GLORIA

GEOMAR Library Ocean Research Information Access

X

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
  • American Association for Cancer Research (AACR)  (14)
  • 1
    Online Resource
    Online Resource
    Abstract 6217: Inhibiting ataxia-telangiectasia mutated and RAD3-related (ATR) by BAY 1895344 overcomes chemoresistance to oxaliplatin and promotes synergistic anti-tumor effect in pancreatic cancer
    American Association for Cancer Research (AACR) ; 2023
    In:  Cancer Research Vol. 83, No. 7_Supplement ( 2023-04-04), p. 6217-6217
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 83, No. 7_Supplement ( 2023-04-04), p. 6217-6217
    Abstract: Pancreatic Ductal Adenocarcinoma (PDAC) is a highly aggressive disease with a poor prognosis and a limited response to most of the treatments. Despite a platinum-based drug such as oxaliplatin or cisplatin is one of the most effective chemotherapy drugs for PDAC, resistance to it is a major limiting factor in PDAC treatment, indicating an urgent need for new approaches. Recently, targeting major DNA damage response (DDR) regulators such as ATM (Ataxia-telangiectasia mutated) or ATR (Ataxia telangiectasia mutated and Rad3-related) kinase has shown therapeutic potential in cancer treatment. This shows that it may be possible to enhance the responsiveness of platinum medicines via a DDR inhibition strategy. The most recently developed ATR inhibitor with the greatest potency, BAY 1895344, showed an anti-proliferative effect in clinical trials. Here, we aimed to evaluate the effect of ATR inhibition using BAY 1895344 on responsiveness to oxaliplatin in pancreatic cancer, for the first time. CFPAC-1 and Capan-2 are selected among six kinds of pancreatic cancer cell lines as oxaliplatin-sensitive and -resistant cells, respectively. According to BRAID analysis, combining the BAY 1895344 and oxaliplatin resulted in strong synergistic effects in both cell lines, particularly in Capan-2. The synergism is also confirmed in all four organoids derived from PDAC patients. We found that p-Chk1, coordinating DDR and cell cycle checkpoint, was considerably suppressed by the combined treatments, which was associated with elevated γ-H2AX intensity, cell cycle arrest and apoptosis. Moreover, we investigated the in vivo synergistic anti-tumor efficacy of combination therapy using a tumor-bearing nude mice model with CFPAC-1 and Capan-2 cells, demonstrating a substantial reduction of tumor growth in combination therapy when compared to single treatment. In conclusion, ATR inhibition enhanced the anticancer effect of oxaliplatin, and this combined therapeutic strategy may be effective in overcoming chemo-resistance in PDAC. (This study is supported by National Cancer Center, Republic of Korea (No. 2212470, 2010330)) Citation Format: Hye Won Shon, Jung Won Chun, Jeong Eun Gong, Mi Rim Lee, Yu-Sun Lee, Sumin Kang, Sunshin Kim, Sang Myung Woo, In Rae Cho, Woo Hyun Paik, Woo Jin Lee, Ji Kon Ryu, Yong-Tae Kim, Sang Hyub Lee, Yun-Hee Kim. Inhibiting ataxia-telangiectasia mutated and RAD3-related (ATR) by BAY 1895344 overcomes chemoresistance to oxaliplatin and promotes synergistic anti-tumor effect in pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6217.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2023-6217
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2023
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 2
    Online Resource
    Online Resource
    Abstract 3682: Enhanced anticancer effect of 5-fluorouracil loaded into thermoresponsive conjugated linoleic acid-incorporated poloxamer hydrogel on metastastic colon cancer models
    American Association for Cancer Research (AACR) ; 2010
    In:  Cancer Research Vol. 70, No. 8_Supplement ( 2010-04-15), p. 3682-3682
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 70, No. 8_Supplement ( 2010-04-15), p. 3682-3682
    Abstract: Background: 5-Fluorouracil (5-FU) is a useful chemotherapeutic agent in the treatment of solid tumors. However, it is very short half-life in plasma circulation greatly limited the in vivo antitumor efficacy, and intravenous 5FU injection is unlikely to achieve optimal dose effectiveness within peritoneal cavity. Conjugated linoleic acid-coupled Pluronic F127 (Plu-CLA) is an effective drug delivery system with numerous advantages and has an anticancer activity. It was also shown that paclitaxel loaded in Plu-CLA demonstrated synergistic tumor suppression through robust cell cycle arrest and enhanced apoptosis in tumor compared to paclitaxel in poloxamer hydrogel. The aim of this work is to evaluate the therapeutic efficacy of Plu-CLA as a new intraperitoneal 5FU delivery system. Methods: Cytotoxicity was evaluated by using CT-26 murine colon carcinoma cell. We established peritoneal metastasis models and hepatic metastasis models for colon cancer using BALB/c mice and firefly luciferase-expressing CT-26 (CT26/Fluc) cells. Tumor progression and response to therapy were monitored by bioluminescence imaging (BLI). Results: MTT assay indicated that 5-FU loaded in Plu-CLA hydrogel (P-FU) could increase the cytotoxic activity of 5-FU in CT-26. P-FU significantly enhanced apoptosis compared with 5-FU control. It was found that Caspase 3 and p21 were up-regulated, whereas Bcl-2 was down-regulated. Moreover, growth of hepatic metastases in vivo was significantly reduced in mice treated with P-FU. Treatment with P-FU substantially delayed tumor growth of intraperitoneal metastasis greatly and tumor-bearing mice treated with P-FU showed a better survival tendency than the 5-FU alone. Conclusion: These results were attributed to the synergistic effect of Plu-CLA. 5-FU administered in Plu-CLA hydrogel led to significant enhancement of tumor growth suppression and cellular apoptosis. Therefore, Plu-CLA could be a potential intraperitoneal carrier for hydrophilic 5-FU for the effective treatment of metastatic colon cancer. . Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3682.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM10-3682
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2010
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 3
    Online Resource
    Online Resource
    Aerosol Delivery of Glucosylated Polyethylenimine/Phosphatase and Tensin Homologue Deleted on Chromosome 10 Complex Suppresses Akt Downstream Pathways in the Lung of K- ras Null Mice
    American Association for Cancer Research (AACR) ; 2004
    In:  Cancer Research Vol. 64, No. 21 ( 2004-11-01), p. 7971-7976
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 64, No. 21 ( 2004-11-01), p. 7971-7976
    Abstract: Difficulties in achieving long-term survival of lung cancer patients treated with conventional therapies suggest that novel approaches are required. Although several genes have been investigated for antitumor activities using gene delivery, problems surrounding the methods used such as efficiency, specificity, and toxicity hinder its application as an effective therapy. This has lead to the re-emergence of aerosol gene delivery as a noninvasive approach to lung cancer therapy. In this study, glucosylated conjugated polyethylenimine (glucosylated PEI) was used as carrier. After confirming the efficiency of glucosylated PEI carriers in lungs, the potential effects of the phosphatase and tensin homologue deleted on chromosome 10 (PTEN) tumor suppressor gene on Akt downstream pathways were investigated. Aerosol containing glucosylated PEI and recombinant plasmid pcDNA3.0-PTEN complex was delivered into K-ras null lung cancer model mice through a nose-only inhalation system. Investigation of proteins in the phosphatidylinositol 3′-kinase/Akt signaling pathway in PTEN-delivered mouse lung revealed that the PTEN protein was highly expressed, whereas the protein levels of PDK1, total Akt1, phospho-(Thr-308)-Akt, phospho-(Ser-2448)-mTOR, p70S6K, and 4E-BP1 were decreased to varying degrees. Additionally, the kinase activities of both Akt and mTOR were suppressed. Finally, apoptosis was detected in PTEN-delivered mouse lung by terminal deoxynucleotidyltransferase-mediated nick end labeling assay, suggesting that our aerosol PTEN delivery is capable of functionally altering cell phenotype in vivo. In summary, Western blot analysis, kinase assays, immunohistochemistry, and terminal deoxynucleotidyltransferase-mediated nick end labeling assays suggest that our aerosol gene delivery technique is compatible with in vivo gene delivery and can be applied as a noninvasive gene therapy.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/0008-5472.CAN-04-1231
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2004
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 4
    Online Resource
    Online Resource
    Abstract 5930: Oral siRNA delivery for colorectal liver metastases cancer therapy
    American Association for Cancer Research (AACR) ; 2018
    In:  Cancer Research Vol. 78, No. 13_Supplement ( 2018-07-01), p. 5930-5930
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 78, No. 13_Supplement ( 2018-07-01), p. 5930-5930
    Abstract: Liver metastasis (CLM) is the lethal secondary hepatic cancer with 5 - 20 months' average survival rate and mostly originated from colorectal cancer (CRC). Surgery and systemic chemotherapy are the currently best options to treat patients. However, over 60% of recurrence rate and severe side effects such as sinusoidal obstruction syndrome and nodular regenerative hyperplasia from the systemic chemotherapy significantly impact on patient's recovery from the treatment. To overcome these side effects and also achieve the synergistic therapeutic effect, we developed a dual padlock system (AR-GT) for oral siRNA delivery to regulate PI3K/Akt signaling pathway, which is highly associated with the progression of CRC to CLM. AR-GT is an about 130 nm nanoparticle consisted of a gold nanoparticle core anchoring siAkt RNA (AR) and a single outer layer of glycol chitosan-taurocholic acid (GT) conjugate. GT layer plays several roles in oral siRNA delivery such as the protection of siRNA in the gastrointestinal (GI) environment, facilitation of ileac uptake of AR-GT in the small intestine and transportation of AR-GT through enterohepatic circulation into the liver. In vitro characterization of AR-GT demonstrated the protection of siRNA under simulated GI pHs for 5 days, facilitation of the trans-epithelial transport in the intestinal Caco2 and ASBT positive cells, and reduction of Akt protein by successful release of siAKT from the AR-GT. Following oral delivery of AR-GT to CLM mouse model, we observed high biodistribution of AR-GT in the ileum, liver, and kidney through intestinal uptake, enterohepatic transportation, and renal excretion. Moreover, CLM mouse after oral delivery of AR-GT (100 μg/kg) manifested about 58 % reduction of the numbers of tumor nodules in the liver and near 100% survival benefit compared to control mouse fed with either saline or AR-Chitosan nanoparticles. Further analysis of liver samples obtained from CLM mouse after oral delivery of AR-GT indicated about 38% reduction of pAkt expression and the enhancement of apoptotic protein expressions such as 2 times or 1.5 times increase of caspase 9 and bax. Theses observation suggests survival benefit and tumor nodule reduction in CLM mouse root on successful AR-GT mediated oral siAkt RNA delivery. we conclude AR-GT oral siRNA delivery system is beneficial in the CLM treatment and further suggest its application to target other cancers. Citation Format: Sung-Hun Kang, Vishnu Revuri, Sungpil Cho, In-Kyu Park, Kwang Jae Cho, Woo Kyun Bae, Yong-Kyu Lee. Oral siRNA delivery for colorectal liver metastases cancer therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5930.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2018-5930
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2018
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 5
    Online Resource
    Online Resource
    Abstract 4925: Promoter methylation of RASSF1A Tumor Suppressor Gene Modulates the Effect of Microtubule-Targeting Agent, docetaxl, in Breast Cancer
    American Association for Cancer Research (AACR) ; 2010
    In:  Cancer Research Vol. 70, No. 8_Supplement ( 2010-04-15), p. 4925-4925
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 70, No. 8_Supplement ( 2010-04-15), p. 4925-4925
    Abstract: RASSF1A has been previously demonstrated to be inactivated by CpG island methylation in breast cancer cell lines and primary tumor tissues. There have been evidences suggesting that methylation of this gene have a significant impact on biological characteristics of breast tumors and have a relationship with prognosis in breast cancer. The tumor suppressive effect of RASSF1A has been reported to be mediated by its 2 important roles in other cells; induction of cell cycle arrest and apoptosis. Therefore, it is possible that expression status of RASSF1A by promoter methylation may alter patient's sensitivity to chemotherapeutic agents affecting cell cycle. However, there is few data regarding the relationship between the methylation status of RASSF1A gene and clinical response to chemotherapeutic agents in breast cancer patients. In this current study, we show that RASSF1A gene expression was suppressed in the human breast cancer cell lines (MCF-7, MDA-MB-231, and ZR75-1) by the mechanism of promoter methylation using methylation -specific PCR. It was confirmed by the results that treatment with the DNA demethylating agent, 5-aza-2′-deoxycytidine, reactivated the expression of RASSF1A at the level of mRNA and protein. Re-expression of RASSF1A gene in breast cancer cell lines could decrease the cell growth and proliferation by both decreasing cyclin D1 expression and inducing cyclin A and B1 accumulation, then resulting in cell cycle arrest at G2/M phase. In addition, re-introduction of RASSF1A further increased docetaxel-induced cell death in breast cancer cells. We next questioned whether the methylation status of RASSF1A gene is associated with clinical response to taxane-based chemotherapy in breast cancer patients. Fresh frozen primary breast cancer tissues were ananlyzed for methylation status of RASSF1A gene using MS-PCR. Thirty three out of 39 patients (84.6%) showed RASSF1A methylation and 6 had un-methylated gene. Patients who had unmethylated or partially methylated RASSF1A gene showed some mRNA in RT-PCR analysis. And, the clinical response to taxane-based chemotherapy was significantly better in the un-, or partially-methylated patient group (100% vs 62.5%). These results suggest that hypermethylation of the CpG island promoter of RASSF1A may play an important role in breast cancer pathogenesis and is a modulating factor for docetaxel activity in breast cancer patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4925.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM10-4925
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2010
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 6
    Online Resource
    Online Resource
    Abstract 4691: Class III beta tubulin is a strong predictive marker for taxane-based first-line palliative chemotherapy in recurrent or metastatic gastric cancer.
    American Association for Cancer Research (AACR) ; 2013
    In:  Cancer Research Vol. 73, No. 8_Supplement ( 2013-04-15), p. 4691-4691
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 73, No. 8_Supplement ( 2013-04-15), p. 4691-4691
    Abstract: Backgrounds. Class III β tubulin (TUBB3) is a prognostic marker in various tumors and role of TUBB3 in advanced gastric cancer is not clearly defined yet. We analyzed the significance of TUBB3 expression along with ERCC1 in recurrent or metastatic gastric cancer patients receiving taxane based first-line palliative chemotherapy. Methods. We reviewed 146 patients with advanced gastric adenocarcinoma who received taxane based first-line palliative chemotherapy between 2004 and 2010 at Chonnam National University Hwasun hospital. Immunohistochemical stain of TUBB3 and ERCC1 was done in paraffin-embedded tumor tissue. We evaluated response to chemotherapy, progression-free survival (PFS), and overall survival (OS). Results. A total of 146 patients with advanced gastric cancer received docetaxel and cisplatin (n=15), or paclitaxel and cisplatin (n=131). The median PFS was significantly shorter for patients with TUBB3 high expression than patients with TUBB3 low expression (3.63 versus 6.67 months, p=0.001). OS was not associated with TUBB3 expression status (12.9 versus 13.1 months, p=0.769). In multivariate analysis, only TUBB3 was related to shorter PFS (HR 2.74, 95% CI 1.91-3.91, p=0.001). Patients with ERCC1 high expression showed lower response rate than patients with ERCC1 low expression (24% versus 63.2%, p=0.001), however ERCC1 showed no clinical influence on PFS and OS. Conclusions. TUBB3 is a strong predictive marker in recurrent or metastatic gastric cancer patients receiving taxane based first-line palliative chemotherapy. Clinical impact of ERCC1 is not evident in this setting. Citation Format: Jun-Eul Hwang, Dae-Eun Kim, Hyun-Jeong Shim, Woo-Kyun Bae, In-Jae Oh, Sang-Hee Cho, Ik-Joo Chung. Class III beta tubulin is a strong predictive marker for taxane-based first-line palliative chemotherapy in recurrent or metastatic gastric cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4691. doi:10.1158/1538-7445.AM2013-4691
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2013-4691
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2013
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 7
    Online Resource
    Online Resource
    Abstract 5061: Molecular mapping of prostate cancer on whole mount prostatectomy specimens using deep neural networks to quantify genotypic heterogeneity
    American Association for Cancer Research (AACR) ; 2022
    In:  Cancer Research Vol. 82, No. 12_Supplement ( 2022-06-15), p. 5061-5061
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 82, No. 12_Supplement ( 2022-06-15), p. 5061-5061
    Abstract: Most primary prostate cancers are multifocal, with multiple genomically independent tumors identified in up to 80% of men undergoing radical prostatectomy for clinically localized disease. The heterogeneity in prostate cancer and the clinical significance of secondary tumors have been explored. However, studies to date have been limited to analyzing prostate biopsies or sections using dominant tumor foci only, not allowing for the evaluation of the inter and intra tumor molecular heterogeneity of the prostate cancer landscape. Recently, we identified mutually exclusive expression patterns of more than one driver molecular aberration in distinct tumor foci. Here, we present a quantitative analysis of tumors with distinct markers and correlate with clinical outcomes. We developed a model to quantify cancerous regions and genotype expression on immunohistochemical (IHC) slides. Our algorithm combines multiple modeling strategies, including deep neural networks and color deconvolution. Dual ERG/SPINK1 IHC staining was performed on whole mount prostatectomy slides. Patches from corresponding slides stained with Hematoxylin/eosin (H & E) were generated to train the model. A color devolution method was used to separate the patches into H & E and other stain channels. For evaluation, patches were generated from IHC slides, which were then transformed into Hematoxylin-only stained patches. Sample patches were analyzed for detection of cancerous regions at the pixel-level. The ratios of cancerous regions were calculated. Our segmentation results were compared with the area positive for ERG or SPINK1. For the ERG stain, the model demonstrated a sensitivity of 62.72% per pixel, whereas it was associated with a sensitivity of 48.37% per pixel for SPINK1. This represents a robust performance for a proof-of-concept model, and sensitivities are expected to improve significantly with additional annotations. To investigate the entire landscape of whole mount samples, training to include recognition of morphological variations such as HGPIN is underway and expected to also increase sensitivity. More detailed analysis will be shared at the time of presentation. We present here a quantitative analysis model that reveals unprecedented details on tumor heterogeneity with respect to molecular markers and tumor localization. To our knowledge, this is the first study on quantitative molecular mapping of cancer and biomarker expression using whole mount samples. The marker expression in each tumor foci can be correlated with clinicopathologic findings. Different molecular subtypes presented with more than one driver molecular aberration in distinct tumor foci may be associated with distinct clinical outcomes such as biochemical recurrence or metastasis, allowing for predicting disease progression and targeted approaches for effective prostate cancer management. Citation Format: Joonyoung Cho, In Hye Suh, Tae-Yeong Kwak, Sun Woo Kim, Hyeyoon Chang, Nallasivam Palanisamy. Molecular mapping of prostate cancer on whole mount prostatectomy specimens using deep neural networks to quantify genotypic heterogeneity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5061.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2022-5061
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 8
    Online Resource
    Online Resource
    A Novel Orally Active Inverse Agonist of Estrogen-related Receptor Gamma (ERRγ), DN200434, A Booster of NIS in Anaplastic Thyroid Cancer
    American Association for Cancer Research (AACR) ; 2019
    In:  Clinical Cancer Research Vol. 25, No. 16 ( 2019-08-15), p. 5069-5081
    Details
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 25, No. 16 ( 2019-08-15), p. 5069-5081
    Abstract: New strategies to restore sodium iodide symporter (NIS) expression and function in radioiodine therapy–refractive anaplastic thyroid cancers (ATCs) are urgently required. Recently, we reported the regulatory role of estrogen-related receptor gamma (ERRγ) in ATC cell NIS function. Herein, we identified DN200434 as a highly potent (functional IC50 = 0.006 μmol/L), selective, and orally available ERRγ inverse agonist for NIS enhancement in ATC. Experimental Design: We sought to identify better ERRγ-targeting ligands and explored the crystal structure of ERRγ in complex with DN200434. After treating ATC cells with DN200434, the change in iodide-handling gene expression, as well as radioiodine avidity was examined. ATC tumor–bearing mice were orally administered with DN200434, followed by 124I-positron emission tomography/CT (PET/CT). For radioiodine therapy, ATC tumor–bearing mice treated with DN200434 were administered 131I (beta ray–emitting therapeutic radioiodine) and then bioluminescent imaging was performed to monitor the therapeutic effects. Histologic analysis was performed to evaluate ERRγ expression status in normal tissue and ATC tissue, respectively. Results: DN200434–ERRγ complex crystallographic studies revealed that DN200434 binds to key ERRγ binding pocket residues through four-way interactions. DN200434 effectively upregulated iodide-handling genes and restored radioiodine avidity in ATC tumor lesions, as confirmed by 124I-PET/CT. DN200434 enhanced ATC tumor radioiodine therapy susceptibility, markedly inhibiting tumor growth. Histologic findings of patients with ATC showed higher ERRγ expression in tumors than in normal tissue, supporting ERRγ as a therapeutic target for ATC. Conclusions: DN200434 shows potential clinical applicability for diagnosis and treatment of ATC or other poorly differentiated thyroid cancers.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    URL: Article
    DOI: 10.1158/1078-0432.CCR-18-3007
    RVK:
    XA 36791
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2019
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 9
    Online Resource
    Online Resource
    Abstract 4344: Intraperitoneal administration of docetaxel loaded in thermo-responsive conjugated linoleic acid-incorporated poloxamer hydrogel for the suppression of peritoneal dissemination of gastric cancer.
    American Association for Cancer Research (AACR) ; 2013
    In:  Cancer Research Vol. 73, No. 8_Supplement ( 2013-04-15), p. 4344-4344
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 73, No. 8_Supplement ( 2013-04-15), p. 4344-4344
    Abstract: Thermo-responsive hydrogel consisting of conjugated linoleic acid-coupled Pluronic F127 (Plu-CLA) is an optimized drug delivery system with anti-cancer activity for controlled release of the hydrophobic drug, docetaxel. In this study, we evaluated the effect of Plu-CLA as a potential new intraperitoneal docetaxel delivery system for peritoneal dissemination of gastric cancer. We have established a peritoneal metastasis models using BALB/c mice by injection with TMK-1 human gastric cancer cells. Mice were injected intraperitoneally with docetaxel alone and docetaxel loaded Plu-CLA at 1 week after TMK1 cells were injected. Tumor progression and response to therapy were monitored by micro-positron emission tomography. The total number of peritoneal tumors and ascites volume were also measured. Compared to docetaxel alone, the combination of docetaxel and Plu-CLA significantly and synergistically reduced cell survival. The combination of docetaxel and Plu-CLA showed excellent anti-tumor activity inducing stronger apoptosis than docetaxel alone. The combination of docetaxel and Plu-CLA also significantly reduced number of peritoneal metastatic nodules and increased the survival in the peritoneal gastric cancer xenograft model. Our results showed that intraperitoneal administration of docetaxel combined with Plu-CLA synergistically inhibited peritoneal metastasis and prolonged the survival in peritoneal gastric cancer model. Therefore, Plu-CLA could be a potential intraperitoneal carrier for hydrophobic docetaxel for the effective treatment of peritoneal metastatic gastric cancer. Citation Format: Woo Kyun Bae, Lothar Hennighausen, Ji Hee Lee, Dae Eun Kim, Jun Eul Hwang, Hyun Jeong Shim, Sang Hee Cho, In-Kyu Park, Ik-Joo Chung. Intraperitoneal administration of docetaxel loaded in thermo-responsive conjugated linoleic acid-incorporated poloxamer hydrogel for the suppression of peritoneal dissemination of gastric cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4344. doi:10.1158/1538-7445.AM2013-4344
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2013-4344
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2013
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 10
    Online Resource
    Online Resource
    Vascular Endothelial Growth Factor Gene Polymorphisms Associated with Prognosis for Patients with Colorectal Cancer
    American Association for Cancer Research (AACR) ; 2008
    In:  Clinical Cancer Research Vol. 14, No. 1 ( 2008-01-01), p. 62-66
    Details
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 14, No. 1 ( 2008-01-01), p. 62-66
    Abstract: Purpose: Vascular endothelial growth factor (VEGF) or its family may be considered to play an important role in lymphangiogenesis and lymphatic tumor spread, thereby affecting prognosis of colorectal cancer. Accordingly, the present study analyzed VEGF gene polymorphisms and their effect on the prognosis for patients with colorectal cancer. Experimental Design: Four hundred and forty-five consecutive patients with surgically treated colorectal adenocarcinoma were enrolled in the present study. The genomic DNA was extracted from fresh colorectal tissue and three VEGF (−2578C & gt;A, −634G & gt;C, and +936C & gt;T) gene polymorphisms were determined using a PCR/denaturing high-performance liquid chromatography assay. Results: Multivariate survival analysis showed that the survival for the patients with the −634 G/C genotype [overall survival (OS): hazard ratio (HR), 0.158; P & lt; 0.001] or C/C genotype (OS: HR, 0.188; P & lt; 0.001) were better than for the patients with the −634G/G genotype, whereas the +936 C/T genotype (OS: HR, 12.809; P & lt; 0.001) or T/T genotype (OS: HR, 37.260; P & lt; 0.001) was associated with a worse survival compared with the +936 C/C genotype. In haplotype analysis, the −2578A/−634G/+936T haplotype exhibited a significantly worse survival when compared with the wild −2578C/−634G/+936C haplotype (OS: HR, 3.866; P & lt; 0.001). Conclusions: VEGF gene polymorphisms were found to be an independent prognostic marker for patients with colorectal cancer. Accordingly, the analysis of VEGF gene polymorphisms can help identify patient subgroups at high risk of a poor disease outcome.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    URL: Article
    DOI: 10.1158/1078-0432.CCR-07-1537
    RVK:
    XA 36791
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2008
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...