• Biomolecules & Therapeutics
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• 제31권4호
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• pp.456-465
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• 2023

Cervical tumors represent a prevalent form of cancer affecting women worldwide; current treatment options involve surgery, radiotherapy, and chemotherapy. Angiogenesis, the process of new blood vessel formation, is a crucial factor in cervical tumor growth. The molecular mechanisms underlying the effects of the liver kinase B1 (LKB1/STK11) tumor suppressor protein on tumor angiogenesis have not been elucidated. Therefore, we investigated the role of LKB1 in cervical tumor angiogenesis both in vitro and in vivo in this study. Our results demonstrated that LKB1 inhibited cervical tumor angiogenesis by suppressing the expression of angiogenesis-related factors such as vascular endothelial growth factor (VEGF) and hypoxia inducible factor-1α. LKB1 directly affected both carcinoma and vascular endothelial cells, resulting in a significant reduction in tumor growth and angiogenesis. Furthermore, LKB1 was found to bind to VEGF receptor 2 (VEGFR-2) and target the VEGFR-2-mediated protein kinase B/mechanistic target of rapamycin signaling pathway in endothelial cells, thereby reducing cervical tumor growth and angiogenesis. Our study provides new insights into the molecular mechanisms underlying the anti-tumor and anti-angiogenic effects of LKB1 in cervical cancer. These findings will help develop new therapeutic strategies for cervical cancer.

• 대한의생명과학회지
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• 제17권1호
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• pp.85-88
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• 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.

• 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.

• Journal of Korean Neurosurgical Society
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• 제62권2호
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• pp.256-262
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• 2019

Objective : Pituitary adenomas (PAs) are often detected as incidental findings. However, the natural history remains unclear. The objective of this study was to evaluate the natural history and growth pattern of untreated PAs. Methods : Between 2003 and 2014, 59 PAs were managed with clinico-radiological follow up for longer than 12 months without any kind of therapeutic intervention. Tumor volumes were calculated at initial and last follow-up visit, and tumor growth during the observation period was determined. Data were analyzed according to clinical and imaging characteristics. Results : The mean initial and last tumor volume and diameter were $1.83{\pm}2.97mL$ and $13.77{\pm}6.45mm$, $2.85{\pm}4.47mL$ and $15.75{\pm}8.08mm$, respectively. The mean annual tumor growth rate was $0.33{\pm}0.68mL/year$ during a mean observation period of $46.8{\pm}32.1months$. Sixteen (27%) PAs showed tumor growth. The initial tumor size (HR, 1.140; 95% confidence interval, 1.003-1.295; p=0.045) was the independent predictive factor that determined the tumor growth. Six patients (11%) of 56 conservatively managed non-symptomatic PAs underwent resection for aggravating visual symptoms with mean interval of 34.5 months from diagnosis. By Cox regression analysis, PAs of last longest diameter over 21.75 mm were a significant prognostic factor for eventual treatment. Conclusion : The initial tumor size of PAs was independently associated with the tumor growth. Six patients (11%) of conservatively managed PAs were likely to be treated eventually. PAs of last follow-up longest diameter over 21.75 mm were a significant prognostic factor for treatment. Further studies with a large series are required to determine treatment strategy.

• East Asian mathematical journal
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• 제36권1호
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• pp.81-90
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• 2020

Many compartment models assume a kinetically homogeneous amount of materials that have well-stirred compartments. However, based on observations from such processes, they have been heuristically fitted by exponential or gamma distributions even though biological media are inhomogeneous in real environments. Fractional differential equations using a specific kernel in Pharmacokinetic/Pharmacodynamic (PKPD) model are recently introduced to account for abnormal drug disposition. We discuss a tumor growth inhibition (TGI) model using fractional-order derivative from it. This represents a tumor growth delay by cytotoxic agents and additionally show variations in the equilibrium points by the change of fractional order. The result indicates that the equilibrium depends on the tumor size as well as a change of the fractional order. We find that the smaller the fractional order, the smaller the equilibrium value. However, a difference of them is the number of concavities and this indicates that TGI over time profile for fitting or prediction should be determined properly either fractional order or tumor sizes according to the number of concavities shown in experimental data.

• Asian Pacific Journal of Cancer Prevention
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• 제14권5호
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• pp.3079-3083
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• 2013

Objective: To investigate the effects of endostar, a recombined humanized endostatin, plus cisplatin on the growth, lymphangiogenesis and lymphatic metastasis of the Lewis lung carcinoma (LLC) in mice. Methods: A tumor model were established in C57BL/6 mice by intravenious transplantation of LLC cells. Then the mice were randomized to receive administration with NS, endostar, cisplatin, or endostar plus cisplatin. After the mice were sacrificed, tumor multiplicity, tumor size and lymph node metastasis were assessed. Then the expression of vascular endothelial growth factor-c (VEGF-C) and podoplanin were determined by immunohistochemical staining. Results: Endostar plus cisplatin significantly suppressed tumor growth. lymphatic metastasis and prolonged survival time of the mice without obvious toxicity. The inhibition of lymphatic metastasis was associated with decreased microlymphatic vessel density (MLVD) and expression of VEGF-C. Conclusions: Endostar combined with cisplatin was more effective to suppress tumor growth and lymphatic metastasis than either agent alone. Thus this may provide a rational alternative for lung carcinoma treatment.

• 대한의생명과학회지
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• 제25권4호
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• pp.398-406
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• 2019

Cancer immunotherapy using gene-modified tumor cells is safe and customized cancer treatment method. In this study, we made gene-modified tumor cells by transferring costimulatory molecules, 4-1BBL and OX40L, into tumor cells using lentivirus vector, and identified anti-cancer effect of gene-modified tumor cells in CT26 mouse colorectal tumor model. We construct pLVX-puro-4-1BBL, -OX40L vector for lentivirus production and optimized the transfection efficiency and transduction efficiency. The transfection efficiency is maximal at DNA:cationic polymer = 1:0.5 and DNA 2 ㎍ for lentivirus production. Then, the lentiviral including 4-1BBL and OX40L was used to deliver CT26 mouse tumor cells to establish optimal delivery conditions according to the amount of virus. The transduction efficiency is maximal at 500 μL volume of lentiviral stock without change in cell shape or growth rate. CT26-4-1BBL, CT26-OX40L significantly inhibited the tumor growth compare with CT26-WT or CT26-β-gal cell line. These data showed the possibility the use of genetically modified tumor cells with costimulatory molecule as cancer immunotherapy agent.

• 식물조직배양학회지
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• 제27권3호
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• pp.203-211
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• 2000

흰독말풀의 tumor조직에서 유도한 tumor callus로부터 scopolamine의 생산을 극대화하기 위한 연구를 수행하였다. Tumor callus의 생장률을 증가시키기 위해서는 초기접종량을 배지의 2%로 하고 배양기간은 4주가 효과적이다. 그래서 만일 이단계배양을 추진하려면 배지교체의 시기는 3주가 가장 적당한 것으로 확인되었다. Scopolamine의 생성을 위한 광의 효과를 알아본 결과, 암상태보다 광상태가 callus생장 및 scopolamine 함량 증가에 효과적이었다. Scopolamine 함량 증가의 최적 광량은 16$\mu$mo1 m$^{-2}$ s$^{-1}$, 광질은 적색파장 그리고 연속광보다 장일조건 (16/8)의 광주기에서 tropane alkaoid인 scopolamine합성이 현저히 촉진되었다. 질소원으로는 산화형 질소인 NO$_{3}$$^{-}$ 를 4 g/L로 증가시키는 것이 가장 효과적인 것으로 확인되었다. Scopolamine의 함량을 증가시키기 위한 elicitor 공급은 10 mg/L chitosan과 15 mg/L yeast추출물이 가장 효과적이었으며, 전구물질로는 0.2 mM tropine과 0.3 mM tropic acid가 가장 우수한 것으로 확인되었다. 이러한 결과를 종합해 보면, 흰독말풀 tumor callus에서 scopolamine 대량생산을 추진할 경우 3주 동안 광상태와 무기이온 조성을 균형 있게 조절하여 생장을 최대로 증가시킨 후, 1주 동안 scopolamine생산을 위해 elicitor, precursors 등이 조합된 배지에서 biotransformation 시키는 것이 가장 효과적일 것으로 판단된다. 또한 tumor callus에 $^{60}$Co${\gamma}$-ray을 조사하여 3K, 4K및 6k tumorcallus를 확보하였으며, 이들로부터 유도한 teratoma는 형태적 변이를 나타내었다. Teratoma로부터 또 다시 새로운 teratoma-callus 세포주를 유도하여 현탁배양을 수행하였던 바, MS 기본 배지에서 1.0 mg/L 2.4-D과 0.5 mg/L kinetin을 조합하여 처리한 callus 의 액체배양에서 cell aggregation이 일어나지 않고 세포가 유리화 되면서 왕성한 생장을 보였다.

• 한국산학기술학회:학술대회논문집
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• 한국산학기술학회 2011년도 춘계학술논문집 2부
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• pp.1068-1071
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• 2011

Cyclooxygenases (COX)-2 has been highly expressed in a variety of tumor cells and involved inflammatory process, tumor-associated angiogenesis, and vascular functions but the underlying mechanism is not clearly elucidated. We here investigated the molecular mechanism by which COX-2 regulates tumor-associated angiogenesis. In vivo, we injected B16-F1 cells overexpressed with COX-2 or mock in wild type or eNOS-deficient mice. Tumor cells overexpressed with COX-2 increase tumor-associated angiogenesis and tumor growth compared with control cells and that the effect of COX-2 was lower in eNOS-deficient mice than wild type mice. These results may contribute to further understanding of the regulation of angiogenesis by COX during tumor metastasis and inflammation.

• Asian Pacific Journal of Cancer Prevention
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• 제16권5호
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• pp.2061-2068
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• 2015

Background: Tumors are largely unable to metabolize ketone bodies for energy due to various deficiencies in one or both of the key mitochondrial enzymes, which may provide a rationale for therapeutic strategies that inhibit tumor growth by administration of a ketogenic diet with average protein but low in carbohydrates and high in fat. Materials and Methods: Thirty-six male BALB/C nude mice were injected subcutaneously with tumor cells of the colon cancer cell line HCT116. The animals were then randomly split into three feeding groups and fed either a ketogenic diet rich in omega-3 fatty acids and MCT (MKD group; n=12) or lard only (LKD group; n=12) or a standard diet (SD group; n=12) ad libitum. Experiments were ended upon attainment of the target tumor volume of $600mm^3$ to $700mm^3$. The three diets were compared for tumor growth and survival time (interval between tumor cell injection and attainment of target tumor volume). Results: The tumor growth in the MKD and LKD groups was significantly delayed compared to that in the SD group. Conclusions: Application of an unrestricted ketogenic diet delayed tumor growth in a mouse xenograft model. Further studies are needed to address the mechanism of this diet intervention and the impact on other tumor-relevant parameters such as invasion and metastasis.