Prognostic Value of the Evolution of HER2-Low Expression after Neoadjuvant Chemotherapy / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Patients with human epidermal growth factor receptor 2 (HER2)–low advanced breast cancer can benefit from trastuzumab deruxtecan. Given the unclear prognostic characteristics of HER2-low breast cancer, we investigated the prognostic characteristics of HER2-low expression from primary tumor to residual disease after neoadjuvant chemotherapy (NACT). @*Materials and Methods@#The data of HER2-negative patients receiving NACT at our center were collected. Pathological complete response (pCR) rate were compared between HER2-0 and HER2-low patients. The evolution of HER2 expression from primary tumor to residual disease and its impact on disease-free survival (DFS) were examined. @*Results@#Of the 690 patients, 494 patients had HER2-low status, of which 72.3% were hormone receptor (HR)–positive (p < 0.001). The pCR rates of HER2-low and HER2-0 patients (14.2% vs. 23.0%) showed no difference in multivariate analysis regardless of HR status. No association was observed between DFS and HER2 status. Of the 564 non-pCR patients, 57 (10.1%) changed to HER2-positive, and 64 of the 150 patients (42.7%) with HER2-0 tumors changed to HER2-low. HER2-low (p=0.004) and HR-positive (p=0.010) tumors before NACT were prone to HER2 gain. HER2 gain patients had a better DFS compared with HER2-negative maintained patients (87.9% vs. 79.5%, p=0.048), and the DFS of targeted therapy group was better than that of no targeted therapy group (92.4% vs. 66.7%, p=0.016). @*Conclusion@#Although HER2-low did not affect the pCR rate and DFS, significant evolution of HER2-low expression after NACT creates opportunities for targeted therapy including trastuzumab.

Impact of molecular subtypes on prognosis of postoperative patients with invasive breast cancer / 中华普通外科杂志

Objective:To investigate the prognostic value of molecular subtypes in patients with resected invasive breast cancer.Methods:Between 2015 and 2018 7 869 patients with invasive breast cancer after undergoing surgery were included in this analysis. Breast cancer was classified into four subtypes according to the status of hormone receptor (HR) and HER2: HR+/HER2-, HR+/HER2+, HR-/HER2+, and HR-/HER2-. Kaplan-Meier curves and COX regression were used to compare disease-free survival (DFS) and overall survival (OS) among different subtypes.Results:The 5-year DFS and OS were 86.30% and 94.29%, respectively. Proportions of HR+/HER2-、HR+/HER2+、HR-/HER2+ and HR-/HER2- were 52.9%、17.5%、14.1%和15.5%, respectively. The 5-year DFS of HR+/HER2- subtype (88.12%) was higher than HR+/HER2+ (84.67%, P=0.026), HR-/HER2+ (84.19%, P<0.001) and HR-/HER2- (83.70%, P<0.001). The 5-year OS of HR+/HER2- (95.38%) was not different from HR+/HER2+ (95.17%, P=0.187), while it was higher than that of HR-/HER2+ (92.26%, P<0.001) and HR-/HER2- (91.69%, P<0.001). Subtype was still a significant factor regarding DFS and OS in multivariable analyses adjusting for age, sex, stage, Ki67, types and time of surgery. The DFS ( P=0.257) and OS ( P=0.511) was not different between HR-/HER2+与HR+/HER2- subtypes, while HR-/HER2+ and HR-/HER2- patients had worse DFS ( P<0.05) and OS ( P<0.05) than that with HR+/HER2-. Conclusions:Molecular subtype is a significant independent prognostic factor for DFS and OS in operable invasive breast cancer. HR+ subtypes have better prognosis compared with HR- subtypes. The DFS and OS were not different between HR+/HER2- and HR+/HER2+, or between HR-/HER2+ and HR-/HER2-.

Novel printed electrode immunosensors for Schistosoma japonicum / 中南大学学报(医学版)

Objective:To improve the sensitivity and the linear range of electrochemical immunosensor to detect Schistosoma japonicum (S.japonicum) antibody.Methods:Carbon inks and silver/silver chloride inks were printed on a polyethylene terephthalate (PET) board to make a two-electrode test strip,where carbon was the working electrode and S.japonicum soluble egg antigen (SEA) was fixed at one end of working electrode by different methods; silver/silver chloride electrode was used as control.We tested the valency of the antibody by cyclic voltammetry (CV) and differential pulse voltammetry (DPV) in an electrochemistry workstation,and conducted comparison with the results of ELISA.Two new immunosensing electrodes have been developed,based on glutaraldehyde cross-linked (GA) or chitosan-glutaraldehyde cross-linked (Chit-GA) transducer fixing S.japonicum antigen.We tested the titer of the antibody by means of CV and DPV.Results:Our experimental S.japonicum antigen (50 μg/L) is the optimal test concentration for the GA sensor,and 10 μg/L for Chit-GA sensors.The immune reaction time of both electrodes is all essentially complete in 1 minute.The linear range for S.japonicura antibody in human positive serum sample detection by the glutaraldehyde cross-linked immunosensor is 1∶1000 to 1∶400,and by the chitosan-glutaraldehyde cross-linked immunosensor is 1∶1000 to 1∶500.As the concentration of dilution ratio of S.japonicum antibody in human positive serum sample increased,the test value of DPV increased proportionally.Conclusion:GA sensor and Chit-GA cross-linked S.japonicum sensors have high sensitivity and broad linear range response,and both exhibited a good linear relationship between the DPV signal and the test antibody titer.

Artificial preparation, indoor passage, and nature breed of Oncomelania hupensis infected with Schistosoma Japonicum / 中南大学学报(医学版)

Objective To prepare the infected Oncomelania hupensis by artificial method for the research on the activity, vaccine, and genetic variation of Schistosoma Japonicum (S. Japonicum).Methods The mature eggs of S. Japonicum were collected by Nylon silk method and the miracidia were incubated under appropriate conditions. Negative snails were infected with miracidia in different proportion by means of individual or collective infection to seek the best method and proportion of infection between miracidia and snails. Infected snails were divided into 12 groups in total. Ⅰ-Ⅵ groups were for individual infection and Ⅶ-Ⅻ groups were for collective infection. There were 200 snails in each group. The infection ratios between snails and miracidia in Group Ⅰ-Ⅵ or screened, numbered, and reared singly. The amount of cercariae was calculated once every 10 days until the infected snails died. Then cercariae shedding quantity, infection quantity, and mortality of infected snails in every group were compared to find the best infection method and the best infection proportion between miracidia and snails. The cercariae were collected from the first generation of infected snails and were used to infect experimental animals. The mature eggs of S. Japonicum were saved from the infected experimental animals and incubated to get miracidia. The snails were artificially infected by miracidium to get the second generation of infected snails. The developmental rates of adult worms, the egg density in fecal and liver were compared between artificially and naturally infected snails. Results In individual infection GroupⅠ-Ⅵ,the average infection value of snails were 0±0,22.7±4.2,31.7±4.5,53.0±5.3,39.3±5.9,32.7±4.7,the average fatality of snails were 21.7±3.1,25.0±3.6,31.3±4.9,44.7±6.5,78.3±9.5,89.7±13.6, and the average value of cercariae shedding from infected snails were 0.0±0.0,308.0±96.6,428.1±146.2,527.0±171.1,571.4±148.9,602.9±356.3, respectively. In collective infection Group Ⅶ-Ⅻ,the average infection value of snails were 0±0,12.3±2.5,18.7±4.7,28.3±4.2,33.3±4.7,29.3±5.5,and the average fatality of snails were 22.7±3.8,23.7±4.5,28.3±5.5,47.0±9.5,75.7±8.5,86.3±12.2, and the average value of cercariae shedding from infected snails were 0±0,244.5±57.3,292.3±74.8,347.1±100.8,477.2±142.1,447.3±161.4, respectively. The second generation of artificially infected snails was obtained successfully. The average infection rate and fatality rate for the second generation of artificially infected snails were 24.65% and 24.50%, both of which were not obviously different from that of the first generation of artificially infected snails (P>0.05). In the animal experiment, the worm growth rate for the naturally infected snails, the first or second generation of artificially infected snails were 68.50%,73.50% or 71.00%. There was no obvious difference among them (P>0.05). The fecal (or liver) eggs per gram for the naturally infected snails, the first or the second generation of artificially infected snails were 1 503±269,1 683±233, or 1 541±117 (or 6 641±1 819,6 272±1 419, or 7 263±1 643). There was no significant difference among the 3 groups (P>0.05). Conclusion Infected snails can be obtained through the artificial method by using S. Japonicum miracidia to infect snails. Individual infection has the advantage over collective infection. The optimal proportion of infection between first and the second generation of artificially infected snails in the average of cercariae shedding, infection, and fatality average of snails. There was no significant difference between artificially and naturally infected snails in the developmental rate of adult worms, fecal and liver eggs per gram.

Study on the immunoprotections of SjRPS4 and SjRPL7 DNA vaccines against Schistosoma japonicum infection in mice / 中国人兽共患病学报

The aim of this research was to study the immunoprotections of Schistosoma japonicum (S. japonicum) DNA vaccines SjRPS4 and SjRPL7 in mice. Fourty Kunming mice were randomly divided into 4 groups (A, B, C and D), and the pcDNA3.0/SjRPS4 and pcDNA3.0/SjRPL7 plasmid DNA vaccines were prepared for experiment. Mice in group A were intramuscularly injected with 100μL normal saline, whereas mice in group B were injected with 100 (g naked plasmid pcDNA3.0 into the quadriceps. Mice in groups C and D were injected with 100μg/100μL eukaryotic recombinant plasmids pcDNA3.0/SjRPS4 and pcDNA3.0/SjRPL7 into the hind leg muscles respectively. The initial injections were followed by two sets of boosters at 2 weeks intervals. In addition, levels of the specific antibodies were detected 2 weeks after the last immunization and all mice were percutaneously infected with 20( 1) S. japonicum cercariae on abdomen. Fourty-two days after the infection, all mice were killed to detect the worm reduction rate and the egg reduction rate. Significant differences of worm burden reduction rates, LEPG reduction rates, IEPG reduction rates and intrauterine eggs reduction rates were observed in both test group (group C and D), comparing with the control groups (group A and B). Results indicated that the DNA vaccines of pcDNA3.0/SjRPS4 and pcDNA3.0/SjRPL7 could induce strong protective immunity against S. japonicum in mice.

Preparation and preliminary application of colloidal carbon dipstick for schistosomiasis japonica / 中南大学学报(医学版)

OBJECTIVE@#To develop a rapid and simple immunoassay to detect antibodies in the sera of patients infect Schistosoma japonicum (S. japonicum).@*METHODS@#Soluble egg antigen (SEA) of S. japonicum conjugated with colloidal carbon in advance was used to react with the antibodies in the sera of patients with schistosomiasis. Then the carbon-antigen-antibody complex would be captured by SEA which had been absorbed on the nitrocellulose membrane and a gray band was shown.@*RESULTS@#A total of 137 sera samples from S. japonicum epidemic area were tested, and the consistency, sensitivity, and specificity of colloidal carbon dipstick assay were 98.54%, 98.99%, and 97.37%, respectively, compared with the IHA method. The gray scale of bands on the dipstick was curvilinear to serum titer which revealed that the assay could be used semi-quantitatively in serum analysis.@*CONCLUSION@#Colloidal carbon dipstick assay is not only rapid and simple, but also sensitive and specific for the detection of serum antibodies of schistosomiasis japonica. It will be a practical immunological assay for the diagnosis of schistosomiasis in the field testing.

Research Progress on Schistosome Vaccine and Prospect of its Application in China / 中国寄生虫学与寄生虫病杂志

Development of vaccine against schistosomiasis japonica has been incorporated into WHO/TDR and China′s main disease control research programs.In recent years,the research on the anti-schistosomiasis vaccine has made significant progress.With the development of proteomics and molecular biology technology,Anti-Schistosoma japonicum vaccine research has been developed to a stage of genetic engineering in our country and DNA vaccines have become the main direction.It reveals new ways to enhance the immunoprotection of Schistosoma japonicum vaccine through screening new candidate antgens,optimizing combination of the mixed/multivalent vaccines,or adjuvant addition.