Aktivitas Sitotoksik Ekstrak Biji Alpukat (Persea americana Mill.) pada Sel Kanker Payudara dan Serviks Secara In Silico dan In Vitro

Kanker payudara dan servik merupakan kanker dengan jumlah terbanyak di Indonesia. Kemoterapi sebagai terapi kanker memiliki banyak efek samping, oleh karena itu diperlukan pengembangan obat antikanker terutama dari bahan alam yang efektif dan memiliki efek samping minimal. Salah satu bahan alam yang diprediksi mempunyai aktivitas antikanker adalah biji alpukat (Persea americana Mill.). Penelitian ini bertujuan untuk menentukan aktivitas sitotoksik ekstrak etanol biji alpukat pada sel kanker payudara dan serviks secara in silico dan in vitro. Senyawa aktif dalam biji alpukat di docking dengan reseptor estrogen (PDB code: 3ERT) and reseptor SIRT1 (PDB code: 4I5I) menggunakan program Molegro Virtual Docker 5.5 (MVD). Aktivitas sitotoksik secara in vitro dilakukan menggunakan metode Microculture Tetrazolium Technique (MTT) pada sel kanker payudara (MCF7), sel kanker serviks (HeLa) dan sel normal (Vero). Biji alpukat berisi 10 senyawa aktif yang diprediksi mempunyai aktivitas sitotoksik. Hasil uji in silico menunjukkan bahwa epicatechin gallate mempunyai nilai rerank score paling rendah yaitu -118,397 kkal/mol pada reseptor estrogen dan -133,694 kkal/mol pada reseptor SIRT1. Aktivitas sitotoksik secara in vitro ditunjukkan dengan nilai IC50 sebesar 537,37 μg/mL (MCF7), 383,21 μg/mL (HeLa) dan 541,67 μg/mL (Vero). Dari hasil uji in vitro menyatakan bahwa ekstrak etanol biji alpukat tidak memiliki aktivitas sitotoksik pada sel kanker MCF7 dan memiliki aktivitas sitotoksik lemah pada sel HeLa.   Breast and cervical cancer are cancers with the highest number in Indonesia. Chemotherapy, as one of the mainstay treatments of cancer, can cause harmful side effects; and, therefore, it is necessary to develop anticancer drug from natural ingredients with good efficacy and minimal side effects. One of the natural ingredients that is predicted to have anticancer activity is avocado seed (Persea americana Mill.). This study aimed to evaluate the in-vitro and in-silico cytotoxic activity of avocado seed extract on breast and cervical cancer cells. The active compounds in avocado seeds were docked with estrogen receptors (PDB code: 3ERT) and SIRT1 receptors (PDB code: 4I5I) using the MVD program. Cytotoxic activity in vitro was carried out using the MTT method on breast cancer cells (MCF7), cervical cancer cells (HeLa) and normal cells (Vero). Avocado seed contains 10 active compounds which are predicted to have cytotoxic activity. The findings from in-silico test showed that the “epicatechin gallate” had the lowest rerank score, i.e. -118.397 kcal/mol for the estrogen receptor and -133.694 kcal/ mol for the SIRT1 receptor. Cytotoxic activity in vitro was shown by IC50 values of 537.37 μg/mL (MCF7), 383.21 μg/mL (HeLa) and 541.67 μg/mL (Vero), respectively. The findings from in-vitro test showed that the avocado seed extract did not have cytotoxic activity on MCF7 cells and had weak cytotoxic activity on HeLa cells

LET as predictor of teaching performance: The case of PNU graduates across disciplines (2007-2010)

This study discusses the relationship between the performance in the Licensure Examination for Teachers (LET) taken by PNU graduates and their teaching performance. The LET scores, obtained from PRC, and teaching performance evaluation scores given by the Head, Peer and Self, were correlated. The results indicate that there is a negligible link between the scores in the LET and the teaching performance of the respondents. However, positive significant correlations, although weak, are found in the case of CLLL, COS, and 2007 examinees. The “Very Satisfactory” or “Outstanding” teaching performance evaluation rating earned by the respondents indicates the knowledge, skills, and philosophies learned during the pre‐service training. Finally, this research posits that an emerging paradigm of teaching performance must be progressively developed

Eculizumab in refractory generalized myasthenia gravis previously treated with rituximab: subgroup analysis of REGAIN and its extension study

Introduction/Aims: Individuals with refractory generalized myasthenia gravis (gMG) who have a history of rituximab use and experience persistent symptoms represent a population with unmet treatment needs. The aim of this analysis was to evaluate the efficacy and safety of eculizumab in patients with refractory anti-acetylcholine receptor antibody-positive (AChR+) gMG previously treated with rituximab. Methods: This post hoc subgroup analysis of the phase 3 REGAIN study (NCT01997229) and its open-label extension (OLE; NCT02301624) compared baseline characteristics, safety, and response to eculizumab in participants who had previously received rituximab with those who had not. Rituximab use was not permitted within the 6 months before screening or during REGAIN/OLE. Results: Of 125 REGAIN participants, 14 had received rituximab previously (7 received placebo and 7 received eculizumab). In the previous-rituximab group, 57% had used at least four other immunosuppressants compared with 16% in the no-previous-rituximab group. Myasthenia Gravis Activities of Daily Living total scores from eculizumab baseline to week 130 of eculizumab treatment improved in both the previous-rituximab and no-previous-rituximab groups (least-squares mean −4.4, standard error of the mean [SEM] 1.0 [n = 9] and least-squares mean −4.6, SEM 0.3 [n = 67], respectively; difference = 0.2, 95% confidence interval −1.88 to 2.22). In addition, in both groups, most patients who were treated with eculizumab for 130 weeks achieved a Myasthenia Gravis Foundation of America post-intervention status of minimal manifestations (66.7% and 65.0%, respectively). The eculizumab safety profile was similar between groups and consistent with its established profile. Discussion: Eculizumab is an effective therapy for patients with refractory AChR+ gMG, irrespective of whether they had received rituximab treatment previously

‘Minimal symptom expression’ in patients with acetylcholine receptor antibody-positive refractory generalized myasthenia gravis treated with eculizumab

Background: The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension. Methods: Attainment of ‘minimal symptom expression’ was evaluated using patient-reported outcome measures of gMG symptoms [MG activities of daily living scale (MG-ADL), 15-item MG quality of life questionnaire (MG-QOL15)] at the completion of REGAIN and during the open-label extension. ‘Minimal symptom expression’ was defined as MG-ADL total score of 0–1 or MG-QOL15 total score of 0–3. Results: At REGAIN week 26, more eculizumab-treated patients achieved ‘minimal symptom expression’ versus placebo [MG-ADL: 21.4% vs 1.7%; difference 19.8%; 95% confidence interval (CI) 8.5, 31.0; p = 0.0007; MG-QOL15: 16.1% vs 1.7%; difference 14.4%; 95% CI 4.3, 24.6; p = 0.0069]. During the open-label extension, the proportion of patients in the placebo/eculizumab group who achieved ‘minimal symptom expression’ increased after initiating eculizumab treatment and was sustained through 130 weeks of open-label eculizumab (MG-ADL: 1.7 to 27.8%; MG-QOL15: 1.7 to 19.4%). At extension study week 130, similar proportions of patients in the eculizumab/eculizumab and placebo/eculizumab groups achieved ‘minimal symptom expression’ (MG-ADL: 22.9% and 27.8%, respectively, p = 0.7861; MG-QOL15: 14.3% and 19.4%, respectively, p = 0.7531). The long-term tolerability of eculizumab was consistent with previous reports. Conclusions: Patients with AChR+ refractory gMG who receive eculizumab can achieve sustained ‘minimal symptom expression’ based on patient-reported outcomes. ‘Minimal symptom expression’ may be a useful tool in measuring therapy effectiveness in gMG. Trial registration: ClinicalTrials.gov NCT01997229, NCT02301624

Correction to: Eculizumab improves fatigue in refractory generalized myasthenia gravis (Quality of Life Research, (2019), 28, 8, (2247-2254), 10.1007/s11136-019-02148-2)

The article “Eculizumab improves fatigue in refractory generalized myasthenia gravis”, written by “Henning Andersen, Renato Mantegazza, Jing Jing Wang, Fanny O’Brien, Kaushik Patra, James F. Howard Jr. and The REGAIN Study Group” was originally published electronically on the publisher’s internet portal (currently SpringerLink) on 23 March 2019 without open access

Eculizumab improves fatigue in refractory generalized myasthenia gravis

To evaluate the effect of eculizumab on perceived fatigue in patients with anti-acetylcholine receptor antibody-positive, refractory, generalized myasthenia gravis (MG) using the Quality of Life in Neurological Disorders (Neuro-QOL) Fatigue subscale, and to evaluate correlations between improvements in Neuro-QOL Fatigue and other clinical endpoints.Purpose: To evaluate the effect of eculizumab on perceived fatigue in patients with anti-acetylcholine receptor antibody-positive, refractory, generalized myasthenia gravis (MG) using the Quality of Life in Neurological Disorders (Neuro-QOL) Fatigue subscale, and to evaluate correlations between improvements in Neuro-QOL Fatigue and other clinical endpoints. Methods: Neuro-QOL Fatigue, MG Activities of Daily Living (MG-ADL), Quantitative MG (QMG), and the 15-item MG Quality of Life (MG-QOL15) scales were administered during the phase 3, randomized, placebo-controlled REGAIN study (eculizumab, n = 62; placebo, n = 63) and subsequent open-label extension (OLE). Data were analyzed using repeated-measures models. Correlations between changes in Neuro-QOL Fatigue and in MG-ADL, QMG, and MG-QOL15 scores were determined at REGAIN week 26. Results: At REGAIN week 26, eculizumab-treated patients showed significantly greater improvements in Neuro-QOL Fatigue scores than placebo-treated patients (consistent with improvements in MG-ADL, QMG, and MG-QOL15 scores previously reported in REGAIN). Improvements with eculizumab were sustained through OLE week 52. Correlations between Neuro-QOL Fatigue and MG-QOL15, MG-ADL, and QMG scores were strong for eculizumab-treated patients at REGAIN week 26, and strong, moderate, and weak, respectively, for placebo-treated patients. Conclusions: Compared with placebo, eculizumab was associated with improvements in perceived fatigue that strongly correlated with improvements in MG-specific outcome measures. Trial ID Registration: NCT01997229, NCT02301624

Long-term safety and efficacy of eculizumab in generalized myasthenia gravis

Introduction: Eculizumab is effective and well tolerated in patients with antiacetylcholine receptor antibody-positive refractory generalized myasthenia gravis (gMG; REGAIN; NCT01997229). We report an interim analysis of an open-label extension of REGAIN, evaluating eculizumab's long-term safety and efficacy. Methods: Eculizumab (1,200 mg every 2 weeks for 22.7 months [median]) was administered to 117 patients. Results: The safety profile of eculizumab was consistent with REGAIN; no cases of meningococcal infection were reported during the interim analysis period. Myasthenia gravis exacerbation rate was reduced by 75% from the year before REGAIN (P < 0.0001). Improvements with eculizumab in activities of daily living, muscle strength, functional ability, and quality of life in REGAIN were maintained through 3 years; 56% of patients achieved minimal manifestations or pharmacological remission. Patients who had received placebo during REGAIN experienced rapid and sustained improvements during open-label eculizumab (P < 0.0001). Discussion: These findings provide evidence for the long-term safety and sustained efficacy of eculizumab for refractory gMG. Muscle Nerve 2019