Two-dimensional (2D) cell culture and in vivo cancer model systems have been used to understand cancer biology and develop drug delivery systems for cancer therapy. Although cell culture and in vivo model studies have provided critical contribution about disease mechanism, these models present important problems. 2D tissue culture models lack of three dimensional (3D) structure, while animal models are expensive, time consuming, and inadequate to reflect human tumor biology. Up to the present, scaffolds and 3D matrices have been used for many different clinical applications in regenerative medicine such as heart valves, corneal implants and artificial cartilage. While tissue engineering has focused on clinical applications in regenerative medicine, scaffolds can be used in in vitro tumor models to better understand tumor relapse and metastasis. Because 3D in vitro models can partially mimic the tumor microenvironment as follows. This review focuses on different scaffold production techniques and polymer types for tumor model applications in cancer tissue engineering and reports recent studies about in vitro 3D polymeric tumor models including breast, ewing sarcoma, pancreas, oral, prostate and brain cancers.
The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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v.21
no.1
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pp.26-37
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2008
Objective : The present study was carried out to investigate the effects of NaisoOkseol-Tang (NOT) on solid tumor in mice in terms of immune-potentiating and direct cytotoxic action of NOT in vitro and vivo study. Methods: The present author investigated thymocyte proliferation and NO production to confirm immune-potentiating activity of NOT and also investigated body/tumor weight and survival rates in tumor bearing mice. In this study, administration of NOT decreased tumor/weight ratio significantly, and prolonged survival duration compared to non-treated control. Treatment with NOT also elevated proliferation rates of thymocytes isolated from tumor bearing mice. Results: In vitro study, treatment with NOT suppressed proliferation rate of Sarcoma 180 (S-180) cells. Contrary, treatment with NOT elevated proliferation rate of thymocytes. These results were co-related with in vivo study. In addition, NO production from abdominal macrophages isolated from normal mice was not affected by treatment with NOT. Conclusion : NOT is useful to treat patient with solid tumor, because NOT has direct toxic action for tumor cell and immune-potentiating action for T cells.
To examine the potentiation of Macrolepiota procera extracts (MPE-4) to act as adjuvant enhancing the tumor specific anti-tumor immune response, tumor vaccine prepared by boiling (HK vaccine) admixed with MPE-4 and immunized in mice. Vaccination of mice with HK vaccine in combination with MPE-4 resulted in higher inhibition in tumor metastasis compared with the mice of HK vaccine alone treatment against live syngeneic tumor cell challenge. The splenocytes from mice immunized HK vaccine mixed with MPE-4 was able to elicit a stronger cytotoxic T lymphocyte (CTL) response as compared with HK vaccine alone. In addition, the splenocytes from MPE-4 admixed HK vaccine immunized mice secreted a higher concentration of Th1 type cytokine such as IFN-${\gamma}$, and GM-CSF. Furthermore, the adoptive transfer of splenocytes from mice immunized HK vaccine and MPE-4 led to a more robust anti-tumour response than the HK vaccine alone. Overall, these results indicate that MPE-4 is a good candidate adjuvant of anti-tumor immune response.
Purpose: This study aimed to clarify the concept of uncertainty in brain tumor patients. Methods: We used the Walker and Avant's concept analysis method. We searched RISS, MEDLINE, CINAHL, and EMBASE for published articles in Korean and English from January 2002 to December 2022. After applying the inclusion and exclusion criteria, 27 articles were selected for the final analysis. Result: "Uncertainty in brain tumor" was defined as a state in which related clues during the process of experiencing a disease after brain tumor diagnosis are unclear or difficult to understand, new experiences different from before, or a condition in which it is difficult to judge fragmentarily. Moreover, the empirical criteria for the attributes of uncertainty in brain tumor patients were ambiguity of the disease process, diversity of information, unpredictability of prognosis, and complexity of management. Conclusion: Brain tumor patients with uncertainty require strategic technology development so that brain tumor patients, their families, and health care providers can use reasonable coping methods.
Park, Sun-Wook;Jeon, Ok-Hee;Ko, Chang-Yong;Kim, Chi-Hyun;Kim, Han-Sung;Chun, Keyoung-Jin;Lim, Do-Hyung
Journal of Biomedical Engineering Research
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v.30
no.5
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pp.444-451
/
2009
Purpose: The aim of present study is to detect longitudinal alterations of mechanical characteristic determined by bone quality (microarchitecture and degree of mineralization) on femur trabecular bone due to metastatic bone tumor Materials and Methods: Each 6 female SD rats (12 weeks old, approximate 250g) were allocated in SHAM and TUMOR Group. W256 (Walker carcinosarcoma 256 malignant breast cancer cell) was injected into the right femur (intraosseous injection) in TUMOR Group, whereas 0.9% NaCl (saline solution) was injected in SHAM Group. The right hind limbs of all rats were scanned by in-vivo micro-CT to acquire structural parameters, bone mineral density, X-ray attenuation and bone mineralization distribution at 0 week and 4 weeks after surgery. Results: BMD, BV/TV and Tb.N of trabecular bone in TUMOR group were markedly decreased (26%, 11% and 23%) while those in SHAM group were significantly increased (34%, 48% and 11%) (p<0.05). BS/BV, Tb.Sp and SMI in TUMOR group were significantly increased (-16%, 38% and 2%) compared with those in SHAM group (-33%, 12% and -16%) (p<0.05). Additionally, bone mineralization in TUMOR group significantly decreased while those in SHAM group was significantly increased (p<0.05). Conclusion: It is identified that how much bone microarchitecture and mineralization are diminished due to the metastatic bone tumor. The results may be helpful to prediction of fracture risk by metastatic bone tumor.
Bujeonghangamtang(扶正抗癌湯) has been used for cure of tumor as a traditional medicine without any experimental evidence to support the rational basis for its clinical use. This study was carried out to evaluate the possible therapeutic or antitumoral effects of Bujeonghangamtang extract against tumor, and to carry out some mechanisms responsible for its effect. Some kinds of tumor were induced by the typical application of 3-methylcholanthrene. (MCA) or by the implantation(s.c) of malignant tumor cells such as leukemia cells(3LL cells) or sarcoma cells(Sl80 cells). Treatment of the Bujeonghangamtang water-extract (dailly 1mg/mouse, i. p.) was continued for 7 days prior to tumor induction and after that the treatment was lasted for 20 days. Against squamous cell carcinoma induced by MCA, Bujeonghangamtang decreased not only the frequency of tumor production but also the number and the weight of tumors per tumor bearing mice (TBM). Bujeonghangamtang also significantly suppressed the development of 3LL cell and S180 cell-implanted tumors in occurrence-frequency and their size, and some developed tumors were regressed by the continuous treatment of Bujeonghangamtang extract into TBM. In vitro, treatment of Bujeonghangamtang extract had no effect on the growth of some kinds of cell line such as FsaII, A431 strain but significantly inhibited the proliferation of 3LL, S180 cells and augmented the DNA synthesis of mitogen-activated lymphocytes. Bujeonghangamtang also stimulated the migrative ability of leukocyte, the MIF and IL-2 production of T lymphocytes, but not IL 6 production of B cells. Bujeonghangamtang-administration to mice enhanced NK cells activities. These results demonstrated that Bujeonghangamtang extract exhibited a significant prophylactic benefits against tumors and its antitumor activity was manifested depending on the type of tumor cells. And these results also suggested that effect of Bujeonghangamtang might be chiefly due to nonspecific enhancement of NK cell activities and cell-mediated immune responses.
Lee, Eun-Young;Kim, Minjeong;Choi, Beom K.;Kim, Dae Hong;Choi, Inho;You, Hye Jin
Molecules and Cells
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v.44
no.11
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pp.784-794
/
2021
Leiomyosarcoma (LMS) is a mesenchymal malignancy with a complex karyotype. Despite accumulated evidence, the factors contributing to the development of LMS are unclear. Here, we investigated the role of tight-junction protein 1 (TJP1), a membrane-associated intercellular barrier protein during the development of LMS and the tumor microenvironment. We orthotopically transplanted SK-LMS-1 cells and their derivatives in terms of TJP1 expression by intramuscular injection, such as SK-LMS-1 Sh-Control cells and SK-LMS-1 Sh-TJP1. We observed robust tumor growth in mice transplanted with LMS cell lines expressing TJP1 while no tumor mass was found in mice transplanted with SK-LMS-1 Sh-TJP1 cells with silenced TJP1 expression. Tissues from mice were stained and further analyzed to clarify the effects of TJP1 expression on tumor development and the tumor microenvironment. To identify the TJP1-dependent factors important in the development of LMS, genes with altered expression were selected in SK-LMS-1 cells such as cyclinD1, CSF1 and so on. The top 10% of highly expressed genes in LMS tissues were obtained from public databases. Further analysis revealed two clusters related to cell proliferation and the tumor microenvironment. Furthermore, integrated analyses of the gene expression networks revealed correlations among TJP1, CSF1 and CTLA4 at the mRNA level, suggesting a possible role for TJP1 in the immune environment. Taken together, these results imply that TJP1 contributes to the development of sarcoma by proliferation through modulating cell-cell aggregation and communication through cytokines in the tumor microenvironment and might be a beneficial therapeutic target.
Olaso, Elvira;Benedicto, Aitor;Lopategi, Aritz;Cossio, Fernando P.;Arteta, Beatriz
Biomolecules & Therapeutics
/
v.30
no.2
/
pp.162-169
/
2022
We utilized Fas21, a resveratrol analog, to modulate the function of hepatic stellate cells (HSCs) and liver sinusoidal endothelial cells (LSECs) during the angiogenic phase of murine liver metastasis by B16 melanoma and 51b colorectal carcinoma. Preangiogenic micrometastases were treated with Fas21 (1 mg/kg/day) or vehicle during the development of intra-angiogenic tracts. Mice treated with Fas21 showed reduced liver tumor foci in both liver metastasis models. Micrometastases were classified immunohistochemically, as well as according to their position coordinates and connection to local microvasculature. The volume of liver occupied by sinusoidal-type foci, containing infiltrating angiogenic capillaries, decreased by ~50% in Fas21-treated mice compared to vehicle-treated ones in both tumor metastasis models. The volume of portal foci, containing peripheral neoangiogenesis within a discontinuous layer of myofibroblasts, was similar in all experimental groups in both tumor metastasis models, but displayed enhanced necrotic central areas devoid of angiogenesis following Fas21 treatment. As a result, sinusoidal tumors from mice treated with Fas21 showed a 50% reduction in desmin(+)/asma(+) HSCs and CD31(+) vessel density, and a 45% reduction in intrametastatic VEGF mRNA compared with sinusoidal tumors from vehicle-treated mice. Necrotic portal metastases increased 2-4-fold in treated mice. In vitro, Fas21 reduced VEGF secretion by HSCs and 51b cells dose-dependently. Additionally, HSCs migration in response to tumor soluble factors was dose-dependently diminished by Fas21, as was LSEC migration in response to HSCs and tumor soluble factors. Resveratrol analog Fas21 inhibits the proangiogenic response of HSCs and LSECs during the development of murine liver metastasis.
The definition of cancer, its diagnosis and its prognosis all depend upon description of growth. To the layman a synonym for cancer is a "growth". There are no quantitative terms for the description of growth or growth rate in clinical use. There has been no attempt to assign values that would define "rapidly" or "slowly" growing. Estimates of growth potentiality are implied in the descriptive phrases "poorly differentiated" or "well differentiated", "highly malignant" or "low grade malignancy". and in systems of grading. These qualifying terms represent a personal impression, clinically useful in prognosis, but relative in nature. They do not lend themselves to uniform application or precise measurement for purpose of comparison. Growth is related to size and time. The volume of tumor depends upon the duration of the period of growth and the rate of growth. If the interval and change in volume are known. the average growth rate can be determined. If the growth rate is determined, and assumed to be constant., the duration of a given tumor and the time of inception can be estimated. The commonest concept of the origin of cancer is that as a result of a mutation involving a single cell, succeeding divisions of cells establish a colony with the characteristics recognizable as cancer. If the growth rate of the hypothetical tumor were constant it could be described in terms of "tumor volume doubling time". In the department of thoracic surgery of St. Mary hospital in Catholic Medical College, a clinical evaluation for the growth rate, degree of malignancy, resectability and prognosis was done on a total 24 cases of primary bronchogenic carcinoma which contour was significant on the chest X-ray film as possible estimating the tumor volume doubling time. The following results were obtained: 1. In the cases of 6.0cm or more in diameter of minor size at operation the resectability rate was lower and in the cases of 60 days or more in the tumor or volume doubling time the resectability rate was higher. 2. If differentiation of cancer cells was lower graded in tissue pathology, the tumor volume was shorter and the resectability rate was lower. 3. The tumor volume doubling time of the primary bronchogenic carcinoma occured more over 60 years of age was slightly shorter than under 60 years of age. 4. The tumor size at operation was more important to evaluate the survival time and prognosis than the tumor volume doubling time because the tumor growth was not always constant, we presume.mor volume doubling time because the tumor growth was not always constant, we presume.
Purpose :This study was performed to determine the optimal treatment velum of Patients treating with radiation therapy for intracranial germ cell tumor. Materials and Methods : From 1993 to 1998, 19 patients with intracranial germ cell tumors treated by gamma knife radiosurgery were analyzed. The location of tumor was as follows; 9 cases on pineal region, 1 case on suprasellar region, and 9 cases of multiple lesion. 7 patients were pathologically verified; 5 cases of germ cell tumor and 2 cases of non germinomatous germ cell tumor. Tumor volume was ranged from 2.4 cm$^{3}$ to 74 cm$^{3}$. Irradiation dose was 10 Gy to 20 Gy with 50% isodose curve. Follow up period was 10 months to 54 months. Results : Recurrences were observed in 14 cases among 19 (74%) patients. Complete remission and partial remission were achieved in 2 (11%) and 10 (53%) respectively. No response was observed in 7 (36%). 2 cases were recurred within original tumor bed. 6 cases were recurred beyond but contiguous with tumor bed. Ventricular relapses separated from pretreatment tumor bed were 3. Spinal recurrences were 4. Among 8 recurred cases of which tumor volume is smaller than 20 cm$^{3}$, 2 were recurred within original tumor bed, 4 were recurred beyond but contiguous with tumor bed, and 1 spinal recurrence. Meanwhile, 6 cases of which tumor volume larger than 20 cm3, 1 case was recurred beyond but contiguous with tumorbed, 2 ventricular recurrences separated with original tumor bed, and 3 spinal recurrences. 5 cases which did not show any recurrence sign showed characteristics of single lesion, tumor volume smaller than 20 cm$^{3}$ and normal tumor marker. All of 4 cases of spinal recurrences happened in the case having ventricular invasion or lesion. Among 9 cases having multiple lesion, only 3 cases recurred within original tumor bed or around tumor bed, the other 6 cases recurred separated from pretreatment tumor bed. Conclusion : Gamma knife radiosurgery is not recommended for the treatment of intracranial germ cell tumor. It is because of small treatment volume and inadequate radiation dose that are characteristics of gamma knife radiosurgery. Tumor volume, ventricular invasion or ventricular lesion in multiple lesion are important factors to be considered for the wide field radiation therapy Tumor volume smaller than 20 cm$^{3}$, single lesion, no ventricular lesion or invasion, and normal tumor marker are ideal indications for small involved field radiation therapy. Prophylactic spinal irradiation seems to be necessary when there is ventricular lesion, ventricular invasion, and multiple lesions. When the tumor volume is larger than 20 cm$^{3}$, multiple lesions, abnormal tumor marker, and whole ventricular irradiation or partial brain irradiation would be possible and neoadjuvant chemotherapy would be most beneficial in these group.
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