• Title, Summary, Keyword: tumor growth

Search Result 1,969, Processing Time 0.068 seconds

Hhip regulates tumor-stroma-mediated upregulation of tumor angiogenesis

  • Agrawal, Vijayendra;Kim, Dong Young;Kwon, Young-Guen
    • Experimental and Molecular Medicine
    • /
    • v.49 no.1
    • /
    • pp.9.1-9.8
    • /
    • 2017
  • Tumor growth is governed by the coordinated action of various types of cells that are present in the tumor environment. Fibroblasts, which constitute a major fraction of the stroma, participate actively in various signaling events and regulate tumor development and metastasis. The Hedgehog (Hh) pathway plays an important role in promoting tumor malignancy via fibroblasts; however, the role of hedgehog interacting protein (hhip; inhibitor of Hh pathway) in tumor growth is poorly understood. Here we implanted B16F10 tumors in hhip+/- mice to study the tumor growth characteristics and the vascular phenotype. Furthermore, the mechanism involved in the observed phenomena was explored to reveal the role of hhip in tumor growth. The tumors that were implanted in hhip+/- mice exhibited accelerated growth and increased tumor angiogenesis. Although we observed a decrease in hypoxia, blood vessels still had abnormal phenotype. We found that increased Hh signaling in tumor fibroblasts induced a high expression of vascular endothelial growth factor (VEGF), which subsequently resulted in an increased proliferation of endothelial cells. Thus, the heterozygous knockdown of hhip in mice could affect Hh signaling in tumor fibroblasts, which could cause the increased production of the growth factor VEGF. This signaling, via a paracrine effect on endothelial cells, increased tumor vascular density.

Computational Analysis of Tumor Angiogenesis Patterns Using a Growing Brain Tumor Model

  • Shim, Eun-Bo;Kwon, Young-Keun;Ko, Hyung-Jong
    • International Journal of Vascular Biomedical Engineering
    • /
    • v.2 no.1
    • /
    • pp.17-24
    • /
    • 2004
  • Tumor angiogenesis was simulated using a two-dimensional computational model. The equation that governed angiogenesis comprised a tumor angiogenesis factor (TAF) conservation equation in time and space, which was solved numerically using the Galerkin finite element method. The time derivative in the equation was approximated by a forward Euler scheme. A stochastic process model was used to simulate vessel formation and vessel elongation towards a paracrine site, i.e., tumor-secreted basic fibroblast growth factor (bFGF). In this study, we assumed a two-dimensional model that represented a thin (1.0 mm) slice of the tumor. The growth of the tumor over time was modeled according to the dynamic value of bFGF secreted within the tumor. The data used for the model were based on a previously reported model of a brain tumor in which four distinct stages (namely multicellular spherical, first detectable lesion, diagnosis, and death of the virtual patient) were modeled. In our study, computation was not continued beyond the 'diagnosis' time point to avoid the computational complexity of analyzing numerous vascular branches. The numerical solutions revealed that no bFGF remained within the region in which vessels developed, owing to the uptake of bFGF by endothelial cells. Consequently, a sharp, declining gradient of bFGF existed near the surface of the tumor. The vascular architecture developed numerous branches close to the tumor surface (the brush-border effect). Asymmetrical tumor growth was associated with a greater degree of branching at the tumor surface.

  • PDF

A Clinical Evaluation of the Tumor Volume Doubling Time in Primary Bronchogenic Carcinoma (폐암환자에서 본 Tumor Doubling Time 의 임상적 의의)

  • 홍기우;이홍균
    • Journal of Chest Surgery
    • /
    • v.6 no.1
    • /
    • pp.15-22
    • /
    • 1973
  • 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.

  • PDF

The Natural History and Growth Rate of Meningiomas

  • Han, Jung-Ho;Seol, Ho-Jun;Kim, Dong-Gyu;Jung, Hee-Won
    • Journal of Korean Neurosurgical Society
    • /
    • v.39 no.3
    • /
    • pp.198-203
    • /
    • 2006
  • Objective : To evaluate the natural histories and growth rates of meningiomas, the authors perform this retrospective observational study and attempt to identify those factors predicting tumor growth. Methods : Between 1993 and 2004, a total of 83 patients were diagnosed by computed tomography[CT] scans or magnetic resonance[MR] imaging as having an intracranial meningioma, and were treated by observation only using regular clinical and radiological examinations. Twenty-six of these 83 patients, with available data were included in this study. Follow up periods ranged from 9 to 137 months [mean, 55.6 mo.; median, 60 mo.]. The tumor volumes, absolute growth rates, and tumor doubling times were calculated. Results : Patient age and sex distributions were comparable to those of other studies, but exceptionally 16 meningiomas [62%] were located at the skull base in the present study. During follow-up monitoring, the majority of meningiomas grew, though 77% showed low absolute annual growth rates [$<1cm^3/yr$]. The tumor doubling times ranged from 2.87 to 201.72 years [mean, 42.91 yr]. Based on Imaging analysis, peritumoral edema and the absence of calcification were probable factors predicting tumor growth. Tumor-related symptoms seemed to be slightly related to tumor growth. Other factors, e.g., gender, age, tumor location, and T2-weighted signal Intensities on MR imaging, were not significantly related to tumor growth. Conclusion : This study shows that the majority of meningiomas are slow growing. However, variations in tumor growth are unexplained, thus individualized optimal treatment strategies should be provided in each meningioma.

Growth Suppression Effect of Traditional Fermented Soybean Paste(Doenjang) on the Various Tumor Cells (순창 재래식 된장의 암세포 성장억제 효과)

  • 최신양;최미정;이정진;김현정;홍석산;정건섭;이봉기
    • Journal of the Korean Society of Food Science and Nutrition
    • /
    • v.28 no.2
    • /
    • pp.458-463
    • /
    • 1999
  • Methanol extract and its fraction of traditional fermented soybean paste(doenjang) from Soonchang area were studied for growth suppression on the various tumor cells and suppression components, by using HPLC and GC were analysed. Hexane fraction of methanol extract was indicated 79%, 76%, 67%, 66%, 78% of growth suppression on L1210, P338D1, HepG2, WiDr and SNU 1 tumor cells, respectively. Ethylacetate fraction of methanol extract also showed 81%, 75%, 75%, 76% and 82% of growth suppression on the same tumor cells, respectively. Peak 8 obtained from HPLC of ethylacetate fraction indicated 81%, 77%, 77%, 75% and 79% of growth suppression on the same tumor cells and identified as a genistein, by comparing with standard one by HPLC analysis. Hexane fraction of methanol extract contained oleic acid, linoleic acid and palmitic acid.

  • PDF

Effect of Neem (Azadirachta indica) oil on the progressive growth of a spontaneous T cell lymphoma

  • Mallick, Sanjaya Kumar;Gupta, Vivekanand;Singh, Mahendra Pal;Vishvakarma, Naveen Kumar;Singh, Nisha;Singh, Sukh Mahendra
    • Advances in Traditional Medicine
    • /
    • v.7 no.5
    • /
    • pp.459-465
    • /
    • 2008
  • The present study was undertaken to investigate the effect of in vivo administration of neem oil intra-peritoneally (i.p.) to mice bearing a progressively growing transplantable T cell lymphoma of spontaneous origin, designated as Daltons lymphoma (DL), on the tumor growth. Mice were administered various doses of neem oil mixed in groundnut oil, which was used as a diluting vehicle or for administration to control DL-bearing mice. Administration of neem oil resulted in an acceleration of tumor growth along with a reduction in the survival time of the tumor-bearing host. Neem oil administered DL-bearing mice showed an augmented apoptosis in splenocytes, bone marrow cells and thymocytes along with an inhibition in the anti-tumor functions of tumor-associated macrophages. Thus this study gives an altogether a novel information that neem oil instead of the popular belief of being anti-tumor and immunoaugmentary may in some tumor-bearing conditions, behave in an opposite way leading to an accelarated tumor progression along with a collapse of the host's anti-tumor machinery. These observations will thus have long lasting clinical significance, suggesting caution in use of neem oil for treatment of cancer.

ANTI-TUMOR EFFECTS OF VASCULAR ENDOTHELIAL GROWTH FACTOR INHIBITOR ON ORAL SQUAMOUS CELL CARCINOMA CELL LINES (혈관내피세포성장인자 억제제에 의한 구강편평상피세포암종 세포주의 성장 억제 효과)

  • Han, Se-Jin;Lee, Jae-Hoon
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
    • /
    • v.35 no.2
    • /
    • pp.66-73
    • /
    • 2009
  • Tumor angiogenesis is a process leading to formation of blood vessels within tumors and is crucial for maintaining a supply of oxygen and nutrients to support tumor growth and metastasis. Vascular endothelial growth factor(VEGF) plays a key role in tumor angiogenesis including induction of endothelial cell proliferation, migration, survival and capillary tube formation. VEGF binds to two distinct receptors on endothelial cells. VEGFR-2 is considered to be the dominant signaling receptor for endothelial cell permeability, proliferation, and differentiation. Bevacizumab(Avastin, Genetech, USA) is a monoclonal antibody against vascular endothelial growth factor. It is used in the treatment of cancer, where it inhibits tumor growth by blocking the formation of new blood vessels. The goal of this study is to identify the anti-tumor effect of Bevacizumab(Avastin) for oral squamous cell carcinoma cell lines. Human squamous cell carcinoma cell line(HN4) was used in this study. We examined the sensitivity of HN4 cell line to Bevacizumab(Avastin) by using in vitro proliferation assays. The results were as follows. 1. In the result of MTT assay according to concentration of Bevacizumab(Avastin), antiproliferative effect for oral squamous cell carcinoma cell lines was observed. 2. The growth curve of cell line showed the gradual growth inhibition of oral squamous cell carcinoma cell lines after exposure of Bevacizumab(Avastin). 3. In the apoptotic index, groups inoculated Bevacizumab(Avastin) were higher than control groups. 4. In condition of serum starvation, VEGFR-2 did not show any detectable autophosphorylation, whereas the addition of VEGF activated the receptor. Suppression of phosphorylated VEGFR-2 and phosphorylated MAPK was observed following treatment with Bevacizumab(Avastin) in a dose-dependent manner. 5. In TEM view, dispersed nuclear membrane, scattered many cytoplasmic vacuoles and localized chromosomal margination after Bevacizumab(Avastin) treatment were observed. These findings suggest that Bevacizumab(Avastin) has the potential to inhibit MAPK pathway in proliferation of oral squamous cell carcinoma cell lines via inhibition of VEGF-dependent tumor growth.

Combined Treatment of Herbal Mixture Extract H9 with Trastuzumab Enhances Anti-tumor Growth Effect

  • Lee, Sunyi;Han, Sora;Jeong, Ae Lee;Park, Jeong Su;Jung, Seung Hyun;Choi, Kang-Duk;Yang, Young
    • Journal of Microbiology and Biotechnology
    • /
    • v.25 no.7
    • /
    • pp.1036-1046
    • /
    • 2015
  • Extracts from Asian medicinal herbs are known to be successful therapeutic agents against cancer. In this study, the effects of three types of herbal extracts on anti-tumor growth were examined. Among the three types of herbal extracts, H9 showed stronger anti-tumor growth effects than H5 and H11 in vivo. To find the molecular mechanism by which H9 inhibited the proliferation of breast cancer cell lines, the levels of apoptotic markers were examined. Proapoptotic markers, including cleaved PARP and cleaved caspases 3 and 9, were increased, whereas the anti-apoptotic marker Bcl-2 was decreased by H9 treatment. Next, the combined effect of H9 with the chemotherapeutic drugs doxorubicin/cyclophosphamide (AC) on tumor growth was examined using 4T1-tumor-bearing mice. The combined treatment of H9 with AC did not show additive or synergetic anti-tumor growth effects. However, when tumor-bearing mice were co-treated with H9 and the targeted anti-tumor drug trastuzumab, a delay in tumor growth was observed. The combined treatment of H9 and trastuzumab caused an increase of natural killer (NK) cells and a decrease of myeloid-derived suppressor cells (MDSC). Taken together, H9 induces the apoptotic death of tumor cells while increasing anti-tumor immune activity through the enhancement of NK activity and diminishment of MDSC.

Short hairpin RNA targeting of fibroblast activation protein inhibits tumor growth and improves the tumor microenvironment in a mouse model

  • Cai, Fan;Li, Zhiyong;Wang, Chunting;Xian, Shuang;Xu, Guangchao;Peng, Feng;Wei, Yuquan;Lu, You
    • BMB Reports
    • /
    • v.46 no.5
    • /
    • pp.252-257
    • /
    • 2013
  • Fibroblast activation protein (FAP) is a specific serine protease expressed in tumor stroma proven to be a stimulatory factor in the progression of some cancers. The purpose of this study was to investigate the effects of FAP knockdown on tumor growth and the tumor microenvironment. Mice bearing 4T1 subcutaneous tumors were treated with liposome-shRNA complexes targeting FAP. Tumor volumes and weights were monitored, and FAP, collagen, microvessel density (MVD), and apoptosis were measured. Our studies showed that shRNA targeting of FAP in murine breast cancer reduces FAP expression, inhibits tumor growth, promotes collagen accumulation (38%), and suppresses angiogenesis (71.7%), as well as promoting apoptosis (by threefold). We suggest that FAP plays a role in tumor growth and in altering the tumor microenvironment. Targeting FAP may therefore represent a supplementary therapy for breast cancer.

Licochalcone A, a Major Phenolic Constituent of Glycyrrhiza inflata, Suppresses Angiogenin Expression in Colon Cancer Cells

  • Kim, Jin-Kyung
    • Biomedical Science Letters
    • /
    • v.17 no.1
    • /
    • pp.85-88
    • /
    • 2011
  • Tumor angiogenesis, which is essential for tumor growth and tumor metastasis, depends on angiogenic factors produced by tumor cells and/or infiltrating cells such as endothelial cells and immune cells in tumor tissue. Previously, we reported that licochalcone A (LicA), an important bioactive compound of Glycyrrhiza inflate, suppresses angiogenesis, tumor growth and metastasis. In this study, we evaluated the effect of LicA on angiogenin production in colon cancer cells because angiogenin is an essential factor to regulate angiogenesis and tumor progression. When we examined the angiogenin levels in three human colon cancer cells, HT-29, SW480 and Caco-2, LicA treatment significantly reduced the amounts of angiogenin among three cancer cell lines. In an in vivo study in which mice were implanted with HT-29 cells, oral administration of LicA reduced angiogenin in tumor tissues when compared with vehicle-administered mice. These results suggest that reduced angiogenin in response to LicA treatment may play essential role to inhibit tumor growth, angiogenesis as well as metastasis.