Identification of High-affinity Novel Targeted Peptides for the Treatment of Human Ovarian Cancer

Background: To investigate the potential of the phage display-identified tumor cellbinding peptide as a biomarker of epithelial ovarian cancer using phage display technology. Method: The Ph.D.-7 Phage Display Peptide Library was used to identify the specific conjugated phages with SKOV3 epithelial ovarian cancer cells, while Chinese hamster ovary cells formed the basis. After employing the rapid differential screening method invitro, the enzyme-linked immunosorbent assay (ELISA), DNA sequencing, immunohistochemistry, immunofluorescence, and the competitive inhibition test of synthetic peptides were used to determine the affinity and specificity of the phages with SKOV3 cells. Results: Using bio panning, we screened the phages, showing a 3590-fold increase after the third round. A total of 61 titers of the phage were randomly selected for ELISA and 10 kinds of the phages with an optical density >0.5 were used for DNA sequencing. Clones of the phage TRRNIPN were derived from DNA sequencing based on ELISA, exhibiting both the brown granular phenomenon and green fluorescence. The specific targeted peptide TRRNIPN was incorporated in tumor cells through the competitive inhibition test. Conclusion: The results of our study indicate that the phage display identified polypeptide TRRNIPN may be an effective biomarker for the early diagnosis and targeted therapy of ovarian cancer

Analysis of the initial symptoms and its diagnostic significance in children with neuroblastoma / 中华实用儿科临床杂志

Objective To explore the significance of the initial clinical symptoms and clinical manifestations of neuroblastoma(NB)to achive early identification of NB. Methods A retrospective study was performed on patients diagnosed with NB,who attended the Hematology Oncology Center,Beijing Childrenˊs Hospital from March 31st ,2007 to March 31st,2015. The clinical characteristics were compared between the children 〈1_year_old and≥1_year_old. The result was analyzed to compare the difference in clinical symptoms and tumor biologic characteristics of patients with different initial clinical symptoms between 2 groups. Results A total of 330 patients were included in the study,43 of them were younger than 1 year old,and their most common symptoms were cough and fever( each 17 cases,and accounted for 39. 5%,respectively);while the most common symptoms in patients≥1_year_old(287 cases)was fe_ver(177 cases,61. 7%),followed by lymphadenopathy(107 cases,37. 3%),bone pain(97 cases,33. 8%)and anemia (48 cases,16. 7%). The frequency of symptoms differed significantly between 2 groups(all P〈0. 05),such as fever (39. 5% vs. 61. 7%,χ2 ﹦6. 68),anemia(4. 7% vs. 16. 7%,χ2 ﹦6. 00),bone pain(0 vs. 33. 8%,χ2 ﹦18. 99),abdo_minal pain(0 vs. 25. 3%,χ2 ﹦10. 19),diarrhea(16. 3% vs. 3. 0%,χ2 ﹦12. 73),lymphadenopathy(7. 0% vs. 37. 3%, χ2 ﹦14. 12)and anorexia(9. 3% vs. 33. 4%,χ2 ﹦9. 21). Datients had fever,anemia,lymphadenopathy,cutaneous hemorrhagic spot or periorbital ecchymosis,bone pain,abdominal pain,exophthalmos,and anorexia early in the initial course of the disease,whose serum lactate dehydrogenase values were significantly increased(P〈0. 05). Datients suf_fered from fever,anemia,lymphadenopathy,bone pain,limbs dysfunctions,abdominal pain at the beginning of the disease,whose urine vanillymandelic acid values were higher than normal(P〈0. 05). Conclusions The study of sympto_mology suggests the most common symptoms in patients with NB 〈1_year_old are cough and fever,while those ≥1_year_old are fever,lymphadenopathy,bone pain,and anemia. Por patients with symptoms mentioned,carrying out the necessary NB_diagnose_related laboratory and imaging studies was statistically relevant to patientsˊ ages(〈1_year_old and≥1_year_old),which may contribute to earlier identification and diagnosis of NB.

Early chemotherapy response to neuroblastoma with N -myc amplification in children / 中华实用儿科临床杂志

Objective To summarize the clinical features of neuroblastoma (NB)with N - myc gene amplifi-cation in order to analyze tumor shrinkage and bone marrow remission in the early stage of chemotherapy,and to eva-luate the children's initial sensitivity to chemotherapy. Methods The medical records of 38 patients with N - myc am-plification of NB were reviewed (bone marrow or tumor tissues were positive during fluorescence in situ hybridization probe),who were treated between February 2012 to December 2016 at the Hematology Oncology Center,Beijing Chil-dren's Hospital,Capital Medical University. The regimens included chemotherapy,surgery,stem cell transplantation, radiotherapy,and maintenance treatment. The data were reviewed for the medical history. The variations of biomarker, bone marrow cells and the primary site were analyzed before and after 2 courses of CAV (Cyclophosphamide + Adriamy-cin + Vincristine)regimen chemotherapy,in order to observe the short - term effect of chemotherapy and the results were described with statistics. Results Total 38 cases were studied,22 boys(58. 9％)and 16 girls(42. 1％). The median age was 30 months. The primary sites of 37 cases of tumor were located in the retroperitoneal and adrenal area,1 case located in the posterior mediastinum. Bone marrow cytology was negative in 12 cases of them,but bone marrow biopsy suggested bone marrow metastasis,while bone marrow cytomorpholigic examinations were positive in the other 26 cases. Of all the 37 cases the lactate dehydrogenase (LDH)levels were reported higher than the normal value. LDH level was under 500 U/ L in one case,9 cases above 4000 U/ L. The neuron specific enolase (NSE)level of all the cases was higher than the normal and NSE level in 36 cases was higher than 100 μg/ L. In one patient the diameter of tumor was less than 5 cm,lager than 10 cm in 32 cases. The lesion of 33 tumor cases before chemotherapy by enhanced CT was ≤100 cm3 in 12 cases,> 100 - 500 cm3 in 11 cases,among which 6 cases ranged from 500 - 1000 cm3 ,4 cases larger than 1000 cm3 . All the 38 cases received 2 courses of chemotherapy. LDH levels of 4 cases became normal,and LDH levels fell under 500 U/ L in 18 cases,while LDH levels of the other 3 cases were above 1000 U/ L. Among 38 cases, the NSE level in 6 cases was reduced to normal,and 16 cases reduced to 25 - 100 μg/ L. The bone marrow examination of 36 cases reversed to negative. According to the image examination,the overall response rate after 2 courses of chemo-therapy was 84. 8％ . One case achieved very good partial remission,21 cases achieved partial response,7 cases a-chieved metastatic remission,2 cases had no remission,while 2 cases showed progression. After 2 courses of chemother-apy,the tumor diameter in 7 cases was less than 5 cm,while that of 22 cases was above 10 cm. Conclusions The ma-jority primary site of NB with N - myc gene amplification is located in retroperitoneal and adrenal area. Patients with the huge tumor have a heavy burden and the biomarker is always high at the early stage. NB with N - myc gene amplifica-tion is sensitive to chemotherapy. After 2 courses of chemotherapy,there is a sharp decrease in the level of biomarker and the tumor burden. Chemotherapy can diminish the burden of tumor in early stage. But because of the huge burden and the huge size of tumor,it's not the best time for surgery and stem cell collection. The patients should go on receiving chemotherapy for remission of disease.

Clinical analysis and prognosis of children with neuroblastoma with pancreatic infiltration / 中华实用儿科临床杂志

Objective To summarize the clinical data and characteristics of neuroblastoma (NB) with pancreatic infiltration and to assess the clinical features and the prognosis of NB.Methods According to NB protocol at Beijing Children's Hospital,Capital Medical University(BCH-NB-2007),based on Hong Kong NB protocol,the patients were divided into 3 groups of low-risk (LR) group,medium risk (MR) group and high-risk (HR) group.All children were followed up till March 31,2017.Diagnosis of pancreatic infiltration of NB was made by abdominal enhancement of CT,enhanced magnetic resonance imaging (MRI) or 18-fluorodeoxyglucose-positron emission tomography-computed tomography(18F-FDG-PET/CT),any of which could suggest NB pancreatic infiltration or postoperative pathology prompted NB to infiltrate the pancreas.Retrospective summary and analysis of indicators were performed,which included the initial diagnosis of primary tumor and metastatic tumor site,tumor markers,clinical stage,risk group,imaging features and treatment.Results (1) Totally 50 eligible patients were included:27 females,23 males,median age of 33 months (7-129 months),10 cases ≤ 18 months,40 cases ＞ 18 months;3 cases were of International Neuroblastoma Staging System(INSS)-Ⅲ,47 cases of INSS-Ⅳ;2 caes of LR,3 cases of MR,45 cases of HR;28 cases had a fever,27 cases with abdominal mass,14 cases with abdominal pain,9 cases with limb pain,5 cases with vomiting,4 cases with diarrhea,and 1 case with jaundice.Forty-nine cases of primary tumor were located in the retroperitoneal adrenal gland,and 1 case in the pelvic cavity.Thirty-two cases had tumor diameter≥ 10 cm.(2)Tumor markers and imaging features:the median serum lactate dehydrogenase (LDH) value in 50 cases was 669 U/L (263-6 762 U/L),of them 19 cases ＞ 1 000 U/L.A total of 80％ cases had neuron specific enolase (NSE) ＞ 0.15 ng/L.Nine cases had elevated amylase (AMY),and 7 cases had elevated lippase (LPS),and all the levels were elevated in 5 cases.A total of 41 cases had pancreas infiltration by abdominal ultrasound,44 cases had pancreas infiltration by abdominal enhancement computed tomography (CT),100％ (14/14 cases)of pancreas infiltration was confirmed by abdominal reconstruction enhancement nuclear imaging MRI,and NB pancreas infiltration was proved in 41.3％ (19/46 cases) by 18F-FDG-PET/CT.Comparison of the above 4 imaging studies:one imaging examination index was positive in 7 cases,accounting for 14.0％,2 positive in 26 cases,accounting for 52.0％,3 positive in 15 cases,accounting for 30.0％,and 4 positive in 2 cases,accounting for 4.0％.(3) Treatment outcomes:totally 50 cases received treatment,including 2 cases of LR,all cases were of INSS-Ⅲ,and 1 case with complete remission (CR).Three cases of MR belonging to INSS-Ⅳ had complete resection of the tumor,1 case had recurrence and died,and the other two were stable.Forty-five cases with HR,median follow-up lasting for 15 (4-53) months,16 cases had occurrence (35.6％),3 cases were relapsed after stopping treatment for 2,3,18 months,respectively;tumor progressed in 12 patients during treatment,and 1 case got severe intracranial infection and gave up treatment before death.Kaplan-Meier analysis showed the expected 3-year event free survival(EFS) rate was 22.1％,and 3-year overall survival(OS) rate was 38.5％.Conclusions Preliminary results show that 90％ with pancreatic infiltration of NB belong to Ⅳ HR group of children,and almost primary tumor is almost located in the retroperitoneal ragion.NB with pancreatic infiltration clinical manifestations is hidden and nonspecific.More than half of the children have no obvious abdominal pain or vomiting,and so imaging examination is needed to determine the situation of pancreatic metastasis further.Abdominal reconstruction enhancement MRI has a high sensitivity and specificity for pancreatic metastatic lesions,which can be used as the basis for early diagnosis.The overall prognosis is poor.The expected 3-year EFS rate can be 22.1％,3-year OS rate was 38.5％.

Study progress in early recognition and initial treatment before referral of childhood malignant solid tumors / 中华实用儿科临床杂志

Childhood malignant solid tumors exhibit a wide variety of vagueness signs and symptoms in the early stage,which are usually nonspecific,therefore the diagnosis of childhood malignant solid tumor can be challenging when the disease is in the early stage.As a result,the delay of diagnosis causes mistreatment,and which makes childhood malignant solid tumors become a leading cause of death in children.Physicians should recognize the early warning signs of childhood cancer,and a good clinical history and careful physical examination can help physicians determine whether the children have cancer and make referrals in time.Some children with possible cancers require immediate initial treatment before referral to be stabilized in order to make the referrals possible and increase the chance of receiving appropriate treatment in time and the possibility of being cured,saving more children with malignant solid tumors to the maximum extent.

Progress of the relationship between the etiology of childhood malignancy and placental disease / 中华实用儿科临床杂志

Childhood cancers are malignancies occured during childhood,which consist of blood-lymphatic system disorders and solid tumor,usually under the age of 15 years old.Among cancers of childhood,solid tumors account for the mainly proportion and most neoplasms are embryonic origin,which are distinctly different from the adult solid tumors.The pathogenesis of children with an oncologic disease,except from the 2 major elements heredity and environment,some experts consider that there are intense correlations between various carcinogenic environment exposure during pregnancy even progestation and childhood cancers.The placenta is a combination of embryo and the maternal tissues,while is a material exchanged organ between 2 parts.One part has a same origin with fetus biological and genetics,and the other provides comprehensive guarantee for fetus normal development in utero.The research of the placental disease of childhood cancers may have a breakthrough in the study of the etiology of pediatric oncology.