• Title/Summary/Keyword: cancer progression

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Role of Neoadjuvant Chemotherapy in the Management of Advanced Ovarian Cancer

  • Zhao, Dan;Wu, Ling-Ying;Wang, Xiao-Bing;Li, Xiao-Guang
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.6
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    • pp.2369-2373
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    • 2015
  • Objective: To analyze efficacy of neoadjuvant chemotherapy for advanced ovarian cancer. Materials and Methods: A total of 107 patients with advanced ovarian cancer undergoing cytoreductive surgery were divided into a neoadjuvant chemotherapy group (n=61) and a primary debulking group (n=46) and retrospectively analyzed. Platinum-based adjuvant chemotherapy was applied to both groups after cytoreductive surgery ande overall and progression-free survival times were calculated. Results: No significant difference was observed in duration of hospitalization ($20.8{\pm}6.1$ vs. $20.2{\pm}5.4$ days, p>0.05). The operation time of neoadjuvant chemotherapy group was shorter than the initial surgery group ($3.1{\pm}0.7$ vs. $3.4{\pm}0.8$ h, p<0.05). There were no significant differences in median overall survival time between neoadjuvant chemotherapy group and surgery group (42 vs. 55 months, p>0.05). Similarly, there was no difference in median progression-free survival between neoadjuvant chemotherapy group and surgery group (16 vs. 17 months, p>0.05). The surgical residual tumor size demonstrated no significant difference between initial surgery and neoadjuvant chemotherapy groups (p>0.05). Multivariate analysis showed that more than 3 cycles of regimen with neoadjuvant chemotherapy was associated with more resistance to chemotherapy compared with patients without receiving neoadjuvant chemotherapy (OR: 5.962, 95%CI: 1.184-30.030, p<0.05). Conclusions:Neoadjuvant chemotherapy can shorten the operation time. However, it does not improve survival rates of advanced ovarian cancer patients.

14-bp Insertion/Deletion Polymorphism of the HLA-G gene in Breast Cancer among Women from North Western Iran

  • Haghi, Mehdi;Feizi, Mohammad Ali Hosseinpour;Sadeghizadeh, Majid;Lotfi, Abbas Sahebghadam
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.14
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    • pp.6155-6158
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    • 2015
  • Background: The human leukocyte antigen-G (HLA-G) gene is highly expressed in cancer pathologies and is one strategy used by tumor cells to escape immune surveillance. A 14-bp insertion/deletion (InDel) polymorphism of the HLA-G gene has been suggested to be associated with HLA-G mRNA stability and the expression of HLA-G. The aim of present study was to assess any genetic association between this polymorphism and breast cancer among Iranian-Azeri women. Materials and Methods: In this study 227 women affected with breast cancer, in addition to 255 age-sex and ethnically matched healthy individuals as the control group, participated. Genotyping was performed using polymerase chain reaction and electrophoresis assays. The data were compiled according to the genotype and allele frequencies, compared using the Chi-square test. Statistical significance was set at P<0.05. Results: In this case-control study, no significant difference was found between the case and control groups at allelic and genotype levels, although there is a slightly higher allele frequency of HLA-G 14bp deletion in breast cancer affected group. However,when the stage I subgroup was compared with stage II plus stage III subgroup of affected breast cancer, a significant difference was seen with the 14 bp deletion allele frequency. The stage II-III subgroup patients had higher frequency of deletion allele (57.4% vs 45.8%) than stage I cases (${\chi}^2=4.16$, p-value=0.041). Conclusions: Our data support a possible action of HLA-G 14bp InDel polymorphism as a potential genetic risk factor for progression of breast cancer. This finding highlights the necessity of future studies of this gene to establish the exact role of HLA-G in progression steps of breast cancer.

LINC01232 Promotes Gastric Cancer Proliferation through Interacting with EZH2 to Inhibit the Transcription of KLF2

  • Liu, Jing;Li, Zhen;Yu, Guohua;Wang, Ting;Qu, Guimei;Wang, Yunhui
    • Journal of Microbiology and Biotechnology
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    • v.31 no.10
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    • pp.1358-1365
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    • 2021
  • To clarify the role of long intergenic nonprotein-coding RNA 1232 (LINC01232) in the progression of gastric cancer and the potential mechanism, we analyzed the expression of LINC01232 in TCGA database using the GEPIA online tool, and the LINC01232 level in gastric cancer cell lines was detected by quantitative real time-polymerase chain reaction (qRT-PCR) as well. Cell proliferation assay, colony formation assay, transwell assay and tumor formation experiment in nude mice were conducted to observe the biological behavior changes of gastric cancer cells through the influence of LINC01232 knockdown. LncATLAS database and subcellular isolation assay were used for subcellular distribution of LINC01232 in gastric cancer cells. The interaction among LINC01232, zeste homolog 2 (EZH2) and kruppel-like factor 2 (KLF2) was clarified by RNA-protein interaction prediction (RPISeq), RNA immunoprecipitation (RIP), qRT-PCR and chromatin immunoprecipitation (ChIP) assay. Rescue experiments were further conducted to elucidate the biological function of LINC01232/KLF2 axis in the progression of gastric cancer. LINC01232 was upregulated in stomach adenocarcinoma (STAD) tissues and gastric cancer lines. LINC01232 knockdown inhibited the proliferative capacities of gastric cancer cells in vitro, and impaired in vivo tumorigenicity. LINC01232 was mainly distributed in the cell nucleus where it epigenetically repressed KLF2 expression via binding to the enhancer of EZH2, which was capable of binding to promoter regions of KLF2 to induce histone H3 lysine 27 trimethylation (H3K27me3). LINC01232 exerts oncogenic activities in gastric cancer via inhibition of KLF2, and therefore, the knockdown of KLF2 could reverse the regulatory effect of LINC01232 in the proliferative ability of gastric cancer cells.

Galectin-1 Promotes Gastric Carcinoma Progression and Cisplatin Resistance Through the NRP-1/c-JUN/Wee1 Pathway

  • Zhengyang Pan;Guoxi Xu;Yan Zhang;Meiling Wu;Jiahui Yu;Xujun He;Wei Zhang;Junfeng Hu
    • Journal of Gastric Cancer
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    • v.24 no.3
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    • pp.300-315
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    • 2024
  • Purpose: Gastric cancer (GC) is among the deadliest malignancies and the third leading cause of cancer-related deaths worldwide. Galectin-1 (Gal-1) is a primary protein secreted by cancer-associated fibroblasts (CAFs); however, its role and mechanisms of action of Gal-1 in GC remain unclear. In this study, we stimulated GC cells with exogenous human recombinant galectin-1 protein (rhGal-1) to investigate its effects on the proliferation, migration, and resistance to cisplatin. Materials and Methods: We used simulated rhGal-1 protein as a paracrine factor produced by CAFs to induce GC cells and investigated its promotional effects and mechanisms in GC progression and cisplatin resistance. Immunohistochemical (IHC) assay confirmed that Gal-1 expression was associated with clinicopathological parameters and correlated with the expression of neuropilin-1 (NRP-1), c-JUN, and Wee1. Results: Our study reveals Gal-1 expression was significantly associated with poor outcomes. Gal-1 boosts the proliferation and metastasis of GC cells by activating the NRP-1/C-JUN/Wee1 pathway. Gal-1 notably increases GC cell resistance to cisplatin The NRP-1 inhibitor, EG00229, effectively counteracts these effects. Conclusions: These findings revealed a potential mechanism by which Gal-1 promotes GC growth and contributes to chemoresistance, offering new therapeutic targets for the treatment of GC.

Status of Oxidative Stress and Antioxidant Levels in Smokers with Breast Cancer from Western Nepal

  • Nagamma, T.;Baxi, Jalaj;Singh, P.P.
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.21
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    • pp.9467-9470
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    • 2014
  • Background: Research indicates that oxidative stress induced by smoking plays a role in breast cancer. In view of these reports, we aimed to study th relationship between smoking and oxidative stress in breast cancer patients from the western region of Nepal. Materials and Methods: The study included a control group of 42 females (non-smoking healthy women) and a test group sudivided into Group I consisting of 46 female breast cancer patients who were smokers and Group II consisting of 42 non-smoking breast cancer patients. Detailed history of the patients was collected with the help of pre-test proforma. Plasma levels of malondialdehyde (MDA), total antioxidant activity (TAA) which represents total dietary antioxidants, vitamin C and ${\alpha}$- tocopherol were estimated by standard methods. Statistical analysis was done using SPSS version 16. Results: The plasma MDA, TAA, vitamin C and ${\alpha}$- tocopherol were $1{\pm}1.4nmol/ml$, $918{\pm}207{\mu}mol/L$, $1{\pm}0.24mg/dL$ and $0.94{\pm}0.31mg/dL$ in controls, $5{\pm}1.2nmol/ml$, $458{\pm}166{\mu}mol/L$, $0.64{\pm}0.32mg/dL$ and $0.5{\pm}0.3mg/dL$ in Group-I and $2.56{\pm}1.2nmol/ml$, $663{\pm}178{\mu}mol/L$, $0.78{\pm}0.2mg/dL$ and $0.77{\pm}0.2mg/dL$ in Group- II, respectively. Vitamin C, ${\alpha}$- tocopherol and TAA (p=0.001) were significantly reduced whereas MDA (p=0.001) was significantly raised in Group-I when compared to controls and Group-II. Conclusions: We observed a significant rise in oxidative stress and low levels of antioxidants in breast cancer patients with smoking habit. It is well known that free radicals facilitate the progression of breast cancer, possibly increasing the risk of progression to the next stage.

Combination Effect of Nimotuzumab with Radiation in Colorectal Cancer Cells (대장암 세포에서 EGFR 저해제 Nimotuzumab의 방사선 병합 효과)

  • Shin, Hye-Kyung;Kim, Mi-Sook;Jeong, Jae-Hoon
    • Radiation Oncology Journal
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    • v.28 no.3
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    • pp.147-154
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    • 2010
  • Purpose: To investigate the radiosensitizing effect of the selective epidermal growth factor receptor (EGFR) inhibitor nimotuzumab in human colorectal cancer cell lines. Materials and Methods: Four human colorectal cancer cell lines, HCT-8, LoVo, WiDr, and HCT-116 were treated with nimotuzumab and/or radiation. The effects on cell proliferation, viability, and cell cycle progression were measured by MTT, clonogenic survival assay, flow cytometry, and Western blot. Results: An immunoblot analysis revealed that EGFR phosphorylation was inhibited by nimotuzumab in colorectal cancer cell lines. Under these experimental conditions, pre-treatment with nimotuzumab increased radiosensitivity of colorectal cancer cell lines, except for cell line HCT-116. However, cell proliferation or cell cycle progression was not affected by the addition of nimotuzumab, irrespective of irradiation. Conclusion: Nimotuzumab enhanced the radiosensitivity of colorectal cancer cells in vitro by inhibiting EGFR-mediated cell survival signaling. This study provided a rationale for the clinical application of the selective EGFR inhibitor, nimotuzumab in combination with radiation in colorectal cancer cells.

Oxaliplatin, 5-Fluorouracil and Leucovorin (FOLFOX-4) as First Line Chemotherapy in Elderly Patients with Advanced Gastric Cancer

  • Haghighi, Shirin;Kasbkar, Hadi;Esmaeilpour, Keihan;Yasaei, Mehrdad
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.7
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    • pp.3277-3280
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    • 2016
  • Background: Gastric cancer is considered the fourth most common cancer and second most common cause of cancer-related mortalities worldwide. Gastric cancer develops more frequently among elderly. The oxaliplatin/5FU/leucovorin (FOLFOX) regimen has shown a notable activity against gastric cancer. Aim: To evaluate the responses and complications of FOLFOX-4 regimen as first line chemotherapy in elderly patients with advanced gastric cancer. Materials and Methods: From October 2014 to November 2015, a total of 21 patients with metastatic or local AGC (advanced gastric cancer) were analyzed. All patients were administered a FOLFOX-4 regimen consisting of a 2h infusion of oxaliplatin $85mg/m^2$ (day 1), continuous infusion of $1000mg/m^2$ 5-Fu in 24h., and leucovorin $200mg/m^2$ in 2h infusion as a first-line chemotherapy. Results: A total of 18 patients were assessable for efficacy and toxicity. One of 18 patients achieved a complete response, and 12 had partial responses, giving an overall response rate of 72.6%. Three (16%) patients demonstrated stable disease and 2 (12%) progression. The median progression free survival was 7.3 months, and the median overall survival was 11.9 months. One patient had grade 3 neuropathy. No other grade 3 or 4 NCI-CTC were seen. Conclusions: The FOLFOX-4 regimen used in our study was both active and acceptable for AGC in elderly patients as neoadjuvant and main therapy.

Overexpression of Twist and Matrix Metalloproteinase-9 with Metastasis and Prognosis in Gastric Cancer

  • Gao, Xing-Hui;Yang, Xue-Qin;Wang, Bi-Cheng;Liu, Shao-Ping;Wang, Fu-Bing
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.9
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    • pp.5055-5060
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    • 2013
  • Objective: Twist, a basic helix-loop-helix transcription factor, plays a key role in the metastatic progression of human cancer. Matrix metalloproteinase (MMP)-9 is an endopeptidase that digests basement membrane type IV collagen, therefore being possibly related to tumor progression. It has been reported that Twist and matrix metalloproteinase-9 (MMP-9) are expressed in gastric cancers. However, the exact roles of Twist and MMP-9 in tumor metastasis and prognosis remain unclear. The aim of this study was to casts light on this question. Methods:Twist and MMP-9 expression in tissue sections of 37 gastric carcinomas was evaluated with immunohistochemistry. The staining results were compared with clinicopatholgic features and to patients' outcome. Results: Twist positive expression was significantly increased in gastric cancer cases with lymph node metastasis (P=0.023). But no correlations were found between MMP-9 overexpression and clinicopathologic features, such as recurrence, TNM stage, and lymph node metastasis. Overall survival (OS) was significantly correlated with recurrence, serosa invasion, TNM stages, distant metastasis, and MMP-9 (P=0.027, 0.021, 0.000, 0.024 and 0.036, respectively). Disease-free survival (DFS) was prominently related to recurrence location, serosa invasion and TNM stages (P=0.000, 0.038 and 0.003, respectively). In the Cox regression multivariate analysis, TNM stage, distant metastasis and MMP-9 were significantly associated with prognosis of gastric cancer (P=0.002, 0.019, and 0.032, respectively). Conclusions: This study showed Twist positive expression to be significantly correlated with lymph node metastasis in gastric cancer. MMP-9 overexpression is associated with OS, suggesting that MMP-9 is a prognostic indicator for survival in patients with gastric cancer.

Synthesis of Novel Pyrazolinecarbothioamide and Evaluation of Its Anti-Cancer Activity (새로운 피라졸린카르보티오아미드 화합물의 합성과 항암효과)

  • Koh, Dongsoo
    • Journal of Applied Biological Chemistry
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    • v.55 no.3
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    • pp.191-194
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    • 2012
  • Novel pyrazolinecarbothioamide (5) was synthesized from chalcone (3) which was prepared from 2'-hydroxy-1'-acetonaphthone (1) and 2-methoxy benzaldehyde (2). Treatment of pyrazolinecarbothioamide (5) on HCT116 cancer cell showed upregulation of p21 and downregulation of cyclin D1 protein. Flowcytometer analysis revealed that pyrazolinecarbothioamide (5) controls the expression of cell cycle regulatory proteins, which blocks cell cycle progression of HCT116 cancer cell at the G1 phase.

Syndecan as a Messenger to Link Diabetes and Cancer

  • Kim, Sung-Jin;Raman, Os Sethu
    • Biomolecules & Therapeutics
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    • v.19 no.3
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    • pp.267-273
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    • 2011
  • Syndecans are membrane-anchored proteoglycans and implicated in the pathogenesis of cancer progression and metastasis. Syndecans also play important roles in interacting with growth factors, extracellular matrix and other cell surface molecules such as IGF-1 receptor. In the present review, we discuss about the syndecan structure, their role in signaling with other receptors, in addition to its general biology. The emerging roles of syndecans in the pathophysiology of human diseases, especially insulin resistance, diabetes and cancer is discussed.