• IMMUNE NETWORK
• /
• v.12 no.6
• /
• pp.269-276
• /
• 2012

The anti-tumor effect of monocyte-derived DC (MoDC) vaccine was studied in lung cancer model with feasible but weak Ag-specific immune response and incomplete blocking of tumor growth. To overcome this limitation, the hematopoietic stem cell-derived DC (SDC) was cultured and the anti-tumor effect of MoDC & SDC was compared in mouse lung cancer minimal residual model (MRD). Therapeutic DCs were cultured from either $CD34^+$ hematopoietic stem cells with GM-CSF, SCF and IL-4 for 14 days (SDC) or monocytes with GM-CSF and IL-4 for 7 days (MoDC). DCs were injected twice by one week interval into the peritoneum of mice that are inoculated with Lewis Lung Carcinoma cells (LLC) one day before the DC injection. Anti-tumor responses and the immune modulation were observed 3 weeks after the final DC injection. CD11c expression, IL-12 and TGF-${\beta}$ secretion were higher in SDC but CCR7 expression, IFN-${\gamma}$ and IL-10 secretion were higher in MoDC. The proportion of $CD11c^+CD8a^+$ cells was similar in both DC cultures. Although both DC reduced the tumor burden, histological anti-tumor effect and the frequencies of IFN-${\gamma}$ secreting $CD8^+$ T cells were higher in SDC treated group than in MoDC. Conclusively, although both MoDC and SDC can induce the anti-tumor immunity, SDC may be better module as anti-tumor vaccine than MoDC in mouse lung cancer.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.11
• /
• pp.4759-4768
• /
• 2015

Background: Several studies have investigated predictive and prognostic biomarkers for patients treated with anti-epidermal growth factor receptor (EGFR) agents in lung cancer. However, the conclusion is controversial. Materials and Methods: A meta-analysis was conducted to evaluate the associations of mutant K-ras, PIK3CA and PTEN deficiency with the efficacy of anti-EGFR agents in lung cancer. The primary endpoint was objective response rate (ORR). The secondary endpoints were overall survival (OS) and progression-free survival (PFS). Results: A total of 61 studies were included in the final meta-analysis. The result showed that K-ras mutation was a good predictor for ORR (RR=0.42, 95%CI, 0.33-0.55, p=0.000) and an effective prognostic marker for OS (HR=1.37, 95%CI, 1.15-1.65, p=0.001) and PFS (HR=1.33, 95%CI, 1.05-1.69, p=0.019). However, PTEN deficiency or PIK3CA mutation did not show any significance predictive value for ORR (PTEN, RR=0.82, 95%CI, 0.56-1.19, p=0.286; PIK3CA, RR=1.08, 95%CI, 0.17-6.66, P=0.938). And PTEN deficiency or expression of PIK3CA did not show significance prognostic value for OS (PTEN, HR=0.88, 95%CI, 0.31-2.46,P=0.805; PIK3CA, HR=0.79, 95%CI: 0.23-2.68, P=0.706). Conclusions: Our meta-analysis showed that K-ras mutation may be an effective predictor in lung cancer patients treated with anti-EGFR agents. Whereas, the predictive and prognostic value of PTEN deficiency and PIK3CA mutation need to be further investigated.

• BMB Reports
• /
• v.53 no.2
• /
• pp.88-93
• /
• 2020

Cisplatin is a widely used anti-cancer agent. However, the effectiveness of cisplatin has been limited by the commonly developed drug resistance. This study aimed to investigate the potential effects of endoplasmic reticulum (ER) stress to overcome drug resistance using the cisplatin-resistant A2780/CisR ovarian cancer cell model. The synthetic chalcone derivative (E)-3-(3,5-dimethoxyphenyl)-1-(2-methoxyphenyl)prop-2-en-1-one (named DPP23) is an ER stress inducer. We found that DPP23 triggered apoptosis in both parental cisplatin-sensitive A2780 and cisplatin-resistant A2780/CisR ovarian cancer cells due to activation of reactive oxygen species (ROS)-mediated unfolded protein response (UPR) pathway in the endoplasmic reticulum. This result suggests that ROS-mediated UPR activation is potential in overcoming drug resistance. DPP23 can be used as a target pharmacophore for the development of novel chemotherapeutic agents capable of overcoming drug resistance in cancer cells, particularly ovarian cancer cells.

• Molecules and Cells
• /
• v.40 no.4
• /
• pp.291-298
• /
• 2017

MicroRNAs (miRNAs) are short non-coding RNAs that regulate genes posttranscriptionally. Past studies have reported that miR-210 is up-regulated in many cancers including cervical cancer, and plays a pleiotropic role in carcinogenesis. However, its role in regulating response towards anti-cancer agents has not been fully elucidated. We have previously reported that the natural compound 1'S-1'-acetoxychavicol acetate (ACA) is able to induce cytotoxicity in various cancer cells including cervical cancer cells. Hence, this study aims to investigate the mechanistic role of miR-210 in regulating response towards ACA in cervical cancer cells. In the present study, we found that ACA down-regulated miR-210 expression in cervical cancer cells, and suppression of miR-210 expression enhanced sensitivity towards ACA by inhibiting cell proliferation and promoting apoptosis. Western blot analysis showed increased expression of mothers against decapentaplegic homolog 4 (SMAD4), which was predicted as a target of miR-210 by target prediction programs, following treatment with ACA. Luciferase reporter assay confirmed that miR-210 binds to sequences in 3'UTR of SMAD4. Furthermore, decreased in SMAD4 protein expression was observed when miR-210 was overexpressed. Conversely, SMAD4 protein expression increased when miR-210 expression was suppressed. Lastly, we demonstrated that overexpression of SMAD4 augmented the anti-proliferative and apoptosis-inducing effects of ACA. Taken together, our results demonstrated that down-regulation of miR-210 conferred sensitivity towards ACA in cervical cancer cells by targeting SMAD4. These findings suggest that combination of miRNAs and natural compounds could provide new strategies in treating cervical cancer.

• Journal of Gynecologic Oncology
• /
• v.29 no.6
• /
• pp.93.1-93.11
• /
• 2018

The introduction of checkpoint inhibitors revolutionized immuno-oncology. The efficacy of traditional immunotherapeutics, like vaccines and immunostimulants was very limited due to persistent immune-escape strategies of cancer cells. Checkpoint inhibitors target these escape mechanisms and re-direct the immune system to anti-tumor toxicity. Phenomenal results have been reported in entities like melanoma, where no other therapy was able to demonstrate survival benefit, before the introduction of immunotherapeutics. The first experience in ovarian cancer (OC) was reported for nivolumab, a fully human anti-programmed cell death protein 1 (PD1) antibody, in 2015. While the data are extraordinary for a mono-immunotherapeutic agent and very promising, they do not match up to the revolutionary results in entities like melanoma. The key to exceptional treatment response in OC, could be the identification of the most immunogenic patients. We hypothyse that BRCA mutation could be a predictor of improved response in OC. The underlying DNA-repair-deficiancy should result in increased immunogenicity because of higher mutational load and more neoantigen presentation. This hypothesis was not tested to date and should be subject to future trials. The present article gives an overview of the immunologic background of checkpoint inhibition (CI). It presents current data on nivolumab and other checkpoint-inhibitors in solid tumors and OC specifically and depicts important topics in the management of this novel substance group, such as side effect control, diagnostic PD-1/programmed cell death-ligand 1 (PD-L1) expression assessment and management of pseudoprogression.

• Journal of Acupuncture Research
• /
• v.20 no.5
• /
• pp.159-171
• /
• 2003

Objective: To study on the anti-cancer, anti-metastasis and immune response improvement effects of Herbal-acupuncture with Asparagus cochinchinensis infusion solution. Methods: we put into Chung-wan(CV12) and Kwanwon(CV4) of C57bl/6 which are corresponding to human body with Asparagus coc hinchinensis infusion solution. We observed the effect on the expres sion of MMP-9. the expression of cytokine gene, number of pulmon ary colony, histological analysis on tissue metastasis of lung and liver. the expression of cytokine gene on PBMC. the number of $CD3e^+/CD4^+$. $CD3e^+/CD8^+$, $NK^+$ cell. Results: The results were obtained as follows I) The effect on expression of MMP-9. the expression of cytokine gen e was inhibited significantly in all the sample groups. compared with control group. 2) In pulmonary colony, sample groups were decreased significantly, compared with control group. especially, the group put into Chung-wan(CV12) was decreased significantly. 3) Histological analysis of sample groups inhibited significantly in all th e sample groups compared with that control groups in both of lung and liver. especially, the group put into Chung-wan(CV12) was inhibited significantly. 4) The effect on cytokine gene expression on PBMC of all the sample groups were increased significantly, compared with control group. 5) In flow cytometry, $CD3e^+/CD4^+$ $CD3e^+/CD8^+$, $NK^+$ cell in sample groups were increased compared with control group.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.27 no.6
• /
• pp.1183-1188
• /
• 1998

This study was carried out to elucidate the immunomodulating activity of protein bound polysac charide extracted from Ganoderma lucidum(PSG). Macrophage drived reactive radicals were known as an effector for antimicrobial and anticancer functions. The promising immune response molecule, reactive oxygen intermediates(ROIs), was determined in TIB 71 cells with PSG at various experimental conditions. Treatment with 0.5mg PSG significantly increased the production of ROIs, superoxide anion as well as hydrogen peroxide, from TIB 71 cells(p<0.001). Under the same concentration, con siderable results were obtained from 24 hour cultivation with 106 cells at 5% CO2 incubator. The cells were trigged with PMA(5.3 M) after primed BCG(100 M) or IFN (100U) alone could not induce the production of ROIs, but it had a significant potentiating effect on ROIs secretion when the cells were treated with PSG.

• Journal of Acupuncture Research
• /
• v.17 no.1
• /
• pp.251-286
• /
• 2000

To study the effects of anti-cancer, anti-metastasis and immune response improvement of aqua-acupuncture with Cistanches Herba infusion solution, we used Cistanches Herba infusion solution(taken by water-alcohol method) put into Chung-wan(CV12) and Chok-Samni(S36) of BALB/c or C57BL/6 which are corresponding to human body. 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, MST, ILS, changes in amount of WBC, RBC, PLT, 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. The cytotoxicity about B16-F10 cell line of $2^0$, $2^{-1}$, $2^{-2}$, $2^{-5}$ diluent groups in Cistanches Herba infusion solution treatment was inhibited significantly, compared with control group. 2. The cytotoxicity about HT1080 cell line of $2^0$, $2^{-1}$, $2^{-2}$, $2^{-3}$, $2^{-5}$, $2^{-8}$ diluent groups in Cistanches Herba infusion solution treatment was inhibited significantly, compared with control group. 3. The effect on expression of MMP-9 gene was decreased in all the sample groups, compared with control group. 4. The effect on the control-ability on the cancer cell proliferation showed cytotooicity significantly in $2^0$, $2^{-1}$, $2^{-2}$, $2^{-3}$, $2^{-4}$, $2^{-5}$ diluent groups. 5. 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(S36) with 20% Cistanches Herba infusion solution treatment group that showed same number of the control group. 6. S-180 cancer cell line transplants in BALB/c mice showed high MST and ILS significantly in almost sample groups, compared with control group. But one group put into Chok-Samni(S36) with 20% Cistanches Herba infusion solution treatment group showed low MST and ILS than control group. 7. The sample group injected in vein with B16-F10 cancer cell line in C57BL/6 mice showed increased ILS compared with control group significantly in anti-metastasis test. 8. The sample group injected in vein with B16-F10 cancer cell line in C57BL/6 mice were increased significantly in the number of WBC and glucose, and decreased significantly in the amount of LDH, compared with control group. However, there's no significant increase or decrease in number of RBC, PLT, total protein and creatinine. 9. We couldn't find any significant relation in spleen weight of the sample group. 10. In pulmonary colony, sample group was decreased significantly, compared with control group. 11. Histological analysis of sample group inhivited compared with that of control group in both of lung and liver. 12. In immune system, all the sample groups showed having more relevancy to the effect on splenic cell proliferation than normal group. 13. The effect on cytokine gene expression of all the sample groups were increased than control group. 14. In flow cytometry there's no significant relation in number of $CD8^+$, $CD19^+$ cell, however, the number of $CD4^+$ cell and NK cell in sample groups were increased than in control group. Above the results showed that aqua-acupuncture of Cistanches Herba infusion solution has effects of anti-cancer, anti-metastasis and immune response improvement.

• IMMUNE NETWORK
• /
• v.5 no.2
• /
• pp.110-116
• /
• 2005

Background: As an attempt to develop a strategy to improve the protective immune response to GM-CSF-secreting CT26 (GM-CSF/CT26) tumor vaccine, we have investigated whether the apoptogenic treatment of GM-CSF/CT26 prior to vaccination enhances the induction of anti-tumor immune response in mouse model. Methods: A carcinogeninduced mouse colorectal tumor, CT26 was transfected with GM-CSF gene using a retroviral vector to generate GM-CSF-secreting CT26 (CT26/GM-CSF). The CT26/GM-CSF was treated with ${\gamma}$-irradiation or mitomycin C to induce apoptosis and vaccinated into BALB/c mice. After 7 days, the mice were injected with a lethal dose of challenge live CT26 cells to examine the protective effect of tumor vaccination in vivo. Results: Although both apoptotic and necrotic CT26/GM-CSF vaccines were able to enhance anti-tumor immune response, apoptotic CT26/GM-CSF induced by pretreatment with ${\gamma}$-irradiation (50,000 rads) was the most potent in generating the anti-tumor immunity, and thus 100% of mice vaccinated with the apoptotic cells remained tumor free for more than 60 days after tumor challenge. Conclusion: Apoptogenic pretreatment of GM-CSF-secreting CT26 tumor vaccine by ${\gamma}$-irradiation (50,000 rads) resulted in a significant enhancement in inducing the protective anti-tumor immunity. A rapid induction of apoptosis of CT26/GM-CSF tumor vaccine at the vaccine site might be critical for the enhancement in anti-tumor immune response to tumor vaccine.

• Molecules and Cells
• /
• v.37 no.3
• /
• pp.189-195
• /
• 2014

The NF-${\kappa}B$ pathway transcriptionally controls a large set of target genes that play important roles in cell survival, inflammation, and immune responses. While many studies showed anti-tumorigenic and pro-survival role of NF-${\kappa}B$ in cancer cells, recent findings postulate that NF-${\kappa}B$ participates in a senescence-associated cytokine response, thereby suggesting a tumor restraining role of NF-${\kappa}B$. In this review, we discuss implications of the NF-${\kappa}B$ signaling pathway in cancer. Particularly, we emphasize the connection of NF-${\kappa}B$ with cellular senescence as a response to chemotherapy, and furthermore, present examples how distinct oncogenic network contexts surrounding NF-${\kappa}B$ produce fundamentally different treatment outcomes in aggressive B-cell lymphomas as an example.