• Title/Summary/Keyword: Cancer therapeutic efficacy

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Verification of the Cancer Therapeutic Efficacy of Lutetium-177 Using Gene Expression (유전자 발현을 활용한 루테튬 (177Lu)의 암 치료 효능 검증)

  • Da-Mi Kim;So-Young Lee;Jae-Cheong Lim;KangHyuk Choi
    • Journal of Radiation Industry
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    • v.17 no.4
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    • pp.417-425
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    • 2023
  • Lutetium(177Lu), with its theranostic properties, is one of the most widely used radioisotopes and has a large share of the radiopharmaceutical market due to its many applications and targeted therapeutic research using lutetium-based radiopharmaceuticals. However, lutetium-based radiopharmaceuticals currently approved by the US Food and Drug Administration (FDA) are limited to the indications of gastrointestinal cancer, pancreatic neuroendocrine cancer and metastatic castration-resistant prostate cancer. To overcome these limitations, we aimed to demonstrate the feasibility of expanding the use of lutetium-based radiopharmaceuticals by verifying the availability and therapeutic efficacy of lutetium produced in a research reactor(HANARO). In this study, we confirmed the therapeutic efficacy of lutetium by using cancer cells from different types of cancer. In addition, we selected cancer biomarkers based on characteristics common to various cancer cells and compared and evaluated the therapeutic efficacy of lutetium by regulating the expression of target genes. The results showed that modulation of cancer biomarker gene expression resulted in higher therapeutic efficacy compared to lutetium alone. In conclusion, this study verified the potential use and therapeutic efficacy of lutetium based on the production of a research reactor (HANARO), providing fundamental evidence for the development of lutetium-based radiopharmaceuticals and the expansion of their indications.

Validation of the production quality and therapeutic efficacy of 47Sc through its anti-cancer effects against EGFR-targeted non-small cell lung cancer

  • Da-Mi Kim;So-Young Lee;Jae-Cheong Lim;Eun-Ha Cho;Ul-Jae Park
    • Journal of Radiopharmaceuticals and Molecular Probes
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    • v.8 no.1
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    • pp.9-15
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    • 2022
  • Anti-cancer and therapeutic effects using therapeutic radioisotopes have been demonstrated by various studies, and it is well-known that therapeutic radioisotopes are useful in cancer treatment. Recently, one of the therapeutic radioisotopes, scandium is emerging as a radioisotope applicable to PET imaging (43Sc, 44Sc) and therapy (47Sc) in cancer theranostic approach. However, 47Sc has little known radiobiological and therapeutic efficacy compared to other therapeutic radioisotopes. Here, we investigated the quality and therapeutic efficacy of 47Sc radioisotope produced by our production/isolation technology at the research reactor 'HANARO' in KAERI (Korea Atomic Energy Research Institute). We showed that the therapeutic efficacy of 47Sc, produced by our production/isolation technology, effectively suppressed epidermal growth factor receptor (EGFR)-targeted non-small cell lung cancer (NSCLC) cells. Consequently, these results suggest that the high quality of the produced 47Sc by our production/isolation technology enables the development of therapeutic strategies for cancer treatment and radiopharmaceuticals using 47Sc.

Continuous DC-CIK Infusions Restore CD8+ Cellular Immunity, Physical Activity and Improve Clinical Efficacy in Advanced Cancer Patients Unresponsive to Conventional Treatments

  • Zhao, Yan-Jie;Jiang, Ni;Song, Qing-Kun;Wu, Jiang-Ping;Song, Yu-Guang;Zhang, Hong-Mei;Chen, Feng;Zhou, Lei;Wang, Xiao-Li;Zhou, Xin-Na;Yang, Hua-Bing;Ren, Jun;Lyerly, Herbert Kim
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.6
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    • pp.2419-2423
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    • 2015
  • Background: There are few choices for treatment of advanced cancer patients who do not respond to or tolerate conventional anti-cancer treatments. Therefore this study aimed to deploy the benefits and clinical efficacy of continuous dendritic cell-cytokine induced killer cell infusions in such patients. Materials and Methods: A total of 381 infusions (from 67 advanced cases recruited) were included in this study. All patients underwent peripheral blood mononuclear cell apheresis for the following cellular therapy and dendritic cells-cytokine induced killer cells were expanded in vitro. Peripheral blood T lymphocyte subsets were quantified through flow cytometry to address the cellular immunity status. Clinical efficacy and physical activities were evaluated by RECIST criteria and Eastern Cooperative Oncology Group scores respectively. Logistic regression model was used to estimate the association between cellular infusions and clinical benefits. Results: An average of $5.7{\pm}2.94{\times}10^9$ induced cells were infused each time and patients were exposed to 6 infusions. Cellular immunity was improved in that cytotoxic $CD8^+CD28^+$ T lymphocytes were increased by 74% and suppressive $CD8^+CD28^-$ T lymphocytes were elevated by 16% (p<0.05). Continuous infusion of dendritic cells-cytokine induced killer cells was associated with improvement of both patient status and cellular immunity. A median of six infusions were capable of reducing risk of progression by 70% (95%CI 0.10-0.91). Every elevation of one ECOG score corresponded to a 3.90-fold higher progression risk (p<0.05) and 1% increase of $CD8^+CD28^-$ T cell proportion reflecting a 5% higher risk of progression (p<0.05). Conclusions: In advanced cancer patients, continuous dendritic cell-cytokine induced killer cell infusions are capable of recovering cellular immunity, improving patient status and quality of life in those who are unresponsive to conventional cancer treatment.

The Effects of Programs Using Strategies for Promoting Self Efficacy in Patients with Lung Cancer (폐암극복을 위한 자기효능 증진 프로그램의 효과)

  • Lee, Jong Kyung;Yang, Young Hee
    • Korean Journal of Adult Nursing
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    • v.18 no.4
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    • pp.642-652
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    • 2006
  • Purpose: This study investigated the effects of a 'overcoming cancer program' on knowledge, self efficacy, and quality of life, therapeutic compliance for patients with lung cancer. Method: Research design of this study was a nonequivalent control group quasi-experimental study. Subjects for this study were 16 lung cancer patients for the control group, and 12 lung cancer patients for the experimental group. The experimental group participated in the program once a week for 4 weeks. Data were collected before and after the program. Nonparametric statistics were used to analyze the data. Results: The results of this study were as follows: In the pretest, there were no significant differences in general characteristics, knowledge, self efficacy and quality of life between the two groups. In the posttest, there were significant differences in knowledge, self efficacy between the experimental and the control groups. But there were no significant differences in therapeutic compliance and quality of life between the two groups. Conclusion: From the results above, it can be concluded that program was effective to improve knowledge and self-efficacy for patients with lung cancer.

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GBA inhibition suppresses ovarian cancer growth, survival and receptor tyrosine kinase AXL-mediated signaling pathways

  • Gang Wang;Baisha Ouyang;Fang Jing;Xiaoyan Dai
    • The Korean Journal of Physiology and Pharmacology
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    • v.27 no.1
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    • pp.21-29
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    • 2023
  • The poor outcome of advanced ovarian cancer under conventional therapy necessitates new strategies to improve therapeutic efficacy. β-glucosidase (encoded by GBA) is a lysosomal enzyme and is involved in sphingolipids metabolism. Recent studies revealed that β-glucosidase plays a role in cancer development and chemoresistance. In this work, we systematically evaluated the expression and role of GBA in ovarian cancer. Our work demonstrates that inhibition of β-glucosidase has therapeutic potential for ovarian cancer. Gene Expression Profiling Interactive Analysis database, western blot and immunohistochemistry analyses of patient samples demonstrated that GBA mRNA and protein expression levels were significantly increased in ovarian cancer compared to normal tissues. Functional studies using gainof-function and loss-of-function approaches demonstrated that GBA overexpression did not affect growth and migration but alleviated cisplatin's efficacy in ovarian cancer cells. In addition, GBA depletion resulted in growth inhibition, apoptosis induction, and enhancement of cisplatin's efficacy. Of note, we found that GBA inhibition specifically decreased receptor tyrosine kinase AXL level, leading to the suppression of AXL-mediated signaling pathways. Our data suggest that GBA represents a promising target to inhibit AXL signaling and overcome cisplatin resistance in ovarian cancer.

Co-Stimulatory Receptors in Cancers and Their Implications for Cancer Immunotherapy

  • Seongju Jeong;Su-Hyung Park
    • IMMUNE NETWORK
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    • v.20 no.1
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    • pp.3.1-3.20
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    • 2020
  • Immune checkpoint inhibitors (ICIs), including anti-PD-1 and anti-CTLA-4 therapeutic agents, are now approved by the Food and Drug Administration for treatment of various types of cancer. However, the therapeutic efficacy of ICIs varies among patients and cancer types. Moreover, most patients do not develop durable antitumor responses after ICI therapy due to an ephemeral reversal of T-cell dysfunction. As co-stimulatory receptors play key roles in regulating the effector functions of T cells, activating co-stimulatory pathways may improve checkpoint inhibition efficacy, and lead to durable antitumor responses. Here, we review recent advances in our understating of co-stimulatory receptors in cancers, providing the necessary groundwork for the rational design of cancer immunotherapy.

The Microbiome-Immune Axis Therapeutic Effects in Cancer Treatments

  • Son, Young Min;Kim, Jihwan
    • Journal of Microbiology and Biotechnology
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    • v.32 no.9
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    • pp.1086-1097
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    • 2022
  • During the last decades, research and therapeutic methods in cancer treatment have been evolving. As the results, nowadays, cancer patients are receiving several types of treatments, ranging from chemotherapy and radiation therapy to surgery and immunotherapy. In fact, most cancer patients take a combination of current anti-cancer therapies to improve the efficacy of treatment. However, current strategies still cause some side effects to patients, such as pain and depression. Therefore, there is the need to discover better ways to eradicate cancer whilst minimizing side effects. Recently, immunotherapy, particularly immune checkpoint blockade, is rising as an effective anti-cancer treatment. Unlike chemotherapy or radiation therapy, immunotherapy has few side effects and a higher tumor cell removal efficacy depend on cellular immunological mechanisms. Moreover, recent studies suggest that tissue immune responses are regulated by their microbiome composition. Each tissue has their specific microenvironment, which makes their microbiome composition different, particularly in the context of different types of cancer, such as breast, colorectal, kidney, lung, and skin. Herein, we review the current understanding of the relationship of immune responses and tissue microbiome in cancer in both animal and human studies. Moreover, we discuss the cancer-microbiome-immune axis in the context of cancer development and treatment. Finally, we speculate on strategies to control tissue microbiome alterations that may synergistically affect the immune system and impact cancer treatment outcomes.

Therapeutic Efficacy of Extracts from Root of Acnthopanax Sessiliflorus as Anti-cancer Drug ; in vivo and in vitro Study

  • Kim, Hyung-Woo;Jeong, Sun;Baek, Gwang-Hyun;Cho, Su-In;Jeon, Byung-Gwan;Kim, Gye-Yeop;Cho, Young-Lim;Jeong, Hyun-Woo
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.21 no.2
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    • pp.518-522
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    • 2007
  • The cortex and root of Acnthopanax sessiliflorus, a herbal medicine, have been used for several diseases including cancer in Oriental countries. In the previous study, we showed that the cortex of this plant have anti-cancer activity. But its therapeutic efficacy of CORTEX ACANTHOPANAX RADICIS (CAR) is not clarified. For these reasons, we investigated immuno-potentiating and anti-cancer properties of CAR compared with CA, in terms of body and tumor weights, proliferation of thymocytes and tumor cells, and nitric oxide production from macrophages through in vitro and in vivo studies. In our results, administration of CAR reduced tumor mass and increased body weights. CAR also inhibited proliferation of tumor cells in vivo and in vitro dose-dependently. Thymocyte proliferation was accelerated by treatment with CAR and NO production was also promoted by CAR in vivo and vitro. In conclusion, we demonstrated that CAR is useful to treat for cancer as complementary or alternative medicine to Western medication, its therapeutic efficacy is involved in direct inhibition of tumor growth and immuno-potentiating activity.

In Vivo Evaluation of Curcumin-loaded Nanoparticles in a A549 Xenograft Mice Model

  • Yin, Hai-Tao;Zhang, De-Geng;Wu, Xiao-Li;Huang, Xin-En;Chen, Gang
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.1
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    • pp.409-412
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    • 2013
  • Curcumin (Cum) has been reported to have potential chemo-preventive and chemotherapeutic activity through influencing various processes, inducing cell cycle arrest, differentiation and apoptosis in a series of cancers. However, the poor solubility of Cum limits its further applications in the treatment of cancer. We have previously reported Cum-loaded nanoparticles (Cum-NPs) prepared with amphilic methoxy poly(ethylene glycol)-polycaprolactone (mPEG-PCL) block copolymers. The current study demonstrated superior antitumor efficacy of Cum-NPs over free Cum in the treatment of lung cancer. In vivo evaluation further demonstrated superior anticancer effects of Cum-NPs by delaying tumor growth compared to free Cum in an established A549 transplanted mice model. Moreover, Cum-NPs showed little toxicity to normal tissues including bone marrow, liver and kidney at a therapeutic dose. These results suggest that Cum-NPs are effective to inhibit the growth of human lung cancer with little toxicity to normal tissues, and could provide a clinically useful therapeutic regimen. They thus merit more research to evaluate the feasibility of clinical application.

Combination Therapy of Gefitinib and Korean Herbal Medicines Could be a Beneficial Option for Patients with Non-Small-Cell Lung Cancer

  • Lee, Kangwook;Ryu, Juyoung;Son, Chang-Gue;Cho, Jung-Hyo;Yoo, Hwa-Seung;Lee, Jonghoon;Kim, Yoon-sik;Lee, Namhun
    • Journal of Pharmacopuncture
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    • v.19 no.3
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    • pp.259-263
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    • 2016
  • Lung cancer has a high mortality rate and is often diagnosed at the metastatic stage. Gefitinib is a targeted molecular therapeutic drug used to treat patients with non-small-cell lung cancer (NSCLC). Korean herbal medicines may also have therapeutic efficacy against lung cancer, reduce the side effects associated with chemotherapy, and improve patient quality of life (QOL). This case report describes the effects of a Korean herbal medicine regimen combined with gefitinib in a patient with NSCLC and bone metastasis. The Korean herbal medicine regimen included woohwanggeosa-dan, hwanggibujeong-dan and geonchilgyebok-jeong. The computed tomography (CT) findings showed that following combination treatment, the size of the tumor was markedly decreased without serious adverse events. Moreover, the Eastern Cooperative Oncology Group (ECOG) performance status was improved and cancer-related pain was decreased. These results suggest that a combination of Korean herbal medicines and gefitinib may be an effective therapeutic option for patients with advanced NSCLC and bone metastasis. Further studies are needed to examine the mechanism and the clinical efficacy of Korean herbal medicines against NSCLC.