• Nuclear Medicine and Molecular Imaging
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• 제40권3호
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• pp.141-147
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• 2006

PET detects only less than 50% of early gastric cancer and 62-98% of advanced gastric cancer. Therefore, mass screening programs are recommended for all adults over the age of 40 for early detection and early treatment of gastric cancer through endoscopy or various radiological tests. The most important step after being diagnosed with gastric cancer is accurate staging, which mainly evaluates tumor resectability to avoid unnecessary surgery. Important factors that affect tumor resectability are whether the tumor can be separated from adjacent organs or important blood vessels, the extent of lymph node metastasis, presence of peritoneal metastasis, or distant organ metastasis. To evaluate the extent of local tumor invasion, anatomical imaging that has superior spatial resolution is essential. There are a few studies on prognostic significance of FDG uptake with inconsistent results between them. In spite of lower sensitivities for lymph node staging, the specificities of CT and PET are very high, and the specificity for PET tends to be higher than that for CT. Limited data published so far show that PET seems less useful in the detection of lung and bone metastasis. In the evaluation of pleural or peritoneal metastasis, PET seems very specific but insensitive as well. When FDG uptake of the primary tumor is low, the distant metastasis is also known to show low FDG uptake reducing its detection. There are only a few data available in the evaluation of recurrence detection and treatment response using FDG PET.

• The Korean Journal of Physiology and Pharmacology
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• 제23권6호
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• pp.501-508
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• 2019

Rosmarinic acid (RA) is a natural polyphenolic compound that exists in many medicinal species of Boraginaceae and Lamiaceae. The previous studies have revealed that RA had therapeutic effects on hepatocellular carcinoma (HCC) in the H22-xenograft models by inhibiting the inflammatory cytokines and $NF-{\kappa}B$ p65 pathway in the tumor microenvironment. However, its molecular mechanisms of immunoregulation and pro-apoptotic effect in HCC have not been fully explored. In the present study, RA at 75, 150, and 300 mg/kg was given to H22 tumor-bearing mice via gavage once a day for 10 days. The results showed that RA can effectively inhibit the tumor growth through regulating the ratio of $CD4^+/CD8^+$ and the secretion of interleukin (IL)-2 and interferon-${\gamma}$, inhibiting the expressions of IL-6, IL-10 and signal transducer and activator of transcription 3, thereby up-regulating Bax and Caspase-3 and down-regulating Bcl-2. The underlying mechanisms involved regulation of immune response and induction of HCC cell apoptosis. These results may provide a more comprehensive perspective to clarify the anti-tumor mechanism of RA in HCC.

• The Korean Journal of Physiology and Pharmacology
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• 제25권3호
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• pp.189-195
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• 2021

Fluoxetine (FLX), a selective serotonin reuptake inhibitor antidepressant, exhibits various other mechanisms of action in numerous cell types and has been shown to induce cell death in cancer cells, paving the way for its potential use in cancer therapy. The aim of this study was to determine the off-target effects of the anti-depressant drug FLX, on the human ovarian granulosa tumor COV434 cells stimulated by forskolin (FSK), by measuring the real-time kinetics of intracellular cyclic AMP (cAMP), ATP level, cytoplasmic calcium ([Ca2+]cyt) and survival of COV434 cells. We show that incubating COV434 cells with FLX (between 0.6 and 10 μM) induces a decrease in intracellular cAMP response to FSK, a drop in ATP content and stimulates cytoplasmic Ca2+ accumulation in COV434 cells. Only the highest concentrations of FLX (5-10 μM) diminished cell viability. The present report is the first to identify an action mechanism of FLX in human tumor ovarian cells COV434 cells and thus opening the way to potential use of fluoxetine as a complementary tool, in granulosa tumor treatments.

• BMB Reports
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• 제55권1호
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• pp.39-47
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• 2022

Adoptive cell transfer (ACT), a form of cell-based immunotherapy that eliminates cancer by restoring and strengthening the body's immune system, has revolutionized cancer treatment. ACT entails intravenous transfer of either tumor-resident or peripheral blood-modified immune cells into cancer patients to mediate anti-tumor response. Although these immune cells control and eradicate cancer via enhanced cytotoxicity against specific tumor antigens, several side effects have been frequently reported in clinical trials. Recently, exosomes, potential cell-free therapeutics, have emerged as an alternative to cell-based immunotherapies, due to their higher stability under same storage condition, lower risk of GvHD and CRS, and higher resistance to immunosuppressive tumor microenvironment. Exosomes, which are nano-sized lipid vesicles, are secreted by living cells, including immune cells. Exosomes contain proteins, lipids, and nucleic acids, and the functional role of each exosome is determined by the specific cargo derived from parental cells. Exosomes derived from cytotoxic effectors including T cells and NK cells exert anti-tumor effects via proteins such as granzyme B and FasL. In this mini-review, we describe the current understanding of the ACT and immune cell-derived exosomes and discuss the limitations of ACT and the opportunities for immune cell-derived exosomes as immune therapies.

• BMB Reports
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• 제56권5호
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• pp.275-286
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• 2023

Cancer immunotherapy has been acknowledged as a new paradigm for cancer treatment, with notable therapeutic effects on certain cancer types. Despite their significant potential, clinical studies over the past decade have revealed that cancer immunotherapy has low response rates in the majority of solid tumors. One of the key causes for poor responses is known to be the relatively low immunogenicity of solid tumors. Because most solid tumors are immune desert 'cold tumors' with antitumor immunity blocked from the onset of innate immunity, combination therapies that combine validated T-based therapies with approaches that can increase tumor-immunogenicity are being considered as relevant therapeutic options. This review paper focuses on immunogenic cell death (ICD) as a way of enhancing immunogenicity in tumor tissues. We will thoroughly review how ICDs such as necroptosis, pyroptosis, and ferroptosis can improve anti-tumor immunity and outline clinical trials targeting ICD. Finally, we will discuss the potential of ICD inducers as an adjuvant for cancer immunotherapy.

• Radiation Oncology Journal
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• 제18권2호
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• pp.127-132
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• 2000

목적 : 두경부 악성 림파절 환자에서 방사선치료중 종양내 간질액 압력을 측정하여 종양내 간질액 압력 및 이의 변화가 갖는 임상적 의의를 밝히고자 하였다. 방법 : 조직학적으로 확진된 26명의 전이성 두경부 악성 림파절 환자를 대상으로 육안적으로 확인 가능하며 접근이 가능한 부위에 위치하고 주사침 끝이 적절히 위치할 수 있도록 적어도 1 cm 이상의 충분한 두께를 갖는 경부 림프절에서 방사선치료 직전 및 방사선치료 중에 종양내 간질액 압력을 측정하였다. 종양의 크기는 촉지하여 임상적으로 측정하고 방사선과적 검사로 측정을 확인하였다. 결과 : 방사선치료 전 TIFP는 25명에서 측정이 가능하였으며 평균치는 24.7 mmHg였다. 방사선치료 전종양의 크기가 클수록 치료 전 TIFP가 높았으며 통계적으로 marginal한 상관관계를 보였고(p=0.06), 치료 전 종양 크기가 크면 치료 후 TIFP의 감소가 큰 경향을 보였으나 통계적인 유의성은 없었다(p=0.43). 방사선치료 중 9명에서 TIFP의 측정이 가능하였으며, 이들의 방사선치료 전과 치료 후 TIFP변화는 평균 12.5 mmHg로 감소하였으며 통계적으로 유의한 결과를 보였다(p=0.009). 치료 전 TIFP가 평균치 이상인 환자군과 이하인 환자군 사이에 방사선치료 결과의 차이가 관찰되지 않았다(p=0.229). 방사선 치료 후 완전 관해를 보인 환자군과 부분관해 이하의 치료 결과를 보인 군 사이에 치료 전 TIFP의 차이는 관찰되지 않았다(p=0.75). 방사선치료 후 완전 관해를 보인 환자군의 TIFP의 치료 전과 치료 중 비교시 평균 36 mmHg 감소하였으며 부분관해 이하의 치료 결과를 보인 군은 29.7 mmHg 감소하여 현재까지는 두 환자군 사이에 유의한 차이는 관찰되지 않았다(p=0.75) 결론 : 방사선치료 전 TIFP의 평균치는 24.7 mmHg였으며 종양의 크기가 클수록 치료 전 TIFP가 높았으며 통계적으로 marginal하게 유의하였다(p=0.06). 방사선치료 후 부분 관해 이하의 치료 결과를 보인 환자군의 치료 전과 치료 중 TIFP를 비교시 평균 29.7 mmHg로 감소하였으나 완전관해를 보인 군은 36mmHg의 더 큰 감소를 보였으나 현재까지는 두 군간의 차이는 유의하지는 않았다.(p=0.75)

• Asian Pacific Journal of Cancer Prevention
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• 제13권9호
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• pp.4393-4402
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• 2012

Colon cancer is the third most common malignant neoplasm in the world and it remains an important cause of death, especially in western countries. The toxic environmental pollutant, 1, 2-dimethylhydrazine (DMH), is also a colon-specific carcinogen. Tannic acid (TA) is reported to be effective against various types of chemically induced toxicity and also carcinogenesis. In the present study, we evaluated the chemopreventive efficacy of TA against DMH induced colon toxicity in a rat model. Efficacy of TA against the colon toxicity was evaluated in terms of biochemical estimation of antioxidant enzyme activities, lipid peroxidation, histopathological changes and expression of early molecular markers of inflammation and tumor promotion. DMH treatment induced oxidative stress enzymes (p<0.001) and an early inflammatory and tumor promotion response in the colons of Wistar rats. TA treatment prevented deteriorative effects induced by DMH through a protective mechanism that involved reduction of oxidative stress as well as COX-2, i-NOS, PCNA protein expression levels and TNF-${\alpha}$ (p<0.001) release. It could be concluded from our results that TA markedly protects against chemically induced colon toxicity and acts plausibly by virtue of its antioxidant, anti-inflammatory and antiproliferative activities.

• Asian Pacific Journal of Cancer Prevention
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• 제15권17호
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• pp.7453-7457
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• 2014

Objective: To observe the efficacy and toxicity of nanoparticle albumin bound paclitaxel (nab-paclitaxel) plus platinum agent (cisplatin or carboplatin) as first line treatment for stage III/IV squamous non-small-cell lung cancer (NSCLC). Methods: Forty chemotherapy naive patients with stage III/IV squamous NSCLC received nab-paclitaxel $125mg/m^2$ on day 1 and day 8, cisplatin $75mg/m^2$ on day 1, carboplatin area under the concentration-time curve of 5 (AUC=5) on day 1. One cycle of treatment was 3 weeks, and at least two were completed in each case. Results: Of the 40 patients who participated in the study, 25 achieved partial responses (PR), 12 reached a stage of stable disease (SD), and 3 suffered progressive disease (PD). The overall response rate (ORR) was 62.5% and the disease control rate (DCR) was 92.5%. Of the 20 patients without surgery or radiotherapy, 10 achieved PR, 7 reached a stage of SD, and 3 PD. The ORR was 50.0% and the DCR was 85.0%. The median progression-free survival time (PFS) of patients without surgery or radiotherapy was 5.0 months. Of the 20 patients receiving surgery or radiotherapy, 15 had PR and 5 p had SD, with an ORR of 75.0% and a DCR of 85.0%. Specifically, the DDP arm demonstrated a significantly higher ORR than the CBP arm (100%vs 54.5%, P<0.05). Common treatment related adverse events were myelosuppression, gastrointestinal response, baldness and neurotoxicity, most of which were grade 1 to 2. Conclusion: Nab-paclitaxel plus platinum agent (cisplatin or carboplatin) is effective as a first-line chemotheraphy for stage III/IV squamous NSCLC, and its adverse effects are tolerable.

• 대한한방내과학회지
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• 제15권2호
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• pp.174-196
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• 1994

In order to investigate the effect of Samulbyulgapchoengpitang(SB) and one herb added(SBA) on anti-tumor and immune response, the author performed this experimental study, Tumor weight(TW), mean survival days(MSD) and body weight(BW) in vivo, natural killer cell activity(NKCA). rosette forming cells(RFC), phagoctic activity in recticuloendomethrial system(PA), delayed type hypersensitivity(DTH), hemoagglutinin titer(HA) and hemolysine(HL) in vitro were measured in mice. 1. MSD was prolonged in both of treated groups(SB and SBA) as compared with control group. 2. TW was decreased in both of treated groups with statistical significance as compared with control group. 3. BW was increased in both of treated groups and just only in SB with statistical significance as compared with control group. 4. DTH was increased in both of treated groups with statistical significance as compared with control group. 5. HA was increased in both of treated groups with statistical significance as compared with control group. 6. HL was increased in both of treated groups with statistical significance as compared with control group. 7. RFC was increased in both of treated groups and just only in SB with statistical significance as compared with control group. 8. NKCA was increased in both of treated groups with statistical significance as compared with control group. 9. PA was increased in both of treated groups with statistical significance as compared with control group. According to the above experimental results, it is suggested that SB and SBA will have anti-tumor substance and enhance the effect of immune response. But we have to consider the longtime prescription of SBA because there have been no experiments in its side effect or accumulation in body.

• Molecules and Cells
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• 제44권10호
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• pp.710-722
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• 2021

Hypoxia, or low oxygen tension, is a hallmark of the tumor microenvironment. The hypoxia-inducible factor-1α (HIF-1α) subunit plays a critical role in the adaptive cellular response of hypoxic tumor cells to low oxygen tension by activating gene-expression programs that control cancer cell metabolism, angiogenesis, and therapy resistance. Phosphorylation is involved in the stabilization and regulation of HIF-1α transcriptional activity. HIF-1α is activated by several factors, including the mitogen-activated protein kinase (MAPK) superfamily. MAPK phosphatase 3 (MKP-3) is a cytoplasmic dual-specificity phosphatase specific for extracellular signal-regulated kinase 1/2 (Erk1/2). Recent evidence indicates that hypoxia increases the endogenous levels of both MKP-3 mRNA and protein. However, its role in the response of cells to hypoxia is poorly understood. Herein, we demonstrated that small-interfering RNA (siRNA)-mediated knockdown of MKP-3 enhanced HIF-1α (not HIF-2α) levels. Conversely, MKP-3 overexpression suppressed HIF-1α (not HIF-2α) levels, as well as the expression levels of hypoxia-responsive genes (LDHA, CA9, GLUT-1, and VEGF), in hypoxic colon cancer cells. These findings indicated that MKP-3, induced by HIF-1α in hypoxia, negatively regulates HIF-1α protein levels and hypoxia-responsive genes. However, we also found that long-term hypoxia (>12 h) induced proteasomal degradation of MKP-3 in a lactic acid-dependent manner. Taken together, MKP-3 expression is modulated by the hypoxic conditions prevailing in colon cancer, and plays a role in cellular adaptation to tumor hypoxia and tumor progression. Thus, MKP-3 may serve as a potential therapeutic target for colon cancer treatment.