the vector pMD18 and the positive clones were sequenced. Sequence data were analyzed with the SeqMan program, and sequence homology searches were performed using the BLAST program. Alignments were conducted using the ClustalX program, and the phylogenetic analyses were performed with the Protein Sequences Program and the Puzzle Program using the Neighbor-joining method. RESULTS: Fifteen, 18 and 22 different genomic DNA sequences were identified as members of the 8-kDa protein gene family from E. granulosus, T. multiceps and T. hydatigena, respectively. Eight, four and six different cDNA clones respectively from E. granulosus, T. multiceps and T. hydatigena were characterized. Analysis of these sequences revealed 54 unique 8-kDa protein sequences. Phylogenetic trees demonstrated that the taeniid 8-kDa proteins are clustered into eight clades at least: Ts18, Ts14, TsRS1, TsRS2, T8kDa-1, T8kDa-2, T8kDa-3 and T8kDa-4. CONCLUSION: We found that the gene family encoding for the taeniid 8-kDa antigens is comprised of many members with high diversity, which will provide molecular evidence for cross-reaction or specific reaction among metacestode infections and may contribute to the development of promising immunological methods for diagnosis of metacestodosis.