• Title/Summary/Keyword: cancer initiation

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Animal Models for Prostatic Cancer

  • Park, Jae-Hak
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2002.11b
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    • pp.118-130
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    • 2002
  • The frequency of prostate cancer has been increasing (1). Afflicting 10% of men older than the age of 65, it repre-sents the most frequently diagnosed cancer in American men, with an even higher incidence in the African-American population. Many investigators have tried to identify prognostic markers that distinguish indolent versus aggressive forms of prostate cancer, and to understand the genetic factors that evoke prostate cancer initiation and progression (2).(omitted)

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Effect of Fiber-Rich Sea Mustard Feeding on AOM-Induced Colon Aberrant Crypt Formation and Colonic Cell Proliferation in Sprague Dawley Rats (미역의 섭취가 화학적으로 유도된 쥐의 대장암화 표지자인 Aberrant Crypt 형성 및 상피세포 분열에 미치는 영향에 관한 연구)

  • 이은주;성미경
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.30 no.3
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    • pp.535-539
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    • 2001
  • The modulating effect of feeding sea mustard (Undarina pinnatifida), a fiber-rich seaweed, during initiation and post-initiation phases of colon carcinogenesis was investigated in Sprague Dawley rats. Four groups of animals were exposed to the two weekly injections of a chemical carcinogen, azoxymethane (AOM). Animals were placed on diet containing 15% sea mustard during initiation. post-initiation or initiation+post-initiation phase of carcinogenesis for 10 weeks, and colonic aberrant crypt formation and cell proliferation were compared to those of rats fed semi-synthetic control diet. Results showed that sea mustard feeding significantly reduced the numbers of both aberrant crypts and aberrant crypt foci. Also, labeling indices and proliferation zones were significantly reduced in the colon of the rats fed sea mustard diets. These results indicate that the diet containing sea mustard may decrease the risk of colon cancer development, and a part of such effect may be mediated through both the blocking of initiation and the suppression of cell proliferation in the colonic crypts, although precise mechanisms should be further examined.

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Contribution of TLR2 to the Initiation of Ganglioside-triggered Inflammatory Signaling

  • Yoon, Hee Jung;Jeon, Sae Bom;Suk, Kyoungho;Choi, Dong-Kug;Hong, Young-Joon;Park, Eun Jung
    • Molecules and Cells
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    • v.25 no.1
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    • pp.99-104
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    • 2008
  • Gangliosides, sialic acid-containing glycosphingolipids, are implicated in many neuronal diseases, but the precise molecular mechanisms underlying their pathological activities are poorly understood. Here we report that TLR2 participates in the initiation of ganglioside-triggered inflammatory signaling responses. Using FACS analysis and immunofluorescence microscopy, we found that gangliosides rapidly enhanced the cell surface expression of TLR2 in microglia, while reducing that of TLR4. The ganglioside-dependent increase of TLR2 expression was also observed at the messenger and protein levels. We also showed that gangliosides stimulate the interaction of TLR2 with Myd88, an adaptor for TLRs, and obtained evidence that lipid raft formation is closely associated with the ganglioside-induced activation of TLR2 and subsequent inflammatory signaling. These results collectively suggest that TLR2 contributes to the ability of gangliosides to cause inflammatory conditions in the brain.

The Multi-Faceted Consequences of NRF2 Activation throughout Carcinogenesis

  • Christopher J. Occhiuto;Jessica A. Moerland;Ana S. Leal;Kathleen A. Gallo;Karen T. Liby
    • Molecules and Cells
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    • v.46 no.3
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    • pp.176-186
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    • 2023
  • The oxidative balance of a cell is maintained by the Kelch-like ECH-associated protein 1 (KEAP1)/nuclear factor erythroid 2-related factor 2 (NRF2) pathway. This cytoprotective pathway detoxifies reactive oxygen species and xenobiotics. The role of the KEAP1/NRF2 pathway as pro-tumorigenic or anti-tumorigenic throughout stages of carcinogenesis (including initiation, promotion, progression, and metastasis) is complex. This mini review focuses on key studies describing how the KEAP1/NRF2 pathway affects cancer at different phases. The data compiled suggest that the roles of KEAP1/NRF2 in cancer are highly dependent on context; specifically, the model used (carcinogen-induced vs genetic), the tumor type, and the stage of cancer. Moreover, emerging data suggests that KEAP1/NRF2 is also important for regulating the tumor microenvironment and how its effects are amplified either by epigenetics or in response to co-occurring mutations. Further elucidation of the complexity of this pathway is needed in order to develop novel pharmacological tools and drugs to improve patient outcomes.

Oxaliplatin Induced Angioedema in a Rectal Cancer Patient: A Clinical Case Report (직장암 환자에서 Oxaliplatin 투여로 인한 혈관부종 발생 증례 보고)

  • Noh, Mi-Hee;Lee, Yu-Jeung
    • Korean Journal of Clinical Pharmacy
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    • v.21 no.4
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    • pp.390-393
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    • 2011
  • We report an unusual case of angioedema induced by intravenous oxaliplatin in a patient with rectal cancer. Intravenous oxaliplatin was administered to the patient according to FOLFOX regimen (oxaliplatin/leucovorin/5-fluorouracil) for the management of his colorectal carcinoma. The patient had been on FOLFOX regimen for several months without reporting any adverse effects, but he experienced angioedema suddenly during his $9^{th}$ cycle of chemotherapy. Angioedema was observed about 2 hours after the initiation of oxaliplatin infusion. Oxaliplatin was stopped then the patient became stable. This case report demonstrates that intravenous oxaliplatin may induce angioedema several hours after the initiation of oxaliplatin infusion in later cycles of chemotherapy.

Function of hepatocyte growth factor in gastric cancer proliferation and invasion

  • Koh, Sung Ae;Lee, Kyung Hee
    • Journal of Yeungnam Medical Science
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    • v.37 no.2
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    • pp.73-78
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    • 2020
  • Cancer incidence has been increasing steadily and is the leading cause of mortality worldwide. Gastric cancer is still most common malignancy in Korea. Cancer initiation and progression are multistep processes involving various growth factors and their ligands. Among these growth factors, we have studied hepatocyte growth factor (HGF), which is associated with cell proliferation and invasion, leading to cancer and metastasis, especially in gastric cancer. We explored the intercellular communication between HGF and other surface membrane receptors in gastric cancer cell lines. Using complimentary deoxyribonucleic acid microarray technology, we found new genes associated with HGF in the stomach cancer cell lines, NUGC-3 and MKN-28, and identified their function within the HGF pathway. The HGF/N-methyl-N'-nitroso-guanidine human osteosarcoma transforming gene (c-MET) axis interacts with several molecules including E-cadherin, urokinase plasminogen activator, KiSS-1, Jun B, and lipocalin-2. This pathway may affect cell invasion and metastasis or cell apoptosis and is therefore associated with tumorigenesis and metastasis in gastric cancer.

The effect of caffeine on initiation step of diethylnitrosamine-initiated hepatic altered foci in a mid-term induction system (Caffeine이 diethylnitrosamine에 의해 유도되는 preneoplastic hepatic altered foci 형성의 initiation 단계에 미치는 효과)

  • Kim, Sung-ho;Lee, Cha-soo
    • Korean Journal of Veterinary Research
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    • v.31 no.3
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    • pp.337-342
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    • 1991
  • Caffeine이 랫트의 간조직에서 diethylnitrosamine(200mg/kg B.W., DEN)에 의해 유도되는 preneoplastic altered foci형성의 initiation단계에 미치는 효과를 관찰한 바 다음과 같은 결과를 얻었다. Altered foci의 지표로 사용되는 glutathione S-transferase(GST-P)-positive foci의 수는 caffeine 음수수 ml 당 2mg병행투여군 $(7.48{\pm}3.33)$ 및 1mg 병행 투여군 $(7.50{\pm}3.32)$ 모두에서 DEN 단독투여대조군$(14.08{\pm}5.16)$에 비하여 현저히 낮게 나타났으며, 면적 또한 caffeine 2mg병행투여군 $(0.29{\pm}0.17)$, 1mg병행투여군 $(0.30{\pm}0.13)$에서 DEN단독투여대조군 $(0.46{\pm}0.21)$에 비하여 유의성 있는 낮은 수치가 관찰되었다. 이러한 결과는 caffeine이 간암발생의 initiation 단계에 작용하여 억제효과를 나타냄을 암시하였다.

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Role of MicroRNAs in the Warburg Effect and Mitochondrial Metabolism in Cancer

  • Jin, Li-Hui;Wei, Chen
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.17
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    • pp.7015-7019
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    • 2014
  • Metabolism lies at the heart of cell biology. The metabolism of cancer cells is significantly different from that of their normal counterparts during tumorigenesis and progression. Elevated glucose metabolism is one of the hallmarks of cancer cells, even under aerobic conditions. The Warburg effect not only allows cancer cells to meet their high energy demands and supply biological materials for anabolic processes including nucleotide and lipid synthesis, but it also minimizes reactive oxygen species production in mitochondria, thereby providing a growth advantage for tumors. Indeed, the mitochondria also play a more essential role in tumor development. As information about the numorous microRNAs has emerged, the importance of metabolic phenotypes mediated by microRNAs in cancer is being increasingly emphasized. However, the consequences of dysregulation of Warburg effect and mitochondrial metabolism modulated by microRNAs in tumor initiation and progression are still largely unclear.

Analysis of Motivating Factors for Smokeless Tobacco Use in Two Indian States

  • Danawala, Saba Ashraf;Arora, Monika;Stigler, Melissa Harrell
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.16
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    • pp.6553-6558
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    • 2014
  • Background: This study was conducted to gauge how the demographic profile of smokeless tobacco (SLT) users from Gujarat and Andhra Pradesh, India, differs from that of smokers. It also addresses how factors associated with the initiation and continuation of smokeless tobacco vary by age, gender, and education. Materials and Methods: We analyzed 2011 cross-sectional survey data collected from 4,759 respondents (smokers/SLT users/non-users) in both states. Chi-square analysis was used to make comparisons between the demographic profiles of smokers and SLT users. Multivariable logistic regression analysis was used to obtain the odds ratios (ORs) for initiation and continuation factors regressed on socio-demographic variables (age, gender, education). Results: Initiation-women were less likely than men to report "peer pressure", "fashion statement", and "stress/coping" as relevant factors for SLT use (OR: 0.45 CI: 0.30-0.70; OR: 0.42 CI: 0.24-0.74; OR: 2.47, CI: 1.47-4.15). Older age groups had lower odds of choosing "peer pressure" than the 15-24 year olds. Respondents with 11 or more years of education were more likely to report "stress/coping" than those with no education (OR: 2.82, CI: 1.06-7.48). Continuation-women were less likely than men to choose "relaxation", and "distance from family" as important continuation factors (OR: 0.50, CI:0.32-0.80; OR: 0.20, CI: 0.06-0.65). All age groups were less likely to choose "stimulation" as a factor than the youngest group. Conclusions: Along with confirming and expanding upon previous literature, the findings of this study should encourage further SLT research in women and younger age groups (15-24 and 24-44). They also confirm the need for SLT prevention and cessation interventions in India in other community-based settings, besides schools.

Third-line Hormonal Therapy to Treat Prostate Cancer Relapse after Initial and Second-line Hormonal Therapy: Report of 52 Cases and Literature Review

  • Matsumoto, Kazuhiro;Hagiwara, Masayuki;Hayakawa, Nozomi;Tanaka, Nobuyuki;Ito, Yujiro;Maeda, Takahiro;Ninomiya, Akiharu;Nagata, Hirohiko;Nakamura, So
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.8
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    • pp.3645-3649
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    • 2014
  • The aim of this study was to evaluate the efficacy of third-line combined androgen blockade (CAB) therapy for castration-resistant prostate cancer that relapsed after primary and second-line CAB. We retrospectively reviewed the medical records of 52 patients who received first-, second-, and third-line CAB therapy (medical or surgical castration, plus steroidal antiandrogen of chlormadinone acetate, or nonsteroidal antiandrogen of flutamide or bicalutamide). For cumulative analysis, we searched the PubMed database and identified a total of 50 cases published in English. Including our cases, this provided a total of 102 cases for analysis. In our study cohort, 11 cases (21.2%) achieved more than 50% reduction of serum prostate-specific antigen (PSA) on initiation of third-line CAB. We found that third-line CAB with nonsteroidal antiandrogen after second-line CAB with steroidal antiandrogen exhibited favorable results, with a positive response in six of 13 patients (46.2%). Cumulative analysis findings were comparable. Regarding the timing of third-line CAB administration, 15 patients had started at a PSA equal to or less than 4.0 ng/ml, and eight of them (53.3%) showed a positive response to treatment, compared to only three of 37 patients (8.1%) whose PSA at the initiation of third-line therapy was higher than 4.0 ng/ml (p<0.001). We conclude that third-line CAB with nonsteroidal antiandrogen would be particularly useful for patients whose cancer progressed after second-line CAB with steroidal antiandrogen. The timing of treatment seems to be important because the higher the PSA at the start of third-line therapy, the lower the PSA response rate.