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.

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.

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.