Establishment and biological characterization of drug-resistant cells and identification of multidrug resistance in small-cell lung cancer / 中国药理学通报

Aim To establish NCI-H446/EP for small cell lung cancer resistant cells resistant to cisplatin and etoposide, and to evaluate their biological characteristics and multidrug resistance. Methods Nude mice were subcutaneously inoculated with NCI-H446 cells of SCLC to construct an in vivo model of xenograft tumor, and were given first-line EP regimen treatment for SCLC, inducing drug resistance in vivo, and stripping tumor tissue in vitro culture to obtain drug-resistant cells. The resistance coefficient, cell doubling time, cell cycle distribution, expression of multidrug resistance gene (MDR1), and drug resistance-related protein were detected in vitro, and the drug resistance to cisplatin and etoposide in vivo were verified. Results Mice with NCI-H446 tumors acquired resistance after eight weeks' EP regimen treatment, and the drug-resistant cell line NCI-H446/EP was obtained by isolation and culture in vitro. The resistance factors of this cell line to cisplatin, etoposide, SN38 and doxorubicin were 12.01, 18.36, 65.4 and 10.12, respectively. Compared with parental cells, the proportion of NCIH446/EP cells in Q

Triple combination of palliative oral metronomic chemotherapy in recurrent and metastatic epithelial ovarian cancer: A retrospective study

Background: Ovarian cancer is a leading cause of death from gynecological cancer in the world and in India. This study aims to evaluate the efficacy and toxicity profile of oral metronomic chemotherapy (MCT) in the form of etoposide, cyclophosphamide, and tamoxifen in recurrent and metastatic ovarian cancer. Methods: This was a retrospective observational study that included those post?treatment patients who had the recurrent or metastatic disease after completion of treatment in 2018 at Regional Cancer Centre, Bikaner, Rajasthan. Forty patients who were unfit for further intensive intravenous chemotherapy were included. The oral MCT constituted etoposide, cyclophosphamide, and tamoxifen. Descriptive statistics and Kaplan?Meier analyses were performed. Progression?free survival (PFS) and overall survival (OS) were assessed. Results: Forty women with a median age of 62 (range: 35?80) years were enrolled in the study to receive oral MCT. The Eastern Cooperative Oncology Group?Performance Status (ECOG?PS) was 0�in 28 patients and 2�in 12 patients. The best clinical response rate post?oral MCT was seen in the first 4 months. Objective response was observed in 24 (60%) of patients in the form of stable disease (19, 47.5%) and partial response (5, 12.5%). Disease progression was observed in 10 (25%) of patients. The median follow?up was 6.4 months (4.5�2 months). The median estimated OS was 6.5 months. The median estimated PFS was 3.7 months. Nineteen (47.5%) patients had grade?I/II mucositis. Grade?III/IV mucositis were observed in 9 (22.5%) patients. Thirty?seven (92.5%) patients died at the end of the study at 1 year. Dose reduction was required in 15 (37.5%) patients. Conclusion: Oral MCT was found to be an effective and well?tolerated regime with good symptomatic control and low?moderate toxicity profile in patients with relapsed and metastatic ovarian cancer. However, 22% of patients showed grade?III/IV thrombocytopenia.

Observation on the therapeutic efficacy and survival rate of oral Etoposide in children with disseminated medulloblastoma after the standard treatment plan / 中华实用儿科临床杂志

Objective:To explore the therapeutic efficacy and toxicity of oral Etoposide chemotherapy in children with disseminated medulloblastoma (MB) after the standard treatment plan.Methods:The clinical data of 86 children with disseminated MB admitted in the Department of Pediatrics, Beijing Shijitan Hospital of Capital Medical University from January 2016 to May 2020 were analyzed retrospectively.The median age of children was 8.8 (3.0-16.7) years old.Among them, 33 children treated with maintenance chemotherapy via oral Etoposide were included in the chemotherapy group, and 53 children without oral maintenance chemotherapy were included in the non-chemotherapy group.The gender distribution, surgical resection range, pathological type, molecular classification, postoperative mutism, M-stage and survival[progression-free survival (PFS) and overall survival (OS)] of the 2 groups were compared.The main adverse events of oral Etoposide chemotherapy were recorded. Chi- square test is used for data comparison, Kaplan-Meier method was used to plot the survival curve of disseminated MB patients, followed by the Log- rank test. Results:There were no significant differences in gender, surgical resection range, pathological type, molecular typing, postoperative mutism and M-stage between the 2 groups (all P>0.05). Of 86 patients, the median PFS and OS were 3.0 (0.2-6.3) years, and 3.6 (0.5-6.3) years, respectively.Twenty five cases (29.1%) relapsed, 13 cases (15.1%) died.The 3-year[(65.8±6.8)% vs.(82.0±7.3)%] and 5-year PFS[(56.8±7.7)% vs.(82.0±7.3)%] in non-chemotherapy group were significantly lower than those of chemotherapy group ( P=0.037). The 3-year[(81.6±5.6)% vs.100.0%] and 5-year OS[(71.2±7.7)% vs.(92.3±7.4)%] in non-chemotherapy group were significantly lower than those of chemotherapy group ( P=0.025). Among the children with the SHH subtype, the PFS of children with oral Etoposide maintenance chemotherapy after a regular treatment was significantly higher than that without oral maintenance chemotherapy (100.0% vs.57.1%)( P=0.021). The major adverse events of oral Etoposide were myelosuppression and gastrointestinal symptoms, which were mostly relieved after a symptomatic treatment.Treatment-related deaths were not reported. Conclusions:The prognosis of disseminated MB in children is relatively poor.Oral Etoposide for maintenance therapy after a standard treatment is beneficial in reducing relapse and improving the 5-year survival, which is well tolerated.

Bizarre presentation of choriocarcinoma: A case report / Philippine Journal of Obstetrics and Gynecology

@#Choriocarcinoma is a malignant subtype of gestational trophoblastic disease that follows any type of pregnancy. It is characterized by rapid hematogenous spread to multiple organs, associated with high human chorionic gonadotropin levels with good response to chemotherapy. We present the case of a 31‑year‑old Filipina who initially presented with severe headaches and blurring of vision 3 years after an unremarkable term pregnancy. The transvaginal ultrasound was normal. After a series of diagnostic tests, the initial working impression was a primary brain tumor with metastases to the lungs, adrenal, kidney, and vulva. Emergency craniotomy was done due to deteriorating status secondary to an intracranial hemorrhage. The histopathology report showed choriocarcinoma. Chemotherapy using Etoposide‑Methotrexate‑Actinomycin D‑Cyclophosphamide‑Vincristine with high‑dose methotrexate and concomitant whole‑brain irradiation was then instituted with good response. This case highlights the importance of having a high index of suspicion for gestational trophoblastic neoplasia to prevent the performance of unnecessary procedures, leading to a delay in diagnosis and the institution of the appropriate treatment.

Clinical Anslysis of Primary Adrenal NK/T-Cell Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical characteristics, diagnosis, and treatment of one patient with primary adrenal natural killer/T-cell lymphoma (PANKTCL), and to strengthen the understanding of this rare type of lymphoma.@*METHODS@#The clinical manifestations, diagnosis and treatment process, and prognosis of the patient admitted in our hospital were retrospectively analyzed.@*RESULTS@#Combined with pathology, imaging, bone marrow examination， etc, the patient was diagnosed with PANKTCL (CA stage, stage II; PINK-E score 3, high-risk group). Six cycles of "P-GemOx+VP-16" regimen（gemcitabine 1 g/m2 d1 + oxaliplatin 100 mg/m2 d 1 + etoposide 60 mg/m2 d 2-4 + polyethylene glycol conjugated asparaginase 3 750 IU d 5） was performed, and complete response was assessed in 4 cycles. Maintenance therapy with sintilimab was administered after the completion of chemotherapy. Eight months after the complete response, the patient experienced disease recurrence and underwent a total of four courses of chemotherapy, during which hemophagocytic syndrome occurred. The patient died of disease progression 1 month later.@*CONCLUSION@#PANKTCL is rare, relapses easily, and has a worse prognosis. The choice of the "P-GemOx+VP-16" regimen combined with sintilimab help to improve the survival prognosis of patient with non-upper aerodigestive tract natural killer /T-cell lymphoma.

Efficacy and Safety of Etoposide Combined with Cyclophosphamide for Autologous Peripheral Blood Stem Cell Mobilization in Patients with Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To evaluate the efficacy and safety of etoposide combined with cyclophosphamide (EC) regimen for mobilization of autologous peripheral blood stem cells (APBSCs) in patients with multiple myeloma (MM).@*METHODS@#The clinical data of 48 MM patients who received APBSC transplantation (APBSCT) in Department of Hematology of the First Affiliated Hospital of Nanchang University from January 2015 to October 2021 were retrospectively analyzed. The mobilization success rate and mobilization optimal rate of EC regimen were counted, and its effect on transplant efficacy, adverse reactions, hematopoietic reconstitution after transplantation, and survival time of MM patients were analyzed.@*RESULTS@#APBSCs were collected on day 14 (10-19) after EC administration. The median of collected CD34+ cells was 6.82 (1.27-22.57)×106/kg, and the median number of apheresis session was 2 (1-4). The mobilization success rate (collecting CD34+ cells≥2×106 cells/kg after completion of apheresis) was 98% (47/48), and mobilization optimal rate (collecting CD34+ cells≥5×106 cells/kg after completion of apheresis) was 71% (34/48). The depth of remission were improved after APBSCT, and the complete remission (CR) rate increased from 45.8% before transplantation to 87.5% after transplantation (P <0.01). There was no transplant-related death, no blood transfusion during mobilization, and no mucositis occurred in the patients. The most common complication was neutropenia, with an incidence of 75.0% (36/48). After transplantation, all the patients successfully achieved hematopoietic reconstitution. The median time to neutrophil engraftment was 10 (9-26) days, and median time to platelet engraftment was 10 (8-33) days. By the end of follow-up, both the median progression-free survival (PFS) and overall survival (OS) time were not reached. The 5-year estimated PFS rate and OS rate was 53.8% and 82.4%, respectively.@*CONCLUSION@#The EC regimen for mobilization of APBSC has a high acquisition success rate and controllable adverse reactions, which can be an effective and safe mobilization regimen in MM patients.

Linfoma de células B de alto grado de malignidad con morfología blastoide durante el embarazo: reporte de un caso / High-grade malignant B-Cell lymphoma with blastoid during pregnancy: a case report

Resumen ANTECEDENTES: Durante el embarazo es más común el linfoma de Hodking que el no Hodking; afecta, en promedio, a mujeres de 30 años (18-44 años) y más. Suele diagnosticarse alrededor de las 28 semanas de embarazo y está documentado que puede llegarse al término. Los esquemas de tratamiento pueden iniciarse en el posparto inmediato o, incluso, antes. La incidencia mundial del linfoma no Hodking es de 0.8 por cada 100,000 mujeres; se desconoce la supervivencia durante el embarazo. CASO CLINICO: Paciente de 34 años, con antecedentes obstétricos de tres embarazos, una cesárea y un aborto y el embarazo actual en curso de las 29 semanas, referida de la ciudad de Colima debido a un reporte de BI-RADS 3 en el ultrasonido de mama y un nódulo mamario palpable, con evidencia de múltiples tumoraciones en la zona hepática, esplénica y peripancreática. La biopsia tomada de las zonas de la lesión reportó: linfoma de células B de alto grado de malignidad, con morfología blastoide y expresión de C-MYC y BCL2. Además, la paciente se encontró con: anemia, dolor abdominal, múltiples nódulos hepáticos y adenopatías abdominales. Se decidió la interrupción del embrazo a las 30 semanas, con la obtención de un recién nacido, sin complicaciones. Enseguida se inició el tratamiento con rituximab-etopósido-prednisolona-vincristina-ciclofosfamida-doxorrubicina (R-EPOCH) con adecuada adaptación por la paciente. CONCLUSION: Puesto que la información bibliográfica de linfoma y embarazo es escasa el caso aquí reportado es relevante por su aporte. La atención multidisciplinaria favorecerá siempre el pronóstico de las pacientes.

Abstract BACKGROUND: Hodking's lymphoma is more common during pregnancy than non-Hodking's lymphoma; it affects, on average, women aged 30 years (18-44 years) and older. It is usually diagnosed around 28 weeks of pregnancy and is documented to be carried to term. Treatment regimens can be initiated in the immediate postpartum period or even earlier. The worldwide incidence of non-Hodking's lymphoma is 0.8 per 100,000 women; survival during pregnancy is unknown. CLINICAL CASE: 34-year-old patient, with obstetric history of three pregnancies, one cesarean section and one abortion and the current pregnancy in progress at 29 weeks, referred from the city of Colima due to a report of BI-RADS 3 on breast ultrasound and a palpable breast nodule, with evidence of multiple tumors in the hepatic, splenic and peripancreatic area. Biopsy taken from the lesion areas reported: high grade malignant B-cell lymphoma, with blastoid morphology and expression of C-MYC and BCL2. In addition, the patient was found to have: anemia, abdominal pain, multiple hepatic nodules and abdominal adenopathies. It was decided to terminate the pregnancy at 30 weeks, with the delivery of an uncomplicated newborn. Rituximab-Etoposide, Prednisone, Vincristine, Cyclophosphamide, and Doxorubicin (R-EPOCH) therapy was started immediately with adequate adaptation by the patient. CONCLUSION: Since bibliographic information on lymphoma and pregnancy is scarce, the case reported here is relevant for its contribution. Multidisciplinary care will always favor the prognosis of patients.

Efficacy and safety of etoposide combined with carboplatin in children with recurrent medulloblastoma / 中国临床药理学与治疗学

AIM: To evaluate the efficacy and safety of etoposide combined with carboplatin in the treatment of recurrent medulloblastoma in children. METHODS: From January 2011 to June 2014, 72 children (aged 3-15 years) with recurrent medulloblastoma were selected from Children's Hospital Affiliated to Medical College of Zhejiang University. According to the random number table method, they were divided into the CE group and control group, with 36 cases each. The CE group received etoposide + carboplatin for chemotherapy. The control group received classical irinotecan + temozolomide + vincristine chemotherapy. Clinical efficacy, KPS score, PedsQLTM4.0 score, total survival (OS) and event-free survival (EFS) of children in the two groups were compared, and the occurrence of adverse drug reactions during treatment was recorded. RESULTS:After treatment, CR of CE group and control group was 41.67% (15 cases/36 cases) and 27.78% (10 cases/36 cases), OR of CE group and control group was 94.44% (34 cases/36 cases) and 77.78% (28 cases/36 cases), and there were statistically significant different in these indicators between the groups. There was no significant difference in KPS scores and PedsQLTM4.0 scores between the two groups before treatment (P>0.05). After treatment, KPS scores of the CE group and the control group were (80±8) and (75±10) points, and PedsQLTM4.0 scores were (89±11) and (84±11) points, and there were statistically significant different in these indicators between the groups (both P0.05). A total of 10 cases with severe adverse reactions occurred during chemotherapy in the CE group, with an incidence of 27.78% (10 cases/36 cases), and 9 cases of that occurred during chemotherapy in the control group, with an incidence of 25.00% (9 cases/36 cases), with no statistical significance (P>0.05). CONCLUSION: Etoposide combined with carboplatin regimen can significantly improve the clinical remission rate and improve the overall survival of children without increasing adverse reactions to chemotherapy, but the effect on event-free survival was not obvious.

Effects of different chemotherapies on prognosis and tumor markers in patients with small cell lung cancer / 国际肿瘤学杂志

Objective@#To explore the effect and safety of two chemotherapy regimens in the treatment of small cell lung cancer.@*Methods@#Ninety-eight patients with extensive small cell lung cancer admitted to Liuzhou People′s Hospital of Guangxi Zhuang Autonomous Region from March 2013 to March 2016 were randomly divided into two groups by random number table method, 49 of whom were treated with lobaplatin + etoposide (EL group), and another 49 cases were treated with cisplatin + etoposide (EP group). The short-term efficacy, 2-year survival rate and adverse reactions of the two groups were observed. The serum levels of gastrin-releasing peptide precursor (ProGRP), neuron-specific enolase (NSE), Ki-67, vascular endothelial growth factor (VEGF) were compared between the two groups before and after treatment.@*Results@#The effective rates of the EL group and the EP group were 48.98% (24/49) and 40.82%(20/49) respectively, and the difference between the two groups was not statistically significant (χ2=0.660, P=0.417). The 2-year survival rates of patients in the EL group and the EP group were 17.07% and 11.11% respectively. The median survival time of the EL group was 17.00 months, and that of the EP group was 15.00 months. There was no significant difference between the two groups (χ2=1.094, P=0.228). The serum level of ProGRP was (978.4±225.7) ng/L and (940.2±237.1) ng/L, NSE was (43.9±10.3) ng/ml and (41.7±11.6) ng/ml, Ki-67 was (287.5±55.3) pg/ml and (279.8±62.6) pg/ml, and VEGF was (566.8±109.4) pg/ml and (538.1±144.0) pg/ml in the EL and EP group before chemotherapy respectively, and there were no significant differences between the two groups (t=0.817, P=0.416; t=0.993, P=0.323; t=0.645, P=0.520; t=1.111, P=0.269). The serum level of ProGRP was (167.3±68.5) ng/L and (180.6±62.1) ng/L, NSE was (17.5±4.8) ng/ml, (19.0±5.3) ng/ml, Ki-67 was (98.0±18.6) pg/ml and (101.4±20.8) pg/ml, VEGF was (430.4±95.8) pg/ml and (442.8±91.0) pg/ml in the EL and EP group after chemotherapy, and there was no significant difference between the two groups (t=-1.007, P=0.316; t=-1.468, P=0.145; t=-0.853, P=0.396; t=-0.657, P=0.513). The serum levels of ProGRP, NSE, Ki-67 and VEGF in EL group and EP group were significantly lower than those before chemotherapy (t=24.072, P<0.001; t=21.694, P<0.001; t=16.263, P<0.001; t=12.459, P<0.001; t=22.736, P<0.001; t=18.931, P<0.001; t=6.566, P<0.001; t=3.916, P<0.001). During chemotherapy, the incidences of diarrhea and myelosuppression (≥grade 2) in the EL group [26.53% (13/49) and 61.22% (30/49)] were lower than those in the EP group [48.98% (24/49) and 81.63% (40/49)], and the differences were statistically significant (χ2=5.254, P=0.022; χ2=5.000, P=0.025).@*Conclusion@#Lobaplatin+ etoposide is less toxic than cisplatin+ etoposide in the treatment of small cell lung cancer, and adverse reactions of its is relatively slighter.

Clinical effects of Shendan-Huoxue capsule combined with etoposide soft capsules in the treatment of advanced ovarian carcinoma in elderly patients / 国际中医中药杂志

Objective To evaluate the clinical effects of Shendan-Huoxue capsule combined with etoposide soft capsule in the treatment of advanced ovarian cancer in the elderly patients. Methods A total of 94 elderly patients with ovarian cancer who met the inclusion criteria were divided into 2 groups using random number table method, 47 patients in each group. All patients were given conventional chemotherapy, the control group was given etoposide soft capsule on this basis, and the observation group was given Shendan-Huoxue capsule on the basis of the control group. Both groups were treated for 12 weeks and followed up for 2 years. Ovarian cancer specificity scale version 4 (FACT-OV4) was used to evaluate the life quality of the patients, flow cytometry was used to detect the level of CD3+, CD4+, CD8+, CD19+. Ovarian cancer was detected by CT, toxic and side effects during treatment were recorded, and clinical efficacy was evaluated. Results The total effective rate in the observation group was 87.2% (41/47), and that in the control group was 70.2% (33/47). The difference between the two groups was statistically significant (χ2=3.782, P=0.041). The 1-year survival rate was 87.2% (41/47) and 2-year survival rate was 61.7% (29/47) in the observation group, and 74.4% (35/47) and 53.2% (25/47) in the control group, respectively. The 1-year and 2-year survival rates of the two groups were statistically significant (χ2=4.109, 4.268 respectively, P=0.038, 0.036). The median total survival time in the observation group and the control group was 13.9 months (95% IC 12.4-16.2) and 10.3 months (95% IC 8.2-14.1), respectively. The median total survival time in the observation group was significantly longer than that in the control group (P<0.05). After treatment, scores of social/family status and functional status in the observation group were significantly higher than those in the control group (t values were 3.711 and 4.003, respectively, P<0.05), and scores of additional attention, physiological status and emotional status were significantly lower than those in the control group (t values were 4.335, 4.522 and 4.202, respectively, P<0.05). After treatment, the levels of CD3+, CD4+, CD8+, CD19+ in the observation group were all higher than those in the control group (t values were 7.217, 7.129, 7.434 and 6.521, respectively, P<0.01 or P<0.05). During the period of treatment , the incidence of skin rash, liver function injury, decreased white blood cell count, nausea and vomiting, peripheral neuropathy, diarrhea and abdominal pain in the observation group were significantly lower than those in the control group (χ2 values were 4.114, 4.782, 4.521, 3.911, 3.931, 3.821, P<0.05, respectively). Conclusions The Shendan-Huoxue capsule combined with etoposide soft capsule can improve the survival time of elderly patients with advanced ovarian cancer, improve the body immunity, reduce toxic and side effects, and the clinical effect is better than conventional chemotherapy.

Randomized Phase III Trial of Irinotecan Plus Cisplatin versus Etoposide Plus Cisplatin in Chemotherapy-Naïve Korean Patients with Extensive-Disease Small Cell Lung Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: This randomized phase III study was designed to compare the efficacy and safety of irinotecan plus cisplatin (IP) over etoposide plus cisplatin (EP) in Korean patients with extensive-disease small-cell lung cancer (SCLC). MATERIALS AND METHODS: Patients were randomly assigned to receive IP, composed of irinotecan 65 mg/m2 intravenously on days 1 and 8+cisplatin 70 mg/m2 intravenously on day 1 every 3 weeks, or EP, composed of etoposide 100 mg/m2 intravenously on days 1, 2, 3+cisplatin 70 mg/m2 intravenously on day 1, every 3 weeks for a maximum of six cycles, until disease progression, or until unacceptable toxicity occurred. The primary endpoint was overall survival. RESULTS: A total of 362 patients were randomized to IP (n=173) and EP (n=189) arms. There were no significant differences between IP and EP arms for the median overall survival (10.9 months vs. 10.3 months, p=0.120) and the median progression-free survival (6.5 months vs. 5.8 months, p=0.115). However, there was a significant difference in response rate (62.4% vs. 48.2%, p=0.006). The pre-planned subgroup analyses showed that IP was associated with longer overall survival in male (11.3 months vs. 10.1 months, p=0.036), < 65 years old (12.7 months vs. 11.3 months, p=0.024), and Eastern Cooperative Oncology Group performance status 0/1 (12.4 months vs. 10.9 months, p=0.040) patient groups. The severity of treatment-related adverse events such as grade 3/4 anemia, nausea and diarrhea was more frequent in patients treated with IP. CONCLUSION: The IP chemotherapy did not significantly improve the survival compared with EP chemotherapy in Korean patients with extensive-disease SCLC.

Lactobionic acid-decorated TPGS nanoparticles to decrease multidrug resistance on hepatocellular carcinoma / Монголын эм зүй, эм судлал

Introduction@#Many effective anticancer drugs are limited to use for hepatocellular carcinoma (HCC) therapy due to drug resistance mechanisms in liver cells. In recent years, tumor-targeted drug delivery and inhibition of drug resistance-related mechanisms become an integrated strategy to combat effectively chemoresistant cancer. @*Aim@#Herein, lactobionic acid-conjugated D-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS-LA conjugate) was developed as a potential asialoglycoprotein receptor (ASG PR (-targeted nanocarrier and an efficient inhibitor of P-glycoprotein (P-gp) to enhance etoposide (ETO) efficacy against HCC. @*Methods@#Main properties of ETO-loaded TPGS-LA nanoparticles (NPs) were tested through in vitro and in vivo studies after prepared using nanoprecipitation method and characterized by dynamic light scattering (DLS). @*Results@#According to the results, smaller sized (~141.43 nm) and positively charged ETO-loaded TPGS-LA NPs were more suitable to provide an efficient delivery to hepatoma cells by avoiding clearance mechanisms. It was found that ETO-loaded TPGS-LA NPs could enhance noticeably cytotoxicity of ETO in HepG2 cells. Besides, markedly higher internalization by ASGPR overexpressed HepG2 cells and efficient accumulation at tumor site in vivo were revealed in TPGS-LA NPs group. More importantly, animal studies confirmed that ETO-loaded TPGS-LA NPs achieved the highest therapeutic efficacy against HCC. Interestingly, ETO-loaded TPGS-LA NPs also exhibited a great inhibitory effect on P-gp compared to ETO-loaded TPGS NPs. @*Conclusion@#These results suggest that TPGSLA NPs could be used as a potential delivery system of ETO against HCC.

Clinical Observation of Appatinib Combined with Systemic Chemotherapy for Liver Metastasis of Gastroenteropancreatic Neu- roendocrine Neoplasm / 中国药房

OBJECTIVE： To observe the efficacy and safety of apatinib combined with systemic chemotherapy for hepatic metastasis of gastroenteropancreatic neuroendocrine neoplasms （GEP-NEN）. METHODS： Totally 60 patients with GEP-NEN in Hubei Provincial Tumor Hospital from Jan. 2016 to Jan. 2018 were randomly divided into systemic chemotherapy group， apatinib group and combination group， with 20 patients in each group. Systemic chemotherapy group was given Etoposide injection 80 mg/m2，once a day d1-5， intravenously+Cisplatin for injection 20 mg/m2，once a day d1-5，intravenously， every 3 weeks for a cycle. Apatinib group was given Apatinib mesylate tablets 0.5 g， once a day. Combination group received treatment as systemic chemotherapy group+apatinib group. All three groups were treated continuously for 3 months. The clinical efficacies of 3 groups were observed. The serum levels of tumor markers （CEA， NSE， CgA and CA19-9） before and after treatment， survival situation after treatment and the occurrence of ADR during treatment were also observed. RESULTS： The objective remission rate， disease control rate， median overall survival and survival rate of combination group were significantly higher or longer than those of systemic chemotherapy group and apatinib group. Median progression-free survival and the incidence of ADR were significantly shorter or lower than systemic chemotherapy group and apatinib group （P＜0.05）. After treatment， the levels of CEA， NSE， CgA and CA19-9 in 3 groups were significantly lower than before treatment， and combination group was significantly lower than systemic chemotherapy group and apatinib group （P＜0.05）. There was no statistical significance in above indexes between systemic chemotherapy group and apatinib group （P＞0.05）. CONCLUSIONS： Apatinib combined with systemic chemotherapy for liver metastasis of GEP-NEN is effective and safe， which can improve the level of serum tumor markers， prolong the survival time of patients and improve survival rate.

Effects of different chemotherapies on prognosis and tumor markers in patients with small cell lung cancer / 国际肿瘤学杂志

Objective To explore the effect and safety of two chemotherapy regimens in the treatment of small cell lung cancer. Methods Ninety-eight patients with extensive small cell lung cancer admitted to Liuzhou People's Hospital of Guangxi Zhuang Autonomous Region from March 2013 to March 2016 were ran-domly divided into two groups by random number table method,49 of whom were treated with lobaplatin + eto-poside (EL group),and another 49 cases were treated with cisplatin + etoposide (EP group). The short-term efficacy,2-year survival rate and adverse reactions of the two groups were observed. The serum levels of gas-trin-releasing peptide precursor (ProGRP),neuron-specific enolase (NSE),Ki-67,vascular endothelial growth factor (VEGF)were compared between the two groups before and after treatment. Results The effec-tive rates of the EL group and the EP group were 48. 98％ (24 / 49)and 40. 82％(20 / 49)respectively,and the difference between the two groups was not statistically significant (χ2 = 0. 660,P = 0. 417). The 2-year sur-vival rates of patients in the EL group and the EP group were 17. 07％ and 11. 11％ respectively. The median survival time of the EL group was 17. 00 months,and that of the EP group was 15. 00 months. There was no significant difference between the two groups (χ2 = 1. 094,P = 0. 228). The serum level of ProGRP was (978. 4 ± 225. 7)ng/ L and (940. 2 ±237. 1)ng/ L,NSE was (43. 9 ±10. 3)ng/ ml and (41. 7 ±11. 6)ng/ ml, Ki-67 was (287. 5 ± 55. 3)pg/ ml and (279. 8 ± 62. 6)pg/ ml,and VEGF was (566. 8 ± 109. 4)pg/ ml and (538. 1 ±144. 0)pg/ ml in the EL and EP group before chemotherapy respectively,and there were no significant differences between the two groups (t = 0. 817,P = 0. 416;t = 0. 993,P = 0. 323;t = 0. 645,P = 0. 520;t =1. 111,P = 0. 269). The serum level of ProGRP was (167. 3 ± 68. 5)ng/ L and (180. 6 ± 62. 1)ng/ L,NSE was (17. 5 ±4. 8)ng/ ml,(19. 0 ±5. 3)ng/ ml,Ki-67 was (98. 0 ± 18. 6)pg/ ml and (101. 4 ± 20. 8)pg/ ml, VEGF was (430. 4 ±95. 8)pg/ ml and (442. 8 ±91. 0)pg/ ml in the EL and EP group after chemotherapy,and there was no significant difference between the two groups (t = - 1. 007,P = 0. 316;t = - 1. 468,P = 0. 145;t = - 0. 853,P = 0. 396;t = - 0. 657,P = 0. 513). The serum levels of ProGRP,NSE,Ki-67 and VEGF in EL group and EP group were significantly lower than those before chemotherapy (t = 24. 072,P < 0. 001;t =21. 694,P < 0. 001;t = 16. 263,P < 0. 001;t = 12. 459,P < 0. 001;t = 22. 736,P < 0. 001;t = 18. 931, P < 0. 001;t = 6. 566,P < 0. 001;t = 3. 916,P < 0. 001). During chemotherapy,the incidences of diarrhea and myelosuppression (≥grade 2)in the EL group [26. 53％ (13 / 49)and 61. 22％ (30 / 49)]were lower than those in the EP group [48. 98％ (24 / 49)and 81. 63％ (40 / 49)],and the differences were statistically significant (χ2 = 5. 254,P = 0. 022;χ2 = 5. 000,P = 0. 025). Conclusion Lobaplatin + etoposide is less toxic than cisplatin +etoposide in the treatment of small cell lung cancer,and adverse reactions of its is relatively slighter.

A spectrum of gestational trophoblastic neoplasia

Gestational trophoblastic disease is a spectrum of diseases caused by overgrowth of chorionic villi of placenta. They range from most Benign to most Malignant. Those with local invasion or metastasis are labelled as Gestational trophoblastic Neoplasia (GTN). We have conducted a retrospective observational study of various Gestational trophoblastic neoplasias (GTN) at NRIGH for a period of 3 years, out of which, one example of each variety is being presented. All these varieties have been successfully treated and all the patients are under follow up.

Preparation and Antitumor Activity of Etoposide-loaded Solid Lipid Nanoparticles / 中国药师

Objective:To prepare solid lipid nanoparticles of etoposide and evaluate the inhibitory rate against Lewis lung cancer cells in mice. Methods:Etoposide-loaded solid lipid nanoparticles were prepared by a hot melting emulsification and high pressure homogenization method. The physicochemical properties such as the appearance, microstructure, particle size distribution and zeta potential of the solid lipid nanoparticles were studied. The in vitro release behavior of the solid lipid nanoparticles were evaluated. The inhibitory effect of etoposide-loaded solid lipid nanoparticles and etoposide injection on Lewis lung cancer cells was compared. Results:Etoposide-loaded solid lipid nanoparticles showed a light blue transparent liquid,which was uniformly spherical under the transmission electron microscope. The average particle size was (153.2 ± 32.8) nm, PdI was (0.185 ± 0.031),and the zeta potential was(-17.4 ± 1.1) mV. The solid lipid nanoparticles could delay the drug release and 52.4% of the drug was released in 24 h. Etoposide-loaded solid lipid nanoparticles could significantly inhibit the growth of Lewis lung cancer cells in mice. And the inhibitory rate of the solid lipid nanoparticles was significantly higher than that of etoposide injection (P < 0.05). Conclusion:The solid lipid nanoparticles prepared by hot melting emulsification and high pressure homogenization method have good antitumor effect on Lewis lung cancer cells,which can be used as a new drug delivery system for etoposide with certain application prospect in lung cancer treatment.

High dose nanocrystallization of etoposide and its blood-brain barrier permeability in vitro / 中国药理学与毒理学杂志

OBJECTIVE To improve the poor water solubility and evaluating poor acitivity of etoposide (VP-16) by preparing VP-16 nanoparticle suspension (VP-16 NP) and its penetration through the blood-brain barrier (BBB).METHODS VP-16 NP was prepared with the anti-solution exchange method.The shape structure and diameter were observed with transmission electron microscopy (TEM) and scanning electron microscopy (SEM) and dynamic light scattering (DLS), respectively. The drug release profiles of the VP-16 powder and VP-16 NP were measured.The effect of VP-16 NP on the growth of KB cells was observed via MTT assay. In addition, primary brain microvascular endothelial cells from 1stto 2nd generation of SD rats at two weeks of age were used to construct an in vitro BBB model.The classic 4 h leak test,trans-epithelial electrical resistance (TEER) test and fluorescein disodium salt(FLU)perme?ability test were conducted to verify whether the in vitro BBB model was successfully established.RESULTS VP-16 NP was a solid sphere with a size of 140 nm detected by TEM,SEM and DLS.The cumulative release rate of VP-16 NP was 3 times that of VP-16 powder. The results of MTT colorimetric assay showed that VP-16 powder had no inhibitory effect on KB cells,while VP-16 NP could effectively inhibit KB cells. In the 4 h leakage experiment, the top and bottom chambers of the Transwell cell model could maintain a liquid surface distance of >0.5 cm,indicating that the in vitro BBB model was initially formed.The effective resistance value of the TEER experiment was 223 Ω·cm2,indicating that the in vitro BBB model was basically established. In FLU permeability experiments, the permeability coefficients were respectively (0.33±0.04)×10-3,(0.42±0.07)×10-3,and (0.52±0.06)×10-3cm·min-1at 15,30 and 60 min, indicating that the model had low permeability.The above three experiments suggested that the BBB in vitro model was successfully constructed. On this basis, the in vitro BBB model was used to evaluate the penetration of VP-16 NP at a permeability coefficient of (1.87±0.03)×10-3cm·min-1at 30 min,showing high permeability.VP-16 NP showed better penetration of BBB.CONCLUSION VP-16 NP is success?fully prepared,which increases the release rate of the drug,enhances the killing effect of the cells,and shows good penetration through the in vitro BBB model evaluation.

Efficacy and safety of etoposide for maintenance therapy of small-cell lung cancer / 医学研究生学报

Objective Small cell lung cancer(SCLC)is generally sensitive to first-line therapy,but it has poor long-term efficacy,short-term recurrence and low sensitivity of second-line therapy.The study aimed to investigate the impact of etoposide capsule for the maintenance therapy of extensive stage SCLC. Methods A retrospective analysis was made on 82 patients with extensive SCLC treated in Tumor Hospital affiliated to Zhengzhou University from January 2014 to September 2015.The patients were divided into etoposide group(n=45,oral etoposide treatment after first-line chemotherapy)and control group(n=45,regular review after first-line therapy). Comparison was conducted in progression-free survival(PFS),total survival time(OS)and adverse reactions between two groups. Results The median PFS of etoposide group was higher than that of control group(3.5months vs 2.8months,P=0.012). The one-year and two-year survival rates of etoposide group were significantly higher than those of control group(59.5% vs 43.9%, 12.6% vs 4.9%,P<0.05). The analysis of Cox proportional hazard model showed first-line therapy(RR=2.036,95%CI:1.127~3.676)and BMI≥25(RR=0.598,95%CI:0.359~0.997),<18(RR=4.607,95%CI:2.203~9.631)were the risk factors for survival. No significant difference was found as to the risk of adverse effects be-tween two groups. Conclusion Maintenance therapy with oral eto-poside may improve progression-free-survival(PFS)in patients with extensive SCLC,which is safe and practical for maintenance therapy.

Efficacy of etoposide capsule on metastatic breast cancer / 实用医学杂志

Objective To evaluate the efficacy and safety of etoposide capsule on metastatic breast cancer. Methods Forty-five advanced breast cancer patients treated with oral etoposide during Feb.1,2012 and Oct.31, 2016 in our department were enrolled in our study,with their general data,median number of treatment lines, treatment effect,common adverse reaction collected. Such indexes of objective response rate,rate of clinical benefit,disease control rate,progression free survival time were anlayzed. Results All patients received median five lines of etoposide capsule therapy. The objective response rate(ORR,CR + PR)was 6.7% and the clinical benefit rate(CBR,CR+PR+SD≥6.0 months)was 26.7% and the disease control rate(DCR,CR+PR+SD) was 68.9%.The median progression free survival time(PFS)was 4.0 months(95% CI:2.3~5.6).The main toxic-ities were grade 1-2 neutropenia(37.8%),grade 3-4 neutropenia(6.7%).Conclusion Etoposide capsule could be an option with efficacy and safety for metastatic breast cancer.

Effect of Ginsenosides on the Pharmacokinetics of Etoposide in Rats / 中国药学杂志

OBJECTIVE: To investigate the pharmacokinetic interaction between ginsenosides and etoposide and provide useful information for clinical practice. METHODS: Eighteen male Wistar rats were randomly divided into three groups: etoposide group(10 mgkg-1),the high dose ginsenoside group(etoposide 10 mgkg-1, ginsenoside 200 mgkg-1), the low dose ginsenoside group(etoposide 10 mgkg-1, ginsenoside 100 mgkg-1). Plasma samples were collected at different times after the drug administration from the orbital veins of the rats. An HPLC method was developed to determine the concentration of etoposide in rat plasma,and the pharmacokinetic parameters were calculated using DAS3.2.7. RESULTS: Compared with the etoposide group,AUC0-t and MRT0-t of the high dose ginsenoside group were increased by 46% and 24% respectively, and CL decreased by 19%, which was statistically significant difference. The AUC0-t of the low dose ginsenoside group had a significant increased(21%) compared with the etoposide group, while other pharmacokinetic parameters had no significant differences. CONCLUSION: Combination of ginsenosides and etoposide could significantly improve the plasma concentration and reduce excretion of etoposide.