Platelet RNA enables accurate detection of ovarian cancer: an intercontinental, biomarker identification study

Platelets are reprogrammed by cancer via a process called education, which favors cancer development. The transcriptional profile of tumor-educated platelets (TEPs) is skewed and therefore practicable for cancer detection. This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n = 3; Netherlands, n = 5; Poland, n = 1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, and early-stage ovarian cancer. However, these observations warrant prospective validations in a larger population before clinical utilities.

Adjuvant chemotherapy versus adjuvant concurrent chemoradiotherapy after radical surgery for early-stage cervical cancer: a randomized, non-inferiority, multicenter trial / 医学前沿

We conducted a prospective study to assess the non-inferiority of adjuvant chemotherapy alone versus adjuvant concurrent chemoradiotherapy (CCRT) as an alternative strategy for patients with early-stage (FIGO 2009 stage IB-IIA) cervical cancer having risk factors after surgery. The condition was assessed in terms of prognosis, adverse effects, and quality of life. This randomized trial involved nine centers across China. Eligible patients were randomized to receive adjuvant chemotherapy or CCRT after surgery. The primary end-point was progression-free survival (PFS). From December 2012 to December 2014, 337 patients were subjected to randomization. Final analysis included 329 patients, including 165 in the adjuvant chemotherapy group and 164 in the adjuvant CCRT group. The median follow-up was 72.1 months. The three-year PFS rates were both 91.9%, and the five-year OS was 90.6% versus 90.0% in adjuvant chemotherapy and CCRT groups, respectively. No significant differences were observed in the PFS or OS between groups. The adjusted HR for PFS was 0.854 (95% confidence interval 0.415-1.757; P = 0.667) favoring adjuvant chemotherapy, excluding the predefined non-inferiority boundary of 1.9. The chemotherapy group showed a tendency toward good quality of life. In comparison with post-operative adjuvant CCRT, adjuvant chemotherapy treatment showed non-inferior efficacy in patients with early-stage cervical cancer having pathological risk factors. Adjuvant chemotherapy alone is a favorable alternative post-operative treatment.

Chemotherapy initiation with single-course methotrexate alone or combined with dactinomycin versus multi-course methotrexate for low-risk gestational trophoblastic neoplasia: a multi-centric randomized clinical trial / 医学前沿

We aimed to evaluate the effectiveness and safety of single-course initial regimens in patients with low-risk gestational trophoblastic neoplasia (GTN). In this trial (NCT01823315), 276 patients were analyzed. Patients were allocated to three initiated regimens: single-course methotrexate (MTX), single-course MTX + dactinomycin (ACTD), and multi-course MTX (control arm). The primary endpoint was the complete remission (CR) rate by initial drug(s). The primary CR rate was 64.4% with multi-course MTX in the control arm. For the single-course MTX arm, the CR rate was 35.8% by one course; it increased to 59.3% after subsequent multi-course MTX, with non-inferiority to the control (difference -5.1%,95% confidence interval (CI) -19.4% to 9.2%, P = 0.014). After further treatment with multi-course ACTD, the CR rate (93.3%) was similar to that of the control (95.2%, P = 0.577). For the single-course MTX + ACTD arm, the CR rate was 46.7% by one course, which increased to 89.1% after subsequent multi-course, with non-inferiority (difference 24.7%, 95% CI 12.8%-36.6%, P < 0.001) to the control. It was similar to the CR rate by MTX and further ACTD in the control arm (89.1% vs. 95.2%, P =0.135). Four patients experienced recurrence, with no death, during the 2-year follow-up. We demonstrated that chemotherapy initiation with single-course MTX may be an alternative regimen for patients with low-risk GTN.

Magnetic Resonance Imaging for Diagnosis of Idiopathic Pediatric Meningiomas / 中国医学科学院学报

Objective To analyze the radiological features of idiopathic pediatric meningiomas and explore their relationships with pathological grading,misdiagnoses,and blood loss during surgery.Methods We retrospectively reviewed 29 cases of pathologically confirmed pediatric meningiomas with pre-operative magnetic resonance imaging in Beijing Tiantan Hospital from November 2014 to July 2018.We assessed the imaging features to explore their relationships with pathological grading,misdiagnoses,and blood loss during surgery. Results Among the 29 cases,7 intraparenchymal meningiomas,5 extraparenchymal meningiomas,4 ventricular meningiomas,and 1 transcranial meningioma were misdiagnosed.Tumor location was significantly associated with possibility of misdiagnoses(

Analysis of the influencing factors for postoperative chronic kidney insufficiency in patients with primary aldosteronism / 中华泌尿外科杂志

Objective:To explore the influencing factors of postoperative chronic kidney disease (CKI) in patients with primary aldosteronism (PA).Methods:The clinical data of 103 patients who underwent adrenalectomy for PA in our center from August 2018 to August 2019 were analyzed retrospectively. There were 53 males and 50 females, aged (47.02±10.06) years old, including 27 diabetes patients (26.2%). The body mass index (BMI) were (24.47±3.24) kg/m 2, tumor maximum diameter were (15.61±5.66) mm, preoperative systolic blood pressure were (166.93±12.22) mmHg(1 mmHg=0.133 kPa), preoperative blood potassium were (3.35 ± 0.48) mmol/L, plasma aldosterone concentration (PAC) were (55.75±8.56)ng/dl, aldosterone-renin ratio(ARR) were (165.13±38.21) and preoperative glomerular filtration rate (GFR) were (77.96±14.77) ml/(min·1.73m 2). All patients underwent laparoscopic adrenalectomy. The operation time and bleeding volume were recorded. The GFR, blood potassium, PAC and ARR were recorded at the third month after surgery. The paired sample t test was used to compare GFR before and after surgery. Pearson correlation analysis was used to evaluate the correlation between the parameters and GFR after surgery. The independent predictors of GFR≤60ml/(min·1.73 m 2) were analyzed by univariate and multivariate logistic regression. Results:The surgery time were (85.37±21.66) min, and the bleeding volume were (10.54±4.84) ml. GFR (62.66±8.53) ml/(min·1.73 m 2) at 3 months after surgery was significantly different from that before surgery ( P<0.01). Univariate analysis showed that age ( OR=1.36, P<0.01), preoperative GFR ( OR=0.81, P<0.01), preoperative blood potassium ( OR=2.95, P=0.02), preoperative PAC ( OR=1.28, P<0.01) and preoperative ARR ( OR=1.08, P<0.01) were significantly correlated with postoperative CKI. In Pearson analysis, older age ( r=-0.51, P<0.01), lower preoperative GFR ( r=0.62, P<0.01), lower preoperative blood potassium( r=0.41, P=0.02), higher preoperative PAC ( r=-0.49, P<0.01) and higher preoperative ARR ( r=-0.56, P<0.01) increased the risk of CKI. Multivariate logistic regression analysis showed that age ( OR=1.26, P=0.05), preoperative GFR ( OR=0.79, P=0.02) and preoperative PAC( OR=1.29, P=0.01) were independent risk factors for postoperative CKI. Conclusions:CKI may occur in PA patients after adrenalectomy. PA patients with older age, higher preoperative PAC, higher preoperative ARR, lower preoperative blood potassium and lower preoperative GFR are more likely to have CKI. Age, preoperative GFR and preoperative PAC were independent predictors of CKI.

Effect of antitubercular treatment on the pregnancy outcomes and prognoses of patients with genital tuberculosis / 医学前沿

This retrospective study aims to demonstrate the effect of antitubercular treatment (ATT) on the pregnancy outcomes and prognoses of patients with genital tuberculosis (GTB) who had received laparoscopy and/or hysteroscopy. This study included 78 patients with infertility and who were diagnosed with GTB through laparoscopy and/or hysteroscopy over the period of November 2005 to October 2015. The recruited patients were divided into ATT and nonATT groups on the basis of ATT duration. The GTB recurrence rates, menstrual patterns, and pregnancy outcomes of the patients were determined at follow-up. Among the 78 patients, 46 received ATT and 32 did not receive ATT. The menstrual volumes of patients in the ATT group significantly decreased relative to those of patients in the nonATT group. GTB did not recur among all patients regardless of treatment. A total of 11 pregnancies (36.7%) in the ATT group and 19 pregnancies (63.3%) in the nonATT group were observed. Pregnancy rates significantly differed (P = 0.002) between the two groups. ATT may decrease the menstrual volume and pregnancy rates of patients who were diagnosed with GTB through laparoscopy and/or hysteroscopy. In addition, ATT did not improve the prognosis of patients with chronic GTB.

Correlation of metallothionein-2A, E-cadherin and cyclin E with biochemical recurrence in prostate cancer / 肿瘤研究与临床

Objective To investigate the expressions of metallothionein-2A (MT-2A), E-cadherin, interleukin-6 (IL-6), cyclin E, proliferating cell nuclear antigen (PCNA) and bcl-2 in prostate cancer tissues and their correlation with biochemical recurrence of prostate cancer. Methods Tissue specimens from 128 cases of prostate cancer who underwent radical prostatectomy in Shanxi Dayi Hospital from October 2012 to October 2017 were processed and transferred into tissue microarrays, the clinicopathological parameters of patients were also recorded. The expression levels of MT-2A, E-cadherin, IL-6, cyclin E, PCNA and bcl-2 were detected by immunohistochemical avidin-biotin complex (ABC) staining. The correlation between different molecular markers and biochemical recurrence of prostate cancer was analyzed. Results The biochemical recurrence rate of 128 patients with prostate cancer was 30.5％ (39/128). The biochemical recurrence rates of low-risk, intermediate-risk and high-risk prostate cancer patients were 14.8％(8/54), 38.7％(24/62) and 58.3％ (7/12), respectively. The risk classification and pathological T stage of patients with prostate cancer were associated with the expressions of MT-2A, cyclin E, IL-6 and E-cadherin (all P< 0.05). Multivariate Cox risk model showed that the high risk classification (HR= 1.81, 95％CI 1.56-2.19, P=0.042), MT-2A positive expression (HR= 2.01, 95％CI 1.08-3.15, P= 0.005), cyclin E positive expression (HR= 1.79, 95％CI 1.08-2.21, P= 0.042) and E-cadherin negative expression (HR= 1.92, 95％ CI 1.22-2.45, P= 0.020) were the independent risk factors for biochemical recurrence of prostate cancer. Conclusion The expression of MT-2A, cyclin E and E-cadherin may serve as independent predictors for biochemical recurrence of prostate cancer.

Precision screening and treatment of human papilloma virus related cervical cancer / 浙江大学学报·医学版

Cervical cancer is a complex disease caused by both genetic susceptibility and environmental factors. Inherited genomic variance, high-risk human papilloma virus (HPV) infection/integration, genome methylation and somatic mutation could all constitute one machine learning model, laying the ground for molecular classification and the precision medicine of cervical cancer. Therefore, for cervical screening, next generation sequencing (NGS)-based HPV DNA and other molecular tests as well as dynamic machine learning models would accurately predict patients with potential to develop the cancer, thereby reducing the burden of repeated screening. Meantime, genome-editing tools targeting HPV would emerge as the next generation gene therapy for HPV-related cervical lesions. In this article, we review the substantial progress on molecular mechanism of cervical cancer development and suggest the future for precise prevention and early treatment of cervical cancer.

Genome editing for the treatment of tumorigenic viral infections and virus-related carcinomas / 医学前沿

Viral infections cause at least 10%-15% of all human carcinomas. Over the last century, the elucidation of viral oncogenic roles in many cancer types has provided fundamental knowledge on carcinogenetic mechanisms and established a basis for the early intervention of virus-related cancers. Meanwhile, rapidly evolving genome-editing techniques targeting viral DNA/RNA have emerged as novel therapeutic strategies for treating virus-related carcinogenesis and have begun showing promising results. This review discusses the recent advances of genome-editing tools for treating tumorigenic viruses and their corresponding cancers, the challenges that must be overcome before clinically applying such genome-editing technologies, and more importantly, the potential solutions to these challenges.

Diagnosis and treatment of active adrenal tuberculosis: case report and literature review / 中华泌尿外科杂志

Objective To investigate the diagnosis and treatment of active adrenal tuberculosis.Method The clinical data of 1 patients with adrenal tuberculosis was retrospectively analyzed and the related literatures were reviewed.The male patient,54 years old,complained abuot the dry cough and intermittent fever for 9 months.He was found the left adrenal gland tumor for 1 weeks and admitted to our hospital on November 1st,2016.The physical examination showed the obvious left kidney percussion tellderness.The local hospital,considered the left adrenal tumor.The pathological diagnosis of left adrenal tumor by biopsy was chronic inflammation.The patient accepted anti-inflammatory therapy,but his symptom was not relieved.In our hospital,blood bacterial culture and urine bacterial culture and PPD was negative.Blood tuberculosis antibody was positive.Triple acid-fast bacilli were negative in urine.Chest CT did not exclude the interstitial pulmonary tuberculosis.Adrenal contrast-enhanced CT showed mild enhancement,strip calcification shadow.Primary diagnosis was left adrenal tumor,which the abscess and tuberculosis could not to be excluded.Then,the patient accepted regularly anti-tuberculosis therapy (Isoniazid,0.3 g/d,rifampicin,0.45 g/d,ethambutol,0.6 g/d).Mter 3 days,his temperature returned to normal.Since the left adrenal mass was too large,which was about 6.8 cm × 5.5 cm,to distinguish with the tumor,the patient accepted successfully retroperitoneal adrenal tumor resection two weeks later.The left adrenal tumor surface was greyish and yellow,which was adherent with spleen and pancreas.After carefully separating,the tumor was successfully removed.Result The operation was successful,which last 85 min.Intraoperative blood loss was about 50 ml.Pathological report showed adrenal tuberculosis.The patients accepted regularly antituberculosis therapy(Isoniazid,0.3 g/d,rifampicin,0.45 g/d,ethambutol,0.6 g/d) for half a year,and followed up for 1 year after operation.No further hormone replacement therapy was used.No fever was noticed and his rhythm cortisol level was normal.Conclusions Adrenal mass associated with recurrent fever,should be suspected as adrenal tuberculosis if antibiotic therapy is not effective.If the adrenal CT showed adrenal calcification associated with the ectepic tuberculosis,patient should be diagnosised active adrenal tuberculosis.They should accept anti-tuberculosis treatment.However,if the volume of tuberculosis is large,or not to exclude tumor possibility,we recommend to proceed adrenal tumor resection for diagnosis.

Diagnosis and treatment of active adrenal tuberculosis: case report and literature review / 中华泌尿外科杂志

Objective To investigate the diagnosis and treatment of active adrenal tuberculosis.Method The clinical data of 1 patients with adrenal tuberculosis was retrospectively analyzed and the related literatures were reviewed.The male patient,54 years old,complained abuot the dry cough and intermittent fever for 9 months.He was found the left adrenal gland tumor for 1 weeks and admitted to our hospital on November 1st,2016.The physical examination showed the obvious left kidney percussion tellderness.The local hospital,considered the left adrenal tumor.The pathological diagnosis of left adrenal tumor by biopsy was chronic inflammation.The patient accepted anti-inflammatory therapy,but his symptom was not relieved.In our hospital,blood bacterial culture and urine bacterial culture and PPD was negative.Blood tuberculosis antibody was positive.Triple acid-fast bacilli were negative in urine.Chest CT did not exclude the interstitial pulmonary tuberculosis.Adrenal contrast-enhanced CT showed mild enhancement,strip calcification shadow.Primary diagnosis was left adrenal tumor,which the abscess and tuberculosis could not to be excluded.Then,the patient accepted regularly anti-tuberculosis therapy (Isoniazid,0.3 g/d,rifampicin,0.45 g/d,ethambutol,0.6 g/d).Mter 3 days,his temperature returned to normal.Since the left adrenal mass was too large,which was about 6.8 cm × 5.5 cm,to distinguish with the tumor,the patient accepted successfully retroperitoneal adrenal tumor resection two weeks later.The left adrenal tumor surface was greyish and yellow,which was adherent with spleen and pancreas.After carefully separating,the tumor was successfully removed.Result The operation was successful,which last 85 min.Intraoperative blood loss was about 50 ml.Pathological report showed adrenal tuberculosis.The patients accepted regularly antituberculosis therapy(Isoniazid,0.3 g/d,rifampicin,0.45 g/d,ethambutol,0.6 g/d) for half a year,and followed up for 1 year after operation.No further hormone replacement therapy was used.No fever was noticed and his rhythm cortisol level was normal.Conclusions Adrenal mass associated with recurrent fever,should be suspected as adrenal tuberculosis if antibiotic therapy is not effective.If the adrenal CT showed adrenal calcification associated with the ectepic tuberculosis,patient should be diagnosised active adrenal tuberculosis.They should accept anti-tuberculosis treatment.However,if the volume of tuberculosis is large,or not to exclude tumor possibility,we recommend to proceed adrenal tumor resection for diagnosis.

Hypo-androgen adrenocortical oncocytoma: 1 case report and literature review / 中华泌尿外科杂志

Objective To analysis the clinical features,diagnosis,treatment and prognosis of adrenal eosinophilic tumor with low testosterone levels.Methods The clinical data of a 22 years old male patient with adrenal eosinophilic tumor and low testosterone levels was analyzed.Blood pressure was 151/88 mmHg.The patient got bilateral gynecomastia.His bilateral testicular was soft and became smaller,with short penisr.Endocrine examination results showed:Estradiol 666 pg/ml,Prolactin 19.08 ng/ml,Testosterone 0.18 ng/ml,follicle stimulating hormone ＜ 0.2 U/L.The CT showed the mass density of soft tissue in the left adrenal region with diameter 7 cm,which was inhomogeneous and enhanced.There were many small vessels enhanced in the CT arterial phase,and the blood flow in the tumor was abundant.Clinical diagnosis of left adrenal tumor was pheochromocytoma.The patient underwent laparoscopic left adrenal tumor resection.The left adrenal gland was located in the superior pole of the left kidney,and there was an independent supply of the artery.Results Pathological result showed the tumor weigh was 60 g,7 cm in diameter and brown in section.The tumor cells were arranged in solid nests or acini,with more eosinophilic granules in cytoplasm.The nuclei was round and the nucleoli was located in the center,had clusters of pleomorphic and clustered cells.The tumor was wrapped in a thick fibrous envelope,mainly consisted of eosinophils,granulation tissue.There was no necrosis,mitosis,and vascular invasion.Immunohistochemical staining showed that the expression of CD56 and syn protein was positive.Pathological diagnosis was left adrenal eosinophilic tumor.After 4 months,the blood testosterone levels rose to 3.90 ng/ml,the blood pressure returned to normal (118/75 mmhg).The estradiol (21 pg/ml) was significantly inhibited.The patient began to appear beards and breasts became smaller.There were no signs of clinical or imaging recurrence.After 16 months follow-up,serum testosterone was 4.68 ng/ml and serum estrogen levels dropped to 33 pg/ml.Semen routine showed no sperm.Conclusions The clinical morbidity of functional adrenocortical oncocytoma with low testosterone levels and high estradiol levels is low.The pathological components are mainly eosinophilic granulation tissue.The adrenocortical oncocytoma are rare and preoperative diagnosis is difficult.Clinical manifestation,imaging examination and adrenal biochemistry examination should be considered to determine the localization and qualitative of tumor.Minimally invasive surgery is an effective treatment.The close follow-up after operation is essential.

Binding of human SWI1 ARID domain to DNA without sequence specificity: A molecular dynamics study / 华中科技大学学报（医学）（英德文版）

SWI1 is a member of a new class of tumor DNA-binding proteins named as the AT-rich interaction domain family (ARID), and considered to bind with AT base pairs specifically. Genomic and functional data support ARID1A as a tumor suppressor because ARID1A/BAF250a (SWI1) subunit of the SWI/SNF chromatin-remodeling complex has emerged as recurrently mutated in a broad array of tumor types. But the crystal structure of SWI1 has not been solved as yet. Using docking and molecular dynamics, we predicted the DNA interaction pattern of human SWI1 ARID and made comparisons with the other two representative ARID family members, human Mrf-2 ARID and Drosophila Dri ARID. Dynamic results revealed that the N-terminal and loop L1 of SWI1 ARID bound with the DNA major groove, while the loop L2 and helix H6 bound with the minor groove. Moreover, it was found that SWI1 ARID bound with DNA apparently in a sequence-nonspecific manner. It was concluded that SWI1 ARID can form stable complex with sequence-nonspecific DNA segment comparing to Mrf-2 ARID/DNA and Dri ARID/DNA sequence-specific complexes.

Expressions of LYVE-1 and PROX-1 in Breast Carcinoma and Their Clinical Significance / 华中科技大学学报(医学版)

Objective To investigate the expressions of LYVE-1 and PROX-1 in human breast carcinoma and the clinical significance of lymphatic vessel density.Methods Immunohistochemistry (SP method)was used to detect the expressions of LYVE-1 and PROX-1 in 80 specimens of breast invasive ductal carcinoma and 35 specimens of breast hyperplasia.Results The density of lymphatic vessels positive for LYVE-1 or PROX-1 was significantly higher in breast carcinoma than in breast hyper-plasia (P<0.01).There was a significant correlation between lymphatic vessel density and lymph node metastasis (P<0.01). A negative correlation was noted between the PROX-1 expression in carcinoma cells and tumor grade (P<0.01)or TNM stage (P < 0.01 ).Conclusion Lymphangiogenesis is increased in breast carcinoma,which is associated with lymph node metastasis.PROX-1 may be involved in tumorigenesis,progression and lymphatic metastasis in breast cancer.

Correlation between molecular biomarkers and risk factors for the clinical progression of benign prostatic hyperplasia using tissue microarray immunostaining / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The pathogenesis of benign prostatic hyperplasia (BPH) has been widely studied, and several biomarkers are known to play roles in its development. This study aimed to investigate the possible role of cysteine-rich protein 61 (CYR61), vascular endothelial growth factor (VEGF), androgen receptor (AR), interleukin-6 (IL-6), cytochrome c, caspase-3, and proliferating cell nuclear antigen (PCNA) in the clinical progression of BPH.</p><p><b>METHODS</b>Tissue specimens from 96 BPH cases who underwent transurethral resection of the prostate were processed and transferred to tissue microarrays. Patient age, prostate volume, serum prostate-specific antigen (PSA) level, and International Prostate Symptom Score (IPSS) of all BPH cases were collected before surgery. The expression of CYR61, VEGF, AR, IL-6, cytochrome c, caspase-3, and PCNA was examined by immunostaining in the BPH specimens, and any possible correlation between the different biomarkers and risk factors for BPH clinical progression was analyzed.</p><p><b>RESULTS</b>The expression of CYR61, VEGF, AR, IL-6, cytochrome c, caspase-3, and PCNA in the BPH cases was 68.8% (66/96), 77.1% (74/96), 43.8% (42/96), 31.3% (30/96), 35.4% (34/96), 56.3% (54/96), and 29.2% (28/96), respectively. The expression of both CYR61 and VEGF was positively correlated with patient age, prostate volume, and serum PSA level (P < 0.05). Furthermore, cytochrome c and caspase-3 expression were inversely related to prostate volume (P < 0.05), and AR expression was positively related to serum PSA level (P < 0.05).</p><p><b>CONCLUSION</b>CYR61 and VEGF expression might serve as biomarkers for predicting the clinical progression of BPH due to effects on stromal cell proliferation and angiogenesis.</p>

HPV16 E5 peptide vaccine in treatment of cervical cancer in vitro and in vivo / 华中科技大学学报（医学）（英德文版）

Human papillomavirus (HPV)-induced cervical cancer is the second most common cancer among women worldwide. Despite the encouraging development of the preventive vaccine for HPV, a vaccine for both prevention and therapy or pre-cancerous lesions remains in high priority. Thus far, most of the HPV therapeutic vaccines are focused on HPV E6 and E7 oncogene. However these vaccines could not completely eradicate the lesions. Recently, HPV E5, which is considered as an oncogene, is getting more and more attention. In this study, we predicted the epitopes of HPV16 E5 by bioinformatics as candidate peptide, then, evaluated the efficacy and chose an effective one to do the further test. To evaluate the effect of vaccine, rTC-1 (TC-1 cells infected by rAAV-HPV16E5) served as cell tumor model and rTC-1 loading mice as an ectopic tumor model. We prepared vaccine by muscle injection. The vaccine effects were determined by evaluating the function of tumor-specific T cells by cell proliferation assay and ELISPOT, calculating the tumor volume in mice and estimating the survival time of mice. Our in vitro and in vivo studies revealed that injection of E5 peptide+CpG resulted in strong cell-mediated immunity (CMI) and protected mice from tumor growth, meanwhile, prolonged the survival time after tumor cell loading. This study provides new insights into HPV16 E5 as a possible target on the therapeutic strategies about cervical cancer.

HPV16 E5 peptide vaccine in treatment of cervical cancer in vitro and in vivo / 华中科技大学学报（医学）（英德文版）

Human papillomavirus (HPV)-induced cervical cancer is the second most common cancer among women worldwide. Despite the encouraging development of the preventive vaccine for HPV, a vaccine for both prevention and therapy or pre-cancerous lesions remains in high priority. Thus far, most of the HPV therapeutic vaccines are focused on HPV E6 and E7 oncogene. However these vaccines could not completely eradicate the lesions. Recently, HPV E5, which is considered as an oncogene, is getting more and more attention. In this study, we predicted the epitopes of HPV16 E5 by bioinformatics as candidate peptide, then, evaluated the efficacy and chose an effective one to do the further test. To evaluate the effect of vaccine, rTC-1 (TC-1 cells infected by rAAV-HPV16E5) served as cell tumor model and rTC-1 loading mice as an ectopic tumor model. We prepared vaccine by muscle injection. The vaccine effects were determined by evaluating the function of tumor-specific T cells by cell proliferation assay and ELISPOT, calculating the tumor volume in mice and estimating the survival time of mice. Our in vitro and in vivo studies revealed that injection of E5 peptide+CpG resulted in strong cell-mediated immunity (CMI) and protected mice from tumor growth, meanwhile, prolonged the survival time after tumor cell loading. This study provides new insights into HPV16 E5 as a possible target on the therapeutic strategies about cervical cancer.

Antitumor and antimetastatic effect of antimicrobial peptide conjugated with tumor homing peptide TMTP1 on the transplanted prostate cancer and gastric cancer in nude mice / 中华肿瘤杂志

<p><b>OBJECTIVE</b>Due to their lower risk for induction of resistance, antimicrobial peptides with selective anticancer effect could be developed into a new generation of anticancer drugs. We conjugated an antimicrobial peptide with tumor-targeting peptides (TMTP1) to explore whether it has inhibiting effect on the progression and metastasis of transplanted prostate cancer and gastric cancer in nude mice.</p><p><b>METHODS</b>Subcutaneously transplanted human prostate cancer and orthotopically transplanted human gastric cancer in nude mice were prepared. 50 µmol/L PBS (control group), 50 µmol/L TMTP1 (TMTP1 group) or 50 µmol/L TMTP1-GG-D(KLAKLAK)(2) (treatment group) were injected i.p. to the three groups of nude mice, respectively. The binding ability of the novel fusion polypeptide TMTP1-GG-D(KLAKLAK)(2) to the tumors and its antitumor effect were assessed by measurement of tumor volume, histopathological examination of the tumor tissues, testing apoptosis index of tumor cells with TUNEL staining, and survival curve plotting of the mice.</p><p><b>RESULTS</b>The median survival time of subcutaneous prostate cancer-bearing mice was 50 days in the control group, 55 days in the TMTP1 group, and 70 days in the TMTP1-GG-D(KLAKLAK)(2) group (P < 0.05). The median survival time of the subcutaneous gastric cancer-bearing mice was 25 days in the control group, 30 days in the TMTP1 group, and 45 days in the TMTP1-GG-D(KLAKLAK)(2) group (P < 0.01). The tumor volume in the subcutaneous prostate cancer-bearing mice was (2.5 ± 0.3)cm(3) in the control group, (1.8 ± 0.2) cm(3) in the TMTP1 group, and (0.3 ± 0.1)cm(3) in the TMTP1-GG-D(KLAKLAK)(2) group (P < 0.01). The tumor volume of the subcutaneous gastric cancer-bearing mice was (3.8 ± 0.4) cm(3) in the control group, (3.2 ± 0.2)cm(3) in the TMTP1 group, and (0.4 ± 0.1) cm(3) in the TMTP1-GG-D(KLAKLAK)(2) group (P < 0.01). Large tumors were observed in the stomach of the orthotopic gastric cancer-bearing mice of the control and TMTP1 groups. The tumor volume of the TMTP1-GG-D(KLAKLAK)(2) group was obviously reduced. White metastases in the liver, spleen and abdominal wall were observed in the control and TMTP1 groups (P < 0.01). TUNEL staining revealed that the apoptosis index of the control group was (31.9 ± 1.5)%, TMTP1 group (37.2 ± 2.3)% and TMTP1-GG-D(KLAKLAK)(2) group (69.7 ± 2.1)% (P < 0.01).</p><p><b>CONCLUSIONS</b>The results of our study demonstrate that the novel fusion peptide of antimicriobial peptide conjugated with TMTP1 can effectively inhibit tumor progression and metastasis, therefore, is promising to be a novel effective anticancer drug.</p>

Preliminary evaluation of safety of conditionally replication adenovirus M4 / 华中科技大学学报（医学）（英德文版）

Conditionally replication adenovirus M4, which was constructed in our lab, was proved to have good clinical application prospect for its good anti-tumor and anti-metastasis effect. However, clinically applying M4 faces many problems. One of the most important is the safety of M4. In this study, we investigated the safety of M4 by comparing with Adv-TK, which was proved to be safe in I-III phase clinical trials. M4 and Adv-TK were injected into mice via the tail vein separately, and the mice were sacrificed at the indicated time. Blood was collected for biochemical tests, the liver was harvested for hematoxylin and eosin (H&E) staining and viral quantification, and splenic lymphocytes were separated for adenovirus specific cellular immune response. Our results showed that M4 had no obvious effect on mouse general symptoms. A transient reversible infiltration of inflammatory cells in collect abbacy was only observed in M4 group, and a transient slight increase in Cr level was detected both after M4 and Adv-TK injection. The adenovirus specific cellular immune response induced by M4 was similar to that by Adv-TK, and the distribution and metabolism of M4 in the mouse liver were also similar to those of Adv-TK. It was concluded that conditionally replication adenovirus M4 had the same safety as Adv-TK. The study provides safety basis for the coming clinical trials of M4.

Profiling of microRNA-mRNA reveals roles of microRNAs in cervical cancer / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Cervical cancer is one of the most common malignant tumors in women. This study was designed to explore the expression profiles of microRNAs (miRNAs) and mRNAs and the gene regulation network in cervical tumorigenesis and to find candidate molecular markers and key tumorigenic genes in cervical cancer.</p><p><b>METHODS</b>miRNAs and mRNAs expression microarrays were used to detect the expression of miRNAs and mRNAs in normal and cancer cervical tissues. TargetScan 5.0 database (UK) was used to predict the target genes of the miRNAs, analyze their intersection with differentially expressed mRNAs and negatively correlate the intersection with miRNAs. Bioinformatic approaches were used to analyze functions and pathways of the target genes and establish miRNA-gene network.</p><p><b>RESULTS</b>Twenty-nine miRNAs and 2036 mRNAs were differentially expressed in normal and cervical tumor tissues. Among them, 13 miRNAs and 754 mRNAs were up-regulated in cervical tumor tissues and 16 miRNAs and 1282 RNA were down-regulated. The 327 target genes negatively related to miRNAs in the intersection were involved in functions and signal pathways. Down-regulated miRNAs targeted genes and up-regulated miRNAs targeted genes were involved in 415 and 163 functions, respectively, and in 37 and 17 significant pathways, respectively (P < 0.05, false discovery rate (FDR) < 0.05). We constructed the miRNAs-gene network and found that hsa-miR-15a, hsa-miR-106b and hsa-miR-20b were key nodes in the network.</p><p><b>CONCLUSIONS</b>The differentially expressed miRNAs and mRNAs in cervical cancer and related miRNA-gene network have been identified. They play important roles in cervical tumorigenesis and are involved in many important biological functions and signal transduction pathways. These findings lay a foundation for research on the molecular mechanism of miRNAs in the pathogenesis of cervical cancer.</p>