• Title/Summary/Keyword: Cancer metastasis

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Role of E-cadherin and cyclin D1 as predictive markers of aggression and clonal expansion in head and neck squamous cell carcinoma

  • Shergill, Khushdeep;Sen, Arijit;Pillai, Hari Janardanan
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.44 no.4
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    • pp.182-190
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    • 2018
  • Objectives: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide. Inconsistency in various histopathologic features for predicting nodal metastasis and overall prognosis and a better understanding of molecular mechanisms of tumourigenesis have shifted the focus to a search for more definitive predictive markers. To identify the role of two immunohistochemical (IHC) markers, E-cadherin and cyclin D1, as predictive markers of aggressiveness in HNSCC and to assess clonal expansion of tumour cells. Materials and Methods: A total of 66 cases of HNSCC with neck node dissection were studied. IHC was performed on primary tumour sections and lymph nodes showing metastatic deposits. Histopathological parameters such as tumour grade and TNM stage together with nodal status were compared according to expression of the two markers. Fischer's chi-square test was used to assess the correlation between the two markers and histopathological parameters. Results: Out of 66 cases studied, 37 showed LN metastasis. Most of the patients were male, and the most common tumour site was buccal mucosa. We found a significant association between loss of E-cadherin and node metastasis (P<0.001) and higher TNM stage (P<0.001). Cyclin D1 overexpression was significantly associated with only nodal metastasis (P=0.007). No significant association with tumour grade was found for either marker. The subgroup of E-cadherin loss with cyclin D1 overexpression was associated with the maximum incidence of nodal metastasis and higher TNM stage, highlighting the importance of using a combination of these two markers. A significant association was noted between the expression of markers at the primary site and at nodal deposits, indicating clonal expansion. Conclusion: A combination of the two markers E-cadherin and cyclin D1 can predict prognosis in HNSCC, although tumour heterogeneity may affect this association in some cases.

Effect of Korean Red Ginseng extract on colorectal lung metastasis through inhibiting the epithelial-mesenchymal transition via transforming growth factor-β1/Smad-signaling-mediated Snail/E-cadherin expression

  • Kee, Ji-Ye;Han, Yo-Han;Mun, Jeong-Geon;Park, Seong-Hwan;Jeon, Hee Dong;Hong, Seung-Heon
    • Journal of Ginseng Research
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    • v.43 no.1
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    • pp.68-76
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    • 2019
  • Background: In colorectal cancer (CRC), 40-60% of patients develop metastasis. The epithelial-mesenchymal transition (EMT) is a pivotal and intricate process that increases the metastatic potential of CRC. The aim of this study was to investigate the effect of Korean Red Ginseng extract (RGE) on colorectal metastasis through inhibition of EMT and the metastatic abilities of CRC cells. Methods: To investigate the effect of RGE on the metastatic phenotypes of CRC cells, CT26 and HT29 cells were evaluated by using an adhesion assay, a wound-healing assay, an invasion assay, zymography, and real-time reverse transcription-polymerase chain reaction. Western-blot analysis was conducted to elucidate the molecular mechanisms of RGE, which showed an inhibitory effect on the transforming growth factor-${\beta}1$ ($TGF-{\beta}1$)-induced EMT in HT29 cells. Additionally, the antimetastatic effect of RGE was evaluated in a mouse model of lung metastasis injected with CT26 cells. Results: RGE decreased the adhesion and migration ability of the CT26 cells and TGF-${\beta}1$-treated HT29 cells. The invasion ability was also reduced by RGE treatment through the inhibition of matrix metalloproteinase-9 expression and activity. Moreover, RGE suppressed the TGF-${\beta}1$-induced EMT via TGF-${\beta}1$/Smad-signaling-mediated Snail/E-cadherin expression in HT29 cells and lung tissue in CT26 tumor-bearing mice. Conclusion: Our results demonstrated that RGE inhibited colorectal lung metastasis through a reduction in metastatic phenotypes, such as migration, invasion, and the EMT of CRC cells.

Epidemiologic Study of Operative Treatment for Spinal Metastasis in Thailand : A Review of National Healthcare Data from 2005 to 2014

  • Luksanapruksa, Panya;Santipas, Borriwat;Ruangchainikom, Monchai;Korwutthikulrangsri, Ekkapoj;Pichaisak, Witchate;Wilartratsami, Sirichai
    • Journal of Korean Neurosurgical Society
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    • v.65 no.1
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    • pp.57-63
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    • 2022
  • Objective : To study the factors relating to operative treatment for spinal metastasis in Thailand during 2005-2014 and to determine the hospital costs, mortality rate, and incidence of perioperative complication. Methods : Inpatient reimbursement data from 2005 to 2014 was reviewed from three national healthcare organizations, including the National Health Security Office, the Social Security Office, and the Comptroller General's Department. The search criteria were secondary malignant neoplasm of bone and bone marrow patients (International Classification of Diseases 10th revision, Thai modification codes [ICD 10-TM], C79.5 and C79.8) who underwent spinal surgical treatment (ICD 9th revision, clinical modification procedure with extension codes [ICD 9-CM], 03.0, 03.4, 03.09, and 81.0) during 2005-2014. Epidemiology, comorbidity, and perioperative complication were analyzed. Results : During the study period, the number of spinal metastasis patients who underwent operative treatment was significantly increased from 0.30 to 0.59 per 100000 (p<0.001). More males (56.14%) underwent surgical treatment for spinal metastasis than females. The most common age group was 45-64 (55.1%). The most common primary tumor sites were the unknown origin, lung, breast, prostate, and hepatocellular/bile duct. Interestingly, the proportion of hepatocellular/bile duct, breast, and lung cancer was significantly increased (p<0.001). The number of patients who had comorbidity or in-hospital complication significantly increased over time (p<0.01); however, the in-hospital mortality rate decreased. Conclusion : During the last decade, operative treatment for spinal metastasis increased in Thailand. The overall in-hospital complication rate increased; however, the in-hospital mortality rate decreased.

Anti-Tumor Effect of IDF-11774, an Inhibitor of Hypoxia-Inducible Factor-1, on Melanoma

  • Kim, Nan-Hyung;Jeong, Jong Heon;Park, Yu Jeong;Shin, Hui Young;Choi, Woo Kyoung;Lee, Kyeong;Lee, Ai-Young
    • Biomolecules & Therapeutics
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    • v.30 no.5
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    • pp.465-472
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    • 2022
  • Melanoma is one of the most aggressive skin cancers. Hypoxia contributes to the aggressiveness of melanoma by promoting cancer growth and metastasis. Upregulation of cyclin D1 can promote uncontrolled cell proliferation in melanoma, whereas stimulation of cytotoxic T cell activity can inhibit it. Epithelial mesenchymal transition (EMT) plays a critical role in melanoma metastasis. Hypoxia-inducible factor-1α (HIF-1α) is a main transcriptional mediator that regulates many genes related to hypoxia. CoCl2 is one of the most commonly used hypoxia-mimetic chemicals in cell culture. In this study, inhibitory effects of IDF-11774, an inhibitor of HIF-1α, on melanoma growth and metastasis were examined using cultured B16F10 mouse melanoma cells and nude mice transplanted with B16F10 melanoma cells in the presence or absence of CoCl2-induced hypoxia. IDF-11774 reduced HIF-1α upregulation and cell survival, but increased cytotoxicity of cultured melanoma cells under CoCl2-induced hypoxia. IDF-11774 also reduced tumor size and local invasion of B16F10 melanoma in nude mice along with HIF-1α downregulation. Expression levels of cyclin D1 in melanoma were increased by CoCl2 but decreased by IDF-11774. Apoptosis of melanoma cells and infiltration of cytotoxic T cells were increased in melanoma after treatment with IDF-11774. EMT was stimulated by CoCl2, but restored by IDF11774. Overall, IDF-11774 inhibited the growth and metastasis of B16F10 melanoma via HIF-1α downregulation. The growth of B16F10 melanoma was inhibited by cyclin D1 downregulation and cytotoxic T cell stimulation. Metastasis of B16F10 melanoma was inhibited by EMT suppression.

Clinical Characteristics of Female Laryngeal Cancer (여성후두암의 임상적 특성)

  • Kwon Soon-Young;Jung Kwang-Yoon;Choi Jong-Ouck
    • Korean Journal of Head & Neck Oncology
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    • v.11 no.2
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    • pp.132-136
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    • 1995
  • The laryngeal cancer is a cancer of secondary sex organ, such as malignant tumors of the mammary gland, endometrium, and prostate. The clinical characteristics of the female laryngeal cancers are considered somewhat to be different from that of male. As cancer of the larynx is principally a disease of men, many investigations have showed the characteristics of the male laryngeal cancers. For understanding the clinical characteristics of the female laryngeal cancers, we analyzed 21 cases of laryngeal cancer in women, diagnosed and treated in our institute during the last 10 years. The results were, 1) In female subjects, supraglottis was most common subsite of laryngeal cancer(85.7%). 2) On histopathologic grade, the moderately differentiated squamous cell carcinoma was the most common (80.9%). 3) The positive neck nodes were 19 %, considered to be lower than that of total laryngeal cancer. 4) The treatment results, the 2 year disease free rate and 5 year survival rate were 88.9%, 83.3%, respectively. These results suggest, therefore, female laryngeal cancers are more likely to be supraglottic cancer than glottic cancer. In spite of high incidence of supraglottic cancer, the nodal metastases are rare, the prognosis appeared to be good.

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Study on the Relationship Between CXCR4 Expression and Perineural Invasion in Pancreatic Cancer

  • Jiang, Yu-Mei;Li, Guang;Sun, Bao-Cun;Zhao, Xiu-Lan;Zhou, Zhong-Kai
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.12
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    • pp.4893-4896
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    • 2014
  • Background: Recent reports have shown that C-X-C chemokine receptor 4 (CXCR4) plays an important role in metastasis. Despite a clear understanding of the protein's structure and properties, its functional role remains elusive. We conducted the present study to evaluate the expressions of CXCR4 in pancreatic cancer, and to investigate its relationship with clinicopathological parameters, especially perineural invasion(PNI). Materials and Methods: The association between CXCR4 expression and perineural invasion was determined by immunohistochemistry in pancreatic cancer patients (n=51). Results: CXCR4 expression was correlated with the existence of PNI and the type of PNI (p=0.042, p=0.040). TIMP-2 expression was also correlated with the existence, the pathway and degree of PNI (p=0.000, p=0.006, p=0.000). Conclusions: Our results suggest an association between PNI and expression of CXCR4 and TIMP-2 in pancreatic cancer. CXCR4 may promote the occurrence of PNI in pancreatic cancer cells by decreasing the inhibition of TIMPs on MMP.

Roles of Oxidative Stress in the Development and Progression of Breast Cancer

  • Nourazarian, Ali Reza;Kangari, Parisa;Salmaninejad, Arash
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.12
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    • pp.4745-4751
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    • 2014
  • Oxidative stress is caused by an imbalance in the redox status of the body. In such a state, increase of free radicals in the body can lead to tissue damage. One of the most important species of free radicals is reactive oxygen species (ROS) produced by various metabolic pathways, including aerobic metabolism in the mitochondrial respiratory chain. It plays a critical role in the initiation and progression of various types of cancers. ROS affects different signaling pathways, including growth factors and mitogenic pathways, and controls many cellular processes, including cell proliferation, and thus stimulates the uncontrolled growth of cells which encourages the development of tumors and begins the process of carcinogenesis. Increased oxidative stress caused by reactive species can reduce the body's antioxidant defense against angiogenesis and metastasis in cancer cells. These processes are main factors in the development of cancer. Bimolecular reactions cause free radicals in which create such compounds as malondialdehyde (MDA) and hydroxyguanosine. These substances can be used as indicators of cancer. In this review, free radicals as oxidizing agents, antioxidants as the immune system, and the role of oxidative stress in cancer, particularly breast cancer, have been investigated in the hope that better identification of the factors involved in the occurrence and spread of cancer will improve the identification of treatment goals.

Pristimerin Inhibits Breast Cancer Cell Migration by Up-regulating Regulator of G Protein Signaling 4 Expression

  • Mu, Xian-Min;Shi, Wei;Sun, Li-Xin;Li, Han;Wang, Yu-Rong;Jiang, Zhen-Zhou;Zhang, Lu-Yong
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.4
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    • pp.1097-1104
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    • 2012
  • Background/Aim: Pristimerin isolated from Celastrus and Maytenus spp can inhibit proteasome activity. However, whether pristimerin can modulate cancer metastasis is unknown. Methods: The impacts of pristimerin on the purified and intracellular chymotrypsin proteasomal activity, the levels of regulator of G protein signaling 4 (RGS 4) expression and breast cancer cell lamellipodia formation, and the migration and invasion were determined by enzymatic, Western blot, immunofluorescent, and transwell assays, respectively. Results: We found that pristimerin inhibited human chymotrypsin proteasomal activity in MDA-MB-231 cells in a dose-dependent manner. Pristimerin also inhibited breast cancer cell lamellipodia formation, migration, and invasion in vitro by up-regulating RGS4 expression. Thus, knockdown of RGS4 attenuated pristimerin-mediated inhibition of breast cancer cell migration and invasion. Furthermore, pristimerin inhibited growth and invasion of implanted breast tumors in mice. Conclusion: Pristmerin inhibits proteasomal activity and increases the levels of RGS4, inhibiting the migration and invasion of breast cancer cells.

Single Center Experience on Causes of Cancer Patients Visiting the Emergency Department in Southwest Turkey

  • Tanriverdi, Ozgur;Beydilli, Halil;Yildirim, Birdal;Karagoz, Ulku
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.2
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    • pp.687-690
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    • 2014
  • Background: Emergency departments are visited by cancer patients for palliation of cancer-related symptoms, management of treatment-related side effects, oncologic emergencies, co-morbidities, and/or end of life care. In this study, we aimed to identify the characteristics of cancer patients admitted to an emergency medicine department in Southwest Turkey. Materials and Methods: In this retrospective descriptive study, a total of 304 emergency department admissions of 102 patients with cancer due to medical conditions were evaluated. Descriptive statistical methods, statistical analysis for correlation, Student's t-test, chi-square tests and logistic regression test were used. Results: The majority of patients visiting to emergency departments were male (n=66, 65%) and over 65 years of age (53, 52%). Some 30% (n=31) had a lung cancer diagnosis, 32% (n=33) presentation with dyspnea, 53% (n=55) with metastasis, 30% (n=16) with multiple metastatic lesions in lung, and 68% (n=70) had a poor ECOG performance status (score 3 to 4). Conclusions: Emergency departments have valuable roles in managing and caring for patients with malignancies.

3-Deazaneplanocin A is a Promising Therapeutic Agent for Ovarian Cancer Cells

  • Shen, Liang;Cui, Jing;Pang, Ying-Xin;Ma, Yan-Hui;Liu, Pei-Shu
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.5
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    • pp.2915-2918
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    • 2013
  • Background: Recent studies have shown that 3-deazaneplanocin A (DZNep), a well-known histone methyltransferase inhibitor, disrupts polycomb-repressive complex 2 (PRC2), and induces apoptosis, while inhibiting proliferation and metastasis, in cancer cells, including acute myeloid leukemia, breast cancer and glioblastoma. However, little is known about effects of DZNep on ovarian cancer cells. Materials and Methods: We here therefore studied DZNep-treated A2780 ovarian cancer cells in vitro. Proliferation of ovarian cancer cells under treatment of DZNep was assessed by MTT and apoptosis by flow cytometry. Cell wound healing was applied to detect the migration. Finally, we used q-PCR to assess the migration-related gene, E-cadherin. Results: DZNep could inhibit the proliferation of A2780 and induce apoptosis Furthermore, it inhibited migration and increased the expression of E-cadherin (P<0.05). Conclusion: DZNep is a promising therapeutic agent for ovarian cancer cells, with potential to inhibite proliferation, induce apoptosis and decrease migration.