Clinical analysis and curative effect of reactivation of retinopathy of prematurity after intravitreous injection of ranibizumab / 中华眼底病杂志

Objective:To observe the clinical characteristics and therapeutic effect of reactivation of retinopathy of prematurity (ROP) patients after intravitreal injection of ranibizumab (IVR).Methods:A retrospective case series study. Eleven children with ROP (21 eyes) who were reactivated after IVR in Shenzhen Eye Hospital from January 2019 to October 2021 were included in the study. Among them, there were 6 males (11 eyes) and 5 females (10 eyes), with the gestational age of (27.6±2.2) weeks and birth weight of (1 034.6±306.5) g. At the first IVR treatment, 14 eyes (63.7%, 14/22) had acute ROP (AROP), 8 eyes (36.3%, 8/22) had threshold lesions. Post-reactivation treatments include IVR, retinal laser photocoagulation (LP), or minimally invasive vitrectomy (MIVS). The follow-up time after treatment was 12 to 18 months. Birth gestational age, birth weight, treatment method, corrected gestational age at treatment, lesion stage before and after treatment, lesion reactivation and regression time were recorded. The clinical characteristics and efficacy were observed and analyzed.Results:The time from initial IVR treatment to reactivation was (8.2±3.5) weeks. The corrected gestational age of the child was (43.62±4.08) weeks. In 21 eyes, AROP, threshold lesion, prethreshold lesion, and stage 4 lesion were in 2, 4, 12, and 3 eyes, respectively. The patients were treated with IVR, LP, IVR+LP, IVR+MIVS in 2, 13, 4 and 2 eyes, respectively. After the first reactivation treatment, the time of regression and stability was (8.4±4.9) weeks after treatment. There were 5 eyes with secondary reactivation of the lesion, and the lesion stages were stage 3, stage 4a and stage 5 in 2, 1 and 2 eyes, respectively. The mean reactivation time was (19.3±6.0) weeks after the last treatment. The patients in stage 3, stage 4a and stage 5 were treated with LP, LP+MIVS and IVR, respecitively, and the lesions subsided steadily during follow-up. At the last follow-up, 19 out of 21 eyes showed complete regression of the lesions, stable photocoagulation, regression of crista-like lesions, no additional lesions, and retinal leveling. All retinal detachment was "funnel-shaped" in 2 eyes.Conclusions:The lesion reactivation of AROP after IVR treatment is more common. The early reactivation rate is higher after treatment. There is a possibility of reactivation twice after re-treatment.

Microvascular changes of macular edema secondary to branch retinal vein occlusion treated with intravitreal conbercept injection / 中华眼底病杂志

Objective:To observe the changes of macular microvascular structure in eyes with macular edema secondary to branch retinal vein occlusion (BRVO-ME) after intravitreal injection of conbercept and analyze its relationship with visual function and central retinal thickness (CRT).Methods:A prospective clinical study. From July 2018 to June 2019, 21 eyes of 21 patients with unilateral temporal BRVO-ME diagnosed in the Department of Ophthalmology of Peking Union Medical College Hospital were included in the study. Among them, there were 14 eyes of 14 males and 7 eyes of 7 females; the average age was 58.0±8.3 years. There were 13 eyes and 8 eyes with occlusion of the superior temporal and inferior temporal branches of the retinal vein, respectively. The affected area was defined as the side of the venous obstruction. All the affected eyes underwent best-corrected visual acuity (BCVA) and optical coherence tomography angiography (OCTA) examination. The BCVA was tested using the international standard logarithmic visual acuity chart, which was converted into the logarithmic minimum angle of resolution (logMAR) visual acuity during statistical analysis. All the eyes were treated with intravitreal injection of conbercept once a month for 3 months, and then treated as needed. A 3 mm × 3 mm scan centered on fovea was obtained and the vascular density of superficial capillary plexus (SCP) and deep capillary plexus (DCP), fovea avascular zone (FAZ) area, perimeter of FAZ (PERIM), acircularity index (AI), foveal vascular density in a 300 μm wide region around FAZ (FD-300) and central retinal thickness (CRT) were measured. The follow-up time after treatment was 6 months. The vascular density and FAZ parameters were compared before and after treatment by paired t test. The correlations of BCVA, CRT and vascular density, FAZ area and the other parameters at 6 months after treatment were analyzed by linear regression analysis. Results:Before treatment, the logMAR BCVA of the eyes was 0.506±0.159, and the CRT was 375.4±81.3 μm; 6 months after treatment, the logMAR BCVA of the eyes was 0.294±0.097, and the CRT was 266.3±46.7 μm. There was a statistically significant difference of logMAR BCVA and CRT between the eyes before and after treatment ( t=8.503, 9.843; P<0.05). There was no statistically significant difference in the overall vascular density of SCP and DCP before and 6 months after treatment ( t=-0.091, -0.320; P>0.05). The foveal vascular density decreased, and the difference was statistically significant ( t=8.801, 3.936; P<0.05). The vascular density of DCP of the affected area increased, and the difference was statistically significant ( t=-2.198, P<0.05). Compared with those before treatment, the FAZ area and PERIM of the affected eyes had an increasing trend, while AI and FD-300 had a decreasing trend, and the differences were statistically significant ( t=-18.071, -12.835, 2.555, 8.610; P<0.05). The linear regression analysis showed that BCVA and FAZ area 6 months after treatment have significant correlation ( t=2.532, P=0.024). Conclusion:CRT decreased and BCVA increased after intravitreal injection of conbercept in BRVO-ME eyes. After treatment, the foveal vascular density of SCP and DCP decreased while the vascular density of DCP of the affected area increased. The FAZ increased and the PERIM and AI decreased during follow-up. The BCVA was significantly correlated with the FAZ area 6 months after treatment.

Chinese expert consensus on antiangiogenic drugs for advanced non-small cell lung cancer (2020 Edition) / 中华肿瘤杂志

Non-small cell lung cancer (NSCLC) is the most common histological type of lung cancer, accounting for more than 80% of primary lung cancer. Platinum-based chemotherapy is the traditional standard for the treatment of advanced NSCLC, but the 5-years survival rate is still very low, less than 5%. Angiogenesis plays an important role in the growth, proliferation and metastasis of solid tumors. Angiogenesis inhibitors affect the tumor microenvironment, degenerate existing tumor blood vessels and inhibit tumor angiogenesis. Angiogenesis inhibitors are now one of the indispensable treatments for patients with advanced NSCLC through continuous development of new angiogenesis inhibitor and improvement of drug accessibility. This consensus is based on the "Expert consensus on anti-angiogenic drug therapy for advanced non-small cell lung cancer in China (2019 Edition)" , combines with clinical research evidence published in the past years and clinical experience. The consensus-writing group compiles a consensus of guiding clinical departments related to lung cancer treatment to use anti-angiogenic drugs in a standardized manner, and further improves the level of standardized diagnosis and treatment of lung cancer.

Apatinib and S-1 combination therapy for the treatment of advanced head and neck neoplasms: Three case reports

Apatinib, one of the novel oral antiangiogenic agents, shows survival benefits in treating advanced or metastatic gastric adenocarcinoma. However, its efficacy in treating advanced head and neck neoplasms has not been reported. Herein, three elderly men with advanced head and neck neoplasms were treated with apatinib and S-1. Their initial diagnoses were hypopharyngeal carcinoma, metastatic squamous cell carcinoma of head and neck, and squamous cell carcinoma of the pyriform sinus. All patients underwent repeated chemotherapy but developed disease progression. As they refused radiotherapy due to its serious adverse reaction, apatinib was administered at a dose of 425 mg daily and S-1 at 60 mg twice daily. Thirty days after apatinib administration, the patients achieved partial response according to the Response Evaluation Criteria in Solid Tumors 1.1 standard. Mild toxicity or drug-related side effect was observed during the treatment. Therefore, apatinib and S-1 could be the new treatment option for advanced head and neck neoplasms. However, clinical trials are required to confirm their efficacy and safety.

Role of brain-specific angiogenesis inhibitor 1 in synapse and cognitive impairment / 中华行为医学与脑科学杂志

Adhesion G protein-coupled receptors(aGPCRs) play a significant role in cognitive impairment related diseases. As an important member of aGPCRs, brain-specific angiogenesis inhibitor 1(BAI1) has a prominent impact on anti-angiogenesis, anti-tumor and participating in immune phagocytosis. Recent research found out that BAI1 exerts a great influence on synaptogenesis and synaptic plasticity, but few studying concerning BAI1 in nervous system. Nowadays, the aging of population aggravates the occurrence of cognitive impairment. The pathogenesis of Alzheimer's disease and vascular cognitive impairment remains elusive, and identification of cognitive impairment at an early stage faces challenges. In the stage of mild cognitive impairment, synaptic damage is evident. BAI1 can regulate the function of postsynaptic membrane, synaptogenesis, synaptic signal transmission and the morphological development of dendritic spines. Therefore, it may potentially act as an early-warning index and intervention target for cognitive impairment.

Autophagy Is a Potential Target for Enhancing the Anti-Angiogenic Effect of Mebendazole in Endothelial Cells

Mebendazole (MBZ), a microtubule depolymerizing drug commonly used for the treatment of helminthic infections, has recently been noted as a repositioning candidate for angiogenesis inhibition and cancer therapy. However, the definite anti-angiogenic mechanism of MBZ remains unclear. In this study, we explored the inhibitory mechanism of MBZ in endothelial cells (ECs) and developed a novel strategy to improve its anti-angiogenic therapy. Treatment of ECs with MBZ led to inhibition of EC proliferation in a dose-dependent manner in several culture conditions in the presence of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) or FBS, without selectivity of growth factors, although MBZ is known to inhibit VEGF receptor 2 kinase. Furthermore, MBZ inhibited EC migration and tube formation induced by either VEGF or bFGF. However, unexpectedly, treatment of MBZ did not affect FAK and ERK1/2 phosphorylation induced by these factors. Treatment with MBZ induced shrinking of ECs and caused G2-M arrest and apoptosis with an increased Sub-G1 fraction. In addition, increased levels of nuclear fragmentation, p53 expression, and active form of caspase 3 were observed. The marked induction of autophagy by MBZ was also noted. Interestingly, inhibition of autophagy through knocking down of Beclin1 or ATG5/7, or treatment with autophagy inhibitors such as 3-methyladenine and chloroquine resulted in marked enhancement of anti-proliferative and pro-apoptotic effects of MBZ in ECs. Consequently, we suggest that MBZ induces autophagy in ECs and that protective autophagy can be a novel target for enhancing the anti-angiogenic efficacy of MBZ in cancer treatment.

Clinical efficacy and safety of apatinib combined with chemotherapy for osteosarcoma and soft tissue sarcoma with pulmonary metastasis / 中华肿瘤杂志

Objective@#To compare the clinical efficacy and drug safety between oral apatinib combined with conventional chemotherapy and conventional chemotherapy alone for the treatment of osteosarcoma and soft tissue sarcoma patients with pulmonary metastasis.@*Methods@#Thirty-three osteosarcoma and soft tissue sarcoma patients with pulmonary metastasis who were treated in the Department of Bone and Soft Tissue Tumor Surgery, Cancer Hospital of China Medical University from January 2015 to December 2017 were enrolled in this study. Patients with osteosarcoma received methotrexate, adriamycin (ADM), cisplatin (CDDP), ifosfamide (IFO) sequential regimen; patients with soft tissue sarcoma were treated with IFO and ADM regimen. Eighteen of these patients received an additional oral dose of apatinib. The patients were followed up regularly for changes in primary tumors and metastases, adverse reactions and prognosis.@*Results@#Before treatment, the maximum diameter of pulmonary metastases in patients of apatinib group and routine treatment group were (4.46±1.70) cm and (4.53±2.00) cm, respectively, without significant difference (P=0.909). After treatment, the maximum diameter of pulmonary metastases in patients of apatinib group was (1.46±1.39) cm, significantly smaller than (3.02±1.20) cm of routine treatment group (P=0.002). After treatment, the maximum diameter of the primary lesions in the apatinib group and the conventional treatment group median decreased 0.31 cm and 0.12 cm, respectively, without significant difference (P=0.542). After treatment, the maximum diameter of the lung metastases in the apatinib group median decreased 0.59 cm, significantly more than 0.18 cm of the conventional treatment group (P=0.027). The median progression-free survival (PFS) was 9.4 months in the 33 patients. The median PFS was 9.6 months and 8.3 months in the apatinib group and the conventional treatment group, respectively, without significant difference (P=0.593). Specific adverse reactions both occurred in apatinib group and routine treatment group, mainly including oral mucosal reactions and digestive tract reactions (including nausea, vomiting and diarrhea).@*Conclusions@#Apatinib can effectively reduce the volume of primary and metastatic lesions in patients with bone and soft tissue sarcoma accompanied by lung metastasis without reducing the survival rate or causing uncontrollable adverse reactions. The safety and clinical efficacy of apatinib are significant.

Role of brain-specific angiogenesis inhibitor 1 in synapse and cognitive impairment / 中华行为医学与脑科学杂志

Adhesion G protein-coupled receptors(aGPCRs) play a significant role in cognitive impairment related diseases.As an important member of aGPCRs,brain-specific angiogenesis inhibitor 1 (BAI1) has a prominent impact on anti-angiogenesis,anti-tumor and participating in immune phagocytosis.Recent research found out that BAI1 exerts a great influence on synaptogenesis and synaptic plasticity,but few studying concerning BAI1 in nervous system.Nowadays,the aging of population aggravates the occurrence of cognitive impairment.The pathogenesis of Alzheimer's disease and vascular cognitive impairment remains elusive,and identification of cognitive impairment at an early stage faces challenges.In the stage of mild cognitive impairment,synaptic damage is evident.BAI1 can regulate the function of postsynaptic membrane,synaptogenesis,synaptic signal transmission and the morphological development of dendritic spines.Therefore,it may potentially act as an early-warning index and intervention target for cognitive impairment.

Evaluation of efficacy and safety of apatinib for patients with recurrent epithelial ovari-an cancer / 中国肿瘤临床

To assess the efficacy and safety of apatinib for patients with epithelial ovarian cancer (EOC) who had failed in second-line chemotherapy. Methods: The clinical data of 46 patients with recurrent EOC who had failed in second-line chemotherapy and were admitted to the Cancer Hospital of Tianjin Medical University from September 2017 to November 2018 were collected. The treatment efficacy of apatinib was evaluated, and treatment-related adverse events (AEs) were recorded to evaluate its safety. Results:A total of 46 eligible patients were enrolled. The median follow-up time was 12 months. The median overall survival (OS) was 6 months (range 2-15 months). The objective response rate (ORR) was 26.1% (12/46 patients), and the disease control rate (DCR) was 86.9% (40/46 patients). AEs occurred in 30 patients (65.2%), and were mainly of grade 1-2. The most common treatment-related AEs were hypertension (39.1%) and hand-foot-skin syndrome (30.4%); only one patient experienced grade 3 treatment-related hyperten-sion. All grade 1-2 AEs could be recovered rapidly and well-tolerated after treatment with medication. Conclusions: Apatinib may be a safe and effective option for patients with advanced EOC who had failed in second-line chemotherapy. Further Studies are warranted in large-scale clinical trials.

Avaliação de fatores prognósticos a curto prazo com o uso de ranibizumabe em pacientes com edema macular diabético / Evaluation of short-term prognostic factors of ranibizumab in patients with dabetic macular edema

Resumo Objetivo: Investigar fatores prognósticos a curto prazo em pacientes portadores de edema macular diabético (EMD) tratados com injeções intravítreas (IV) de ranibizumabe (RZB). Métodos: Estudo descritivo transversal, retrospectivo, analisou-se 41 prontuários de uma clínica privada na cidade de Belo Horizonte - Minas Gerais, do período de agosto de 2016 a maio de 2017. Verificou-se dados gerais e história pregressa de pacientes que receberam IV mensais consecutivas para EMD, investigando-se sexo, idade e presença de tratamento prévio como possíveis fatores prognósticos determinantes nas mudanças na acuidade visual após o procedimento mensal. Resultados: No total da amostra, 51,2% eram indivíduos do sexo feminino. A média de idade foi de 64,20 ± 7,54 anos. Não houve associação estatisticamente significativa entre idade, gênero ou realização de tratamento prévio e melhora na acuidade visual. Conclusão: A principal estratégia de tratamento para o EMD estabelecida atualmente é através das injeções IV que apresentam eficácia comprovada na melhora da acuidade visual. Entretanto, aproximadamente metade dos pacientes não exibem resposta completa ou são refratários a essa abordagem terapêutica. Nesse sentido, o reconhecimento de fatores prognósticos pode ajudar os oftalmologistas a tomar decisões mais individualizadas, decidindo quais pacientes com EMD responderá às terapias anti-VEGF. Tendo em vista que não há estudos para averiguar os efeitos a curto prazo após injeções IV, no contexto apenas dessa melhora visual, esse trabalho se propôs a avaliar os possíveis fatores prognósticos, que se refletem em uma melhor resposta ao tratamento anti-VEGF, a partir da análise da melhor acuidade visual corrigida, em um contexto real da prática oftalmológica.

Abstract Purpose: Study the prognostic factors for short-term visual improvement in pacients treated with ranibizumab (IVR) for diabetic macular edema (DME). Methods: cross-sectional descriptive study in which 41 eletronic medical records of patients who attended in a private medical clinic in Belo Horizonte - Minas Gerais in a period of August / 2016 to May / 2017. It was verified general data and previous history of patients who received consecutive monthly IVR for DME, analyzing sex, age and presence of previous treatment as possible prognostic factors determining the changes in visual acuity measured by the Snellen table after the monthly procedure. Results: In the total sample, 51.2% were female subjects. The mean age was 64.20 ± 7.54 years. Age, previous treatment and gender were not correlated with better visual acuity in any time. Conclusion: The major strategy of DME treatment nowadays is intravitreal injections, which have proved to be an effetive way of visual acuity improvement. However, many patients do not exhibit the expected outcome or are refractory to treatment. Aiming to predict the treatment efficacy in short term - also to provide the patient a reasonable expectation about the outcome - based on prognostic factors, new clinical studies are necessary since there are so few that approach this subject - such an important treatment of a very prevalent disease.

1-Methoxycarbony-β-carboline from Picrasma quassioides exerts anti-angiogenic properties in HUVECs in vitro and zebrafish embryos in vivo / 中国天然药物

Angiogenesis is a crucial process in the development of inflammatory diseases, including cancer, psoriasis and rheumatoid arthritis. Recently, several alkaloids from Picrasma quassioides had been screened for angiogenic activity in the zebrafish model, and the results indicated that 1-methoxycarbony-β-carboline (MCC) could effectively inhibit blood vessel formation. In this study, we further confirmed that MCC can inhibit, in a concentration-dependent manner, the viability, migration, invasion, and tube formation of human umbilical vein endothelial cells (HUVECs) in vitro, as well as the regenerative vascular outgrowth of zebrafish caudal fin in vivo. In the zebrafish xenograft assay, MCC inhibited the growth of tumor masses and the metastatic transplanted DU145 tumor cells. The proteome profile array of the MCC-treated HUVECs showed that MCC could down-regulate several angiogenesis-related self-secreted proteins, including ANG, EGF, bFGF, GRO, IGF-1, PLG and MMP-1. In addition, the expression of two key membrane receptor proteins in angiogenesis, TIE-2 and uPAR, were also down-regulated after MCC treatment. Taken together, these results shed light on the potential therapeutic application of MCC as a potent natural angiogenesis inhibitor via multiple molecular targets.

1-Methoxycarbony-β-carboline from Picrasma quassioides exerts anti-angiogenic properties in HUVECs in vitro and zebrafish embryos in vivo / 中国天然药物

Angiogenesis is a crucial process in the development of inflammatory diseases, including cancer, psoriasis and rheumatoid arthritis. Recently, several alkaloids from Picrasma quassioides had been screened for angiogenic activity in the zebrafish model, and the results indicated that 1-methoxycarbony-β-carboline (MCC) could effectively inhibit blood vessel formation. In this study, we further confirmed that MCC can inhibit, in a concentration-dependent manner, the viability, migration, invasion, and tube formation of human umbilical vein endothelial cells (HUVECs) in vitro, as well as the regenerative vascular outgrowth of zebrafish caudal fin in vivo. In the zebrafish xenograft assay, MCC inhibited the growth of tumor masses and the metastatic transplanted DU145 tumor cells. The proteome profile array of the MCC-treated HUVECs showed that MCC could down-regulate several angiogenesis-related self-secreted proteins, including ANG, EGF, bFGF, GRO, IGF-1, PLG and MMP-1. In addition, the expression of two key membrane receptor proteins in angiogenesis, TIE-2 and uPAR, were also down-regulated after MCC treatment. Taken together, these results shed light on the potential therapeutic application of MCC as a potent natural angiogenesis inhibitor via multiple molecular targets.

Research Progress and Therapeutic Prospect of Angiogenesis Inhibitors in the Microvascular Complication of Diabetic Mellitus / 中山大学学报(医学科学版)

Microvascular complications of diabetic mellitus injure entire organs of the body. Diabetic retinopathy,foot ulcer, erectile dysfunction and diabetic nephropathy are the major pathogenesis of blindness,non-traumatic amputation,kidney failure and even death,respectively. Thus,early intervention of microvascular complications is the optimized strategy for improving the quality and prolonging the lifespan. Angiogenesis is the one of most significant pathologic features in microvascular complications of diabetic mellitus.Angiogenesis inhibitors are closely involved in the balance regulation of angiogenesis. Therefore ,this review aims to present the research progress and the therapeutic prospect of angiogenesis inhibitors in the microvascular complication of diabetic mellitus.

Development of a Pulmonary Arteriovenous Fistula after a Modified Glenn Shunt in Tetralogy of Fallot and Its Resolution after Shunt Takedown in a 57-Year-Old Patient

Pulmonary arteriovenous fistula (PAVF) is a complication of the Glenn shunt. A 57-year-old tetralogy of Fallot (TOF) patient, who had undergone a Glenn shunt and TOF total correction, complained of dyspnea and cyanosis. PAVFs were present in the right lung, and right lung perfusion was nearly absent. After coil embolization, takedown of the Glenn shunt, and reconstruction of the right pulmonary artery, the patient's symptoms were relieved. Extrapulmonary radioisotope uptake caused by the PAVFs shown in lung perfusion scans decreased, and right lung perfusion increased gradually. Although the development and resolution of PAVFs after a Glenn shunt have been reported in the pediatric population, this may be the first report on this change in old age.

Ciclooxygenase inhibitor and metronomic chemotherapy association for the treatment of metastatic anal sac carcinoma in dog: case report / Inibidor de ciclo-oxigenase associado à quimioterapia metronômica no tratamento de carcinoma de saco anal metastático canino: relato de caso

Metronomic chemotherapy consists of an anticancer modality treatment. It is applicable in patients at an advanced stage, with the objective of increasing overall survival. The aim of this study was to report an anal sac apocrine carcinoma case in a dog with lymph node metastasis treated with metronomic chemotherapy sequential to surgery and conventional chemotherapy using gemcitabine and carboplatin. Metronomic chemotherapy was associated with cyclooxygenase-2 (COX-2) inhibitors, due to strong tumor COX-2 immunohistochemistry expression. Metronomic chemotherapy was initiated with cyclophosphamide, but it was replaced by lomustine, also in metronomic dosage, due to adverse effects. Treatment showed effectiveness, since the patient's overall survival exceeded 1095 days (36 months), considerably higher than the mean overall survival expected for this pathology.(AU)

Quimioterapia metronômica consiste em uma modalidade de tratamento anticancerígeno, aplicável a pacientes em estadiamento avançado, com o objetivo de aumentar a sobrevida global. O objetivo deste trabalho foi relatar um caso de carcinoma apócrino do saco anal, em uma cadela, com metástase em linfonodo tratado com quimioterapia metronômica sequencial à cirurgia e quimioterapia convencional utilizando-se gencitabina e carboplatina. O tratamento metronômico foi associado ao uso de inibidores de ciclo-oxigenase-2 (COX-2), baseando-se na constatação de sua expressão tumoral. A terapia metronômica iniciou-se com ciclofosfamida, mas houve necessidade de substituição pela lomustina, também em dose metronômica, devido à ocorrência de efeitos adversos. O tratamento mostrou ser eficaz, pois a sobrevida do paciente ultrapassa 1095 dias (36 meses) desde a cirurgia, sendo consideravelmente maior que a média relatada para essa patologia.(AU)

Progress in the treatment of cervical carcinoma / 中国综合临床

The incidence of cervical cancer is the first place in gynecological malignant tumors in China. About 500,000 new cases accounts for 5% of all new cancer patients appeared per year all over the world.How to prolong the progression free survival and overall survival of patients with cervical carcinoma is a very important issue in the field of gynecology.So it is very important to take effective treatment.This paper reviewed the research progress of cervical carcinoma treatment in recent years,including surgical treatment,chemotherapy drugs thera?py,angiogenesis inhibitors targeted therapy,immunization therapy.

Antitumor effects of peptide HM-3 against non-small cell lung cancer xenografts in nude mice / 中国药理学通报

Aims Toevaluatethepharmacodynamic efficacy of different types of antiangiogenic agents as HM-3 on a non-small cell lung cancer xenografts tumor model .To explore the interaction between the antian-giogenic agents and the tumor microenvironment,and to offer suggestions for clinical therapy.Methods Thenon-smallcelllungcarcinomaxenograftmodelwas established in Balb/c nude mice.The model mice were treated with Docetaxel(10 mg·kg-1 )as the positive control.The mice were parallelly treated with,HM-3 at the doses of 3 mg · kg-1 and 48 mg · kg-1 and, Avastin(5 mg·kg-1 ).The parameters include tumor volume,tumor weight and immunohistochemical analy-sis.Result Animalexperimentsshowedthatdocetaxel had good anti-tumor activity.Tumor growth inhibition by tumor weight of G2 docetaxel(10 mg·kg-1 )group was 60. 80%.Tumor growth inhibition by tumor weight of G3 HM-3(3 mg·kg-1 )group,G4 HM-3(48 mg· kg-1 )group ,G4 Avastin(5 mg·kg-1 )group,were 43. 60%,-34. 80%,44. 40%,respectively.Con-clusion Theantigiogeniceffectisaffectedbytumor growth stage,tumor microenvironment and their work-ing mechanisms.Angiogenesis inhibitors HM-3 has a certain effect of inhibiting tumor growth,but to little a-vail.HM-3 shows on inhibitory effect in a dose-de-pendent manner at the doses of 0~6 mg·kg-1 .HM-3 at a high dose of 48 mg · kg-1 has no inhibitory but promoting effects on human non-small cell lung carci-noma A549 xenografts in nude mice .Special dose-effect relationship indicates that dosage should be paid attention to in the clinical use of blood vessel inhibi-tors.

Major clinical research advances in gynecologic cancer in 2014 / 부인종양

In 2014, 9 topics were selected as major advances in clinical research for gynecologic oncology: 2 each in cervical and corpus cancer, 4 in ovarian cancer, and 1 in breast cancer. For cervical cancer, several therapeutic agents showed viable antitumor clinical response in recurrent and metastatic disease: bevacizumab, cediranib, and immunotherapies including human papillomavirus (HPV)-tumor infiltrating lymphocytes and Z-100. The HPV test received FDA approval as the primary screening tool of cervical cancer in women aged 25 and older, based on the results of the ATHENA trial, which suggested that the HPV test was a more sensitive and efficient strategy for cervical cancer screening than methods based solely on cytology. For corpus cancers, results of a phase III Gynecologic Oncology Group (GOG) 249 study of early-stage endometrial cancer with high-intermediate risk factors are followed by the controversial topic of uterine power morcellation in minimally invasive gynecologic surgery. Promising results of phase II studies regarding the effectiveness of olaparib in various ovarian cancer settings are summarized. After a brief review of results from a phase III study on pazopanib maintenance therapy in advanced ovarian cancer, 2 outstanding 2014 ASCO presentations cover the topic of using molecular subtypes in predicting response to bevacizumab. A review of the use of opportunistic bilateral salpingectomy as an ovarian cancer preventive strategy in the general population is presented. Two remarkable studies that discussed the effectiveness of adjuvant ovarian suppression in premenopausal early breast cancer have been selected as the last topics covered in this review.

Expression of anti-angiogenic vascular endothelial growth factor isoforms VEGFxxxb in human retinal pigment epithelium cells / 中华实验眼科杂志

Background Hypoxia can increase the secretion of vascular endothelial growth factor-A (VEGF A) by retinal pigment epithelium (RPE) cells and initiate choroidal neovascularization (CNV) consequently.Two VEGF-A isoforms,the angiogenic VEGF-A family (VEGFxxx) and the anti-angiogenic VEGF-A family (VEGFxxxb),are found and formed by alternative splicing.However,the expressing changes and its effect in human RPE cells under the normoxia and hypoxia are unclear.Objective This study was to investigate the expression of VEGFxxx b in human RPE cells under hypoxia.Methods ARPE-19,a human RPE cell line,were cultured.CoCl2 150 μmol/L was added into the medium to mimic the hypoxia environment for 0 hour (normoxia group),3,12 and 24 hours to induce the hypoxia cells.The cells or suspension was harvested at various time points.The expressions of VEGFxxx mRNA and VEGFxxxb mRNA in the cells were detected,and the expressions of the total VEGF-A protein and VEGFxxxb protein in the cells were assayed by Western blot.ELISA was used to determine the contents of total VEGF-A and VEGFxxxb proteins in suspension.Results VEGFxxx mRNA and VEGFxxxb mRNA were expressed in the ARPE-19 cells in both normoxia and hypoxia,and multiple VEGFxxx mRNA isoforms appeared,including VEGF121 mRNA,VEGF165 mRNA and extremely faint VEGF189 mRNA,but only VEGF165b band was seen in VEGFxxxb mRNA.With the prolong of hypoxia culture,the expression of VEGFxxx mRNA showed gradual increase,while VEGFxxx b mRNA appeared gradual decrease.Western blot exhibited that VEGFxxxb was expressed in the cells cultured by normoxia and hypoxia with the strongest expression in VEGF165b.The VEGFxxxb content in suspension of medium was (166.82± 2.55) pg/ml under the normoxia environment and (125.35 ±2.10) pg/ml in 24 hours under the hypoxia,and the total VEGF-A protein elevated from (294.27 ± 11.97) pg/ml under the normoxia environment to (582.26 ± 12.98) pg/ml in 24 hours under the hypoxia.In addition,the proportion of VEGFxxxb to total VEGF-A in the cells lowed from (56.71 ± 1.02) ％ under the normoxia environment to (21.53 ±0.08) ％ in 24 hours under the hypoxia.Conclusions VEGFxxxb isoforms are expressed in both normoxia and hypoxia ARPE-19 cells.VEGFxxxb isoform is a predominant isoform in normoxia ARPE-19 cells.In hypoxia ARPE-19 cells,however,the expression of VEGF A is significantly stronger than that of VEGFxxxb.

Angiogenic Inhibitor Induced Complicated Reflux Esophagitis / 이화의대지

Sunitinib an inhibitor of the vascular endothelial growth factor receptor, is highly effective against renal cell carcinoma and is now widely used in patients with metastatic disease. Gastroesophageal reflux disease (GERD) is rarely reported as a side effect of sunitinib. We report two cases of GERD with upper gastrointestinal bleeding related to sunitinib administration. Both cases responded well to conservative management. Microscopic findings in both cases showed cellular atypia such as hyperchromasia, increases in nuclear size, and multinucleation. The cellular atypia of the squamous mucosa appears to be associated with reparative processes.