Establishment and preliminary application of organoids in ovarian cancer / 中华妇产科杂志

Objective:To explore the establishment and application of ovarian cancer organoids.Methods:Fresh ovarian tumor tissues, obtaining from patients underwent surgery in the First Affiliated Hospital of Nanjing Medical University between October 2021 and March 2022, were collected, enzymatic degraded, digested, and embedded into matrigel to establish organoids. A total of 32 ovarian cancer samples were collected. Hematoxylin eosin (HE) staining and immunofluorescence (IF) procedure were used to verify the morphological structure of organoids and their expression of molecular markers. 3D cyto-live or dead assay was used to detecte the live or dead cells in organoids. Carboplatin with a concentration ranging from 5 to 80 μmol/L (5, 10, 20, 40, 80 μmol/L) was added to organoids to calculate the 50% inhibitory concentration (IC 50) in different organoids. Results:(1) Organoids from a total of 32 patients were established, of which 18 cases could be passaged stably in the long term in vitro, while 14 could be passaged in the short time. The average amplification time of long-term passage in vitro was over 3 months, and the longest reached 9 months. (2) In HE staining, significant nuclei atypia and local micropapillary structures were observed in organoids. IF staining revealed that ovarian cancer organoids expressed molecular markers similar to primary tumor tissues, such as Pan cytokeratin (Pan-CK), p53, paired box gene 8 (PAX8), and Wilms tumor gene 1 (WT1). (3) In 3D cyto-live or dead assay, a large number of apoptotic cells were observed inside and around the organoids after added carboplatin. The sensitivity to carboplatin varied in 18 organoids could amplify in the long term, with an average IC 50 of (29.5±15.8) μmol/L. Moreover, IC 50 values of 4 organoids derived from patients received neoadjuvant chemotherapy were much higher than the 14 organoids which did not received neoadjuvant chemotherapy [(48.7±11.3) μmol/L vs (24.0±12.1) μmol/L; t=3.429, P=0.022]. Conclusions:Organoids recapitulate ovarian cancers in vitro and could be stably passaged. Organoids derived from patients received neoadjuvant chemotherapy have higher resistance to carboplatin.

Clinical efficacy of paclitaxel and carboplatin with versus without bevacizumab in treatment of advanced non-small cell lung cancer: A systematic review and meta-analysis / 中国胸心血管外科临床杂志

@#Objective    To systematically evaluate the clinical efficacy and adverse reactions of paclitaxel and carboplatin with or without bevacizumab in the treatment of non-small cell lung cancer (NSCLC). Methods    The databases including PubMed, The Cochrane Library, EMbase, CNKI, Wanfang Data, VIP and CBM were searched from inception to October 2022 to collect randomized controlled trials of the clinical efficacy of paclitaxel and carboplatin with or without bevacizumab for the treatment of NSCLC. RevMan 5.4 software was used for meta-analysis. Results    Eight randomized controlled trials were enrolled, involving a total of 1 724 patients. Meta-analysis showed that for the treatment of NSCLC, the disease control rate, overall response rate, 1-year survival rate, and 2-year survival rate were higher in the trial group (paclitaxel and carboplatin combined with bevacizumab) than those in the control group (paclitaxel and carboplatin) (P<0.05); however, the incidences of the adverse reactions, such as leukopenia, hemorrhage, proteinuria and hypertension, etc, were higher in the trial group than those in the control group (P<0.05). There were no statistical differences between the trial group and the control group in the incidences of fatigue, thrombocytopenia, neutropenia or hyponatremia, etc (P>0.05). In addition, the median progression-free survival and overall survival were longer in the trial  group than those in the control group. Conclusion    For the treatment of NSCLC, paclitaxel and carboplatin combined with bevacizumab is superior in terms of disease control, overall response and prolonging patient survival, etc, but will be associated with more adverse reactions.

Effect of the area under the curve of carboplatin dosage on therapeutic efficacy and safety in Chinese patients with epithelial ovarian cancer / 西安交通大学学报(医学版)

【Objective】 To retrospectively analyze the average carboplatin dosage and calculate the area under the curve (AUC) using the Calvert formula in first-line chemotherapy in patients with epithelial ovarian cancer in The First Affiliated Hospital of Xi’an Jiaotong University so as to evaluate the effect of the AUC difference in the Chinese population on therapeutic efficacy and safety. 【Methods】 We enrolled patients who underwent first-line chemotherapy with paclitaxel and carboplatin 3-week regimen in our hospital from January 1, 2012 to January 1, 2022. According to the median of AUC, the patients were divided into high-dose group and low-dose group. The overall response rate (ORR), disease control rate (DCR), progression free survival (PFS), overall survival (OS), and the incidence of adverse events (AEs) were compared. 【Results】 A total of 153 patients were enrolled in this study and the median AUC of carboplatin was 3.981 (range 2.314-5.446). Only 10.46% patients (16/153) had an AUC above 5. There were 77 patients with the AUC0.05). The ORR in the low-dose group and the high-dose group was 59.74% and 57.89%, respectively, and the DCR was 87.01% and 85.53%, respectively. The median PFS of the two groups was 14 and 15.5 months, respectively, and the median OS was 50 and 55 months, respectively. None of the above outcomes were statistically different between the two groups (P>0.05). The two groups showed significant differences in the incidence of anemia, neutropenia, and thrombocytopenia (P<0.05). The incidence of nausea and vomiting, grade 1-2 diarrhea or constipation, and grade 1-2 fever showed significant differences (P<0.05). In addition, the incidence of dose limiting toxicity (DLT), including grade 4 thrombocytopenia and febrile neutropenia (FN), was significantly increased in the high-dose group (P<0.05). 【Conclusion】 Compared with the recommended AUC 5-6 of carboplatin abroad, the actual carboplatin dosage in the first-line chemotherapy for patients with epithelial ovarian cancer was generally insufficient in our hospital. There was no difference in therapeutic efficacy between the patients with AUC<4 and AUC≥4. However, considering the increased risk of some AEs and DLT in the high-dose group, it is not recommended to increase the carboplatin AUC blindly.

Carboplatin-loaded surface modified-PLGA nanoparticles confer sustained inhibitory effect against retinoblastoma cell in vitro / Nanopartículas de PLGA com superfície modificada carregada com carboplatina conferem efeito inibitório sustentado contra células de retinoblastoma in vitro

ABSTRACT Purpose: To investigate the antiproliferative effect of carboplatin-loaded surface-modified poly(lactide-co-glycolide) on retinoblastoma cells. Methods: Carboplatin-loaded poly(lactide-co-glycolide) with or without sodium alginate surface modification was prepared using sodium alginate-poly(lactide-co-glycolide) and poly(lactide-co-glycolide). The zeta potential and carboplatin release behavior were investigated. The cellular uptake of the released drug was observed in the retinoblastoma cell line Y79. The inhibitory effect of carboplatin-loaded nanoparticles against the Y79 cell line was evaluated using methyl thiazolyl tetrazolium assay and western blot. Native carboplatin and void nanoparticles without carboplatin loading were used as controls. Results: The zeta potential was -(26.1 ± 3.1) mV for carboplatin-loaded poly(lactide-co-glycolide) and-(43.1 ± 8.1) mV for carboplatin-loaded sodium alginate-poly(lactide-co-glycolide). The burst release percentages of carboplatin-loaded poly(lactide-co-glycolide) and sodium alginate-poly(lactide-co-glycolide) were (40.0% ± 8.2%) and (18.9% ± 4.3%) at 24 hours, respectively. A significant difference was identified regarding drug release between carboplatin-loaded sodium alginate-poly(lactide-co-glycolide) and carboplatin-loaded poly(lactide-co-glycolide). Fluorescence detection revealed that intense uptake of carboplatin into the cytoplasm of the Y79 cell line that was exposed to carboplatin-loaded sodium alginate-poly(lactide-co-glycolide). Carboplatin-loaded poly(lactide-co-glycolide) or sodium alginate-poly(lactide-co-glycolide) exposure inhibited proliferating cell nuclear antigen expression in Y79 cells on day 3. Extension of exposure to day 5 revealed that the sodium alginate-poly(lactide-co-glycolide) surface modification was superior to that of poly(lactide-co-glycolide) in terms of proliferating cell nuclear antigen inhibition. The cell viability test using methyl thiazolyl tetrazolium revealed a similar inhibitory effect. Furthermore, the carboplatin-loaded nanoparticles of lower concentration inhibited cell viability more strongly than native carboplatin of higher concentration in methyl thiazolyl tetrazolium assay. Conclusions: Carboplatin-loaded sodium alginate-poly(lactide-co-glycolide) inhibited retinoblastoma cell proliferation with superior effect as compared with poly(lactide-co-glycolide) and native carboplatin. Sodium alginate surface modification offers a potential strategy for the sustained carboplatin release system.

RESUMO Objetivo: Investigar o efeito antiproliferativo de poli (lactídeo-coglicolídeo) com superfície modificada carregada com carboplatina contra células de retinoblastoma. Métodos: Preparou-se poli (lactídeo-co-glicolídeo) carregado com carboplatina com ou sem alginato de sódio para modifição da superfície, poli com alginato de sódio (lactídeo-co-glicolídeo) e poli (lactídeo-co-glicolídeo). O potencial zeta e o comportamento de liberação de carboplatina foram investigados. A captação celular do fármaco liberado foi observada na linha celular de retinoblastoma Y79. O efeito inibitório das nanopartículas carregadas com carboplatina contra a linha celular Y79 foi avaliado através do ensaio de metiltiazol tetrazólio e Western-blot. Carboplatina nativa e nanopartículas vazias sem carga de carboplatina serviram como controles. Resultados: O potencial zeta de poli carregado com carboplatina (lactídeo-co-glicolídeo) foi - (26,1 ± 3,1) mV versus - (43,1 ± 8,1) mV em poli com alginato de sódio carregado com carboplatina (lactídeo-co-glicolídeo). A percentagem de libertação de explosão de poli carregado com carboplatina (lactídeo-co-glicolídeo) e poli com alginato de sódio (lactídeo-co-glicolídeo) foram (40,0 ± 8,2)% e (18,9 ± 4,3)% às 24 horas, respectivamente. Uma diferença significativa foi identificada em relação à liberação de fármaco entre poli com alginato de sódio carregado com carboplatina (lactídeo-co-glicolídeo) e poli carregado com carboplatina (lactídeo-co-glicolídeo). A detecção de fluorescência revelou que a carboplatina foi assimilada intensamente no citoplasma da linha celular Y79 que foi exposta ao poli com alginato de sódio carregado com carboplatina (lactídeo-co-glicolídeo). A exposição de poli carregada com carboplatina (lactídeo-co-glicolídeo) ou poli com alginato de sódio (lactídeo-co-glicolídeo) inibiu a expressão de antígeno nuclear de proliferação celular em células Y79 no 3º dia. A extensão da exposição no 5º dia revelou que poli com alginato de sódio (lactídeo-co-glicolídeo) para modificação da superfície foi superior a poli (lactídeo-co-glicolídeo) em termos de inibição do antígeno nuclear de proliferação celular. O teste de viabilidade celular via metiltiazol tetrazólio mostrou um efeito inibitório semelhante. Além disso, as nanopartículas carregadas com carboplatina de concentração mais baixa inibiram a viabilidade celular mais fortemente em comparação com a carboplatina nativa de concentração mais alta no ensaio de metiltiazol tetrazólio. Conclusões: Poli com alginato de sódio carregado com carboplatina (lactídeo-co-glicolídeo) inibiu a proliferação de células de retinoblastoma com efeito superior em contraste com poli (lactídeo-co-glicolídeo) e carboplatina nativa. O alginato de sódio para modificação da superfície oferece uma estratégia potencial para o sistema de liberação de carboplatina sustentada.

Efficacy and survival outcomes of dose-dense carboplatin plus paclitaxel as neoadjuvant chemotherapy for triple-negative breast cancer / 中华肿瘤杂志

Objective: To evaluate the efficacy and survival outcomes of dose-dense (biweekly) carboplatin plus paclitaxel (PC) as neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC), and to explore an optimal neoadjuvant chemotherapy regimen for TNBC. Methods: Patients diagnosed as TNBC(cT1-4N0-3M0) in Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College Between January 2008 and September 2018 who received dose-dense PC and standard 3-weekly PC as NAC were 1∶1 matched using propensity score matching (PSM) to compare the efficacy, safety and survival outcomes. Results: One hundred of TNBC patients were enrolled (50 patients were divided in dose-dense group, 50 patients in standard group). The objective response rate (ORR) of dose-dense group and standard group were both 90.0% (45/50). The grade 3-4 neutropenia in dose-dense group was less than that of standard group (32.7% vs. 68.0%, P=0.001), while the rate of ALT/AST elevation in dose-dense group was higher than that of standard group (57.1% vs. 32.0%, P=0.012). The pathological complete response (pCR) rates were 34.0% (17/50) in dose-dense group and 38.0% (19/50) in standard group, without statistically significance (P=0.677). The median follow-up time was 55 months (3-150 months). The 5-year recurrence-free survival (RFS) in dose-dense group and standard group were 83.5% and 75.2%, respectively the 5-year overall survival (OS) in dose-dense and standard group were 87.9% and 84.5% the difference were not statistically significant (P=0.322 and 0.647, respectively). Patients with residual disease (tumor size≥1 cm or lymph node positive) had poor prognosis, the 5-year RFS and OS were 59.3% and 68.5%, respectively. Conclusions: Dose-dense PC has similar efficacy with standard 3-weekly PC and has a good safety profile. Since dose-dense regimen can shorten the duration of therapy, it can be an alternative in TNBC.

Mechanism of Huangqintang in Alleviating Side Effect of Chemotherapy for Endometrial Cancer Based on Network Pharmacology and Molecular Docking / 中国实验方剂学杂志

ObjectiveTo evaluate the utility and mechanism of Huangqintang combined with carboplatin in chemotherapy of endometrial cancer by experiments as well as network pharmacology and molecular docking. MethodThe xenograft model of endometrial carcinoma was induced in BALB/c nude mice. When the tumor volume reached about 100 mm3，24 nude mice were randomly assigned into a model group， a Huangqintang group （3.5 g·kg-1），a carboplatin group （50 mg·kg-1），and a combination group （3.5 g·kg-1 Huangqintang + 50 mg·kg-1 carboplatin）， with six mice in each group. The mice in the model group received 200 μL of normal saline by gavage， twice a day. The volume of the tumor and the body weight of the mice were measured every two days. After drug intervention for 20 days， the blood of the mice was collected for renal function and blood routine tests. Then the nude mice were euthanized and the tumor was weighted. In combination with the experimental results，the underlying mechanism of Huangqintang combined carboplatin was predicted through network pharmacology and the binding sites of active components were predicted by molecular docking. ResultThe tumor inhibition rates of the Huangqintang group，the carboplatin group， and the combination group were 8.87%，50.33% （P<0.05），and 64.66% （P<0.01），respectively. Compared with the results in the model group，the body weight，leukocyte，erythrocyte， and hemoglobin in the carboplatin group decreased，and creatinine and uric acid increased （P<0.05）. Compared with the carboplatin group，the combination group showed increased body weight，leukocyte， and hemoglobin （P<0.05），and decreased creatinine and uric acid （P<0.05）. A total of 114 potential active components of Huangqintang involved 200 targets related to the side effects of carboplatin. The core genes involved were mainly heat shock protein 90AA1 （HSP90AA1），transcription factor c-Jun （JUN）， and mitogen-activated protein kinase （MAPK）. Molecular docking showed that baicalein and wogonin could form a stable protein complex with HSP90AA1， serving as potential active molecules. Kyoto Encyclopedia of Genes and Genomes （KEGG） analysis revealed that it might be related to the regulation of tumor necrosis factor（TNF） signaling pathway，interleukin（IL）-17 signaling pathway， MAPK signaling pathway， and toll-like receptor pathway. ConclusionHuangqintang has no obvious inhibitory effect on endometrial cancer，and the tumor suppression effect is not significantly enhanced after combination with carboplatin，but Huangqintang can alleviate carboplatin-induced side effects. The mechanism may be related to the complex network of Chinese medicine.

Clinical efficacy of docetaxel combined with carboplatin in patients with metastatic castration-resistant prostate cancer / 北京大学学报(医学版)

OBJECTIVE@#To observe the early efficacy and toxicity of docetaxel combined with carboplatin in patients with metastatic castration-resistant prostate cancer (mCRPC).@*METHODS@#From May 2017 to July 2019, fifteen patients with mCRPC treated in Peking University First Hospital were collected. The median age was 70 years (43-77 years), and the pathological types were all adenocarcinoma, which was confirmed as distant metastasis by imaging examination. They were given the chemotherapy of docetaxel combined with carboplatin. The specific method was as follows: each cycle was 28 days. Androgen deprivation therapy was administered routinely throughout the treatment period. Blood routine, liver and kidney function, blood clotting function and prostate-specific antigen (PSA) tests were performed before each cycle. Docetaxel was administered intravenously on the first day of each cycle at a dose of 75 mg/m2, and carboplatin was administered intravenously on the second day at the dose calculated by Calvert formula. The main outcome measures including PSA decline range, pain remission rate and occurrence of adverse reactions were observed and analyzed.@*RESULTS@#Among the 15 patients, 12 had completed at least 4 cycles of chemotherapy and had short-term efficacy evaluation. PSA decline range > 50% was observed in 8 patients (66.7%). Among the 9 patients with bone pain, remarkable pain relief was observed in 4 patients (44.4%). Among the 4 patients with measurable metastatic lesions, 2 achieved partial response, 1 was evaluated as stable disease, and 1 was evaluated as progressive disease. The main adverse reactions of chemotherapy included bone marrow suppression, gastrointestinal reactions, fatigue and neurological disorders, and most of them were within the tolerable range.@*CONCLUSION@#This report is a case series study of docetaxel combined with carboplatin in the treatment of mCRPC reported in China and the conclusions are representative. The chemotherapy of docetaxel combined with carboplatin has positive short-term efficacy and high safety in patients with mCRPC, which is worthy of further promotion and exploration in clinical practice.

Response evaluation of locally advanced carcinoma ovary to neoadjuvant chemotherapy at a tertiary care centre

Background: Clear cell and mucinous types of epithelial ovarian cancers are relatively chemo resistant and have a poorer prognosis compared to other histologies. Aim of the study was to study the biochemical and histopathological response and surgical outcome of various histologies to standard platin based chemotherapy.Methods: All 42 cases of locally advanced carcinoma ovary who received several cycles of neoadjuvant chemotherapy (NACT) followed by, interval cytoreductive surgery (ICS) were included in this study. Serum CA125 levels before and after neoadjuvant chemotherapy, the ability to achieve optimal cytoreduction and the presence of residual tumour in the surgical specimen were the parameters measured. Continuous variables were compared by one-way ANOVA. Categorical variables were compared by the Pearson chi-square test. Significance was defined by p values less than 0.05. Survival analysis was done using Kaplan-Meier estimation.Results: There was a 95,84% reduction in serum CA125 levels for papillary serous carcinoma compared to clear cell and mucinous varieties, which had 81.2% and 78.5% reduction, respectively. More number of papillary serous tumours were able to achieve optimal cytoreduction (72%) compared to mucinous variety (25%). Residual tumour was present in 68% of serous papillary tumours compared to 87.5% in mucinous and 80% in clear cell histology.Conclusions: Our study concludes that mucinous and clear cell types of EOC are relatively chemo resistant compared to the serous subtype. We recommend more aggressive surgery especially for mucinous tumours. In the case of ovarian cancer, we observed that the mucinous and clear cell types of EOC are relatively chemoresistant compared to the serous subtype. From the results, we recommend the more aggressive strategy of surgery as a preliminary choice of treatment especially for mucinous tumours rather than chemotherapy in patients with EOC.

A comparative study on concurrent chemoradiation using cisplatin versus carboplatin in the management of locoregionally advanced non-small cell lung cancer

Background: Concurrent chemoradiation is considered the standard care for locoregionally advanced non-small cell lung cancer. This study aimed to compare the treatment response, progression free survival and treatment toxicities between cisplatin and carboplatin based concurrent chemoradiation.Methods: Between October 2015 and September 2017, 60 eligible patients were enrolled and divided into two arms of 30 patients each. Arm A received EBRT to chest (60Gy/30 fractions) with concurrent weekly Injection Cisplatin 35mg/m2. Arm B received EBRT to chest (60Gy/30 fractions) with concurrent weekly Injection Carboplatin at a dose of AUC-2. Early treatment response was assessed at 1 month and late treatment response at 6 months after completion of radiation using RECIST criteria. Treatment toxicities was assessed using RTOG toxicity criteria. All statistical analysis was carried out using SPSS version 21.Results: Most patients were in the age range of 61-70 years. Mean age of presentation was 67.53±11.038 years in Arm A and 66.03±12.794 years in Arm B. Median follow up was 16 months for both arms. Response rate of was slightly better in Arm A (73.3% versus 60%). 1 year PFS rate was 53.33% in Arm A and 36.67% in Arm B. Median time to progression was better in Arm A (11 months vs 10 months). Toxicities were almost comparable in both the arms.Conclusions: Use of carboplatin in combination with radiation therapy is comparable to cisplatin in terms of treatment outcomes with better compliance and lower toxicity.

Three-dimensional speckle tracking imaging in evaluation on left ventricular systolic function of Paclitaxel combined with Carboplatin in patients with ovarian cancer / 中国介入影像与治疗学

Objective: To explore the application value of three-dimensional speckle tracking imaging (3D-STI) in evaluation on changes of left ventricular systolic function caused by Paclitaxel combined with Carboplatin for treatment of ovarian cancer. Methods: Thirty patients with pathologically diagnosed ovarian cancer (ovarian cancer group) were selected and treated with Paclitaxel combined with Carboplatin chemotherapy. 3D-STI examination was performed before chemotherapy and at the end of 3 and 6 cycles of chemotherapy to obtain left ventricular end diastolic volume (LVEDV), left ventricular end systolic volume (LVESV), left ventricular ejection fraction (LVEF), spherical index (SPI), left ventricular end diastolic mass (LVEDmass), left ventricular end systolic mass (LVESmass), left ventricular global longitudinal strain (GLS), global circumferential strain (GCS), global radial strain (GRS) and global area strain (GAS), and the indexes compared with those of 30 healthy volunteers (control group). ROC curve was used to analyze the diagnostic efficacy of various strain parameters for cardiac function abnormalities in patients with ovarian cancer after chemotherapy. Results: Compared with control group, LVEDV and LVEF decreased, LVEDmass and LVESmass increased, and left ventricular GLS, GCS, GRS and GAS decreased after 3 and 6 cycles of chemotherapy in ovarian cancer group (all P<0.05). ROC curve of systolic peak strain parameters for diagnosis of cardiac function in patients with ovarian cancer after chemotherapy showed that AUC (0.944) and specificity (96.67%) of GAS were the highest at the end of 3 cycles of chemotherapy while GLS and GCS had the highest sensitivity (90.00%).At the end of 6 cycles of chemotherapy, GAS had the highest AUC (0.953) and specificity (96.67%), and GLS had the highest sensitivity (93.33%). Conclusion: 3D-STI can early detect of left ventricular systolic function in patients with ovarian cancer treated with Paclitaxel combined with Carboplatin.

Carcinoma seroso de ovario. Serie de 14 casos y revisión de la bibliografía / Serous ovarian cancer. Report of 14 cases and review of the bibliography

Resumen OBJETIVO: Describir las características epidemiológicas, clínicas, de laboratorio, de tratamiento médico-quirúrgico y patología, en una serie de 14 pacientes con carcinoma seroso de ovario atendidas en un hospital de alta complejidad y revisión de la bibliografía con el fin de actualizar los conceptos. MATERIALES Y MÉTODOS: Estudio de serie de casos retrospectivo y descriptivo de pacientes con cáncer de ovario seroso confirmado por patología. Las pacientes se estudiaron en un hospital general de alta complejidad entre 2013 y 2016. Variables de estudio: epidemiológicas, clínicas, de laboratorio, del tratamiento médico quirúrgico, comorbilidades y patología. Revisión narrativa de la bibliografía correspondiente a la información relacionada con las variables evaluadas. RESULTADOS: Se diagnosticaron 14 mujeres, de 50 a 80 años; 3 casos con antecedente de histerectomía y 1 de salpingoclasia. Diagnóstico histológico: 10 con tumor seroso de alto grado, 2 moderadamente diferenciado, 1 seroso de bajo grado y otro no clasificado. Procedimientos quirúrgicos: histerectomía, salpingooforectomía bilateral, linfadenectomía, omentectomía en 8 casos. Clasificación en estadios: IV en 6, 3 IIIB, 2 IC, 1 IIIC y una 1 IB. Tratamiento: 10 mujeres con carboplatino y paclitaxel. Revisión de 2227 artículos encontrados, 41 seleccionados. CONCLUSIONES: El carcinoma seroso de ovario se clasifica, actualmente, en bajo y alto grado (más frecuente y agresivo). Este tipo fue el más frecuente, los factores de riesgo encontrados, por el número reducido de pacientes, no permiten emitir conclusiones.

Abstract OBJECTIVE: To describe the epidemiological, clinical, laboratory, surgical medical management and pathology characteristics in a series of 14 patients with serous ovarian carcinoma in a highly complex hospital and review of the literature in order to update the concepts. MATERIALS AND METHODS: Retrospective and descriptive case series study of a patient with serous ovarian cancer confirmed by pathology. The patients were studied in a highly complex general hospital between 2013 and 2016. Study variables: Epidemiological, clinical, laboratory surgical medical treatment, comorbidities, and pathology. Narrative review of the bibliography corresponding to information related to the evaluated variables. RESULTS: Fourteen women between the ages of 50 and 80 were diagnosed, 3 with a history of hysterectomy and 1 with tubal ligation. Histological diagnosis: 10 with high-grade serous tumor, 2 moderately differentiated, 1 low-grade serous and one not classified. Surgical procedures: hysterectomy, bilateral salpinges-oophorectomy, lymphadenectomy, omentectomy in 8 cases. They classified into states: IV in 6, 3 IIIB, 2 IC, 1 IIIC and 1 IB. Treatment 10 women with carboplatin and paclitaxel. Review 2227 articles were found, 41 sectioned. CONCLUSIONS: Serous ovarian carcinoma is currently classified as low and high grade (more frequent and aggressive). This type was the most frequent, the risk factors found by the reduced number do not allow conclusions to be drawn.

Preparation of Highly Water-soluble Platinum Antitumor Drugs and Evaluation of Antitumor Efficacy on Tumor Cell Lines / 中国药学杂志

OBJECTIVE: To design and synthesize a new kind of highly water-soluble platinum antitumor compounds, and then evaluate their cytotoxicity in order to confirm their antitumor efficacy. METHODS: Diamide-diiodide platinum was firstly synthesized from potassium chloroplatinate, which was then reacted with Ag2SO4 to obtain intermediate . Using disodium 2-amino-alkyl malonate or N-substituted amino alkyl malonate as the intermediate Ⅱ, the two intermediates reacted at 1∶1 molar ratio to obtain the target compound III in the presence of acid. RESULTS: A new class of platinum compounds were synthesized, which had much better water solubility than that of the existing three-generation platinum compounds. Their antitumor efficacy was confirmed against a variety of tumor cell lines which was higher than that of carboplatin. IIIg was similar to cisplatin in antitumor efficacy on some tumor cell lines. Some target compounds were effective against cisplatin-resistant cell lines. CONCLUSION: Currently in the clinical trial, the target compound IIIg is a new platinum-base antitumor candidate, which exhibits good water solubility and antitumor efficacy in vitro, and the LD50 based on mice shows its lower toxicity than that of cisplatin and carboplatin in vivo.

Bevacizumab with paclitaxel and carboplatin for locally advanced (Stage IIIB) metastatic adenocarcinoma of lung: A feasibility study from tertiary care center

Background: Lung cancer is the most common cancer and leading cause cancer-related death in worldwide and also in India. Around 42% of these patients have adenocarcinoma. Most of these patients presented in locally advanced stage or metastatic disease. There is no significant difference in effectiveness among different chemotherapy regimens with median survival of 8 months only. Hence, additional treatment option including newer monoclonal antibodies is needed to improve tumor control and survival. Vascular endothelial growth factor (VEGF) is critical determinant of tumor angiogenesis, a process that is necessary component of tumor growth, invasion, and metastasis. Bevacizumab (Bev), a humanized monoclonal antibody (IgG1) targeting VEGF, effective in colorectal cancer, renal cell carcinoma, glioblastoma multiforme, and non-small cell lung cancer and approved for clinical use since 2004. Objectives: The aim of our study is feasibility of the combination of Bev with paclitaxel and carboplatin in locally advanced (Stage IIIB) metastatic adenocarcinoma of lung in our institute, N.R.S. Medical College and Hospital, Kolkata. Materials and Methods: Between February 2015 and December 2018, ninety-eight previously untreated patients with locally advanced metastatic (Stages IIIB and IV) adenocarcinoma of lung treated with Bev with paclitaxel and carboplatin. Paclitaxel at a dose of 175 mg/m2, carboplatin at an AUC 6 mg/ml/min, and Bev at a dose of 15 mg/kg given on the 1st day of chemotherapy. Chemotherapy administered every 3 weeks up to 6 cycles with maintenance Bev until disease progression or unacceptable toxicity whichever is earlier. Patients ECOG 2 or more, brain metastasis, squamous cell histology, and hemoptysis were not included in the study. Results: The Median overall survival (OS), progression free survival (PFS) were 9.4 and 5.2 months, respectively. Anemia (19%) and neutropenia (16 %) are most common toxicity. Conclusion: Bev with paclitaxel and carboplatin in selected patients with adenocarcinoma of lung is safe and confers survival benefit with acceptable toxicity.

A Study On Carboplatin –PACLITAXEL Induced Peripheral Neuropathy In Cancer Patients

Background: Peripheral neuropathy is a common treatment related adverse effect and affects long term quality of life. AIM: To study the Carboplatin–Paclitaxel induced peripheral neuropathy in patients with lung or ovarian cancer. Methods: The study was carried out in the Department of Oncology, Government Rajaji Hospital, Madurai, after obtaining clearance from Institutional ethical committee, Government Rajaji Hospital, Madurai.Thirty newly diagnosed patients suffering from Lung or ovarian cancer attending Oncology department were selected. After satisfying inclusion and exclusion criteria,Patient received Injection Carboplatin AUC 6 and Injection Paclitaxel 175mg/m2 . Nerve conduction study was done to assess the peripheral neuropathy. It was done before starting the chemotherapy.Patients with grade 0 neuropathy were included for the study.Nerve conduction study was repeated after each cycle. The time taken to develop peripheral neuropathy was assessed using Cancer Institute – Common Toxicity Criteria version 3.0. The data were analyzed with SPSS statistical software package (Version 16.0 SPSS Inc., Chicago, USA ). Results: There is a statistically significant reduction in sensory nerve (sural) amplitude (SNAP) and latency (p<0.05) indicating significant axonal damage. The time taken to develop peripheral neuropathy was 4 Cycles with Grade 2/4. Conclusions: In this present study , the neurotoxicity induced by Carboplatin–Paclitaxel in patients with lung or ovarian carcinoma was observed. More effective dosing– schedules of treatment decreases the incidence of long lasting peripheral neurotoxicity thus providing better results withlonger survival rate and less disability.

Effects of ultrasound combined with microbubbles on intracellular Ca 2+ homeostasis in carboplatin-treated microenvironment of A549 cell line / 中华超声影像学杂志

Objective To investigate the effects of ultrasound combined with microbubbles on intracellular Ca2+ homeostasis in carboplatin ( CBP )-treated A549 cell and its possible mechanisms of inhibiting A549 cell line activity . Methods According to whether SonoVue was used or not ,and the different dose of CBP ,the groups A-F were arranged as the ultrasound(US) group(group A) ,the ultrasound combined with microbubbles ( USMB) group( group B) ,the low dose CBP ( 100 μg/ml) + US group( group C) ,the low dose CBP+USMB group( group D) ,the high dose CBP ( 200 μg/ml)+ US group ( group E) and the high dose CBP+USMB group( group F) .A549 cells were bathed and washed by a calcium-free buffer , loaded with Ca2+ indicator fluo-4 AM . Real-time images were acquired using laser confocal microscopy .The fluorescence intensity of intracellular calcium ion concentration ([Ca2+ ]i) in individual living cell was observed and the calcium overload was analyzed . Results After ultrasound irradiation ,the normalized fluorescence intensity of [Ca2+ ]i increased rapidly ,then returned to a new homeostasis (selected cells in groups A ,B ,E ,F) or experienced a second calcium oscillation ( some cells in group C and D) . All the selected cells in group B and some cells in group C and D exhibited superimposed oscillations . The calcium overloading time in group D was longer than those of any other groups . Four cells in group A experienced delayed calcium oscillations . Compared with group A ,the selected cells in other groups exhibited a larger amplitude of calcium oscillation( all P < 0 .05) and the selected cells in group B and D exhibited calcium oscillation for a longer period of time( all P <0 .05) . Conclusions In the calcium-free buffer ,US ,USMB , CBP+ US ,CBP + USMB are direct stimuli of calcium overload in A 549 cells . SonoVue ,CBP ,CBP +SonoVue are all synergistic stimuli of calcium overload in A 549 cells irradiated by ultrasound .US ,USMB and CBP may synergistically induce calcium release from intracellular store sites in A 549 cells . Calcium overload is a possible mechanism of ultrasound combined with microbubbles in assisting CBP chemotherapy .

Efficacy and safety of recombinant human endostatin combined with gemcitabine and carboplatin as first-line treatment of advanced NSCLC with liver metastases / 肿瘤

Objective: To compare the efficacy and safety of GC (gemcitabine plus carboplatin) regimen combined with recombinant human endostatin (rh-endostatin) and GC regimen alone in the first-line treatment of advanced non-small cell lung cancer (NSCLC) with liver metastases. Methods: The clinical and pathological data of patients with advanced NSCLC and liver metastases, who were diagnosed from October 2013 to July 2017 in Hunan Cancer Hospital and treated with rh-endostatin combined with GC regimen or GC regimen alone as the firstline treatment, were retrospectively analyzed. A total of 94 patients were enrolled, including 46 cases in combination group and 48 cases in chemotherapy group. All patients received at least 2 cycles of treatment (21 days per cycle). Objective response rate (ORR), progressionfree survival (PFS), overall survival (OS), and adverse events were observed and compared between the two groups. Results: After 2 cycles of treatment, the ORR in the combination group and the chemotherapy group were 27.1% and 10.9%, respectively; while the ORR in the combination group was significantly higher than that in the chemotherapy group (P = 0.046). Subgroup analysis showed that the patients in adenocarcinoma subgroup could benefit more from the combination treatment (combination group vs chemotherapy group: 35.0% vs 11.1%, P = 0.048). The median PFS time was 4.5 months and 3.4 months in the combination group and the chemotherapy group, respectively; while the median OS time was 7 months and 6 months in the two groups, respectively; so the PFS and OS in the combination group were significantly prolonged (both P < 0.001). In the patients receiving 4 or more cycles of treatment, the survival benefit of combination therapy was more significant as compared with the chemotherapy group (PFS: 7 months vs 4 months, P < 0.001; OS: 10 months vs 6 months, P < 0.001). The main adverse reactions in the two groups were nausea, vomiting and myelosuppression, in which myelosuppression was mainly caused by leukopenia and neutropenia. Conclusion: Compared with the chemotherapy alone, rh-endostatin combined with GC regiment as the first-line treatment can significantly improve the median PFS, median OS and ORR in the patients with advanced NSCLC and liver metastases, and has good safety and clinical application prospects.

Effects of ultrasound combined with microbubbles on intracellular Ca 2+ homeostasis in carboplatin‐treated microenvironment of A549 cell line / 中华超声影像学杂志

To investigate the effects of ultrasound combined with microbubbles on intracellular Ca2+ homeostasis in carboplatin ( CBP )‐treated A549 cell and its possible mechanisms of inhibiting A549 cell line activity . Methods According to whether SonoVue was used or not ,and the different dose of CBP ,the groups A‐F were arranged as the ultrasound( US) group( group A ) ,the ultrasound combined with microbubbles ( USMB) group( group B) ,the low dose CBP ( 100 μg/ml) + US group( group C) ,the low dose CBP+USMB group( group D) ,the high dose CBP ( 200 μg/ml)+ US group ( group E) and the high dose CBP+USMB group( group F) .A549 cells were bathed and washed by a calcium‐free buffer , loaded with Ca2+ indicator fluo‐4 AM . Real‐time images were acquired using laser confocal microscopy . T he fluorescence intensity of intracellular calcium ion concentration ( [ Ca 2+ ] i ) in individual living cell was observed and the calcium overload was analyzed . Results After ultrasound irradiation ,the normalized fluorescence intensity of [ Ca2+ ] i increased rapidly ,then returned to a new homeostasis ( selected cells in groups A ,B ,E ,F ) or experienced a second calcium oscillation ( some cells in group C and D ) . All the selected cells in group B and some cells in group C and D exhibited superimposed oscillations . T he calcium overloading time in group D was longer than those of any other groups . Four cells in group A experienced delayed calcium oscillations . Compared with group A ,the selected cells in other groups exhibited a larger amplitude of calcium oscillation ( all P ＜ 0 .05 ) and the selected cells in group B and D exhibited calcium oscillation for a longer period of time( all P ＜0 .05) . Conclusions In the calcium‐free buffer ,US ,USMB , CBP+ US ,CBP + USMB are direct stimuli of calcium overload in A 549 cells . SonoVue ,CBP ,CBP +SonoVue are all synergistic stimuli of calcium overload in A 549 cells irradiated by ultrasound .US ,USMB and CBP may synergistically induce calcium release from intracellular store sites in A 549 cells . Calcium overload is a possible mechanism of ultrasound combined with microbubbles in assisting CBP chemotherapy .

Analysis of the efficacy of poly ADP?ribose polymerases inhibitor combined with chemotherapeutics in the treatment of triple negative breast cancer / 中国综合临床

Objective To investigate the effects of poly adenosine diphosphate ribose polymerase (PARP) inhibitor AG014699 on the proliferation of triple negative breast cancer (TNBC) cell line MDA?MB?231.Methods Cell proliferation and cytotoxicity test kit ( CCK?8) was used to detect the proliferation of MDA?MB?231 cells in different concentrations of AG014699 (0.1,1.0,10.0,20.0 and 40.0 mmol／L), DTX (10－9,10－8,10－7,10－6 and 10－5 mol／L) and CBP (10－6,10－5,10－4 and 10－3 mol／L).Flow cytometry was used to detect cell apoptosis and cell cycle distribution.Results The effects of AG01469 at different concentrations (0.1,1.0,10.0,20.0 and 40.0 μmol／L) on proliferation activity of MDA?MB?231 cells were (94.83 ± 3.93)%, ( 79.42 ± 5.52)%, ( 63.75 ± 4.34)%, ( 38.97 ± 8.42)%, ( 29.70 ± 3.35 )%, with statistically significant differences (F＝75.54,P＜0.01,different concentrations pairwise comparison: all P ＜0.05). The efficacy of AG014699 in combination with DTX at different concentrations (( 69.77 ±17.94)%,(58.34± 2.59)%,( 52.81 ± 2.01)%, ( 41.23 ± 3.38)%, ( 24.82 ± 0.73)%) was compared with that of single DTX (( 81.24 ± 11.91)%, ( 85.74 ± 3.10)%, ( 72.74 ± 4.66)%, ( 55.18 ± 3.19)%, (45.95±3.82)%).The differences were statistically significant (t values were －0.923,－11.748,－6.802,－5.199,－9.410,respectively,with P＞0.05 at 10－9 concentration and P＜0.01 at all other concentrations ). The efficacy of AG014699 combined with CBP ((78.33± 2.89)%,( 60.44± 1.95)%,( 50.55± 3.07)%, (12.07± 1.63)%) and single CBP (( 90.00 ± 6.18)%, ( 87.87 ± 2.30)%,( 76.82 ± 3.37)%,( 40.71 ±1.68)%) was compared,and the cell activity was significantly reduced,indicating statistically significant differences ( t values were －1.935,－15.756,－9.981,－21.192, respectively, and P＞0.05 at 10－6 concentration,P＜0.05 at all the other concentrations ).The q value was＞1.15 when AG014699 was combined with 10－3 mmol／L CBP, which showed synergistic effect.When combined with other effective concentrations of DTX or CBP,the q value was between 0.85 and 1.15,showing additive effect.Conclusion PARP inhibitor AG014699 assisted DTX or CBP can inhibit the proliferation of TNBC cell line MDA?MB?231.By means of simple addition or systematic effect,it can inhibit the triple negative breast cancer.

Functional and transcriptomic characterization of carboplatin-resistant A2780 ovarian cancer cell line

BACKGROUND: Ovarian cancer is a significant cancer-related cause of death in women worldwide. The most used chemotherapeutic regimen is based on carboplatin (CBDCA). However, CBDCA resistance is the main obstacle to a better prognosis. An in vitro drug-resistant cell model would help in the understanding of molecular mechanisms underlying this drug-resistance phenomenon. The aim of this study was to characterize cellular and molecular changes of induced CBDCA-resistant ovarian cancer cell line A2780. METHODS: The cell selection strategy used in this study was a dose-per-pulse method using a concentration of 100 µM for 2 h. Once 20 cycles of exposure to the drug were completed, the cell cultures showed a resistant phenotype. Then, the ovarian cancer cell line A2780 was grown with 100 µM of CBDCA (CBDCA-resistant cells) or without CBDCA (parental cells). After, a drug sensitivity assay, morphological analyses, cell death assays and a RNA-seq analysis were performed in CBDCA-resistant A2780 cells. RESULTS: Microscopy on both parental and CBDCA-resistant A2780 cells showed similar characteristics in morphology and F-actin distribution within cells. In cell-death assays, parental A2780 cells showed a significant increase in phosphatidylserine translocation and caspase-3/7 cleavage compared to CBDCA-resistant A2780 cells (P < 0.05 and P < 0.005, respectively). Cell viability in parental A2780 cells was significantly decreased compared to CBDCA-resistant A2780 cells (P < 0.0005). The RNA-seq analysis showed 156 differentially expressed genes (DEGs) associated mainly to molecular functions. CONCLUSION: CBDCA-resistant A2780 ovarian cancer cells is a reliable model of CBDCA resistance that shows several DEGs involved in molecular functions such as transmembrane activity, protein binding to cell surface receptor and catalytic activity. Also, we found that the Wnt/3-catenin and integrin signaling pathway are the main metabolic pathway dysregulated in CBDCA-resistant A2780 cells.

Safety of gemcitabine combined with platinum-based adjuvant chemotherapy for upper urinary tract urothelial carcinoma / 国际外科学杂志

Objective To investigate the safety of gemcitabine combined with cisplatin (GC) / carboplatin (GCa) regimen in adjuvant chemotherapy for upper urinary tract urothelial carcinoma.Methods The clinical and follow-up data of 80 patientswho underwent GC or GCa chemotherapy withinfourcycles of upper tract urothelial carcinoma (UTUC) admitted to Beijing Friendship Hospital,Capital Medical University from June 2012 to January 2018 were analyzed retrospectively,including 39 males and 41 females,aged 36 to 81 years,with a median age of 64.0 years.According to the chemotherapy regimen,all patients were divided into GC group (n =54) and GCa group (n =26).The software of SPSS 22.0 was used to calculate the incidence of adverse reactions of chemotherapy.The independent risk factors for serious adverse reactions were analyzed.The incidence of serious adverse reactions and the safety of renal function in patients with renal insufficiency during chemotherapy were explored.Results For adverse reactions to chemotherapy,GC group had 20 patients (37.0％) with severe myelosuppression,9 patients (16.4％) with non-hematological toxicity,3 patients (5.6％) with delayed chemotherapy due to serious chemotherapy adverse reactions,and 12 patients (22.2％) withdrawn chemotherapy early due to inability to tolerate chemotherapy toxicity.In GCa group,12 patients (46.2％) had severe myelosuppression,5 patients(19.2％) had severe non-hematologic toxicity,6 patients(23.1％) had delayed chemotherapy due to serious chemotherapy adverse reactions,and 6 patients (23.1％) had withdrawn chemotherapy early due to inability to tolerate chemotherapy toxicity.Pre-chemotherapye GFR ＜ 60 ml ·(min · 1.73 m2)-1 (OR =5.074,95％ CI:1.222-21.068) was an independent risk factor for severe myelosuppression in GC group (P ＜ 0.05).There was no significant difference in severe adverse reactions between the two groups (P ＜ 0.05).For the renal function decline between the two groups,Cr and eGFR decreased to a certain extent in the two groups during chemotherapy (P ＜ 0.05),but there was no significant difference in the extent and degree during chemotherapy (P ＜ 0.05).Conclusions Both GC and GCa adjuvant chemotherapy have certain toxicity and side effects.The process of chemotherapy needs to be closely monitored and timely symptomatic treatment if needed.Most patients can eventually endure chemotherapy.For patients with renal insufficiency,under the precondition of strict monitoring and adequate hydration,GC and GCa regimens adjuvant chemotherapy within four cycles may be the same safe level ofchemotherapy.