• Title/Summary/Keyword: Clinical Trials

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Interleukin-18 Binding Protein (IL-18BP): A Long Journey From Discovery to Clinical Application

  • Soohyun Kim;Hyeon Yu;Tania Azam;Charles A. Dinarello
    • IMMUNE NETWORK
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    • v.24 no.1
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    • pp.1.1-1.6
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    • 2024
  • IL-18 binding protein (IL-18BP) was originally discovered in 1999 while attempting to identify an IL-18 receptor ligand binding chain (also known as IL-18Rα) by subjecting concentrated human urine to an IL-18 ligand affinity column. The IL-18 ligand chromatography purified molecule was analyzed by protein microsequencing. The result revealed a novel 40 amino acid polypeptide. To isolate the complete open reading frame (ORF), various human and mouse cDNA libraries were screened using cDNA probe derived from the novel IL-18 affinity column bound molecule. The identified entire ORF gene was thought to be an IL-18Rα gene. However, IL-18BP has been proven to be a unique soluble antagonist that shares homology with a variety of viral proteins that are distinct from the IL-18Rα and IL-18Rβ chains. The IL-18BP cDNA was used to generate recombinant IL-18BP (rIL-18BP), which was indispensable for characterizing the role of IL-18BP in vitro and in vivo. Mammalian cell lines were used to produce rIL-18BP due to its glycosylation-dependent activity of IL-18BP (approximately 20 kDa). Various forms of rIL-18BP, intact, C-terminal his-tag, and Fc fusion proteins were produced for in vitro and in vivo experiments. Data showed potent neutralization of IL-18 activity, which seems promising for clinical application in immune diseases involving IL-18. However, it was a long journey from discovery to clinical use although there have been various clinical trials since IL-18BP was discovered in 1999. This review primarily covers the discovery of IL-18BP along with how basic research influences the clinical development of IL-18BP.

An Updated Meta-analysis and System Review:is Gemcitabine+Fluoropyrimidine in Combination a Better Therapy Versus Gemcitabine Alone for Advanced and Unresectable Pancreatic Cancer?

  • Tu, Chao;Zheng, Feng;Wang, Jin-Yu;Li, Yuan-Yuan;Qian, Ke-Qing
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.14
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    • pp.5681-5686
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    • 2015
  • Background: Pancreatic cancer ranks fourth in deaths caused by cancers throughout the world. Gemcitabine chemotherapy is the primary method of treatment of advanced pancreatic cancer, and in asco2014, it is still firstline chemotherapy. Howeve,r gemcitabine+fluorouracil regimens are also licensed and widely used worldwide. Clinical trials are the best way to evaluate drug efficacy. In this study, we performed a systematic review and a meta-analysis of randomized controlled trials (RCTs) to assess whether gemcitabine+fluoropyrimidine combination therapy improves the prognosis of unresectable pancreatic cancer compared with gemcitabine treatment alone. Materials and Methods: A quantitative up-to-date meta-analysis was undertaken to investigate the efficacy of gemcitabine-based combination treatment compared with gemcitabine monotherapy for locally advanced or metastatic pancreatic cancer. Inclusion was limited to high-quality randomized clinical trials. Results: A total of 12 studies were included in the present analysis, with a total of 3,038 patients recruited. The studies were divided into three subgroups including 5-FU / CAP / S-1 combined with gemcitabine. For the primary endpoint of overall survival (OS), gemcitabine-based combination therapy demonstrated significantly better outcome (HR, 0.88; 95% CI, 0.81-0.95) than gemcitabine monotherapy. The analysis of progression free survival (PFS) also provided a significant result for the combined therapy in a total of 8 trials (2,130 patients) (HR, 0.74; 95% CI, 0.63-0.86). With subgroup analysis according to the method of dosing delivery, we found that in the injection group with 3 trials (889 patients), a negative result was found (HR, 0.93; 95% CI, 0.77-1.12); while a positive result was observed in the oral group with 9 trials (2,149 patients) (HR, 0.87; 95% CI, 0.80-0.95). Conclusions: Gemcitabine combination therapy provides a modest improvement of survival, but is associated with more toxicity compared with gemcitabine monotherapy.

Radiomics and Deep Learning from Research to Clinical Workflow: Neuro-Oncologic Imaging

  • Ji Eun Park;Philipp Kickingereder;Ho Sung Kim
    • Korean Journal of Radiology
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    • v.21 no.10
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    • pp.1126-1137
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    • 2020
  • Imaging plays a key role in the management of brain tumors, including the diagnosis, prognosis, and treatment response assessment. Radiomics and deep learning approaches, along with various advanced physiologic imaging parameters, hold great potential for aiding radiological assessments in neuro-oncology. The ongoing development of new technology needs to be validated in clinical trials and incorporated into the clinical workflow. However, none of the potential neuro-oncological applications for radiomics and deep learning has yet been realized in clinical practice. In this review, we summarize the current applications of radiomics and deep learning in neuro-oncology and discuss challenges in relation to evidence-based medicine and reporting guidelines, as well as potential applications in clinical workflows and routine clinical practice.

Analysis of physical and biological delivery systems for DNA cancer vaccines and their translation to clinical development

  • Christopher Oelkrug
    • Clinical and Experimental Vaccine Research
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    • v.13 no.2
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    • pp.73-82
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    • 2024
  • DNA cancer vaccines as an approach in tumor immunotherapy are still being investigated in preclinical and clinical settings. Nevertheless, only a small number of clinical studies have been published so far and are still active. The investigated vaccines show a relatively stable expression in in-vitro transfected cells and may be favorable for developing an immunologic memory in patients. Therefore, DNA vaccines could be suitable as a prophylactic or therapeutic approach against cancer. Due to the low efficiency of these vaccines, the administration technique plays an important role in the vaccine design and its efficacy. These DNA cancer vaccine delivery systems include physical, biological, and non-biological techniques. Although the pre-clinical studies show promising results in the application of the different delivery systems, further studies in clinical trials have not yet been successfully proven.

Methodologic Lessons Learned from Multicenter, Randomized, Controlled Clinical Trial of Acupuncture for Hot Flashes in Peri- and Postmenopausal Women (갱년 및 폐경 후 여성의 안면홍조에 대한 침 치료 다기관 임상연구 : 수행보고 및 방법론적 교훈)

  • Kim, Kun-Hyung;Kim, Dong-Il;Hwang, Deok-Sang;Lee, Jin-Moo;Kim, Hyung-Jun;Yoon, Hyun-Min;Jung, Hee-Jung;Kang, Kyung-Won;Lee, Myeong-Soo;Choi, Sun-Mi
    • The Journal of Korean Obstetrics and Gynecology
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    • v.23 no.1
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    • pp.42-52
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    • 2010
  • Purpose: This report aims to administer methodologic issues around recently conducted multicenter study for evaluating the effects of acupuncture on menopusal hot flashes and discuss practical issues for further implementation of acupuncture clinical trial for hot flashes. Methods: Study process were mentioned, and issues related to avoiding risk of bias, designing appropriate control group, optimal outcome measurement, potential different effects of menopausal status on study outcomes, and suggestions for developing future clinical trials are discussed. Results: Shortcomings of our multicenter study include lack of allocation concealment and assessor blinding, subjective outcome measurement, short-term follow-up, and fixed acupuncture regimen despite pragmatic purpose of this study. Improving trial design, using objective or validated outcomes, assessing long-term effects of acupuncture, and individualizing acupuncture regimen are needed in future clinical trials. Conclusion: We expect these practical discussions to enable researchers to plan and develop future well-designed clinical trials for evaluating the effects of acupuncture on hot flashes or other women's health issues.

Bisphosphonates for Osteoporosis in Nonmetastatic Prostate Cancer Patients Receiving Androgen-deprivation Therapy: A Systematic Review and Meta-analysis

  • Ding, Hui;Yang, Li;Du, Wan;Teng, Yang;Fu, Sheng-Jun;Tao, Yan;Lu, Jian-Zhong;Wang, Zhi-Ping
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.5
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    • pp.3337-3343
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    • 2013
  • This systematic review was conducted to assess the efficacy and safety of bisphosphonates for prevention and treatment of osteopenia or osteoporosis in men with non-metastatic prostate cancer receiving androgendeprivation therapy. We searched for randomised controlled trials (RCTs) of bisphosphonates compared with placebo from Pubmed, Embase, the Cochrane Library, and ISI - Science Citation Index. Meta-analyses of prespecified outcomes (bone mineral density, fractures, and adverse events) were performed using Review Manager. Ten RCTs with a total patient population of 1,017 were identified. There was generally more improvement in bone mineral density of the lumbar spine for patients who received bisphosphonate treatment than placebo or other medical treatment at 12 months (WMD 6.02,95%CI 5.39 to 6.65). Similar effects were also observed for total hip, trochanter or femoral neck bone mineral density. However, there was no significant reduction in fractures. Fever and gastrointestinal symptoms were the most common adverse events (10.4% vs. 1.2%; 0.10% vs. 0.03%). Currently, our meta-analysis suggested that oral and intravenous bisphosphonates caused a rapid increase in spine and hip or femoral BMD in non-metastatic prostate cancer patients receiving androgen-deprivation therapy. Fever and gastrointestinal symptoms were common with the use of bisphosphonates. These short-term trials (maximum of 12 months) did not show fracture reduction. In future, more efficient performance of higher quality, more rigorous, large sample, long-term randomised controlled trials (>12 months) are needed where outcomes are detailed.

Review on the Study of Dry Eye Syndrome in the Journal of Korean Medicine (한의학 학술지에 게재된 안구건조증에 대한 논문 고찰)

  • Lim, Kyeong Min;Kang, Byung Soo;Kim, Hye Hwa;Na, Ga Young;Jeong, Ji Won;Choi, Jung Hwa;Park, Soo Yeon;Kim, Jong Han;Jung, Min Yeong
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.31 no.2
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    • pp.94-104
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    • 2017
  • By analyzing the research of Dry Eye Syndrome that have been published in the Journals of Korean Medicine, we wished to provide fundamental data for clinical application's development We found 13 research papers related to Dry Eye Syndrome in Electronic databases(OASIS, RISS, NDSL, KISS) from 1995 to 2016. We subdivided the research into published year, published journal, the type of study, methods, etc. 13 research are composed of 4 systematic reviews, 2 clinical studies, and 7 clinical trials. According to the studies, patients with Dry Eye Syndrome tend to be chronic and have Yin-deficieny, and in their clinical trials, various Korean medical treatments were introduced. In the research, Korean medical treatments can be expected positive impact on Dry Eye Syndrome. But we think a variety of clinical treatment methods and additional studies are needed to increase.

Electroacupuncture for Treatment of Primary Dysmenorrhea: Systematic Review of Randomized Controlled Trials (원발성 월경통의 전침 치료 연구에 관한 체계적 문헌 고찰)

  • Park, Nam-Chun;Kang, Na-Hoon;Yoo, Eun-Sil;Lee, Jin-Wook;Yoon, Jun-Geol;Lee, Jin-Moo;Lee, Chang-Hoon;Jang, Jun-Bok;Hwang, Deok-Sang
    • The Journal of Korean Obstetrics and Gynecology
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    • v.30 no.2
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    • pp.81-92
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    • 2017
  • Objectives: This review aims to report the efficacy and safety of electroacupuncture in the treatment of primary dysmenorrhea. Methods: We searched for randomized controlled studies (RCTs) using electroacupuncture on primary dysmenorrhea up to Dec 2016. The following databases were searched : OASIS, PubMED, EMBASE, CENTRAL. The results of the studies were analyzed and the risk of bias was assessed. Results: Five studies were included in this review. In most studies, the effect of electroacupuncture at Sameumgyo (SP6) was better than that of electroacupuncture at Hyeonjong (GB39), nonacupoint and no intervention about Visual analog scale (VAS), Verbal rating scale (VRS) and Retrospective symptom scale (RSS). But there were no significant effects on Resistance Index (RI) and S/D ratio (the ratio between peak systolic to end-diastolic flow velocity in uterine arteries). Serous adverse events were not reported. Conclusions: This review shows that electroacupuncture is effective on primary dysmenorrhea with no serious adverse events.

Review of Domestic Research on Traditional Korean Medicine for Breast Cancer (유방암에 대한 국내 한의학 연구 동향 고찰 - 국내 한의학 논문을 중심으로 -)

  • Han, Ga-jin;Son, Ji-young;Seong, Sin;Kim, Sung-su
    • The Journal of Internal Korean Medicine
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    • v.39 no.1
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    • pp.44-68
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    • 2018
  • Objective: This study aimed to investigate the trend in the research on breast cancer using traditional Korean medicine (TKM) and establish the direction for further study. Methods: Breast cancer studies using Korean medicine were searched using the Oriental Medicine Advanced Searching Integrated System (OASIS). The search term was 'breast' and there was no restriction in year. The searched studies were analyzed according to the type of research. Results: 1. 83 studies were searched. The types and numbers of study were as follows: 42 were in vitro studies, 5 were in vivo studies, 12 were studies for review, and 27 were clinical research including case reports. 2. Various cell lines such as MCF-7, MDA-MB-231, SKBR3, and MCF-10A were used for in vitro studies. The studies reported a decrease in cell viability, induction of apoptosis, and change of expression in cancer-related genes. In vivo studies also reported induction of apoptosis, and anti-proliferative activity of herbal medicine against the cancer cells. 3. Among the clinical research, 8 were cross-sectional studies, 3 were controlled-trial, and 15 were case reports. The baseline characteristics of breast cancer patients were analyzed in the cross-sectional studies. Interventions such as pharmacopuncture, herbal medicine, massage, Qi gong, acupuncture, electroacupuncture and moxibustion were used in clinical research. 4. Research on the review of breast cancer covered various subjects as follows: herbal medicine, acupuncture, pattern identification of breast cancer in traditional Korean medicine, analysis of previous experimental studies, and clinical trials. Conclusion: We have found the applicability of TKM for treatment of breast cancer through this review. It is necessary to conduct further studies, such as well-designed clinical trials based on the results from experimental research.

The Recent Trends of Clinical Research on General Anxiety Disorder in Chinese Herbal Medicine (범불안장애의 중의학 약물 임상시험 최신 동향)

  • No, Dong-Jin;Lee, Sang-Ryong;Jung, In-Chul
    • Journal of Oriental Neuropsychiatry
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    • v.20 no.4
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    • pp.79-89
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    • 2009
  • Objectives : To address suitable method for designing clinical trial intervening Traditional Korean Herbal Medicine on General anxiety disorder through the recent clinical research in Chinese Herbal Medicine. Methods : Randomized, controlled trials(RCTs) of treatment of general anxiety disorder intervening herbal medicine were searched through CNKI databases. We examined several item of studies and evaluated using Jadad scale. We searched articles in CNKI with the key word "General anxiety disorder or 廣範性焦慮症", among them we selected the clinical trial studies related with herbal medicine except for case reports, studies of acupuncture therapy or west medicines. Results : 11 RCT studies of herbal medicine met inclusion criteria. The Studies used CCMD-3, HAMA as inclusion tool and mainly HAMA as a evaluation tool. Studies were progressed for 2-8 weeks, mostly used various positive control. Experiment medicine were mainly 理氣劑, 安神劑. In most studies, experiment group made similar or higher efficacy in comparison with control group. Mean Jadad score of studies was $1.3{\pm}0.67$, and only one study was double-blinded among 11 studies. Conclusions : RCT studies on general anxiety disorder of chinese herbal medicine tend to focus on investigating effect of herbal medicine through setting positive control group with CCMD-3 and HAMA. But, most studies had low quality of trial, for lack of pattern identification, evaluation and inclusion tool of chinese medicine. Clinical trials of general anxiety disorder should provide good quality by randomization, double-blinding, and multi-site trial.

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