• Maxillofacial Plastic and Reconstructive Surgery
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• 제35권1호
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• pp.1-12
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• 2013

Purpose: Vascular endothelial growth factor (VEGF)-C and its tyrosine kinase receptor, VEGF receptor (VEGFR)-3 are recently known to have lymphangiogenic activities in various tumor types. In this study, we determined whether the expression of lymphangiogenic factors correlate with nodal metastasis or survival in a nude mouse model of oral squamous cell carcinoma (OSCC). Methods: Three OSCC cells (KB, SCC4, SCC9) were xenografted into the right mandibular gland of athymic nude mice. The mice were followed for tumor development and growth, and the mice were sacrificed when they had lost more than 20% of their initial body weight, or the diameter of the induced tumor exceeds 20 mm. After necropsy, the murine tumors were examined histologically and radiologically (micro-positron emission tomography computed tomography) for regional or distant metastasis. We performed immunohistochemical assays with anti-VEGF-C, VEGFR-3, CD105, and D2-40 antibodies. Immunofluorescence double staining for LYVE-1/CD31 was also performed. To quantify the VEGF-C and VEGFR-3 level in the cancer tissue, Western blotting was performed. Finally, we determined the correlation between the degree of expression of VEGF-C/VEGFR-3 and the mean survival time. Results: OSCC tumor cells into the mandibular gland of the nude mice successfully resulted in the formation of recapitulating orthotopic tumor. Tumor cells of the induced tumor did not express VEGF-C. VEGF-C/VEGFR-3 expression was mainly distributed in the endothelial cells of the stromal area. There were no correlation between the degree of expression of VEGF-C/VEGFR-3 and the mean survival time of mice injected with different OSCC cell lines. Conclusion: An recapitulating orthotopic model of OSCC in nude mice was established, which copies the cervical nodal metastasis of human OSCC. Overexpression of lymphangiogenic factors seems to have no effect on survival of hosts in this in vivo experiment.

• 응용통계연구
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• 제23권5호
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• pp.871-882
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• 2010

동물종양 실험에서는 종양발생 시간이 직접 관찰되지 않고 단지 자연사로 인한 관찰 시점이나 강제적으로 희생시킨 시점 이전에 종양이 발생했는지 유무만을 알 수 있다. 이와 같은 형태의 결측을 가진 자료를 분석하기 위해 3단계(건강$\rightarrow$종양발생$\rightarrow$사망) 모형이 널리 사용되고 있다. 본 논문에서는 자연사로 인한 사망 시간이 종속적인 중도절단으로 작용하여 사망 시간과 종양발생 시간이 종속될 때, 이를 모형에 반영하기 위해 감마 프레일티 효과를 도입하였다. 모수 추정은 종양발생 시간과 프레일티 효과의 결측을 다루기 위해 EM 알고리즘 방법을 사용하였다. 제안한 추정량의 소표본 성질을 살펴보기 위해 제안한 방법을 Lindsey와 Ryan (1993, 1994)의 방광암 자료에 적용하여 모수를 추정하였으며, 그 추정값을 바탕으로 모의실험을 수행하였다.

• 대한의생명과학회지
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• 제19권4호
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• pp.303-309
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• 2013

Oncolytic vaccinia virus is an engineered vaccinia virus that selectively destroys cancer cells and induces tumor immune response. Oncolytic vaccinia expressing mouse GM-CSF showed cytotoxic activity against various kinds of cancer cells when oncolytic vaccinia virus expressing human GM-CSF and mouse GM-CSF is intravenously administered in the mouse CT26 colon tumor model. Cancer cells treated with isolated immunoglobulin G from the serum with complement showed these cytotoxic activity and complement observed dose-dependent cytotoxic effect. These results suggest that oncolytic vaccinia virus expressing mouse GM-CSF can increase oncolytic vaccinia virus by inducing anticancer antibody in a mouse tumor model. Further studies are needed on antitumor immunity of GM-CSF.

• Radiation Oncology Journal
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• 제20권1호
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• pp.1-16
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• 2002

Purpose : Three dimensional conformal radiotherapy planning is being used widely for the treatment of patients with brain tumor. However, it takes much time to develop an optimal treatment plan, therefore, it is difficult to apply this technique to all patients. To increase the efficiency of this technique, we need to develop standard radiotherapy plant for each site of the brain. Therefore we developed several 3 dimensional conformal radiotherapy plans (3D plans) for tumors at each site of brain, compared them with each other, and with 2 dimensional radiotherapy plans. Finally model plans for each site of the brain were decide. Materials and Methods : Imaginary tumors, with sizes commonly observed in the clinic, were designed for each site of the brain and drawn on CT images. The planning target volumes (PTVs) were as follows; temporal $tumor-5.7\times8.2\times7.6\;cm$, suprasellar $tumor-3\times4\times4.1\;cm$, thalamic $tumor-3.1\times5.9\times3.7\;cm$, frontoparietal $tumor-5.5\times7\times5.5\;cm$, and occipitoparietal $tumor-5\times5.5\times5\;cm$. Plans using paralled opposed 2 portals and/or 3 portals including fronto-vertex and 2 lateral fields were developed manually as the conventional 2D plans, and 3D noncoplanar conformal plans were developed using beam's eye view and the automatic block drawing tool. Total tumor dose was 54 Gy for a suprasellar tumor, 59.4 Gy and 72 Gy for the other tumors. All dose plans (including 2D plans) were calculated using 3D plan software. Developed plans were compared with each other using dose-volume histograms (DVH), normal tissue complication probabilities (NTCP) and variable dose statistic values (minimum, maximum and mean dose, D5, V83, V85 and V95). Finally a best radiotherapy plan for each site of brain was selected. Results : 1) Temporal tumor; NTCPs and DVHs of the normal tissue of all 3D plans were superior to 2D plans and this trend was more definite when total dose was escalated to 72 Gy (NTCPs of normal brain 2D $plans:27\%,\;8\%\rightarrow\;3D\;plans:1\%,\;1\%$). Various dose statistic values did not show any consistent trend. A 3D plan using 3 noncoplanar portals was selected as a model radiotherapy plan. 2) Suprasellar tumor; NTCPs of all 3D plans and 2D plans did not show significant difference because the total dose of this tumor was only 54 Gy. DVHs of normal brain and brainstem were significantly different for different plans. D5, V85, V95 and mean values showed some consistent trend that was compatible with DVH. All 3D plans were superior to 2D plans even when 3 portals (fronto-vertex and 2 lateral fields) were used for 2D plans. A 3D plan using 7 portals was worse than plans using fewer portals. A 3D plan using 5 noncoplanar portals was selected as a model plan. 3) Thalamic tumor; NTCPs of all 3D plans were lower than the 2D plans when the total dose was elevated to 72 Gy. DVHs of normal tissues showed similar results. V83, V85, V95 showed some consistent differences between plans but not between 3D plans. 3D plans using 5 noncoplanar portals were selected as a model plan. 4) Parietal (fronto- and occipito-) tumors; all NTCPs of the normal brain in 3D plans were lower than in 2D plans. DVH also showed the same results. V83, V85, V95 showed consistent trends with NTCP and DVH. 3D plans using 5 portals for frontoparietal tumor and 6 portals for occipitoparietal tumor were selected as model plans. Conclusion : NTCP and DVH showed reasonable differences between plans and were through to be useful for comparing plans. All 3D plans were superior to 2D plans. Best 3D plans were selected for tumors in each site of brain using NTCP, DVH and finally by the planner's decision.

• 대한의생명과학회지
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• 제18권3호
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• pp.210-217
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• 2012

Oncolytic viral vectors have shown good candidates for cancer treatment but have many limitations. To improve the therapeutic potential of oncolytic vaccinia virus, we developed a recombinant vaccinia virus expressing the 4-1BBL co-stimulatory molecule or CCL21. 4-1BBL and CCL21 expression was identified by FACS analysis and immunoblotting. rV-4-1BBL vaccination shows significant tumor regression compared to rV-LacZ, but rV-CCL21 shows rapid tumor growth compared to rV-LacZ in the poorly immunogenic B16 murine melanoma model. 4-1BBL expression resulted in the increase of the number of CD8+ T cells and especially the increase of effector (CD62L-CD44+) CD8+ T cells. These data suggest 4-1BBL may be the potential target for enhancement of tumor immunotherapy.

• Journal of Chest Surgery
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• 제54권6호
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• pp.460-465
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• 2021

Background: Metastasis and recurrence of primary cancer are the main causes of cancer mortality. Disseminated tumor cells refer to cancer cells that cause metastasis from primary cancer to other organs. Several recent studies have suggested that circulating tumor cells (CTCs) are associated with the clinical stage, cancer recurrence, cancer metastasis, and prognosis. There are several methods of isolating CTCs from whole blood; in particular, using a membrane filtration system is advantageous due to its cost-effectiveness and availability in clinical settings. In this study, an animal model of lung cancer was established in nude mice using the human large cell lung cancer cell line H460. Methods: Six-week-old nude mice were used. The H460 lung cancer cell line was injected subcutaneously into the nude mice. Blood samples were obtained from the orbital area before cell line injection, 2 weeks after injection, and 2 weeks after tumor excision. Blood samples were filtered using a polycarbonate 12-well Transwell membrane (Corning Inc., Corning, NY, USA). An indirect immunofluorescence assay was performed with the epithelial cell adhesion molecule antibody. The number of stained cells was counted using fluorescence microscopy. Results: The average size of the tumor masses was 35.83 mm. The stained cells were counted before inoculation, 2 weeks after inoculation, and 2 weeks after tumor excision. Cancer cells generally increased after inoculation and decreased after tumor resection. Conclusion: The CTC detection method using the commercial polycarbonate 12-well Transwell (Corning Inc.) membrane is advantageous in terms of cost-effectiveness and convenience.

• Molecules and Cells
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• 제21권2호
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• pp.213-217
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• 2006

Although AIMP1 (previously known as p43) is one of three auxiliary proteins bound to a macromolecular aminoacyl tRNA complex, it is also secreted as a cytokine controlling both angiogenesis and immune responses. Here we show that systemically administered purified recombinant human AIMP1 had anti-tumor activity in mouse xenograft models. In Meth A-bearing Balb/c mice, tumor volume increased about 28 fold in the vehicle treatment group, while an increase of about 16.7 fold was observed in the AIMP1-treated group. We also evaluated the anti-tumor activity of AIMP1 in combination with a sub-clinical dose of the cytotoxic anti-tumor drug, paclitaxel. The growth of NUGC-3 human stomach cancer cells was suppressed by 84% and 94% by the combinations of 5 mg/kg paclitaxel + 25 mg/kg AIMP1 (p = 0.03), and 5 mg/kg paclitaxel + 50 mg/kg AIMP1 (p = 0.02), respectively, while 5 mg/kg paclitaxel alone suppressed growth by only 54% (p = 0.02). A similar cooperative effect of AIMP1 and paclitaxel was observed in a lung cancer xenograft model. These results suggest that AIMP1 may be useful as a novel anti-tumor agent.

• KSII Transactions on Internet and Information Systems (TIIS)
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• 제18권1호
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• pp.105-125
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• 2024

Gliomas are the most common malignant brain tumor and cause the most deaths. Manual brain tumor segmentation is expensive, time-consuming, error-prone, and dependent on the radiologist's expertise and experience. Manual brain tumor segmentation outcomes by different radiologists for the same patient may differ. Thus, more robust, and dependable methods are needed. Medical imaging researchers produced numerous semi-automatic and fully automatic brain tumor segmentation algorithms using ML pipelines and accurate (handcrafted feature-based, etc.) or data-driven strategies. Current methods use CNN or handmade features such symmetry analysis, alignment-based features analysis, or textural qualities. CNN approaches provide unsupervised features, while manual features model domain knowledge. Cascaded algorithms may outperform feature-based or data-driven like CNN methods. A revolutionary cascaded strategy is presented that intelligently supplies CNN with past information from handmade feature-based ML algorithms. Each patient receives manual ground truth and four MRI modalities (T1, T1c, T2, and FLAIR). Handcrafted characteristics and deep learning are used to segment brain tumors in a Global Convolutional Neural Network (GCNN). The proposed GCNN architecture with two parallel CNNs, CSPathways CNN (CSPCNN) and MRI Pathways CNN (MRIPCNN), segmented BraTS brain tumors with high accuracy. The proposed model achieved a Dice score of 87% higher than the state of the art. This research could improve brain tumor segmentation, helping clinicians diagnose and treat patients.

• 한국임상수의학회지
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• 제23권4권
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• pp.388-392
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• 2006

80두의 가토 간에 $1{\sim}2mm^3$ 크기의 VX2 종양세포를 직접 주입하여 단일간암모델을 만들고, 종양이식 후1주, 2주, 3주째에 CT촬영을 실시하여 생성된 종양의 크기와 조영 양상을 관찰하고 조직병리학적검사로 종양의 진위 여부를 확인하였다. 80두 중 66두(82.5%)에서 단일 종양이 만들어졌다. 나머지 12두 중 1두에서 간외종앙의 생성, 그리고 다른 1두에서 육아종성 종괴가 관찰되었으며, 4두는 폐사하였다. 나머지 8두에서는 종양이 생성되지 않았다. 조영 CT에서 관찰된 종양의 크기는 1주, 2주 그리고 3주째에 각각 $7.4{\times}6.3,\;14.2{\times}10.8,\;16.2{\times}12.6cm$로 측정되었다. 모양은 둥글거나 타원형이었으며, 동맥기에서 중앙에 저감쇠와 변연에 조영증강을 보였으며, 문맥기에는 저감쇠를 나타내었다. 종양조직의 이식은 균질한 단일종양모델을 만드는데 매우 유용하고 적합한 방법이며, 조영 CT 촬영술은 간종양 진단 및 다양한 치료방법 적용 후 추적검사에 매우 유용하게 활용될 것으로 판단된다.

• Current Optics and Photonics
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• 제3권1호
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• pp.54-65
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• 2019

To develop a biomarker predicting tumor treatment efficacy is helpful to reduce time, medical expenditure, and efforts in oncology therapy. In clinics, microvessel density using immunohistochemistry has been proposed as an indicator that correlates with both tumor size and metastasis of cancer. In the preclinical study, we hypothesized that vascular morphometrics using optical coherence tomography angiography (OCTA) could be potential indicators to estimate the treatment efficacy of breast cancer. To verify this hypothesis, a 13762-MAT-B-III rat breast tumor was grown in a dorsal skinfold window chamber which was applied to a nude mouse, and the change in vascular morphology was longitudinally monitored during tumor growth and metronomic cyclophosphamide treatment. Based on the daily OCTA maximum intensity projection map, multiple vessel parameters (vessel skeleton density, vessel diameter index, fractal dimension, and lacunarity) were compared with the tumor size in no tumor, treated tumor, and untreated tumor cases. Although each case has only one animal, we found that the vessel skeleton density (VSD), vessel diameter index and fractal dimension (FD) tended to be positively correlated with tumor size while lacunarity showed a partially negative correlation. Moreover, we observed that the changes in the VSD and FD are prior to the morphological change of the tumor. This feasibility study would be helpful in evaluating the tumor vascular response to treatment in preclinical settings.