• Title/Summary/Keyword: Anti-metastatic

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What is the Mechanism of Progression with Trastuzumab Treatment - Escape or Resistance?

  • Sendur, Mehmet Ali Nahit;Aksoy, Sercan;Ozdemir, Nuriye Yildirim;Zengin, Nurullah;Altundag, Kadri
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.11
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    • pp.5915-5916
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    • 2012
  • Human epidermal growth factor receptor (HER) 2 overexpression, observed in 20-25 percent of invasive breast cancers, is well known to be associated with a more aggressive phenotype and poor prognosis, with resistance to certain chemotherapeutic agents. The majority of patients with metastatic breast cancer who initially respond to trastuzumab, demonstrate disease progression within 1 year of treatment initiation. Furthermore, lack of response in some patients and relapse during the course of therapy, continue to challenge researchers and clinicians. A better understanding of the fundamental mechanisms of trastuzumab action is required so that new therapies directed at HER2 can be developed. We present here findings for mechanisms, both of Trastuzumab action and clinical resistance or escape.

Sesquicillin, an Extracellular Matrix Adhesion Inhibitor, Inhibits the Invasion of B16 Melanoma Cells In vitro

  • Lee, Ho-Jae;Chun, Hyo-Kon;Chung, Myung-Chul;Lee, Choong-Hwan;Kho, Yung-Hee
    • Journal of Microbiology and Biotechnology
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    • v.9 no.1
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    • pp.119-121
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    • 1999
  • Tumor cell interaction with the extracellular matrix is defined as the critical event of tumor invasion that signals the initiation of a metastatic cascade. Sesquicillin has been identified as an inhibitor of melanoma cell adhesion to the components of the extracellular matrix (ECM) in cultured broth of fungal strain F60063. Sesquicillin strongly inhibited the adhesion of B16 melanoma cells to laminin, fibronectin, and typeIV collagen. It also inhibited B16 melanoma cell invasion of reconstituted basement membrane Matrigel in vitro in a dose-dependent manner. These results suggest that sesquicillin is a new class of nonpeptidic ECM adhesion inhibitor having anti-invasive activity.

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Anti-angiogenic Activity of Ursolic Acid (우르솔릭산의 혈관형성 억제활성)

  • 손경희;이옥희;이열남;정해영;이정준;김규원
    • YAKHAK HOEJI
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    • v.37 no.5
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    • pp.532-537
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    • 1993
  • Angiogenesis refers to the formation of new capillary blood vessels, or neovascularization occurring under various physical conditions, such as development of the embryo, formation of corpus luteum, wound healing and pathological conditions including tumor growth and metastases, hemangiomas, diabetic retinopathy, rheumatoid arthritis. There are many evidences that angiogenesis is important for the progressive growth of solid tumors and also permits the shedding of metastatic tumors from the primary site. Thus, treatment of angiogenesis inhibitors might be a novel strategy for tumor growth inhibition. Normal vascular endothelial cells are in a state of differentiation and angiogenic endothelial cells migrate and proliferate, and they subsequently differentiate into vessel-forming quiescent phenotype cells, Therfore, it was speculated that a modifier of cell differentiation could also affect angiogenesis. In order to identify new antiangiogenic factors, the research was conducted to estimate the inhibitory activities of cell differentiation agents by means of chick embryo chorioallantoic membrane(CAM) assay. Hence, we have established the CAM assay for the screening of antiangiogenic agents. Using the CAM assay, we found that ursolic acid, a tumor cell differentiation-inducing agent, showed a markedly inhibitory effect on chick embryonic angiogenesis.

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Role of GALNT14 in lung metastasis of breast cancer

  • Kim, Mi-Young
    • BMB Reports
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    • v.50 no.5
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    • pp.233-234
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    • 2017
  • Aberrant expression of the polypeptide N-acetyl-galactosaminyltransferase (GALNTs) has been associated with cancer, but their function(s) in metastasis remains elusive. We have recently identified GALNT14, one of the O-GalNAc glycosylation-initiating enzymes, as a prognostic marker for pulmonary relapse in breast cancer patients. Furthermore, we showed that GALNT14 promotes lung metastasis by the following novel mechanisms: 1) enhancing metastasis initiation by inhibiting the anti-metastatic effect of BMP produced from the lung stroma, 2) exploiting growth signals (e.g. FGF) supplied by macrophages, for their growth into macrometastases in the lung environment. These multi-faceted roles of GALNT14 in lung metastasis are achieved by GALNT14-mediated inhibition and activation of the BMP and FGF signaling pathways, respectively. The link among GALNT14, its downstream pathways and lung metastasis, provides us with an opportunity to develop effective therapeutic intervention for breast cancer.

Brain metastasis in human epidermal growth factor receptor 2-positive breast cancer: from biology to treatment

  • Koo, Taeryool;Kim, In Ah
    • Radiation Oncology Journal
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    • v.34 no.1
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    • pp.1-9
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    • 2016
  • Overexpression of human epidermal growth factor receptor 2 (HER2) is found in about 20% of breast cancer patients. With treatment using trastuzumab, an anti-HER2 monoclonal antibody, systemic control is improved. Nonetheless, the incidence of brain metastasis does not be improved, rather seems to be increased in HER2-positive breast cancer. The mainstay treatment for brain metastases is radiotherapy. According to the number of metastatic lesions and performance status of patients, radiosurgery or whole brain radiotherapy can be performed. The concurrent use of a radiosensitizer further improves intracranial control. Due to its large molecular weight, trastuzumab has a limited ability to cross the blood-brain barrier. However, small tyrosine kinase inhibitors such as lapatinib, has been noted to be a promising agent that can be used as a radiosensitizer to affect HER2-positive breast cancer. This review will outline general management of brain metastases and will focus on preclinical findings regarding the radiosensitizing effect of small molecule HER2 targeting agents.

Cancer Chemopreventive Potential of Procyanidin

  • Lee, Yongkyu
    • Toxicological Research
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    • v.33 no.4
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    • pp.273-282
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    • 2017
  • Chemoprevention entails the use of synthetic agents or naturally occurring dietary phytochemicals to prevent cancer development and progression. One promising chemopreventive agent, procyanidin, is a naturally occurring polyphenol that exhibits beneficial health effects including anti-inflammatory, antiproliferative, and antitumor activities. Currently, many preclinical reports suggest procyanidin as a promising lead compound for cancer prevention and treatment. As a potential anticancer agent, procyanidin has been shown to inhibit the proliferation of various cancer cells in "in vitro and in vivo". Procyanidin has numerous targets, many of which are components of intracellular signaling pathways, including proinflammatory mediators, regulators of cell survival and apoptosis, and angiogenic and metastatic mediators, and modulates a set of upstream kinases, transcription factors, and their regulators. Although remarkable progress characterizing the molecular mechanisms and targets underlying the anticancer properties of procyanidin has been made in the past decade, the chemopreventive targets or biomarkers of procyanidin action have not been completely elucidated. This review focuses on the apoptosis and tumor inhibitory effects of procyanidin with respect to its bioavailability.

A Case of Metastatic Brain Tumor Patient with Nausea and Vomiting Treated with Gamibokryungbanha-tang (전이성 뇌종양 환자에게 발생한 오심(惡心), 구토(嘔吐)에 대해 가미복령반하탕으로 호전된 치험 1례)

  • Jeong, Jong-Soo;Park, Jae-Woo;Yoon, Seong-Woo
    • The Journal of Internal Korean Medicine
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    • v.28 no.4
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    • pp.956-962
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    • 2007
  • In cancer patients showing nausea and vomiting, a number of factors can be considered as the cause including brain tumor, electrolyte imbalance, gastrointestinal diseases or types of chemotherapy agents and dose of the drugs. Though nausea and vomiting can be minimized through the use of various anti-emetic drugs, many people still suffer from severe nausea and vomiting with poor quality of life compared with patients who do not show significant nausea and vomiting. In this report, we introduce a case of a cancer patient who suffered from severe nausea and vomiting. The patient was female and 59 years old with NSCLC (non small cell lung cancer) with metastatic brain tumor. Though western conventional medical treatment was used to reduce the symptoms, persistent nausea and vomiting were noted during the admission period. Herbal decoction Gamibokryungbanha-tang was used for nausea and vomiting which were uncontrolled under conventional western medicine; the patient showed remarkable improvement in terms of frequency and severity of nausea and vomiting. Further study will be needed in order to determine the long-term effectiveness of oriental medical treatment on cancer patient with nausea and vomiting.

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Dendrosomal Curcumin Inhibits Metastatic Potential of Human SW480 Colon Cancer Cells through Down-regulation of Claudin1, Zeb1 and Hef1-1 Gene Expression

  • Esmatabadi, Mohammad Javad Dehghan;Farhangi, Baharak;Safari, Zahra;Kazerooni, Hanif;Shirzad, Hadi;Zolghadr, Fatemeh;Sadeghizadeh, Majid
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.6
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    • pp.2473-2481
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    • 2015
  • Colon cancer is one of the leading causes of cancer-associated death worldwide. The prognosis for advanced colorectal cancers remains dismal, mainly due to the propensity for metastatic progression. Accordingly, there is a need for effective anti-metastasis therapeutic agents. Since a great body of research has indicated anticancer effects for curcumin, we investigated the effects of dendrosomal curcumin (DNC) on cellular migration and adhesion of human SW480 cells and possible molecular mechanisms involved. Different methods were applied in this study including MTT, Scratch and adhesion assays as well as real-time PCR and transwell chamber assays. Based on the results obtained, DNC inhibits metastasis by decreasing Hef 1, Zeb 1 and Claudin 1 mRNA levels and can reduce SW480 cell proliferation with $IC_{50}$values of 15.9, 11.6 and $7.64{\mu}M$ at 24, 48 and 72h post-treatment. Thus it might be considered as a safe formulation for therapeutic purpose in colorectal cancer cases.

Inhibitory Effect of BCG Cell-Wall Skeletons (BCG-CWS) Emulsified in Squalane on Tumor Growth and Metastasis in Mice

  • Yoo, Yung-Choon;Hata, Katsusuke;Lee, Kyung-Bok;Azuma, Ichiro
    • Archives of Pharmacal Research
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    • v.25 no.4
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    • pp.522-527
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    • 2002
  • The antimetastatic effect of BCG-CWS, which was emulsified in an oil-in-water form with either Drakeol 6VR mineral oil (BCG-CWS/DK) or squalane (BCG-CWS/SQA), on lung metastasis produced by highly metastatic murine tumor cells, Colon26-M3.1 carcinoma cells and B16-BL6 melanoma cells, was investigated in syngeneic mice. An intravenous (i.v.) administration of BCG-CWS (100 mg/mouse) 1 day after tumor inoculation significantly inhibited tumor metastasis of both Colon26-M3.1 carcinoma and B16-BL6 melanoma cells in experimental lung metastasis models. No differences in the antitumor activity of the two oil-based formulations (BCG-CWS/DK and BCG-CWS/SQA) were obverved. However, BCG-CWS/SQA administered through subcutaneous (s.c.) route was shown to be effective only when it was consecutively injected (3 times) after tumor inoculation. An in vivo analysis for tumor-induced angiogenesis shwed that a single i.v. administration of BCG-CWS/SQA inhibited the number of tumor-induced blood vessels and suppressed tumor growth. Furthermore, the multiple administration of BCG-CWS/SQA given at on week intervals led to a significant reduction in spontaneous lung metastasis of B16-BL6 melanoma cells in a spontaneous metastasis model. These results suggest that BCG-CWS emulsified with squalane is a potent inhibitory agent of lung metastasis, and that the anti metastatic effect of BCG-CWS is related to the suppression of tumor growth and the inhibition of tumor-induced angiogenesis.