1. Evaluation Of The Therapeutic Effect Of ²¹¹At-labeled Octreotide On Non-small Cell Lung Cancer; 2. Construction And Analysis Of A Weighted Gene Co-expression Network For Thyroid Cancer

Background:In recent years,based on the high specificity and high selectivity of receptor and ligand binding,peptide receptor radionuclide therapy（PRRT）has been paid much attention and developed as a new treatment strategy for NSCLC.It is discover that somatostatin receptor（SSTR）expressed in NSCLC tissue can be specifically interacted with somatostatin（SST）,affording a potential target for NSCLC therapy.Octreotide is a most widely used SST analogue with high binding affinity for SSTR2.Alpha particle ²¹¹At has been researched for radio therapy of kinds of tumor.It has cytotoxicity by irreversible DNA damage.in order to explore its potential targeted-radionuclide therapy for NSCLC,²¹¹At labeled octreotide was synthesized through direct and indirect labeling method in our group.The preliminary result showed that this kind of The aims of this study were to confirm the ²¹¹At labeled octreotide’s cytotoxicity can function in short time and pinpoint the biodistribution of this labelled peptides.1.The Study of the labeling method of ²¹¹At in octreotideObjectives To explore the optimal labeling method of ²¹¹At to label octreotide for further evaluation of its distribution in vivo and anti-tumor effect.Methods NBS direct labeling method was used to synthesize ²¹¹At-octreotide and determine its labeling rate.SPC as intermediate coupling indirect labeling method was used to synthesize ²¹¹At-SPC-octreotide and determine its labeling rate.Subsequently,the stability of the crude products obtained by the two methods in the serum of mice for 1 h-24 h was further compared.Results Statination of octreotide by direct and indirect labeling method was achieved with about 60%and 30%labeling yields（non-decay corrected）,respectively.direct labeling method(²¹¹At-octreotide)resulted in severe dehalogenation within 2 h and only about 5.9%of labeled octreotide remained after6 h,in comparison,indirect labeling method(²¹¹At-SPC-octreotide)afforded relatively higher stability in vitro.Conclusions Direct labeling rate was higher than indirect labeling method.Although indirect labeling is less efficient,it is more stable in the environment of serum and PBS.Indirect labeling method perform far better.Indirect labeling method is more suitable to carry further research.2.The study of ²¹¹At labelled octreotide distribution and damage effect in the cancer cellObjectives To investigate the distribution of ²¹¹At-labeled octreotide in mice and evaluate its cytotoxic effect and range of action on non-small cell lung cancer.Methods The distribution of ²¹¹At-SPC-octreotide and free ²¹¹At in normal mice was compared.The cytotoxic effects of ²¹¹At-SPC-octreotide（20μCi和10μCi）,free ²¹¹At,octreotide and PBS on nude mice were compared by HE and TUNEL methods.Results The uptake in blood,liver,lung,kidney and stomach reached the highest activity concentration at 0.5 h and decreased continuously.Heart,spleen,intestines and muscle demonstrated their highest level of radioactivity at 1h,Low levels of radioactivity were observed in all tissues at 24 h.On the contrary,free ²¹¹At accumulated in all organs with a slow metabolism.Conclusions The distribution studies showed that ²¹¹At-SPC-octreotide showed higher uptake in the lung than other non-target organs in the early stage after injection,which demonstrated the apoptosis induction ability in a dose-dependent manner,and had significant potential in the targeted treatment of non-small cell lung cancer in the future.Background the incidence and mortality of thyroid cancer has been increasing steadily all over the world.Research on molecular mechanism of thyroid cancer incidence help improve disease risk stratification and prognosis.Methods The R package of DESeq2 was applied to detect differentially expressed genes between 57 paired thyroid cancer and noncancerous tissues using RNA sequencing d Ata from The Cancer Genome Atlas d Atabase.Weighted gene co-expression network analysis was used to construct co-expression modules and study the rel Ationship between co-expression modules and clinical traits.Results a cohort of 750 up-regul Ated and 296 down-regul Ated genes were identified in thyroid cancer.The weighted gene co-expression network analysis identified 5 gene co-expression modules.The turquoise module was significantly positively associ Ated with p Atients’ age,cancer stage and multifocality.The blue module was significantly neg Atively associ Ated with p Atients’ age and cancer stage.SERPINA1 and MRO were their hub genes respectively.Conclusions the bioinform Atics study identifies the turquoise and blue co-expression modules and their hub genes SERPINA1 and MRO may become molecular biomarkers in thyroid cancer.