• Title/Summary/Keyword: anti-cancer response

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SIRT1: roles in aging and cancer

  • Kim, Eun-Joo;Um, Soo-Jong
    • BMB Reports
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    • v.41 no.11
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    • pp.751-756
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    • 2008
  • Aging and cancer both occur as a result of accumulated cellular damage, and both are related to the regulation of specific genes in the damage response. Recent research has unveiled connections between the mechanisms of aging and cancer, but how to prevent the development of cancer and increase longevity remain unknown. SIRT1 (the mammalian Sir2), which has $NAD^+$-dependent class III histone deacetylase activity, may be a key gene linking the modulation of cancer and aging. SIRT1 has broad biological functions in growth regulation, stress response, tumorigenesis, endocrine signaling, and extended lifespan. Here, we focus on the current knowledge regarding the role of SIRT1 in aging and cancer, and discuss the implications of SIRT1 as a therapeutic target for the optimal balance between anti-aging and anti-cancer activities.

Clinical Perspectives to Overcome Acquired Resistance to Anti-Programmed Death-1 and Anti-Programmed Death Ligand-1 Therapy in Non-Small Cell Lung Cancer

  • Lee, Yong Jun;Lee, Jii Bum;Ha, Sang-Jun;Kim, Hye Ryun
    • Molecules and Cells
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    • v.44 no.5
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    • pp.363-373
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    • 2021
  • Immune checkpoint inhibitors have changed the paradigm of treatment options for non-small cell lung cancer (NSCLC). Monoclonal antibodies targeting programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) have gained wide attention for their application, which has been shown to result in prolonged survival. Nevertheless, only a limited subset of patients show partial or complete response to PD-1 therapy, and patients who show a response eventually develop resistance to immunotherapy. This article aims to provide an overview of the mechanisms of acquired resistance to anti-PD-1/PD-L1 therapy from the perspective of tumor cells and the surrounding microenvironment. In addition, we address the potential therapeutic targets and ongoing clinical trials, focusing mainly on NSCLC.

Successful Treatment of Advanced Gastric Cancer with Brain Metastases through an Abscopal Effect by Radiation and Immune Checkpoint Inhibitor Therapy

  • Muto, Momotaro;Nakata, Hirotaka;Ishigaki, Kenichi;Tachibana, Shion;Yoshida, Moe;Muto, Mizue;Yanagawa, Nobuyuki;Okumura, Toshikatsu
    • Journal of Gastric Cancer
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    • v.21 no.3
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    • pp.319-324
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    • 2021
  • The abscopal effect refers to the phenomenon in which local radiotherapy is associated with the regression of metastatic cancer that is distantly located from the irradiated site. Here, we present a case of a patient with advanced gastric cancer and brain metastases who was successfully treated with brain radiotherapy and anti-programmed death-1 (PD-1) therapy-induced abscopal effect. Although anti-PD-1 therapy alone could not prevent disease progression, the metastatic lesions in the brain and also in the abdominal lymph node showed a drastic response after brain radiotherapy and anti-PD-1 therapy. To our knowledge, this is the first reported case of successful treatment of advanced gastric cancer with multiple brain and abdominal lymph node metastases, possibly through anti-PD-1 therapy combined with brain radiotherapy-induced abscopal effect. We suggest that the combination of brain radiotherapy and anti-PD-1 therapy may be considered as a therapeutic option for advanced gastric cancer, especially when there is brain metastasis.

Immunosignature: Serum Antibody Profiling for Cancer Diagnostics

  • Chapoval, Andrei I;Legutki, J Bart;Stafford, Philip;Trebukhov, Andrey V;Johnston, Stephen A;Shoikhet, Yakov N;Lazarev, Alexander F
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.12
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    • pp.4833-4837
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    • 2015
  • Biomarkers for preclinical diagnosis of cancer are valuable tools for detection of malignant tumors at early stages in groups at risk and screening healthy people, as well as monitoring disease recurrence after treatment of cancer. However the complexity of the body's response to the pathological processes makes it virtually impossible to evaluate this response to the development of the disease using a single biomarker that is present in the serum at low concentrations. An alternative approach to standard biomarker analysis is called immunosignature. Instead of going after biomarkers themselves this approach rely on the analysis of the humoral immune response to molecular changes associated with the development of pathological processes. It is known that antibodies are produced in response to proteins expressed during cancer development. Accordingly, the changes in antibody repertoire associated with tumor growth can serve as biomarkers of cancer. Immunosignature is a highly sensitive method for antibody repertoire analysis utilizing high density peptide microarrays. In the present review we discuss modern methods for antibody detection, as well as describe the principles and applications of immunosignature in research and clinical practice.

Immune checkpoint inhibitors: recent progress and potential biomarkers

  • Darvin, Pramod;Toor, Salman M.;Nair, Varun Sasidharan;Elkord, Eyad
    • Experimental and Molecular Medicine
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    • v.50 no.12
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    • pp.10.1-10.11
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    • 2018
  • Cancer growth and progression are associated with immune suppression. Cancer cells have the ability to activate different immune checkpoint pathways that harbor immunosuppressive functions. Monoclonal antibodies that target immune checkpoints provided an immense breakthrough in cancer therapeutics. Among the immune checkpoint inhibitors, PD-1/PD-L1 and CTLA-4 inhibitors showed promising therapeutic outcomes, and some have been approved for certain cancer treatments, while others are under clinical trials. Recent reports have shown that patients with various malignancies benefit from immune checkpoint inhibitor treatment. However, mainstream initiation of immune checkpoint therapy to treat cancers is obstructed by the low response rate and immune-related adverse events in some cancer patients. This has given rise to the need for developing sets of biomarkers that predict the response to immune checkpoint blockade and immune-related adverse events. In this review, we discuss different predictive biomarkers for anti-PD-1/PD-L1 and anti-CTLA-4 inhibitors, including immune cells, PD-L1 overexpression, neoantigens, and genetic and epigenetic signatures. Potential approaches for further developing highly reliable predictive biomarkers should facilitate patient selection for and decision-making related to immune checkpoint inhibitor-based therapies.

Study on the Anti-cancer, Anti-metastasis and Immune response improvement Effects of Aqua-acupuncture with Rubi Fructus infusion solution (항암(抗癌) 및 면역효과(免疫效果)에 복분자약침(覆盆子藥鍼)이 미치는 영향(影響))

  • Lee, Seon-Hee;Lee, Byung-Ryul
    • Journal of Acupuncture Research
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    • v.17 no.1
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    • pp.189-219
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    • 2000
  • To study the effects of anti-cancer, anti-metastasis and immune response improvement effects of aqua-acupuncture with Rubi Fructus infusion solution, we used Rubi Fructus infusion solution(taken by water-alcohol method) put into Chung-wan (CV12) and Chok-Samni(ST36) of BALB/c or C57BL/6 which are corresponding to humanbody. We observed the cytotoxicity, the effect on the expression of MMP-9 gene, the ability to control cancer cell proliferation, change of body weight, surviving number, median surviving time, increase of life span, changes in amount of leukocyte, erythrocyte, platelet, total protein, creatinine, glucose and LDH, weight of spleen, number of pulmonary colony, histological analysis on tissue metastasis of lung and liver, splenic cell proliferation, the expression of cytokine gene, the number of $CD4^+$, $CD8^+$, $CD19^+$ and NK cell, and concluded like this. The results were obtained as follows : 1. Effects of Anti-cancer 1) The cytotoxicity about B16-F10 cell line of $2^0$, $2^{-1}$, $2^{-2}$, $2^{-3}$, $2^{-5}$, $2^{-6}$, $2^{-7}$, $2^{-8}$ diluent groups in Rubi Fructus infusion solution treatment was inhibited significantly, compared with control group. 2) The cytotoxicity about HT1080 cell line of $2^0{\sim}2^{-8}$ diluent groups in Rubi Fructus infusion solution treatment was inhibited significantly, compared with control group. 3) The effect on expression of MMP-9 gene was inhibited significantly in all the sample groups, compared with control group. 4) The effect on the control-ability on the cancer cell proliferation showed cytotoxicity significantly in $2^0$, $2^{-1}$, $2^{-2}$, $2^{-3}$, $2^{-4}$, $2^{-5}$, $2^{-6}$, $2^{-7}$, diluent groups. 2. Effects of Anti-metastasis 1) S-180 cancer cell line transplants in BALB/c mice were inhibited significantly in weight increase in all the sample groups, compared with control group. The surviving number increased in almost sample groups, except one group put into Chok-Samni(ST36) with 20% Rubi Fructus infusion solution treatment group that showed same number of the control group. 2) S-180 cancer cell line transplants in BALB/c mice showed high MST significantly in almost sample groups, compared with control group. But one group put into Chok-Samni(ST36) with 20% Rubi Fructus infusion solution showed low MST than control group. 3) The group injected in vein with B16-F10 cancer cell line in C57BL/6 mice showed increased ILS than control group significantly in anti-metastasis test. 3. Effects of Immune response improvement 1) The group injected in vein with B16-F10 cancer cell line in C57BL/6 mice were increased significantly in the number of leukocyte and glucose, and decreased significantly in the amount of platelet and LDH, compared with control group. However, there's no significant increase or decrease in number of erythrocyte, total protein and creatinine. 2) We couldn't find any significant relation in spleen weight of the sample group. 3) In pulmonary colony, sample group was decreased significantly, compared with control group. 4) Histological analysis of sample group inhivited compared with that of control group in both of lung and liver. 5) In immune system, all the sample groups showed having more relevancy to the effect on splenic cell proliferation than normal group. 6) Cytokine gene increased in almost sample groups, except one group treated with $50{\mu}g/m{\ell}$ Rubi Fructus infusion solution on IL-12. 7) In flow cytometry there's no significant relation in number of $CD8^+$ cell, however, the number of $CD4^+$, $CD19^+$ cell and NK cell in sample group had more relation than in control group. Above the results showed that aqua-acupuncture of Rubi Fructus solution has effects of anti-cancer, and-metastasis and immune response improvement.

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Tumor bioenergetics: An emerging avenue for cancer metabolism targeted therapy

  • Kee, Hyun Jung;Cheong, Jae-Ho
    • BMB Reports
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    • v.47 no.3
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    • pp.158-166
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    • 2014
  • Cell proliferation is a delicately regulated process that couples growth signals and metabolic demands to produce daughter cells. Interestingly, the proliferation of tumor cells immensely depends on glycolysis, the Warburg effect, to ensure a sufficient amount of metabolic flux and bioenergetics for macromolecule synthesis and cell division. This unique metabolic derangement would provide an opportunity for developing cancer therapeutic strategy, particularly when other diverse anti-cancer treatments have been proved ineffective in achieving durable response, largely due to the emergence of resistance. Recent advances in deeper understanding of cancer metabolism usher in new horizons of the next generation strategy for cancer therapy. Here, we discuss the focused review of cancer energy metabolism, and the therapeutic exploitation of glycolysis and OXPHOS as a novel anti-cancer strategy, with particular emphasis on the promise of this approach, among other cancer metabolism targeted therapies that reveal unexpected complexity and context-dependent metabolic adaptability, complicating the development of effective strategies.

Effects of Orostachys Japhonicus Herbal-Acupuncture on Transferred Hepatic Cancer of Mouse Induced by Colon26-L5 Human Colon Cancer Cells (와송(瓦松) 약침(藥鍼)이 mouse의 간전이 암모델에 미치는 영향)

  • Sohn, Seong-Hyoun;Park, Hee-Soo
    • Journal of Acupuncture Research
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    • v.23 no.6
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    • pp.61-76
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    • 2006
  • To study the effects of anti-cancer, anti-metastasis and immune response improvement effects of herbal-accupunture with Orostachys japhonicus A.Berger, infusion solution put into Kansu(BL18) of mouse induced by Colon26-L5 human colon cancer cells, which are corresponding to humanbody. We observed the change of body weight, surviving number, median surviving time, increase of life span, changes in amount of leukocyte, erythrocyte, platelet, total protein, creatinine, glucose and LDH, weight of spleen and kidney, histological analysis on tissue metastasis of liver, splenic cell proliferation, the expression of cytokine gene, the number of CD4+, CD8+, CD9+ and NK cell, and concluded like this. The results were obtained as follows ; 1. In acute and sub-acute cytotoxicity experiment, significantly signs were not appeared in all groups. 2. Antimetastatic experiment in vitro and in vivo showed that Orostachys Japhonicus A.Berger Herbal-acupuncture at Kansu(BL18) has antimetastatic effects. 3. The spleen cells proliferation of the experimental groups treated with Orostachys Japhonicus A.Berger infusion solution extract has increased significantly compared with that of the control group. 4. As compared with control, the population of total T cell, helper T cell, cytotoxic T cell and macrophage were increased. 5. The production of Th 1 type cytokines from splenocyte and cytokines which is associated with anti-tumor activity form macrophage were increased significantly. Above the results revealed that herbal-accupunture with Orostachys Japhonicus A.Berger infusion solution has effects of anti-cancer, anti-metastasis and immune response improvement.

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Somatic mutation patterns and compound response in cancers

  • He, Ningning;Kim, Nayoung;Yoon, Sukjoon
    • BMB Reports
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    • v.46 no.2
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    • pp.97-102
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    • 2013
  • The use of various cancer cell lines can recapitulate known tumor-associated mutations and genetically define cancer subsets. This approach also enables comparative surveys of associations between cancer mutations and drug responses. Here, we analyzed the effects of ~40,000 compounds on cancer cell lines that showed diverse mutation-dependent sensitivity profiles. Over 1,000 compounds exhibited unique sensitivity on cell lines with specific mutational genotypes, and these compounds were clustered into six different classes of mutation-oriented sensitivity. The present analysis provides new insights into the relationship between somatic mutations and selectivity response of chemicals, and these results should have applications related to predicting and optimizing thera-peutic windows for anti-cancer agents.

Anti-proliferative Properties of p-Coumaric Acid in SNU-16 Gastric Cancer Cells (SNU-16 위암 세포주에서 p-coumaric acid의 세포성장 억제 효과)

  • Jang, Mi Gyeong;Ko, Hee Chul;Kim, Se-Jae
    • Journal of Life Science
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    • v.29 no.7
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    • pp.809-816
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    • 2019
  • The ubiquitous plant metabolite p-coumaric acid (p-CA) has antioxidant and anti-inflammatory properties, but its anti-cancer activity has not been established in gastric cancer cell lines. In this study, we investigated the effects of p-CA on the proliferation and transcriptome profile of SNU16 gastric cancer cells. Treatment with p-CA induced apoptosis of the SNU-16 cells by regulating the expression of pro-apoptotic and anti-apoptotic proteins, such as Bcl-2, poly (ADP-ribose) polymerase (PARP), Bax, procaspase-3, and cleaved-caspase-3. The genes differentially expressed in response to p-CA treatment of the SNU-16 cells were identified by RNA sequencing analysis. Genes regulated by p-CA were involved mainly in the inflammatory response, apoptotic processes, cell cycle, and immune response. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that the phosphatidylinositol-3-kinase-Akt and cancer signaling pathways were altered by p-CA. Protein-protein interaction (PPI) network analysis also revealed that p-CA treatment was correlated with differential expression of genes associated with the inflammatory response and cancer. Collectively, these results suggest that p-CA has potential utility in gastric cancer prevention.