• Title/Summary/Keyword: metastatic cells

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Inhibition of Transient Receptor Potential Melastain 7 Enhances Apoptosis Induced by TRAIL in PC-3 cells

  • Lin, Chang-Ming;Ma, Ji-Min;Zhang, Li;Hao, Zong-Yao;Zhou, Jun;Zhou, Zhen-Yu;Shi, Hao-Qiang;Zhang, Yi-Fei;Shao, En-Ming;Liang, Chao-Zhao
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.10
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    • pp.4469-4475
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    • 2015
  • Transient receptor potential melastain 7 (TRPM7) is a bifunctional protein with dual structure of both ion channel and protein kinase, participating in a wide variety of diseases including cancer. Recent researches have reported the mechanism of TRPM7 in human cancers. However, the correlation between TRPM7 and prostate cancer (PCa) has not been well studied. The objective of this study was to investigate the potential the role of TRPM7 in the apoptosis of PC-3 cells, which is the key cell of advanced metastatic PCa. In this study, we demonstrated the influence and potential function of TRPM7 on the PC-3 cells apoptosis induced by TNF-related apoptosis inducing-ligand (TRAIL). The study also found a novel up-regulated expression of TRPM7 in PC-3 cells after treating with TRAIL. Suppression of TRPM7 by TRPM7 non-specific inhibitors ($Gd^{3+}$ or 2-aminoethoxy diphenylborate (2-APB) ) not only markedly eliminated TRPM7 expression level, but also increased the apoptosis of TRAIL-treated PC-3 cells, which may be regulated by the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway accompany with up-regulated expression of cleaved Caspase-3, (TRAIL-receptor 1, death receptors 4) DR4, and (TRAIL-receptor 2, death receptors 5) DR5. Taken together, our findings strongly suggested that TRPM7 was involved in the apoptosis of PC-3 cells induced by TRAIL, indicating that TRPM7 may be applied as a therapeutic target for PCa.

Endothelial Cell Proliferation and Vascular Endothelial Growth Factor Expression in Primary Colorectal Cancer and Corresponding Liver Metastases

  • Raluca, Balica Amalia;Cimpean, Anca Maria;Cioca, Andreea;Cretu, Octavian;Mederle, Ovidiu;Ciolofan, Alexandru;Gaje, Pusa;Raica, Marius
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.11
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    • pp.4549-4553
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    • 2015
  • Background: Colorectal carcinoma (CRC) is one of the major causes of cancer death worldwide. Data from the literature indicate differences between the proliferation rate of endothelial cells relative to the morphology growth type, possibly due to origin of specimens (autopsy material, surgery fragments) or quantification methods. Vascular endothelial growth factor (VEGF) is a factor that stimulates the proliferation of endothelial cells. It is expressed in more than 90% of cases of metastatic CRC. Aim: The aim of this study was to evaluate the endothelial cell proliferation and VEGF expression in primary tumors and corresponding liver metastases. Materials and Methods: Our study included 24 recent biopsies of primary tumors and corresponding liver metastases of CRC cases. CD34/Ki67 double immunostaining and RNA scope assay for VEGF were performed. Results: In the primary tumors analysis of VEGFmRNA expression indicated no significant correlation with differentiation grade, proliferative and non-proliferative vessels in the intratumoral and peritumoral areas. In contrast, in the corresponding liver metastases, VEGFmRNA expression significantly correlated with the total number of non-proliferative vessels and total number of vessels. CD34/Ki67 double immunostaining in the cases with poorly differentiated carcinoma indicated a high number of proliferating endothelial cells in the peritumoral area and a low number in the intratumoral area for the primary tumor. Moderately differentiated carcinomas of colon showed no proliferating endothelial cells in the intratumoral area in half of the cases included in the study, for both, primary tumor and liver metastasis. In well differentiated CRCs, in primary tumors, a high proliferation rate of endothelial cells in the intratumoral area and a lower proliferation rate in the peritumoral area were found. A low value was found in corresponding liver metastasis. Conclusions: The absence of proliferative endothelial cells in half of the cases for the primary tumors and liver metastases in moderately differentiated carcinoma suggest a vascular mimicry phenomenon. The mismatch between the total number of vessels and endothelial proliferation in primary tumors indicate that a functional vascular network is already formed or the existence of some mechanisms influenced by other angiogenic factors.

Proteomic Analysis and the Antimetastatic Effect of N-(4methyl)phenyl-O-(4-methoxy) phenyl-thionocarbamate-Induced Apoptosis in Human Melanoma SK-MEL-28 cells

  • Choi Su-La;Choi Yun-Sil;Kim Young-Kwan;Sung Nack-Do;Kho Chang-Won;Park Byong-Chul;Kim Eun-Mi;Lee Jung-Hyung;Kim Kyung-Mee;Kim Min-Yung;Myung Pyung-Keun
    • Archives of Pharmacal Research
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    • v.29 no.3
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    • pp.224-234
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    • 2006
  • We employed human SK-MEL-28 cells as a model system to identify cellular proteins that accompany N-(4-methyl)phenyl-O-(4-methoxy)phenyl-thionocarbamate (MMTC)-induced apoptosis based on a proteomic approach. Cell viability tests revealed that SK-MEL-28 skin cancer cells underwent more cell death than normal HaCaT cells in a dose-dependent manner after treatment with MMTC. Two-dimensional electrophoresis in conjunction with matrixassisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry analysis or computer matching with a protein database further revealed that the MMTC-induced apoptosis is accompanied by increased levels of caspase-1, checkpoint suppressor-1, caspase-4, NF-kB inhibitor, AP-2, c-Jun-N-terminal kinase, melanoma inhibitor, granzyme K, G1/S specific cyclin D3, cystein rich protein, Ras-related protein Rab-37 or Ras-related protein Rab-13, and reduced levels of EMS (oncogene), ATP synthase, tyrosine-phosphatase, Cdc25c, 14-3-3 protein or specific structure of nuclear receptor. The migration suppressing effect of MMTC on SK-MEL-28 cell was tested. MMTC suppressed the metastasis of SK-MEL-8 cells. It was also identified that MMTC had little angiogenic effect because it did not suppress the proliferation of HUVEC cell line. These results suggest that MMTC is a novel chemotherapeutic and metastatic agents against the SK-MEL-28 human melanoma cell line.

THE ROLE OF TUMOR-ASSOCIATED MACROPHAGES ON MICROVESSEL DENSITY AFTER NEOADJUVANT CHEMOTHERAPY IN TONGUE CANCER (설암에서 신부가화학요법후 미세혈관밀도에 대한 종양관련 대식세포의 역할)

  • Park, Bong-Wook;Chung, In-Kyo;Kim, Jong-Ryoul;Kim, Uk-Kyu;Park, Bong-Soo;Kim, Gyoo-Cheon;Byun, June-Ho
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.32 no.3
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    • pp.209-215
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    • 2006
  • Preoperative neoadjuvant chemotherapy using cisplatin and 5-FU is generally given in oral and maxillofacial cancer. At tissue level both inflammation and fibrosis occur after chemotherapy. The cellular changes mimic those of a granulating wound, with activated macrophages and fibroblasts replacing the malignant cells as they are erradicated. Stromal cells, together with extracellular matrix components, provide the microenvironment that is pivotal for tumor cell growth, invasion, and metastatic progression. Vascular endothelial growth factor(VEGF), an important regulator of angiogenesis in cancer, induces mitogenesis of vascular endothelial cells, and vascular permeabilization and microvessel formation in a tumor are associated with tumor nutrition and oxygenation. Also, they are associated with chemotherapeutic drug delivery. Oxygen delivery to tumor appears to rely on a network of microvessels, On the other hand, the tumor microvessel is clearly an important factor in chemotherapeutic drug delivery to cancer cells, and the efficacy of drug delivery can be high in richly vascularized tumors. So, this study was conducted to evaluate the effect of neoadjuvant chemotherapy on microvessel density from 11 patients with tongue cancers. Our results showed that neoadjuvant chemotherapy was seemed to decrease VEGF expression in tumor cells, however, it did not significantly alter VEGF expression in tumor-associated macrophages. Also, Neoadjuvant chemotherapy had little effect on the microvessel density using CD34, and tumor-associated macrophage level using CD68. Thus, tumorassociated macrophages seem to be the key factor associated with the maintenance of microvessel density after neoadjuvant chemotherapy in tongue cancer.

Inhibition of Migration and Invasion of LNCap Human Prostate Carcinoma Cells by Doxorubicin through Inhibition of Matrix Metalloproteinase Activity and Tightening of Tight Junctions (Doxorubicin에 의한 치밀결합 강화 및 MMPs의 활성 억제를 통한 LNCap 전립선 암세포의 이동성 및 침윤성의 억제)

  • Choi, Yung Hyun;Shin, Dong Yeok;Kim, Wun-Jae
    • Journal of Life Science
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    • v.24 no.6
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    • pp.700-706
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    • 2014
  • Doxorubicin (trade name adriamycin), an anthracycline antibiotic, is commonly used in the treatment of a wide range of cancers, including hematological malignancies, many types of carcinoma, and soft tissue sarcomas. It is closely related to the natural product daunomycin, and like all anthracyclines, it works by intercalating DNA. Its most serious adverse effect is life-threatening heart damage. Its anti-metastatic mechanisms in human prostate carcinomas are not fully understood. In this study, we used LNCap human prostate carcinoma cells to investigate the inhibitory effects of doxorubicin on cell motility and invasion, two critical cellular processes that are often deregulated during metastasis. Doxorubicin treatment inhibited cell migration and invasiveness of LNCap cells without showing any toxicity. Doxorubicin treatment also suppressed the activity and expression of matrix metalloproteinase (MMP)-2 and MMP-9, which were associated with up-regulated expression of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 in LNCap cells. Doxorubicin treatment also attenuated the expression levels of claudin family members (claudin-1, -2,-3 and -4), major components of tightening of tight junctions (TJs) and increased the tightening of TJs, as demonstrated by an increase in transepithelial electrical resistance. The present findings demonstrate that doxorubicin reduces the migration and invasion of prostate carcinomas LNCap cells by modulating the activity of TJs and MMPs.

Analysis of Anti-Tumor Activity of Flammulina velutipes Extract on B16 cells (B16 흑색종에 대한 팽이버섯 추출물의 항암활성 비교)

  • Lee, Si-Rim;Nam, Dong-Yun;Lee, Hyun-Jin;Park, Chul-Hong;Heo, Jin-Chul;Kim, Jong-Guk;Lee, Jin-Man;Lee, Chang-Yun;Park, Hee-Ju;Lee, Sang-Han
    • Food Science and Preservation
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    • v.16 no.4
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    • pp.599-603
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    • 2009
  • To evaluate the anti-tumor activity of Flammulina velutipes extract, we used an in vitro wound-healing assay, and an in vivo approach using a mouse melanoma model. Wound-healing activity in B16 cells was affected by the extract in a dose-dependent manner, indicating that the extract had anti-metastatic activity. The extract also exhibited strong anti-tumor activity against lung cancer when B16 cells were injected into mouse veins together with B16 melanoma cells. The results indicatethat the Flammulina velutipes extract decreased B16 cancer cell growth by inhibition of cell migration both in vitro and in vivo.

BLT2, a leukotriene B4 receptor 2, as a novel prognostic biomarker of triple-negative breast cancer

  • Park, JaeIn;Jang, Jae-Hyun;Park, Geun-Soo;Chung, Yunro;You, Hye Jin;Kim, Jae-Hong
    • BMB Reports
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    • v.51 no.8
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    • pp.373-377
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    • 2018
  • Triple-negative breast cancer (TNBC) is considered to be a notorious type of cancer due to its aggressive metastatic potential and poor prognosis. Recent evidence suggests that BLT2, a low-affinity $LTB_4$ receptor is critically associated with the phenotypes of TNBC cells, including invasion, metastasis, and survival. Furthermore, in a group of 545 breast cancer patients with metastasis, we observed that the high-BLT2 subgroup had a lower disease-free-survival rate than the low-BLT2 subgroup. Thus, we theorized that anti-BLT2 strategies could facilitate the development of new therapies used for TNBC. This review focuses on recent discoveries regarding BLT2 and its roles in as a novel prognostic biomarker in TNBC.

A Case of Thyroid Metastasis from Nasopharyngeal Carcinoma (갑상선으로 전이된 비인강암 1예)

  • Kim Min-Sik;Yoo Young-Hwa;Cho Kwang-Jae;Cho Seung-Ho
    • Korean Journal of Head & Neck Oncology
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    • v.18 no.2
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    • pp.203-206
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    • 2002
  • Metastatic carcinomas to the thyroid gland are rare, and thyroid involvement by secondary carcinomas commonly results from direct the extension of malignant cells from adjacent organs such as the larynx or the trachea. The common primary sites of thyroid metastasis are kidney, breast, lung, and lymphoid tissue. Among head and neck cancers, nasopharyngeal carcinoma has a relatively high incidence of distant metastases to other sites and commonly involving sites are bone, lung, and liver. Recently, we experienced a case of a 43-year-old male who had been presented with neck mass for 3 months. He was diagnosed non-keratinizing nasopharyngeal carcinoma in 1993. And, thyroid metastasis of nasopharyngeal carcinoma was confirmed by total thyroidectomy. So we report this rare case with the review of literatures.

Electron Microscopic Study on Fine Needle Aspiration Cytology of Metastatic Malignant Melanoma (세침흡인 검체의 전자현미경 검색으로 진단된 전이성 악성 흑색종 1예)

  • Lee, Dong-Wha;Jin, So-Young;Kwon, Kye-Hyun
    • The Korean Journal of Cytopathology
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    • v.3 no.2
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    • pp.82-89
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    • 1992
  • Electron microscopy (EM) can provide a valuable contribution to light microscopy (LM) In the Interpretation of fine needle aspiration cytology (FNAC) specimen, especially in the diagnosis of the tumor. However, considerable care in processing the specimen is mandatory to recover the cells and avoid altering the fine structures. We experienced a case of malignant melanoma in 33-yrs-old female, diagnosed by EM study of FNAC specimen from the axillary mass, who was initially thought as disseminated carcinomatosis on LM study. The technique of EM study on FNAC specimen consisted of washing the needle and syringe in 2.5% glutaraldehyde after a rapid stain (Diff-Quik), which was used to obtain a preliminary diagnostic impression and to assure the adequacy of the EM specimen. After centrifugation in the steps of fixation and dehydration, the sediment was made into an epon block and examined. The whole processing time of EM study can be shortened within 7 or 8 hours, and results can be available within 48 to 72 hours. Our experience suggests the EM study on FNAC can be a useful diagnostic method in the diagnosis of difficult FNAC cases.

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Metastatic lipid-rich mammary carcinoma in a dog

  • Kim, Myung-Chul;Kim, So-Yeon;Lee, Su-Hyung;Kim, Dae-Yong;Yoon, Jung-Hee;Kim, Wan Hee;Lee, Jeong-Ha;Kim, Yongbaek
    • Korean Journal of Veterinary Research
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    • v.54 no.4
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    • pp.265-268
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    • 2014
  • An adult female dog was presented for evaluation of mammary gland masses. Complete blood count and serum chemistry data were within normal limits. Fine-needle aspiration cytology of the mammary masses revealed clusters of malignant epithelial cells with clear cytoplasmic vacuoles. Based on histopathological findings, a diagnosis of lipid-rich mammary carcinoma was made. Approximately 5 weeks after surgical removal, the tumor recurred at the surgery site and metastasis to the tibia was detected. Due to the poor prognosis and deterioration of the condition, the dog was euthanized.