• Current Optics and Photonics
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• v.3 no.6
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• pp.555-565
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• 2019

Development of a biomarker for predicting tumor-treatment efficacy is a matter of great concern, to reduce time, medical expense, and effort in oncology therapy. In a preclinical study, we hypothesized that the blood-flow parameter based on laser speckle flowmetry (LSF) could be a potential indicator to estimate the efficacy of breast-cancer treatment. To verify this hypothesis, a 13762-MAT-B-III rat breast tumor was grown in a dorsal skinfold window chamber applied to a nude mouse, and the change in blood flow rate (BFR) - or the speckle flow index (SFI) is used together as the same meaning in this manuscript - was longitudinally monitored during tumor growth and metronomic cyclophosphamide treatment. Based on the daily LSF angiogram, several BFR parameters (baseline SFI, normalized SFI, and △rBFR) were compared to tumor size in the normal, treated, and untreated tumor groups. Despite the incomplete tumor treatment, we found that the daily changes in all BFR parameters tended to have partially positive correlation with tumor size. Moreover, we observed that the changes in baseline SFI and normalized SFI responded one day earlier than the tumor shrinkage during chemotherapy. However, daily variations in the hypercapnia-induced △rBFR lagged tumor shrinkage by one day. This study would contribute not only to evaluating tumor vascular response to treatment, but also to monitoring blood-flow-mediated diseases (in brain, skin, and retina) by using LSF in preclinical settings.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.30 no.2
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• pp.81-84
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• 2004

It is well known that malignant tumor have hypoxic cell fraction, which is radio resistant and is one of the most important cause of local recurrence after radiotherapy. One of the causes of hypoxia in tumor is blood flow decrease due to increase in blood flow resistance and one of the causes of increased blood flow resistance could be attributed to the increase in blood viscosity. For the evaluation of the change of blood viscosity in oral cancer, experiments were carried out to test the change of blood viscosity among the normal control and xenografted oral cancer nude mice. Relative viscosity measured against distilled water was $3.30{\pm}0.14$ for normal control, and $3.67{\pm}0.62$ for tumor bearing mice at the first time of blood sampling in experimental period ($100mm^3$ $200mm^3$). There was no statistically significant difference between the control group and experimental group (p>0.05). However, as the tumor grew, significant difference of blood viscosity was detected at the third time of blood sampling (control group:$3.37{\pm}0.59$, and experimental group: $4.31{\pm}0.41\;300mm^3$

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.30 no.3
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• pp.181-185
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• 2004

Malignant tumor have hypoxic cell fraction, which makes radio-resistant and hypoxia in tumor is a result from the blood flow decrease caused by increase in blood flow resistance. Blood viscosity increase is major factor of increased blood flow resistance and it could be attributed to the decrease in blood deformability index. For the evaluation of the change of blood viscosity and blood deformability in oral squamous cell carcinoma, we perform the test of the change of those factors between the normal control group and oral squamous cell carcinoma cell patient group. Relative viscosity measured against distilled water was $5.25{\pm}0.14$ for normal control group, and $5.78{\pm}0.26$ for the SCC patient group and there was statistical significance between the groups. However, there was no significant difference between the groups in blood viscosity between the groups by tumor size (T1+T2 vs T3+T4). Also, there was no significant difference between the normal control group and SCC patient group in blood deformability index and between the groups by tumor size (T1+T2 vs T3+T4). Increase in blood viscosity was confirmed with this study and it can be postulated that modification blood viscosity might contribute to decrease of hypoxia fraction in oral squamous cell carcinoma, thus improve the effect of radiotherapy and it can be assumed that the main factor of blood viscosity increase is not decrease of blood deformability in oral squamous cell carcinoma.

• Radiation Oncology Journal
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• v.12 no.1
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• pp.17-25
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• 1994

We evaluated the effect of nicotinamide on cellular $O_{2}$ consumption and metabolic status i.e., adenylate phosphates and $NAD^{+}$in-vitro, and changes in blood flow in-vivo, to determine whether changes in cellular metabolism or increased oxygen availability, was responsible for increased tumor oxygenation. Thirty min, pre-incubation of cells with$\∼$4mM (= 500mg/kg) nicotinamide resulted in no change in cellular $O_{2}$ consumption. Similarly neither the adenylate Phosphates nor the cellular $NAD^{+}$levels were altered in the presence of $\∼$4mM nicontinamide. In-vivo, nicotinamide (500mg/kg) increased $O_{2}$ availability as estimated by changes in relative tumor blood flow (RBC flux). The changes in RBC flux measured by the laser Doppler method, were tumor volume dependent and increased from$\∼$35$ \% $ in$\∼$ 150$mm_{3}$tumors to$\∼$~75$ \% $ in$\∼$500$mm^{3}$ tumors. In conclusion, these observations indicate a reduction in local tissue $O_{2}$ consumption is not a mechanism of improved tumor oxygenation by nicotinamide in FSa II murine tumor model. The primary mechanism of increased $pO_{2}$ appears to be an increased local tumor blood flow.

• Journal of Veterinary Clinics
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• v.40 no.5
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• pp.375-381
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• 2023

A large abdominal mass was incidentally found in a 13-year-old mixed-breed dog and was confirmed to be a cecal gastrointestinal stromal tumor (GIST). Contrast-enhanced ultrasound and post-contrast computed tomography (CT) showed mild contrast enhancement of the mass, indicating low blood flow. The tumor origin was determined to be the cecum by identifying the vessels supplying the mass on post-contrast CT. The exophytic growth of the tumor left the cecal lumen intact without obstruction. This report described the CEUS and CT perfusion of the cecal GIST and perfusion evaluation can help diagnose and characterize GISTs in dogs.

• Radiation Oncology Journal
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• v.20 no.2
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• pp.155-164
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• 2002

Purpose : A ginkgo biloba extract (GBE) has been known as a hypoxic cell radiosensitizer. Its mechanisms of action are increase of the red blood cell deformability, decrease the blood viscosity, and decrease the hypoxic cell fraction in the tumor. The aims of this study were to estimate the effect of GBE on fractionated radiotherapy and to clarify the mechanism of action of the GBE by estimating the blood flow in tumor and normal muscle. Materials and Methods : Fibrosarcoma (FSall) growing in a C3H mouse leg muscle was used as the tumor model. When the tumor size reached 7 mm in diameter, the GBE was given intraperitoneally at 1 and 25 hours prior to irradiation. The tumor growth delay was measured according to the various doses of radiation (3, 6, 9, 12 Gy and 15 Gy) and to the fractionation (single and fractionated irradiation) with and without the GBE injection. The radiation dose to the tumor the response relationships and the enhancement ratio of the GBE were measured. In addition, the blood flow of a normal muscle and a tumor was compared by laser Doppler flowmetry according to the GBE treatment. Results : When the GBE was used with single fraction irradiation with doses ranging from 3 to 12 Gy, GBE increased the tumor growth delay significantly (p<0.05) and the enhancement ratio of the GBE was 1.16. In fractionated irradiation with 3 Gy per day, the relationships between the radiation dose (D) and the tumor growth delay (TGD) were TGD $(days)=0.26{\times}D$ (Gy)+0.13 in the radiation alone group, and the TGD $(days)=0.30{\times}D$ (Gy)+0.13 in the radiation with GBE group. As a result, the enhancement ratio was 1.19 ($95\%$ confidence interval; $1.13\~1.27$). Laser Doppler flowmetry was used to measure the blood flow. The mean blood flow was higher in the muscle (7.78 mL/100 g/min in tumor and the 10.15 mL/100 g/min in muscle, p=0.005) and the low blood flow fraction (less than 2 mL/100 g/min) was higher in the tumor $(0.5\%\;vs.\;5.2\%,\;p=0.005)$. The blood flow was not changed with the GBE in normal muscle, but was increased by $23.5\%$ ( p=0.0004) in the tumor. Conclusion : Based on these results, it can be concluded that the GBE enhanced the radiation effect significantly when used with fractionated radiotherapy as well as with single fraction irradiation. Furthermore, the GBE increased the blood flow of the tumor selectively.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7645-7649
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• 2013

Background: Immune functions and their relation to prognosis in breast cancer patients have become areas of great interest in recent years. Correlations between survival outcomes and peripheral blood flow cytometry parameters are therefore of interest. Here we focused on patients with non-metastatic breast cancer (BC). Materials and Methods: A total of 29 patients with pathological confirmed breast carcinoma and flow cytometry data were assessed for overall survival (OS) and progression free survival (PFS). Results: The median age of the patients was 54 years (range, 29-83). Multivariate analysis revealed that OS was significantly associated with absolute cytotoxic T cell count (95%CI, coef 2.26, p=0.035), tumor size (95%CI, coef -14.5, p 0.004), chemotherapy (95%CI, coef 12.9, p 0.0001), MFI of CD4 (95%CI, coef -5.1, P 0.04), MFI of HLA DR (95%CI, coef -5.9, p 0.008) and tumor grade (95%CI, coef -13, P 0.049) with R-Sq(adj)=67%. Similar findings were obtained for PFS. Conclusions: OS and PFS were significantly associated with tumor grade, tumor size, chemotherapy, MFI of CD4, HLA DR and absolute cytotoxic T cell count. The study revealed that MFI of basic CD markers and absolute cytotoxic T cell number may be a prognostic factors in women with non-metastatic BC.

• Korean Journal of Digital Imaging in Medicine
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• v.3 no.1
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• pp.206-210
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• 1997

• ETRI Journal
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• v.37 no.2
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• pp.233-240
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• 2015

The novelty of this study resides in a 6"-wafer-level microfabrication protocol for a microdevice with a fluidic control system for the separation of circulating tumor cells (CTCs) from human whole blood cells. The microdevice utilizes a lateral magnetophoresis method based on immunomagnetic nanobeads with anti-epithelial cell adhesive molecule antibodies that selectively bind to epithelial cancer cells. The device consists of a top polydimethylsiloxane substrate for microfluidic control and a bottom substrate for lateral magnetophoretic force generation with embedded v-shaped soft magnetic microwires. The microdevice can isolate about 93% of the spiked cancer cells (MCF-7, a breast cancer cell line) at a flow rate of 40/100 mL/min with respect to a whole human blood/buffer solution. For all isolation, it takes only 10 min to process 400 mL of whole human blood. The fabrication method is sufficiently simple and easy, allowing the microdevice to be a mass-producible clinical tool for cancer diagnosis, prognosis, and personalized medicine.

• The Korean Journal of Nuclear Medicine
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• v.33 no.1
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• pp.1-10
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• 1999

Cancer cells are known to show increased rates of glycolysis metabolism. Based on this, PET studies using F-18-fluorodeoxyglucose have been used for the detection of primary and metastatic tumors. To account for this increased glucose uptake, a variety of mechanisms has been proposed. Glucose influx across the cell membrane is mediated by a family of structurally related proteins known as glucose transporters (Gluts). Among 6 isoforms of Gluts, Glut-1 and/or Glut-3 have been reported to show increased expression in various tumors. Increased level of Glut mRNA transcription is supposed to be the basic mechanism of Glut overexpression at the protein level. Some oncogens such as src or ras intensely stimulate Glut-1 by means of increased Glut-1 mRNA levels. Hexokinase activity is another important factor in glucose uptake in cancer cells. Especially hexokinase type II is considered to be involved in glycolysis of cancer cells. Much of the hexokinase of tumor cells is bound to outer membrane of mitochondria by the porin, a hexokinase receptor. Through this interaction, hexokinase may gain preferred access to ATP synthesized via oxidative phosphorylation in the inner mitochondria compartment. Other biologic factors such as tumor blood flow, blood volume, hypoxia, and infiltrating cells in tumor tissue are involved. Relative hypoxia may activate the anaerobic glycotytic pathway. Surrounding macrophages and newly formed granulation tissue in tumor showed greater glucose uptake than did viable cancer cells. To expand the application of FDG PET in oncology, it is important for nuclear medicine physicians to understand the related mechanisms of glucose uptake in cancer tissue.