• Applied Biological Chemistry
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• 제49권4호
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• pp.343-348
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• 2006

본 연구에서는 매생이 열수추출물의 항암 및 면역 활성을 알아보기 위하여 적정 추출 및 정제조건, 당 조성, 암세포독성, sarcoma-180 성장저지 효과, 백혈구수 변화, 보체계 활성, 장관 면역 활성, 경구독성 등을 검토하였다. 매생이 보체계 활성물질은 $100^{\circ}C$의 물로 3시간 동안 추출하여 4배량의 주정으로 24시간 침전시킨 다음 투석 및 한외여과하여 분자량 300kDa 이상의 고분자 물질을 분리정제 하였으며 당 조성은 xylose 19.01%, fucose 15.29%, mannose 4.23%, galactose 7.92%로 나타났다. In vitro에서 매생이 보체계 활성물질의 인체 암세포에 대한 독성은 고농도($10-30{\mu}g/ml$)에서만 경미하게 나타났으며, in vivo시험에서는 매생이 추출물의 투여로 마우스 고형암의 성장이 대조군에 비하여 40.13-59.42%가 저해되었다. 그러나 수명 연장율은 실험군간에 통계적 유의차가 없었다. 정제한 매생이 추출물을 마우스의 복강에 투여한 결과, 혈중 백혈구수가 대조군에 비하여 20mg/kg 투여군 39%, 50mg/kg 투여군 70%, 100mg/kg 투여군 83%가 증가하는 것으로 나타났으며, 면역과 관련이 있는 간장, 비장, 흉선의 중량이 증가하였다. 매생이 추출물을 마우스에 경구투여하고 분변으로 배출되는 IgA 항체의 양을 측정한 결과, 대조군이 $2,092{\pm}123.0{\mu}g/mg$인 데에 비하여 매생이 추출물 투여군은 $2,454{\pm}113.8-2,670{\pm}133.1{\mu}g/mg$로 높게 나타났다. 매생이로부터 추출한 면역증강물질은 마우스에 대한 급성독성을 측정한 결과, 체중 1kg당 2,000mg 투여 시 까지도 독성을 나타내지 않아 인체에도 무해할 것으로 사료되었다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권16호
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• pp.6991-6996
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• 2015

In the past decade, the incidence and mortality rates of cholangiocarcinoma (CCA) have been increasing worldwide. The relatively low responsiveness of CCA to conventional chemotherapy leads to poor overall survival. Recently, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL or Apo2L) has emerged as the most promising anti-cancer therapeutic agent since it is able to selectively induce apoptosis of tumor cells but not normal cells. In this study, we aimed to investigate the therapeutic effect of TRAIL in CCA cell lines (M213, M214 and KKU100) compared with the immortal biliary cell line, MMNK1, either alone or in combination with a subtoxic dose of 5-fluorouracil (5-FU). We found that recombinant human TRAIL (rhTRAIL) was a potential agent which significantly inhibited cell proliferation and mediated caspase activities (caspases 8, 9 and 3/7) and apoptosis of CCA cells. The combined treatment of rhTRAIL and 5-FU effectively enhanced inhibition of CCA cell growth with a smaller effect on MMNK1. Our finding suggests TRAIL to be a novel anti-cancer therapeutic agent and advantage of its combination with a conventional chemotherapeutic drug for effective treatment of CCA.

• Asian Pacific Journal of Cancer Prevention
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• 제13권9호
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• pp.4793-4799
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• 2012

Hypoxia is commonly featured during glioma growth and plays an important role in the processes underlying tumor progression to increasing malignancy. Here we compared the gene expression profiles of rat C6 malignant glioma cells under normoxic and hypoxic conditions by cDNA microarray analysis. Compared to normoxic culture conditions, 180 genes were up-regulated and 67 genes were down-regulated under hypoxia mimicked by $CoCl_2$ treatment. These differentially expressed genes were involved in mutiple biological functions including development and differentiation, immune and stress response, metabolic process, and cellular physiological response. It was found that hypoxia significantly regulated genes involved in regulation of glycolysis and cell differentiation, as well as intracellular signalling pathways related to Notch and focal adhesion, which are closely associated with tumor malignant growth. These results should facilitate investigation of the role of hypoxia in the glioma development and exploration of therapeutic targets for inhibition of glioma growth.

• BMB Reports
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• 제48권8호
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• pp.431-437
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• 2015

Notch signaling plays a pivotal role in cell fate determination, cellular development, cellular self-renewal, tumor progression, and has been linked to developmental disorders and carcinogenesis. Notch1 is activated through interactions with the ligands of neighboring cells, and acts as a transcriptional activator in the nucleus. The Notch1 intracellular domain (Notch1-IC) regulates the expression of target genes related to tumor development and progression. The Notch1 protein undergoes modification after translation by posttranslational modification enzymes. Phosphorylation modification is critical for enzymatic activation, complex formation, degradation, and subcellular localization. According to the nuclear cycle, Notch1-IC is degraded by E3 ligase, FBW7 in the nucleus via phosphorylation-dependent degradation. Here, we summarize the Notch signaling pathway, and resolve to understand the role of phosphorylation in the regulation of Notch signaling as well as to understand its relation to cancer. [BMB Reports 2015; 48(8): 431-437]

• 대한핵의학회지
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• 제38권2호
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• pp.171-174
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• 2004

Angiogenesis, the formation of new capillaries from existing vessels, increases oxygenation and nutrient supply to ischemic tissue and allows tumor growth and metastasis. As such, angiogenesis targeting provides a novel approach for cancer treatment with easier drug delivery and less drug resistance. Therapeutic anti-angiogenesis has shown impressive effects in animal tumor models and are now entering clinical trials. However, the successful clinical introduction of this new therapeutic approach requires diagnostic tools that can reliably measure angiogenesis in a noninvasive and repetitive manner. Molecular imaging is emerging as an exciting new discipline that deals with imaging of disease on a cellular or genetic level. Angiogenesis imaging is an important area for molecular imaging research, and the use of radiotracers offers a particularly promising technique for its development. While current perfusion and metabolism radiotracers can provide useful information related to tissue vascularity, recent endeavors are focused on the development of novel radioprobes that specifically and directly target angiogenic vessels. Presently available proges include RGD sequence containing peptides that target ${\alpha}_v\;{\beta}_3$ integrin, endothelial growth factors such as VEGF or FGF, metalloptoteinase inhibitors, and specific antiangiogenic drugs. It is now clear that nuclear medicine techniques have a remarkable potential for angiogenesis imaging, and efforts are currently continuing to develop new radioprobes with superior imaging properties. With future identification of novel targets, design of better probes, and improvements in instrumentation, radiotracer angiogenesis imaging promises to play an increasingly important role in the diagnostic evaluation and treatment of cancer and other angiogenesis related diseases.

• Asian Pacific Journal of Cancer Prevention
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• 제16권3호
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• pp.1235-1239
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• 2015

Background: Fragile histidine triad (FHIT) gene is a tumor suppressor gene which involved in breast cancer pathogenesis. Epigenetics alterations in FHIT contributes to tumorigenesis of breast cancer. Objective: Our objective was to study FHIT promoter region hypermethylation in Egyptian breast cancer patients and its association with clinicopathological features. Materials and Methods: Methylation-specific polymerase chain reaction was performed to study the hypermethylation of FHIT promoter region in 20 benign breast tissues and 30 breast cancer tissues. Results: The frequency of hypermethylation of FHIT promoter region was significantly increased in breast cancer patients compared to bengin breast disease patients. The Odd's ratio (95%CI) of development of breast cancer in individuals with FHIT promoter hypermethylation (MM) was 11.0 (1.22-250.8). There were also significant associations between FHIT promoter hypermethylation and estrogen, progesterone receptors negativity, tumor stage and nodal involvment in breast cancer pateints. Conclusions: Our results support an association between FHIT promotor hypermethylation and development of breast cancer in Egyptian breast cancer patients. FHIT promoter hypermethylation is associated with some poor prognostic features of breast cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제15권14호
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• pp.5909-5916
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• 2014

Human papillomavirus infection (HPV) and HPV related immune perturbation play important roles in the development of cervical cancer. Since mature dendritic cells (DCs) are potent antigen-presenting cells (APC), they could be primed by HPV antigens against cervical cancers. In this study we were able to generate, maintain and characterize, both phenotypically and functionally, patient specific dendritic cells in vitro. A randomized Phase I trial with three arms - saline control (arm I), unprimed mature DC (arm II) and autologous tumor lysate primed mature DC (arm III) and fourteen patients was conducted. According to WHO criteria, grade 0 or grade one toxicity was observed in three patients. One patient who received tumor lysate primed dendritic cells and later cis-platin chemotherapy showed a complete clinical response of her large metastatic disease and remained disease free for more than 72 months. Our findings indicate that DC vaccines hold promise as adjuvant sfor cervical cancer treatment and further studies to improve their efficacy need to be conducted.

• 한국발생생물학회지:발생과생식
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• 제18권1호
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• pp.65-71
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• 2014

Cell cycle process is regulated by a number of protein kinases and among them, serine/threonine kinases carry phosphate group from ATP to substrates. The most important three kinase families are Cyclin-dependent kinase (Cdk), Polo-like kinase (Plk), and Aurora kinase. Polo-like kinase family consists of 5 members (Plk1-Plk5) and they are involved in multiple functions in eukaryotic cell division. It regulates a variety of aspects such as, centrosome maturation, checkpoint recovery, spindle assembly, cytokinesis, apoptosis and many other features. Recently, it has been reported that Plks are related to tumor development and over-expressed in many kinds of tumor cells. When injected the anti-Plk antibody into human cells, the cells show aneuploidy, and if inhibit Plks, most of the mitotic cell division does not proceed properly. For that reasons, many inhibitors of Plk have been recently emerged as new target for remedy of the cancer therapeutic research. In this paper, we reviewed briefly the characteristics of Plk families and how Plks work in regulating cell cycles and cancer formation, and the possibilities of Plks as target for cancer therapy.

• Radiation Oncology Journal
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• 제36권4호
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• pp.265-275
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• 2018

Cancer is a complex multifaceted illness that affects different patients in discrete ways. For a number of cancers the use of chemotherapy has become standard practice. Chemotherapy is a use of cytostatic drugs to cure cancer. Cytostatic agents not only affect cancer cells but also affect the growth of normal cells; leading to side effects. Because of this, radiotherapy gained importance in treating cancer. Slaughtering of cancerous cells by radiotherapy depends on the radiosensitivity of the tumor cells. Efforts to improve the therapeutic ratio have resulted in the development of compounds that increase the radiosensitivity of tumor cells or protect the normal cells from the effects of radiation. Amifostine is the only chemical radioprotector approved by the US Food and Drug Administration (FDA), but due to its side effect and toxicity, use of this compound was also failed. Hence the use of herbal radioprotectors bearing pharmacological properties is concentrated due to their low toxicity and efficacy. Notably, in silico methods can expedite drug discovery process, to lessen the compounds with unfavorable pharmacological properties at an early stage of drug development. Hence a detailed perspective of these properties, in accordance with their prediction and measurement, are pivotal for a successful identification of radioprotectors by drug discovery process.

• 생명과학회지
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• 제33권11호
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• pp.887-896
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• 2023

염증반응(inflammation)은 발병, 진행, 악성 전이를 포함한 암의 진행과정(tumorigenesis)에서 중요한 역할을 수행하기 때문에 암 치료를 위한 전략으로 고려되고 있다. 감태(Ecklonia cava) 열수추출물(AEC)의 항암활성 동안 나타나는 항염증 반응을 연구하기 위하여, 비만세포(mast cells)의 분포, inducible nitric oxide synthase (iNOS)단백질, cyclooxygenase-2 (COX-2)단백질, nuclear factor (NF)-κB단백질, inflammasome 구성 단백질, inflammatory cytokines 발현의 변화는 AEC를 5주간 경구투여한 CT26 대장암을 내포하는 BALB/cKorl syngeneic 마우스에서 분석하였다. AEC를 처리한 후, 고형암의 무게와 조직 절편의 괴사 부위가 vehicle처리그룹에 비하여 감소하였다. 비만세포의 수는 vehicle처리그룹에 비하여 AEC처리그룹에서 증가했지만 COX-2와 iNOS의 발현은 AEC처리그룹에서 감소하였다. 또한, NF-κB, NLR family pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC)과 Caspase-1 (Cas-1)단백질의 발현도 유사한 감소가 관찰되었다. 더불어, tumor necrosis factor-α (TNF-α), interleukin-1α (IL-1α)와 interleukin-6 (IL-6)의 mRNA 발현이 vehicle처리그룹에 비하여 AEC처리그룹에서 감소하였다. 이러한 결과는 AEC가 CT26 고형암을 내포하는 BALB/cKorl syngeneic 마우스에서 항암활성은 염증반응과 밀접한 관련이 있음을 제시하고 있다.