Development of a CLDN18.2-targeting immuno-PET probe for non-invasive imaging in gastrointestinal tumors

Claudin18.2(CLDN18.2)is a tight junction protein that is overexpressed in a variety of solid tumors such as gastrointestinal cancer and oesophageal cancer.It has been identified as a promising target and a potential biomarker to diagnose tumor,evaluate efficacy,and determine patient prognosis.TST001 is a recombinant humanized CLDN18.2 antibody that selectively binds to the extracellular loop of human Claudin18.2.In this study,we constructed a solid target radionuclide zirconium-^(89)(^(89)Zr)labled-TST001 to detect the expression of in the human stomach cancer BGC823CLDN18.2 cell lines.The[^(89)Zr]Zr-desferrioxamine(DFO)-TST001 showed high radiochemical purity(RCP,>99%)and specific activity(24.15±1.34 GBq/mmol),and was stable in 5%human serum albumin,and phosphate buffer saline(>85%RCP at 96 h).The EC_(50) values of TST001 and DFO-TST001 were as high as 0.413±0.055 and 0.361±0.058 nM(P>0.05),respectively.The radiotracer had a significantly higher average standard uptake values in CLDN18.2-positive tumors than in CLDN18.2-negative tumors(1.11±0.02 vs.0.49±0.03,P=0.0016)2 days post injection(p.i.).BGC823CLDN18.2 mice models showed high tumor/muscle ratios 96 h p.i.with[^(89)Zr]Zr-DFO-TST001 was much higher than those of the other imaging groups.Immunohistochemistry results showed that BGC823CLDN18.2 tumors were highly positive(+++)for CLDN18.2,while those in the BGC823 group did not express CLDN18.2().The results of ex vivo biodistribution studies showed that there was a higher distribution in the BGC823CLDN18.2 tumor bearing mice(2.05±0.16%ID/g)than BGC823 mice(0.69±0.02%ID/g)and blocking group(0.72±0.02%ID/g).A dosimetry estimation study showed that the effective dose of[^(89)Zr]Zr-DFO-TST001 was 0.0705 mSv/MBq,which is within the range of acceptable doses for nuclear medicine research.Taken together,these results suggest that Good Manufacturing Practices produced by this immuno-positron emission tomography probe can detect CLDN18.2-overexpressing tumors.

A study of environmental impact on manufacturing products trade in Shandong,China

Based on the situation that the trade of manufactured goods takes the main position in Shandong Province,this paper identifies Shandong industrial pollutant discharge by three indices,which are industrial effluent discharge,industrial SO2 emission,and solid waste disposal.Furthermore,it conducts an empirical analysis of the trade terms of pollution content transfer on nine identified industrial sectors.The conclusion is that the increase in industrial effluent discharge,industrial SO2 emission,and solid waste disposal has paralleled the growth of the GDP in Shandong.The rapid economic growth brings obvious negative impact on the environment.Compared with that in 1998,the increase in the pollution content of exports in 2007 indicated that more environmental costs were generated with the economic development in Shandong.There is a need for optimization of foreign trade structure in Shandong,especially the need for increasing import of the pollution intensive products and decreasing the export of the pollution intensive products.The research on the relationship between manufactured goods trade and the environmental impact will make a contribution to the adjustment of foreign trade and environmental policies.

Cell sheet technology for regeneration of esophageal mucosa

The progress of tissue-engineering technology has realized development of new therapies to treat various disorders by using cultured cells. Cell-and tissue-based therapies have been successfully applied to human patients, and several tissue-engineered products have been approved by the regulatory agencies and are commercially available. In the review article, we describe our experience of development and clinical application of cell sheet-based regenerative medicine.Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) have been shown to be useful for removal of gastrointestinal neoplasms with less invasiveness compared with open surgery, especially in esophageal surgery. However, postoperative inflammation and stenosis are major complications observed after intensive mucosal resection. Therefore, we have developed novel regenerative medicine to prevent such complications and promote wound healing of esophageal mucosa after EMR or ESD. Transplantable oral mucosal epithelial cell sheets were fabricated from patients' own oral mucosa. Immediately after EMR or ESD, fabricated autologous cell sheets were endoscopically transplanted to the ulcer sites. We performed a preclinical study with a canine model. In human clinical settings, cell culture and cell sheet fabrication were performed in clean rooms according to good manufacturing practice guidelines, and pharmaceutical drugs were used as supplements to culture medium in place of research regents used in animal study. We believe that cell-based regenerative medicine would be useful to improve quality of life of patients after EMR or ESD.

Modified mesenchymal stem cells in cancer therapy: A smart weapon requiring upgrades for wider clinical applications

Mesenchymal stem stromal cells(MSC)are characterized by the intriguing capacity to home toward cancer cells after systemic administration.Thus,MSC can be harnessed as targeted delivery vehicles of cytotoxic agents against tumors.In cancer patients,MSC based advanced cellular therapies were shown to be safe but their clinical efficacy was limited.Indeed,the amount of systemically infused MSC actually homing to human cancer masses is insufficient to reduce tumor growth.Moreover,induction of an unequivocal anticancer cytotoxic phenotype in expanded MSC is necessary to achieve significant therapeutic efficacy.Ex vivo cell modifications are,thus,required to improve anti-cancer properties of MSC.MSC based cellular therapy products must be handled in compliance with good manufacturing practice(GMP)guidelines.In the present review we include MSCimproving manipulation approaches that,even though actually tested at preclinical level,could be compatible with GMP guidelines.In particular,we describe possible approaches to improve MSC homing on cancer,including genetic engineering,membrane modification and cytokine priming.Similarly,we discuss appropriate modalities aimed at inducing a marked cytotoxic phenotype in expanded MSC by direct chemotherapeutic drug loading or by genetic methods.In conclusion,we suggest that,to configure MSC as a powerful weapon against cancer,combinations of clinical grade compatible modification protocols that are currently selected,should be introduced in the final product.Highly standardized cancer clinical trials are required to test the efficacy of ameliorated MSC based cell therapies.

Is Financial Development Another Source of Comparative Advantage? Evidence from China

Using panel data for 29 provinces in China during 1990-2004, the present paper attempts to explore a possible link between financial development and China＇s foreign trade. Three measures of comparative advantage in manufactured goods have been applied in our study, including Balassa＇s revealed comparative advantage, the net manufactured export index, and the Michaely index. We also use four indicators of financial development to identify the different functions of regional financial development, and to determine both size and efficiency features of financial institutions. The estimation results suggest that besides factor endowments, foreign firms and infrastructure, financial development has a quantitatively large and robust effect on China ＇ s manufactured goods trade. Therefore, further reform of China＇s financial system should be encouraged to fully exploit the comparative advantage of China＇s foreign trade.

An Advocacy of Trade Liberalization between China and MRB Countries

This study provides a systematic analysis of the bilateral trade relationships between China and the Mekong River Basin （ MRB ） countries and the new phenomenon where China＇s foreign direct investment（FDI） flows to these countries in the past few years. The paper highlights the new development of China＇s trade with the MIKB countries and reviews the bilateral trade that has been substantially increasing from US S3.35 billion in 2000 to US $18.39 billion in 2007. The paper also explores the features of trade composition between the two sides. China＇s exports have largely concentrated on the manufactured goods while the exports of M1KB countries to China have been natural resources and agricultural goods, which reflects the relative comparative advantages for China and MRB countries and further reinforces the important strategy for the MRB countries to develop their industrialization further and increase their manufacturing capacity. Lastly, the overall results suggest that the impact of China＇s trades to the MRB countries is positive, but not as strong as currently expected.

Microbiological assessment of street foods at the point of sale in Maputo(Mozambique)

Objectives:The aim of this study was to assess the microbiological quality and safety of street food sold in the main streets and informal markets of Maputo,the capital of Mozambique.Materials and Methods:From 83 different vendors selling different types of foods,83 samples of ready-to-eat(RTE)street food were analyzed.Mesophiles,Escherichia coli and total coliforms were used as quality and hygiene indicators.Listeria monocytogenes(L.monocytogenes)Salmonella and coagulase-positive staphylococc were used as food safety indicators.Results:High proportions of unsatisfactory food samples were found in both traditional hot(76.7%)and cold(75%)foods.L.monocytogenes and Salmonella were tested negative in this survey.However,when coagulase-positive staphylococci was used as a food safety indicator,approximately 25%(23/83)of the food samples analyzed were classified as unsatisfactory/potentially hazardous.Conclusions:These results,showing that street food sold in Maputo clearly requires adequate sanitary conditions for its preparation and sale,contribute to the development of good manufacturing practices(GMP)for street food in Maputo,Mozambique.This is the first report on the microbiological quality and safety of street food in Mozambique.