• Title/Summary/Keyword: bevacizumab

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[18F]FET PET is a useful tool for treatment evaluation and prognosis prediction of anti-angiogenic drug in an orthotopic glioblastoma mouse model

  • Kim, Ok-Sun;Park, Jang Woo;Lee, Eun Sang;Yoo, Ran Ji;Kim, Won-Il;Lee, Kyo Chul;Shim, Jae Hoon;Chung, Hye Kyung
    • Laboraroty Animal Research
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    • v.34 no.4
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    • pp.248-256
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    • 2018
  • O-2-$^{18}F$-fluoroethyl-l-tyrosine ($[^{18}F]FET$) has been widely used for glioblastomas (GBM) in clinical practice, although evaluation of its applicability in non-clinical research is still lacking. The objective of this study was to examine the value of $[^{18}F]FET$ for treatment evaluation and prognosis prediction of anti-angiogenic drug in an orthotopic mouse model of GBM. Human U87MG cells were implanted into nude mice and then bevacizumab, a representative anti-angiogenic drug, was administered. We monitored the effect of anti-angiogenic agents using multiple imaging modalities, including bioluminescence imaging (BLI), magnetic resonance imaging (MRI), and positron emission tomography-computed tomography (PET/CT). Among these imaging methods analyzed, only $[^{18}F]FET$ uptake showed a statistically significant decrease in the treatment group compared to the control group (P=0.02 and P=0.03 at 5 and 20 mg/kg, respectively). This indicates that $[^{18}F]FET$ PET is a sensitive method to monitor the response of GBM bearing mice to anti-angiogenic drug. Moreover, $[^{18}F]FET$ uptake was confirmed to be a significant parameter for predicting the prognosis of anti-angiogenic drug (P=0.041 and P=0.007, on Days 7 and 12, respectively, on Pearson's correlation; P=0.048 and P=0.030, on Days 7 and 12, respectively, on Cox regression analysis). However, results of BLI or MRI were not significantly associated with survival time. In conclusion, this study suggests that $[^{18}F]FET$ PET imaging is a pertinent imaging modality for sensitive monitoring and accurate prediction of treatment response to anti-angiogenic agents in an orthotopic model of GBM.

Overview of Risk-Sharing Schemes: Focusing on Anticancer Drugs (위험분담제도에 대한 고찰: 항암제 사례를 중심으로)

  • Sohn, Hyun Soon;Shin, Hyun Taek
    • Korean Journal of Clinical Pharmacy
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    • v.23 no.2
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    • pp.89-96
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    • 2013
  • This article aimed to introduce 'risk sharing' schemes for pharmaceuticals between drug manufacturers and healthcare payer. Published literature review was undertaken to summarize risk sharing concepts and collect information on existing scheme examples in other countries focusing on new anticancer drugs. Risk sharing schemes could be categorized into health outcomes-based and non-outcomes (financial) based ones. Outcome-based schemes could be broken down into performance-linked reimbursement and conditional coverage. Performance-linked reimbursement can be further broken into outcomes guarantee and pattern or process of care and conditional coverage included coverage with evidence development and conditional treatment continuation schemes. Non-outcome based schemes included market share and price volume at population level, and utilization caps and manufacturer funded treatment initiation at patient level. We reviewed the fifteen examples for anticancer drugs that risk sharing agreements in response to the inherent uncertainties and increased costs of eleven anticancer drugs. Of them, eight cases were coverage with evidence development schemes. The anticancer drugs except bevacizumab and cetuximab were all listed on the national health insurance formulary in Korea, with reimbursement criteria defined on the basis of approved indications and administrations. Risk sharing approach may be a useful tool to ensure values for drug expenditure, but there are a number of concerns such as high administration costs, lack of transparency and conflicts of interest, especially for performance-based health outcomes reimbursement schemes.

Comparative Analysis of the Seriousness of the Adverse Events and Risk of Targeted Therapy for Metastatic Renal Cell Carcinoma Among Medical Professionals (전이성신세포암 표적치료제의 부작용 심각도 및 위해에 대한 전문가그룹별 비교분석)

  • Park, Mi-Hae;Rhee, Jin-Nie;Lee, Eui-Kyung
    • Korean Journal of Clinical Pharmacy
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    • v.21 no.2
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    • pp.100-105
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    • 2011
  • The perception of the 20 adverse events of targeted therapy for metastatic renal cell carcinoma was compared among medical professionals. Thirty-seven oncologists, 167 nurses and 79 pharmacists participated in the survey, and the response rate was 61.9%, 98.2%, 84.9%, respectively. Results showed that the most serious adverse event was GI perforation (8.83 points, 10 being the most serious), whereas the least serious was anemia (5.32 points). There were significant differences among oncologists, nurses and pharmacists especially for the moderately-serious adverse event such as wound-healing complication and lymphopenia. Adverse Events Composite Score (AECS) for each targeted therapy was calculated by multiplying adverse event incidence rate and seriousness score. Sunitinib had the highest score at 6.86 point and bevacizumab had the lowest at 2.1. Among professional groups oncologists showed the lowest AECS, whereas nurses had the highest. The gap on the perception of the adverse events among medical professionals needs to be reduced to get better outcomes of medical therapies for cancer patients.

A Case Report of FOLFIRI-Induced Diarrhea in Patient with Metastatic Rectal Cancer Treated with Modified Wiryeong-tang (전이 직장암 환자의 FOLFIRI 유발 설사에 위령탕 가감방 치험 1례)

  • Yoon, Sung Soo;Kim, Eun Hye;Lee, Jee Young;Yoon, Seong Woo
    • Journal of Korean Traditional Oncology
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    • v.23 no.1
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    • pp.15-21
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    • 2018
  • Objectives : This study was aimed to describe a case of a patient with FOLFIRI-induced diarrhea, which was improved by treatment with Korean herbal medicine, modified Wiryeong-tang. Methods : The patient with metastatic rectal cancer recieved FOLFIRI plus bevacizumab as a palliative chemotherapy and showed repetitive diarrhea despite administration of loperamide, which was treated with modified Wiryeong-tang. To evaluate the effect of the treatment, the Bristol Stool Form Scale and bowel movement frequency were checked. Results : During the treatment, the stool form using Bristol Stool Form Scale was improved from diarrhea to normal stool, and the bowel movement frequency was decreased. Conclusions : The result suggest that modified Wiryeong-tang may be an effective treatment for FOLFIRI-induced diarrhea.

The Value of Tumor Treating Fields in Glioblastoma

  • Zhang, Chaochao;Du, Jianyang;Xu, Weidong;Huang, Haiyan;Gao, Li
    • Journal of Korean Neurosurgical Society
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    • v.63 no.6
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    • pp.681-688
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    • 2020
  • Glioblastoma (GBM) is one of the most common tumors of the central nervous system, which is the most lethal brain cancer. GBM treatment is based primarily on surgical resection, combined with radiotherapy and chemotherapy. Despite the positive treatment, progression free survival and overall survival were not significantly prolonged because GBM almost always recurs. We are always looking forward to some new and effective treatments. In recent years, a novel treatment method called tumor treating fields (TTFields) for cancer treatment has been proposed. TTFields devices were approved by the Food and Drug Administration (FDA) for adjuvant treatment of recurrent and newly diagnosed GBMs in 2011 and 2015, respectively. This became the first breakthrough treatment for GBM in the past 10 years after the FDA approved bevacizumab for patients with relapsed GBM in 2009. This paper summarized the research results of TTFields in recent years and elaborated the mechanism of action of TTFields on GBM, including cell and animal experimental research, clinical application and social benefits.

Appraisal of re-irradiation for the recurrent glioblastoma in the era of MGMT promotor methylation

  • Kim, Il Han
    • Radiation Oncology Journal
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    • v.37 no.1
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    • pp.1-12
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    • 2019
  • Despite recent innovation in treatment techniques and subsequently improved outcomes, the majority of glioblastoma (GBL) have relapses, especially in locoregional areas. Local re-irradiation (re-RT) has been established as a feasible option for recurrent GBL of all ages with safety, tolerability, and effectiveness both in survival and quality of life regardless of fractionation schedule. To keep adverse effects under acceptable range, cumulative dose limit in equivalent dose at 2 Gy fractions by the linear-quadratic model at α/β = 2 for normal brain tissue (EQD2) with narrow margin should be observed and single/hypofractionated re-RT should be undertaken very carefully to recurrent tumor with large volume or adjacent to the brainstem. Promising outcome of re-operation (re-Op) plus re-RT (re-Op/RT) need to be validated and result from re-RT with temozolomide/bevacizumab (TMZ/BV) or new strategy is expected. Development of new-concept prognostic scoring or risk group is required to select patients properly and make use of predictive biomarkers such as O(6)-methylguanine-DNA methyltransferase (MGMT) promotor methylation that influence outcomes of re-RT, re-Op/RT, or re-RT with TMZ/BV.

Biochemical bone markers of bisphosphonate-related osteonecrosis of the jaw (BRONJ) and nonbisphosphonate drugs in osteonecrosis of the jaw (임상가를 위한 특집 2 - Bisphosphonate-related osteonecrosis of the jaw(BRONJ)에 대한 biochemical bone markers와 악골괴사와 연관된 nonbisphosphonate drugs)

  • Lee, Deok-Won;Lee, Hyun-Woo;Kwon, Yong-Dae
    • The Journal of the Korean dental association
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    • v.52 no.4
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    • pp.203-217
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    • 2014
  • Bisphosphonates are widely used in the treatment of many medical conditions, such as osteoporosis, multiple myeloma, Paget's disease, etc. However, side effect has been documented in the published data during the past years, osteonecrosis of the jaw in patients receiving long-term bisphosphonate therapy. Although pathogenesis of BRONJ(bisphophonate-related osteonecrosis of the jaw) is not yet fully understood, it is currently known to be a disease associated with suppressed bone turnover by bisphopbonate. Recent literature has indicated a similar association with nonbisphosphonate drugs used in cancer therapy including monoclonal antibodies denosumab and bevacizumab and multikinase inhibitor sunitinib. Accordingly, many studies have been carried out on the biochemical markers examination to assess the risk for BRONJ. The treatment of BRONI is reported with a review of the relevant literature. However, there is still a controversial discussion about the adequate treatment. It is necessary to accumulate further studies in order to establish more useful biochemical markers and effective treatment for BRONJ.

Epigenetic Silencing of CHOP Expression by the Histone Methyltransferase EHMT1 Regulates Apoptosis in Colorectal Cancer Cells

  • Kim, Kwangho;Ryu, Tae Young;Lee, Jinkwon;Son, Mi-Young;Kim, Dae-Soo;Kim, Sang Kyum;Cho, Hyun-Soo
    • Molecules and Cells
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    • v.45 no.9
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    • pp.622-630
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    • 2022
  • Colorectal cancer (CRC) has a high mortality rate among cancers worldwide. To reduce this mortality rate, chemotherapy (5-fluorouracil, oxaliplatin, and irinotecan) or targeted therapy (bevacizumab, cetuximab, and panitumumab) has been used to treat CRC. However, due to various side effects and poor responses to CRC treatment, novel therapeutic targets for drug development are needed. In this study, we identified the overexpression of EHMT1 in CRC using RNA sequencing (RNA-seq) data derived from TCGA, and we observed that knocking down EHMT1 expression suppressed cell growth by inducing cell apoptosis in CRC cell lines. In Gene Ontology (GO) term analysis using RNA-seq data, apoptosis-related terms were enriched after EHMT1 knockdown. Moreover, we identified the CHOP gene as a direct target of EHMT1 using a ChIP (chromatin immunoprecipitation) assay with an anti-histone 3 lysine 9 dimethylation (H3K9me2) antibody. Finally, after cotransfection with siEHMT1 and siCHOP, we again confirmed that CHOP-mediated cell apoptosis was induced by EHMT1 knockdown. Our findings reveal that EHMT1 plays a key role in regulating CRC cell apoptosis, suggesting that EHMT1 may be a therapeutic target for the development of cancer inhibitors.

A Case Report of Abducens Nerve Palsy after Cancer Immunotherapy Treated with Korean Medicine (항암면역치료 후 발생한 외전신경마비 한방 치험 1례)

  • Kim, Jae-Ho;Ko, Hye-Yeon;Kim, Min-Hee
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.35 no.3
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    • pp.114-122
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    • 2022
  • Objective : The purpose of this study is to report the effect of Korean medicine treatments of abducens nerve palsy after cancer immunotherapy. Methods : A 63-year-old male patient who was suffering hepatocellular carcinoma had left eye abduction restriction, diplopia, and decreased visual acuity after taking 5th cancer immunotherapy(atezolizumab + bevacizumab). Western medicine was administered for 3 weeks, but there was no response. The patient was treated with herbal medicine, acupuncture, electroacupuncture, moxibustion and bee venom pharmacoacupuncture for 4 weeks. Result : The patient's eye abduction restriction and diplopia were resolved. Visual acuity was improved from NRS(Numerical Rating Scale) 8 to NRS 2. The patient continued immunotherapy and there was no worsening of symptoms. No adverse events were observed. Conclusions : This study shows that Korean medicine treatments were effective on abducens nerve palsy after cancer immunotherapy.

A Predictive Model for Evaluating Responsiveness to Pemetrexed Treatment in Patients with Advanced Colorectal Cancer

  • Wu, Xue-Yan;Huang, Xin-En;Cao, Jie;Shi, Lin;Xu, Xia;Qian, Zhi-Ying
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.14
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    • pp.5941-5944
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    • 2014
  • Purpose: To highlight the potential factors that could predict the response rate of patients with metastatic colorectal cancer (mCRC) treated with pemetrexed combined chemotherapy after first- or second-line chemotherapy using the FOLFOX regimen. Materials and Methods: Between January 2007 and July 2014, 54 patients diagnosed and pathologically-confirmed with advanced colorectal cancer in Jiangsu Cancer Hospital and Research Institute, were enrolled. They received pemetrexed at a dose of $500mg/m^2$ by 10 minute infusion on day 1, repeated every 3 weeks. Doses were modified depending on nadir counts of blood cells. Combined chemotherapeutic agents included irinotecan, lobaplatin, carboplatin, oxaliplatin, gemcitabine, cis-platinum or bevacizumab. Multiple variables (age, sex, hemoglobin, platinum drugs combined, metastasis sites, LDH, ALP, CEA>40 ug/ml) reported earlier were selected. We used logistic regression analysis to evaluate relationships between these and tumor response. Results: On multivariable analysis, we found that age was significant in predicting the responsiveness to pemetrexed (p<0.05) combined with oxaliplatin. We did not find any other factors which were significantly associated with the response rate to chemotherapy with pemetrexed and irinotecan. Conclusions: By multivariate analysis, we found that age had significant impact on the responsiveness of pemetrexed when combined with oxaliplatin. Additional research based on genomic properties of host and tumors are needed to clarify markers for better selection of patients who could benefit from pemetrexed combined chemotherapy.