• Advances in Traditional Medicine
• /
• 제1권2호
• /
• pp.36-44
• /
• 2000

The polysaccharide fractions were isolated and purified from Phellodendron chinese SCHNEID, and antitumor activities using the melanoma B-16-derived metastatic tumors were examined at dosages of 2, 5 and 10 mg/100 g. F-7 and F-8 showed the highest tumor metastatic inhibitory activities (inhibition ratio 60 and 80% in 2 mg/100 g), and in dose of 5 mg/100 g, the inhibitory ratios were 85 and 70%, respectively. Furthermore, 10 mg/100 g of intraperitoneal (i.p.) injection gave 90 and 95% of inhibition. When the effects of polysaccharides on hypersensitivity were examined, the inhibitory activities were not markedly observed in oral administration, indicating that the polysaccharides are directly acting to immune system. Also, the polysaccharides increased the number of circulating blood leukocytes and total peritoneal exudate cells. Although implantation of tumor cells greatly decreased the productivity of antibody (antibody-mediated) and T lymphocyte reactivity (delayed-type) as 6.3 from 9.3 and 5.9 from 7.7, represented by the increase of footpad thickness, respectively. the polysaccharides elevated the reactivity of T lymphocyte in tumor-bearing mice, which were rapidly recovered by discontinuance of sample treatments. Especially, F-2, F-5, F-7 and F-8 remarkably recovered the decreased sensitivity. These results clearly indicated that the i.p. injection is much effective to suppress tumor growth than oral administration.

• BMB Reports
• /
• 제54권9호
• /
• pp.470-475
• /
• 2021

Low-dose metronomic chemotherapy has been introduced as a less toxic and effective strategy to inhibit tumor angiogenesis, but its anti-angiogenic mechanism on endothelial progenitor cells (EPCs) has not been fully elucidated. Here, we investigated the functional role of regulated in development and DNA damage response 1 (REDD1), an endogenous inhibitor of mTORC1, in low-dose doxorubicin (DOX)-mediated dysregulation of EPC functions. DOX treatment induced REDD1 expression in bone marrow mononuclear cells (BMMNCs) and subsequently reduced mTORC1-dependent translation of endothelial growth factor (VEGF) receptor (Vegfr)-2 mRNA, but not that of the mRNA transcripts for Vegfr-1, epidermal growth factor receptor, and insulin-like growth factor-1 receptor. This selective event was a risk factor for the inhibition of BMMNC differentiation into EPCs and their angiogenic responses to VEGF-A, but was not observed in Redd1-deficient BMMNCs. Low-dose metronomic DOX treatment reduced the mobilization of circulating EPCs in B16 melanoma-bearing wild-type but not Redd1-deficient mice. However, REDD1 overexpression inhibited the differentiation and mobilization of EPCs in both wild-type and Redd1-deficient mice. These data suggest that REDD1 is crucial for metronomic DOX-mediated EPC dysfunction through the translational repression of Vegfr-2 transcript, providing REDD1 as a potential therapeutic target for the inhibition of tumor angiogenesis and tumor progression.

• BMB Reports
• /
• 제57권6호
• /
• pp.305-310
• /
• 2024

T-plastin (PLST), a member of the actin-bundling protein family, plays crucial roles in cytoskeletal structure, regulation, and motility. Studies have shown that the plastin family is associated with the malignant characteristics of cancer, such as circulating tumor cells and metastasis, by inducing epithelial-mesenchymal transition (EMT) in various cancer cells. However, the role of PLST in the EMT of human lung cancer cells remains unclear. In this study, we observed that PLST overexpression enhanced cell migratory and invasive abilities, whereas its downregulation resulted in their suppression. Moreover, PLST expression levels were associated with the expression patterns of EMT markers, including E-cadherin, vimentin, and Slug. Furthermore, the phosphorylation levels of focal adhesion kinase (FAK) and AKT serine/threonine kinase (AKT) were dependent on PLST expression levels. These findings indicate that PLST induces the migration and invasion of human lung cancer cells by promoting Slug-mediated EMT via the FAK/AKT signaling pathway.

• Asian Pacific Journal of Cancer Prevention
• /
• 제16권17호
• /
• pp.7561-7566
• /
• 2015

Ziziphus jujuba (ZJ) fruit is rich in bioactive functional components such as polysaccharides, triterpenoid acid, flavonoids and oleamide. It has been commonly used in the treatment of various diseases including diabetes, digestive disorders, diarrhea, skin infections, liver and urinary diseases. However, its dietary effect on chemoprevention of colon cancer has never been studied. The present study was to evaluate the protective effects of dietary ZJ on colitis-associated colon carcinogenesis in azoxymethane (AOM)-dextran sodium sulphate (DSS)-treated mice. AOM was injected (10 mg/kg b.wt., i.p.) and three cycles of 2% DSS in drinking water for 7 days with 14 days of normal drinking water in-between was administered to induce colitis-associated colon cancer. ZJ fruit was supplemented in feed as 5 and 10%. Dietary ZJ significantly attenuated aberrant crypt foci (ACF) formation thereby decreasing the progression of hyperplasia to dysplasia. In addition, it significantly reduced circulating white blood cells, lymphocytes, neutrophils, monocytes, eosinophils, basophils and platelets compared to colon cancer mice. We conclude that ZJ supplementation delayed the progression of colon cancer from hyperplasia to dysplasia and ultimately adenocarcinoma and cancer. In addition, it decreased circulating tumor-related leucocytes, main regulators of cancer inflammation. Therefore, dietary consumption of ZJ fruit attenuated the formation of ACF and delayed the progression of colon cancer.

• Asian Pacific Journal of Cancer Prevention
• /
• 제17권7호
• /
• pp.3601-3604
• /
• 2016

Background: The monocyte chemoattractant protein-1 (MCP-1/CCL2) is a potent chemoattractant for natural killer cells, monocytes, and memory T lymphocytes. However, any role in the genesis of salivary gland tumors (SGT) is unknown. To assess the diagnostic relevance of chemokines in SGT, MCP-1 levels in the serum of patients were investigated in association with tumor progression and clinical aggressiveness. Materials and Methods: Using an ELISA kit, we assessed and compared the circulating levels of MCP-1 in blood serum of 70 SGT patients with 44 healthy control samples. Results: The results of this study showed that the concentration of MCP-1 was significantly lower in patients with benign ($463.8{\pm}158.5pg/ml$, P=0.033) and malignant ($454.8{\pm}190.4pg/ml$, P=0.007) SGT than in healthy subjects ($645.7{\pm}338.9$). No significant difference in mean serum levels of MCP-1 was observed between the benign and malignant group (p=0.9). While MCP-1 levels were lower in patients with an advanced clinical stage, advanced tumor size, higher tumor grade, or lymph node involvement, but the mean MCP-1 level between groups showed no statistically significant difference (p>0.05). Conclusions: MCP-1 levels in the serum of patients with SGT were decreased, indicating that this might a good marker for discriminating patients with SGT from healthy people. However, no clear-cut relationship was detected between MCP-1 levels and clinicopathologic factors, and MCP-1 is not a good marker for evaluating tumor dissemination.

• Biomolecules & Therapeutics
• /
• 제20권2호
• /
• pp.158-164
• /
• 2012

Inhibiting the bioactivities of circulating endothelial progenitor cells (EPCs) results in significant inhibition of neovessel formation during tumor angiogenesis. To investigate the potential effect of phloroglucinol as an EPC inhibitor, we performed several in vitro functional assays using $CD34^+$ cells isolated from human umbilical cord blood (HUCB). Although a high treatment dose of phloroglucinol did not show any cell toxicity, it specifically induced the cell death of EPCs under serum free conditions through apoptosis. In the EPC colony-forming assay (EPC-CFA), we observed a significant decreased in the small EPC-CFUs for the phloroglucinol group, implying that phloroglucinol inhibited the early stage of EPC commitment. In addition, in the in vitro expansion assay using $CD34^+$ cells, treatment with phloroglucinol was shown to inhibit endothelial lineage commitment, as demonstrated by the decrease in endothelial surface markers of EPCs including $CD34^+$, $CD34^+/CD133^+$, $CD34^+/CD31^+$ and $CD34^+/CXCR4^+$. This is the first report to demonstrate that phloroglucinol can inhibit the functional bioactivities of EPCs, indicating that phloroglucinol may be used as an EPC inhibitor in the development of biosafe anti-tumor drugs that target tumor angiogenesis.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권6호
• /
• pp.2613-2618
• /
• 2014

Aims: Dysfunction of the host immune system in cancer patients can be due to a number of factors, including lymphocyte apoptosis. Several studies showed that $Foxp3^+T$ cells take part in inducing this process by expressing FasL in tumor patients. However, the relationship between apoptosis, $CD8^+T$ cells and $Foxp3^+T$ cells in HCC patients is still unclear. The present study was designed to investigate the correlation between apoptosis levels and Fas/FasL expression in $CD8^+T$ lymphocytes and $Foxp3^+T$ cells in patients with HCC. Methods: $CD8^+T$ cells and $CD3^+Foxp3^+T$ cells were tested from peripheral blood of HCC patients and normal controls and subjected to multicolor flow cytometry. The expression of an apoptosis marker (annexin V) and the death receptor Fas in $CD8^+T$ cells and FasL in $CD3^+Foxp3^+T$ cells were evaluated. Serum TGF-${\beta}1$ levels in patients with HCC were measured by enzyme-linked immunosorbent assay. The relationship between apoptosis and Fas expression, as well as FasL expression in $CD3^+Foxp3^+T$ cells was then evaluated. Results: The frequency of $CD8^+T$ cells binding annexin V and Fas expression in $CD8^+T$ cells, were all higher in HCC patients than normal controls and the proportion of apoptotic $CD8^+T$ cells correlated with their Fas expression. Serum TGF-${\beta}1$ levels correlated inversely with $CD3^+Foxp3^+T$ cells. Conclusions: Fas/FasL interactions might lead to excessive turnover of $CD8^+T$ cells and reduce anti-tumor immune responses in patients with HCC. Further investigations of apoptosis induction in $Fas^+CD8^+T$ cells in vitro are required.

• Radiation Oncology Journal
• /
• 제34권4호
• /
• pp.305-312
• /
• 2016

Purpose: The objective of this prospective study was to evaluate the relationship between the circulating lymphocyte subpopulation counts during preoperative chemoradiotherapy (CRT) and tumor response in locally advanced rectal cancer. Materials and Methods: From August 2015 to June 2016, 10 patients treated with preoperative CRT followed by surgery were enrolled. Patients received conventional fractionated radiotherapy (50.4 Gy) with fluorouracil-based chemotherapy. Surgical resection was performed at 4 to 8 weeks after the completion of preoperative CRT. The absolute blood lymphocyte subpopulation was obtained prior to and after 4 weeks of CRT. We analyzed the association between a tumor response and change in the lymphocyte subpopulation during CRT. Results: Among 10 patients, 2 (20%) had evidence of pathologic complete response. In 8 patients with clinically node positive, 4 (50%) had nodal tumor response. All lymphocyte subpopulation counts at 4 weeks after CRT were significantly lower than those observed during pretreatment (p < 0.01). A high decrease in natural killer (NK) cell, count during CRT (baseline cell count - cell count at 4 weeks) was associated with node down staging (p = 0.034). Conclusion: Our results suggest that the change of lymphocyte subset to preoperative CRT may be a predictive factor for tumor response in rectal cancer.

• Radiation Oncology Journal
• /
• 제24권1호
• /
• pp.51-57
• /
• 2006

목적: 마우스 대퇴부에 심은 종양에 43 도의 열을 가한 뒤 수지상 세포를 종양내에 주입하여 국소 및 원격 항종양 효과를 관찰하였다. 대상 및 방법 : 마우스 우측 대퇴부에 MCA-102 fibrosarcoma를 피하로 주입하여 종양을 만들었고, 7일째는 반대편 대퇴부에도 주입하여 종양을 만들었다. 종양 세포를 접종한 지 7 일째 약 6 mm 가 된 종양에 43도의 열을 30 분간 가하고 골수 유래 미성숙 동종 수지상 세포를 종양내에 직접 주입하고, 이를 1 주 간격으로 2회 더 시행했다. $3{\sim}4$일 간격으로 양측 대퇴부의 종양의 크기를 측정하여 국소 및 원격 항종양 효과를 평가하였다. 또한 종양 특이적 면역 반응을 평가하기 위해 마우스의 비장 세포를 분리하여 cytotoxicity를 측정하였다. 결과 : 온열치료는 apoptosis를 유도하고 heat shock protein 발현을 증가시켰고, 6시간 경에 최고치를 보였다. 치료한 국소 종양에 있어서 온열 요법 단독만으로 종양의 성장을 억제했지만, 온열 요법 후 수지상세포를 주입했을 때는 그 성장 억제 효과는 온열요법 단독의 효과보다 높게 나왔다. (p<0.05). 한편 치료하지 않은 원 격종양에 있어서도 온열 요법 단독으로 원격 종앙의 성장 억제 효과를 보였으며 온열 요법 후 수지상 세포 를 주입했을 때도 원격 종양의 성장 억제 효과가 온열 요법 단독보다 높았으나, 그 억제 정도가 온열 요법 단독과 비교하여 통계적인 차이는 없었다 (p>0.05). Cytotoxicity 검사에서 온열요법과 수지상 세포 복합 치료 군에서 가장 높은 세포살해능을 보였고 (p<0.05), 이러한 면역 반응은 종양 특이적이었다. 결론 : 온열요법으로 apoptosis 와 heat shock protein 을 유도하고 종양내에 동종의 미성숙 수지상 세포를 주입하여 국소 및 원격 종양에 높은 항종양 효과를 유도할 수 있었다. 이러한 새로운 치료법은 암 치료에 응용 될 수 있을 것이다.

• 전자통신동향분석
• /
• 제29권5호
• /
• pp.105-113
• /
• 2014

주치의에게는 암환자의 암 전이 여부가 초미의 관심사다. 암환자의 10명 중 9명이 전이암으로 사망하기 때문이다. 암의 전이 초기에 그 전이 여부를 방사선 진단법으로 가능하지 않다. 혈액을 채취하여 암의 전이 유무를 진단 하는 기술이 개발되고 있다. 이 혈중 암세포는 혈구세포 10억개당 1~100개 정도의 극히 미량이 존재하여 암세포 분리기술이 특별히 잘 개발되어야 한다. 최근 마이크로바이오칩 형태의 분리기술이 큰 기술적 진화를 보이고 있어 본고에 소개하고자 한다. 이 기술은 한 가지 큰 의미를 갖는다. 그것은 암환자의 암 전이 모니터링에 필요한 도구가 될 수 있기 때문이다. 전이암세포 검출 키트로 전이암세포를 계수 하여 환자에게 투약한 항암제가 적합한지에 대한 답을 의사는 얻을 수 있다. 전이암세포 진단용 마이크로바이오칩 기술이 기존의 영상진단법만큼 중요한 임상 수단이 될 것으로 전망된다.