Natural killer (NK) cells have cytotoxic effects on tumor cells and viral pathogens. NK cell-derived exosomes (NK-exosomes) also express typical NK cell markers and cytotoxic molecules, therefore, exert anti-tumor and immune homeostatic activities. In this study, canine NK-exosomes separated from cytotoxic NK cell supernatant carried specific markers such as CD81, Alix, and Perforin 1. We examined the anti-tumor effects of NK-exosomes in an experimental murine model using the canine mammary carcinoma cells, REM134. REM134 cells were xenografted of mammary fat pad of mice. CD133, Bmi-1, MMP-3, IL-6, TNF-α, and PCNA are useful as a molecular marker for tumorigenesis and metastasis. The treatment of canine NK-exosomes inhibited tumor growth and significantly (p<0.01) downregulated the expression of Bmi-1, MMP-3, IL-6, TNF-α, and PCNA in REM134-treated mice. Also, the expression of CD133, potent cancer stem cell marker, was significantly downregulated in the canine NK-exosomes-treated mice compared with that of the tumor group. Collectively, these results suggested that canine NK-exosomes has a potential capacity for regulation of cancer progression and metastasis against canine mammary carcinoma.

자기공명영상은 고해상도의 연부조직에 대한 영상정보를 제공하며, 뇌종양 등 연부조직 진단에 활용된다. 본 연구는 합성곱신경망 인공지능을 통해 뇌종양 자기공명영상 분류성능을 확인해 보고자 한다. 4개 종류로 구분된 3264 장의 MRI 데이터 세트(data set)를 이용하였으며, 인공지능 학습을 위해 훈련용 데이터와 시험용 데이터를 9 : 1, 훈련용 데이터의 10%를 검증용 데이터로 구분하였다. 합성곱신경망은 기본 CNN과 VGG16으로 구성하였으며, 학습 평가는 정확도와 손실율로 확인하였으며, 생성된 모델을 통해 분류성능 정확도를 확인하였다. 실험 결과 과적합은 없었으며, 분류성능은 기본 CNN과 VGG16 각각 67%와 80%의 분류성능을 보였다. 도출된 뇌종양 자기공명영상 분류 결과를 통해 자기공명영상과 인공지능 접목에 관한 기초 자료로 사용될 수 있을 것이라 사료된다.

Canine mammary tumors account for ~30% of all tumors in the female dogs and approximately 50% of the tumors are malignant. Exosomes have been the focus of great interest, as they appear to be involved in numerous important cellular processes. In this study, we examined the anti-tumor effects of canine mesenchymal stem cells-derived exosomes (MSC-exosomes) in an experimental murine mammary tumor model using canine mammary carcinoma cells, REM134. The MSC-exosomes were injected tumor site and tail vein of REM134 xenografted mice. We found that tumor size of the MSC-exosomes-treated group decreased compared to those of the only tumor group in REM134-driven tumorigenic mouse model. In addition, the MSC-exosomes-treated tumor group showed meaningfully reduced expression levels of the MMP-3, IL-1β, IL-6, and TNF-α compared to those in the tumor group. Specifically, we confirmed that the expression level of the CD133, potent cancer stem cell (CSC) markers, decreased in the MSC-exosomes-treated tumor group compared to the tumor group. This study suggests that the MSC-exosomes exhibited anti-tumor effects through downregulating CSC-related markers in the canine mammary tumor murine model. Further study is needed in the future, and we are conducting research on the detailed anti-tumor mechanism of the MSC-exosomes.

Human natural killer (NK) cells are major players in innate immune response. The functions of these cells as a scavenger of cancer cells are enhanced by cytokines such as interleukin-2 (IL-2), which play an important role in immune response in both tumors and virally infected cells. Liver cancer has a high incidence rate and is a major cause of death in Korea. We provide evidence that human NK cells inhibit tumor growth of the hepatocellular carcinoma cell line SNU-354. NK cells were cultured with human IL-2 for 14 days, yielding an enriched NK cell population containing 35% CD8+ cells, 6% CD4+ cells, and 51% CD16+ /CD56+ cells. Intravenous injection of NK cells at doses from 2.5 to 10 million cells/mouse was administered once per week in a nude mouse model that retains human liver tumor induced by implantation of SNU-354 cells. The results showed that human NK cells were recruited within tumor tissue and inhibited SNU-354 tumor growth by 32%, 58%, and 65%. The current data suggest the potential for use of NK cell-based immunotherapy for treatment of human liver cancer.

Photodynamic therapy (PDT) is a clinically approved and ra pidly developing cancer treatment regimen, It is a minimally invasive procedure that requires the administration of a photosens iti zer foll owed by the illumination of the tumor with Iigh t of an appropriate wavelength, In the presence of molecular oxygen, cytotoxic intermedi a ries a re produced‘ thus damaging cellular structures containing the photosensitizer , In the present study. we exa mined the effectiveness of newly d evelped chlorin e6- induced PDT on malignant animal tumor model of 3prague-Da wley (3D) ra t Three-week-old male 3D rats we re inocula ted s ,c, on the right f1 ank with our previously esta blished k- ras-trans formed RK3E cell line (RK3E- ras. tota l, 5xl07 cell s) , The experiments were carried out 1 week after inoculation of tumor cell s , by which time the tumors had r eached about 0,7 mm to 1.0 cm in diameter, L3-chlorin e6 (L8 Pharm Co" Gwa ngju, Korea) was admin istrated intravenous ly by the tail vein of 3D rat at a dosage of 10 mg/kg after inhalation a nesthesia of ether, Twenty- four hours a fter L8-chlorin e6 ad ministration, PDT was pe rfol‘med using a laser diode (Geumgwang Co ‘ Ltd‘’ Daejeon, Korea) a t a light dose of 100 J /cm2 and wavelength of 664 nm, A..nimals were monitered daily and tumor volume was measured by calipel The tumor t reated with PDT using Ce6 had significant reduction in tumor s ize examined by gross tumor volume , softex x- ray image, molecular imaging a nalysis, respectively, PCNA immunostaining and TUNEL assay revealed that the treat ed tu mor caused signifi cant inlübition of tumor formati on with decreased tumor cell proliferation a nd increased a poptosis , Our dat a showed Ce6-induced PDT effecti vely arrested the tumor growth by inhibi t ing cell proliferation a nd inducing a poptosis , These findings provide the potential value of Ce6- induced PDT as an a lternative candidate for a nt i- tumor therapy, Furthel bi ochemical and cellular studies will reveal the precise molecul ar mecha ni sm of cell death induced by PDT

Indirubin is the ac ti ve ingredi ent of a traditional Chinese herbal medicine, Danggui Longhui Wan, used for t he t reatment of chronic myelocytic leukemia Here, we report that novel indirubin ,- 11‘ ivative‘ 5’ - nitro-indirubinoxime (5’ NIO) , has potent anti- proliferative activity on va rious human cancel‘ cells and oncogenic RK3E- ras rat kidney cells with ha lf- inhibi tory concentrati ons (1C50) ra nging from 1- 12 M, Treatment with indirubin derivative induced the activation 01' caspase 7 rollowed by apoptos is in RK3E- ras cells. lndirubin derivative showed strong anti-tumor activity in rat solid and oral tUll10r models , Direct inj ection of indirubin deri vative every other day for 10 days induced signifi cant inhi bition of tumor growth in Sprague-Dawley rats bearing RK3E- ras-induced tumors Histologically. t reatment with indiru bin de ri vative caused s ignifi cant inhi bit ion of tumor formation with increased apoptosis and decreased tumor cell prolife ration, These f indings provide the potent ial va lue of indirubin deri vative a s a novel candidate for ant i-tumor agents

lndil‘ ubin is the active ingredient of Danggui Longhui Wan‘ a mixture of herbal medici l1e t hat is used to treat chronic myelocytic leukemia in tradi t ional Chinese medicine‘ He re, we show that new indirubin deri vatives 5' -ni tro-indirubinoxime, 5' -f1 uoro-indiru binoxime and 5’ -tri rnethylacetamino-i nd i 1'1.1 bi noxi me‘ have potent a n ti- proliferative activity on various human cancer cells and oncogenic RK3E-ras rat kidney cells with lC50 con centration ranging from 1-25 μ M, When the RK3E-ras cells were treated with indirubin derivatives for 24 h, the activity of caspase-3 and caspasc-7 was induccd followed by apoptosis , 011 the other hand, the activity of SAPK/JNK was inhi bited over the same period , lndirubin deri vatives a lso s howed strong ant i-tumor activity in rat s이 id and oral tumor models The inhibition of tlUl10r g:rowth was observed in animals beaJ‘ing RK3E-ras-induced turnor given subcutaneous dose of 100 mg/kg every other day for 10 days, Histologically, μeatment of indirubin derivatives caused significant inhibition of tumor formation associated wi th increased apoptosis and decreased proliferation of tumor cell s , These findings provide the potential value of indirubin derivatives as a novel candi date fOl 없l tJ -cancer agents ,