• Title/Summary/Keyword: therapeutic rationale

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The emerging role of myeloid-derived suppressor cells in radiotherapy

  • Kang, Changhee;Jeong, Seong-Yun;Song, Si Yeol;Choi, Eun Kyung
    • Radiation Oncology Journal
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    • v.38 no.1
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    • pp.1-10
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    • 2020
  • Radiotherapy (RT) has been used for decades as one of the main treatment modalities for cancer patients. The therapeutic effect of RT has been primarily ascribed to DNA damage leading to tumor cell death. Besides direct tumoricidal effect, RT affects antitumor responses through immune-mediated mechanism, which provides a rationale for combining RT and immunotherapy for cancer treatment. Thus far, for the combined treatment with RT, numerous studies have focused on the immune checkpoint inhibitors and have shown promising results. However, treatment resistance is still common, and one of the main resistance mechanisms is thought to be due to the immunosuppressive tumor microenvironment where myeloid-derived suppressor cells (MDSCs) play a crucial role. MDSCs are immature myeloid cells with a strong immunosuppressive activity. MDSC frequency is correlated with tumor progression, recurrence, negative clinical outcome, and reduced efficacy of immunotherapy. Therefore, increasing efforts to target MDSCs have been made to overcome the resistance in cancer treatments. In this review, we focus on the role of MDSCs in RT and highlight growing evidence for targeting MDSCs in combination with RT to improve cancer treatment.

CKD-581 Downregulates Wnt/β-Catenin Pathway by DACT3 Induction in Hematologic Malignancy

  • Kim, Soo Jin;Kim, Suntae;Choi, Yong June;Kim, U Ji;Kang, Keon Wook
    • Biomolecules & Therapeutics
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    • v.30 no.5
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    • pp.435-446
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    • 2022
  • The present study evaluated the anti-cancer activity of histone deacetylase (HDAC)-inhibiting CKD-581 in multiple myeloma (MM) and its pharmacological mechanisms. CKD-581 potently inhibited a broad spectrum of HDAC isozymes. It concentration-dependently inhibited proliferation of hematologic cancer cells including MM (MM.1S and RPMI8226) and T cell lymphoma (HH and MJ). It increased the expression of the dishevelled binding antagonist of β-catenin 3 (DACT3) in T cell lymphoma and MM cells, and decreased the expression of c-Myc and β-catenin in MM cells. Additionally, it enhanced phosphorylated p53, p21, cleaved caspase-3 and the subG1 population, and reversely, downregulated cyclin D1, CDK4 and the anti-apoptotic BCL-2 family. Finally, administration of CKD-581 exerted a significant anti-cancer activity in MM.1S-implanted xenografts. Overall, CKD-581 shows anticancer activity via inhibition of the Wnt/β-catenin signaling pathway in hematologic malignancies. This finding is evidence of the therapeutic potential and rationale of CKD-581 for treatment of MM.

Study on the Applications of Prescriptions including Rhizoma Cyperi as a Main Component in Dongeuibogam (향부자(香附子)의 방제(方劑) 활용(活用)에 대한 고찰(考察)(동의보감(東醫寶鑑) 중심(中心)으로))

  • Hu, Jin;Lee, Jung-Hwan;Yun, Young-Gab
    • Herbal Formula Science
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    • v.19 no.2
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    • pp.161-178
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    • 2011
  • Objectives : The aim of this study is to find the therapeutic meaning of Rhizoma Cyperi in herbal medication. Methodes : In this study, we investigate 85 prescriptions related to the use of Rhizoma Cyperi main blended from Dongeuibogam. we research about field of therapy, symtoms of a disease, the chief virtue of a medicine, the cause of a disease, the pathology of a disease, dosage, contents of composition. Results : The following conclusions were reached through investigations on the prescriptions that use Rhizoma Cyperi as the main ingredient. Prescriptions that Rhizoma Cyperi was taken as a monarch drug are utilized for 24 therapeutic purpose, for example, woman disease, uterine disease, vitality and abdominal mass. In particular, 16.4% of prescriptions appear in the chapter of woman, and 15.2% of those appear in the chapter of uterus. Prescriptions that utilize Rhizoma Cyperi as the main ingredient are used in the treatment of menstrual disorder, pain due to disorder of Gi, infertility, irregular menstruation and abdominal mass. Rhizoma Cyperi is used in pathogenic factors such as seven modes of emotions and used in pathology related to the stagnation of blood system. The dosage of Rhizoma Cyperi is 6li(about 0.23g) to 6don(about 22.5g), however 1don(about 3.75g) has been taken the most for clinical application. Gyogamdan and Yukmisamleunghwan are the most useful base prescriptions which use the Rhizoma Cyperi as the main component. Conclusions : This information provide the rationale for establishing Basic evidance in the oriental medical prescription.

Music as a Therapeutic Intervention for Patients with Schizophrenia: Systematic Review (조현병 환자 대상 음악중재에 대한 체계적 고찰)

  • Kim, Young Shil
    • Journal of Music and Human Behavior
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    • v.12 no.2
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    • pp.37-60
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    • 2015
  • The purpose of this study was to systematically review music intervention studies for patients with schizophrenia. The researcher searched nine electronic databases for clinical trials published since 2000, using combinations of keyword related to schizophrenia and music interventions. The initial search identified 272 studies, and fifteen studies were selected by reviewing the titles, abstracts and full articles, In addition, three articles were added by examining other review articles. Thus, a total of 18 articles were analyzed in terms of their general and intervention characteristics, and the PEDro scale was used to evaluate the methodological quality of the included studies. The results demonstrated that, due to the lack of randomization and blinding, the methodological qualities of the studies with high quality music interventions were often rated low. Eight Music interventions conducted by qualified music therapists included active music-making, therapeutic relationship, and supervision systems for improving intervention quality. In conclusion, the randomization, blinding, and the therapeutic rationale of intervention are recommended in future clinical trials for patients with schizophrenia.

Review of the Research in China on Music Interventions for Adult Patients With Brain Injuries (중국 내 성인 뇌손상 환자 대상 음악중재 연구 고찰)

  • Yu, Huiyan
    • Journal of Music and Human Behavior
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    • v.18 no.2
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    • pp.67-85
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    • 2021
  • This study reviewed the research in China on music interventions for adult brain injury patients. Eighty-three studies that met the inclusion criteria were included for analysis. Our review revealed that the number of intervention studies using music with adult brain injury patients has been on the rise since 2012, and random control research design methods have been dominant. Studies focused on the physical domain and emotional domain together were most common. Researchers in fields outside of music therapy conducted 43 of the studies, and music therapists carried out 14 of the studies as intervention providers. Most of the studies carried out by experts in fields other than music therapy used listening activities involving preexisting recorded music. However, most of the studies conducted by music therapists adopted reconstructed music and played it live during their intervention. The specificity of the described content of the interventions and level and relevance of stated rationale to the target goal of the intervention suggests that high quality of intervention was conducted with a therapist/investigator who has completed adequate professional education/training, which would emphasize the importance of music therapy professionalism. This study provides the baseline data for how music intervention research has been implemented in China and presents implications for future clinical practice and research.

PKCβ Positively Regulates RANKL-Induced Osteoclastogenesis by Inactivating GSK-3β

  • Shin, Jihye;Jang, Hyunduk;Lin, Jingjing;Lee, Soo Young
    • Molecules and Cells
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    • v.37 no.10
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    • pp.747-752
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    • 2014
  • Protein kinase C (PKC) family members phosphorylate a wide variety of protein targets and are known to be involved in diverse cellular signaling pathways. However, the role of PKC in receptor activator of NF-${\kappa}B$ ligand (RANKL) signaling has remained elusive. We now demonstrate that $PKC{\beta}$ acts as a positive regulator which inactivates glycogen synthase kinase-$3{\beta}$ (GSK-$3{\beta}$) and promotes NFATc1 induction during RANKL-induced osteoclastogenesis. Among PKCs, $PKC{\beta}$ expression is increased by RANKL. Pharmacological inhibition of $PKC{\beta}$ decreased the formation of osteoclasts which was caused by the inhibition of NFATc1 induction. Importantly, the phosphorylation of GSK-$3{\beta}$ was decreased by $PKC{\beta}$ inhibition. Likewise, down-regulation of $PKC{\beta}$ by RNA interference suppressed osteoclast differentiation, NFATc1 induction, and GSK-$3{\beta}$ phosphorylation. The administration of PKC inhibitor to the RANKL-injected mouse calvaria efficiently protected RANKL-induced bone destruction. Thus, the $PKC{\beta}$ pathway, leading to GSK-$3{\beta}$ inactivation and NFATc1 induction, has a key role in the differentiation of osteoclasts. Our results also provide a further rationale for $PKC{\beta}$'s therapeutic targeting to treat inflammation-related bone diseases.

Curcumin Induces Apoptosis in SGC-7901 Gastric Adenocarcinoma Cells via Regulation of Mitochondrial Signaling Pathways

  • Xue, Xia;Yu, Jin-Long;Sun, De-Qing;Kong, Feng;Qu, Xian-Jun;Zou, Wen;Wu, Jing;Wang, Rong-Mei
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.9
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    • pp.3987-3992
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    • 2014
  • Curcumin, a polyphenol compound derived from the rhizome of the plant Curcuma longa L. has been verified as an anticancer compound against several types of cancer. However, understanding of the molecular mechanisms by which it induces apoptosis is limited. In this study, the anticancer efficacy of curcumin was investigated in human gastric adenocarcinoma SGC-7901 cells. The results demonstrated that curcumin induced morphological changes and decreased cell viability. Apoptosis triggered by curcumin was visualized using Annexin V-FITC/7-AAD staining. Curcumin-induced apoptosis of SGC-7901 cells was associated with the dissipation of mitochondrial membrane potential (MMP) and the release of cytochrome c into the cytosol. Furthermore, the down-regulation of Bcl-2 and up-regulation of Bax that led to the cleavage of caspase-3 and increased cleaved PARP was observed in SGC-7901 cells treated with curcumin. Therefore, curcumin-induced apoptosis of SGC-7901 cells might be mediated through the mitochondria pathway, which gives the rationale for in vivo studies on the utilization of curcumin as a potential cancer therapeutic compound.

Growth of Human Colon Cancer Cells in Nude Mice is Delayed by Ketogenic Diet With or Without Omega-3 Fatty Acids and Medium-chain Triglycerides

  • Hao, Guang-Wei;Chen, Yu-Sheng;He, De-Ming;Wang, Hai-Yu;Wu, Guo-Hao;Zhang, Bo
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.5
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    • pp.2061-2068
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    • 2015
  • Background: Tumors are largely unable to metabolize ketone bodies for energy due to various deficiencies in one or both of the key mitochondrial enzymes, which may provide a rationale for therapeutic strategies that inhibit tumor growth by administration of a ketogenic diet with average protein but low in carbohydrates and high in fat. Materials and Methods: Thirty-six male BALB/C nude mice were injected subcutaneously with tumor cells of the colon cancer cell line HCT116. The animals were then randomly split into three feeding groups and fed either a ketogenic diet rich in omega-3 fatty acids and MCT (MKD group; n=12) or lard only (LKD group; n=12) or a standard diet (SD group; n=12) ad libitum. Experiments were ended upon attainment of the target tumor volume of $600mm^3$ to $700mm^3$. The three diets were compared for tumor growth and survival time (interval between tumor cell injection and attainment of target tumor volume). Results: The tumor growth in the MKD and LKD groups was significantly delayed compared to that in the SD group. Conclusions: Application of an unrestricted ketogenic diet delayed tumor growth in a mouse xenograft model. Further studies are needed to address the mechanism of this diet intervention and the impact on other tumor-relevant parameters such as invasion and metastasis.

Therapeutic Effect of Amantadine in Traumatic Brain Injury Patients : Two Cases and Review (외상성 뇌손상 환자에서 Amantadine의 치료적 효과 : 2증례 및 고찰)

  • Jung, Han Yong;Lee, Soyoung Irene;Kim, Yang Rae
    • Korean Journal of Biological Psychiatry
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    • v.8 no.1
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    • pp.156-161
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    • 2001
  • We reported two cases of amantadine treatment in traumatic brain injury patients and reviewed the literature of amantadine treatment of those patients. Problems with short-term memory, attention, planning, problem solving, impulsivity, disinhibition, poor motivation, and other behavioral and cognitive deficit could occur following traumatic brain injury or other types of acquired brain injury. This report described results of amantadine using in two patients with this type of symptom profile. Patients received neuropsychiatric examination as well as BPRS and Barthel index. These patients were improved, respectively from 57 point to 82 point(case 1), from 85 to 94(case 2) in Barthel index, and from 66 point to 35 point(case 1), from 55 to 32 point(case 2) in BPRS. These two patients did not reveal any other adverse effect. The rationale for using amantadine were discussed.

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Combination of BEZ235 and Metformin Has Synergistic Effect on Cell Viability in Colorectal Cancer Cells

  • Kim, Taewan;Kim, Taehyung;Choi, Soonyoung;Ko, Hyeran;Park, Deokbae;Lee, Youngki
    • Development and Reproduction
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    • v.22 no.2
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    • pp.133-142
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    • 2018
  • Patients with type II diabetes mellitus are more susceptible to colorectal cancer (CRC) incidence than non-diabetics. The anti-diabetic drug metformin is most commonly prescribed for the treatment of this disease and has recently shown antitumor effect in preclinical studies. The aberrant mutational activation in the components of RAS/RAF/MEK/ERK and PI3K/AKT/mTOR signaling pathway is very frequently observed in CRC. We previously reported that metformin inhibits the phosphorylation of ERK and BEZ235, a dual inhibitor of PI3K and mTOR, has anti-tumor activity against HCT15 CRC cells harboring mutations of KRAS and PIK3CA. Therefore, we hypothesized that simultaneous inhibition of two pathways by combining metformin with BEZ235 could be more effective in the suppression of proliferation than single agent treatment in HCT15 CRC cells. Here, we investigated the combinatory effect of metformin and BEZ235 on the cell survival in HCT15 CRC cells. Our study shows that both of the two signaling pathways can be blocked by this combinational strategy: metformin suppressed both pathways by inhibiting the phosphorylation of ERK, 4E-BP1 and S6, and BEZ235 suppressed PI3K/AKT/mTOR pathway by reducing the phosphorylation of 4E-BP1 and S6. This combination treatment synergistically reduced cell viability. The combination index (CI) values ranged from 0.44 to 0.88, indicating synergism for the combination. These results offer a preclinical rationale for the potential therapeutic option for the treatment of CRC.