Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.3.1.21 (CPT)
4,580 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report a case of advanced gastric cancer that showed a complete histological response to neoadjuvant chemotherapy. The patient, a 56-year-old man, was diagnosed as having advanced gastric cancer with lymph node metastases( cT3 cN1 cH0 cP0 cM0, cStageIIIA). He was initially treated with combined neoadjuvant chemotherapy comprising CPT-11+S-1. S-1(120 mg/day)was administered orally for 21 days, followed by CPT-11(130 mg/body)divon days 1 and 15. The primary lesion and lymph node metastases were diminished by 2 courses of chemotherapy, and no serious toxicities were observed. Distal gastrectomy and lymph node dissection(D2)were performed. Only a small ulcer was observed on the resected stomach. Histological examination of the resected stomach and lymph nodes revealed no remaining viable cancer cells. The patient has been doing well without any recurrence for 1 year since the start of treatment.
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PMID:[Advanced gastric cancer showing complete response to neoadjuvant chemotherapy with CPT-11 and S-1-a case report]. 1915 74

We have developed software for an Electronic Medical Record (EMR) to be used by oncologists and researchers. It has rapid, structured data entry, visualization of clinical information and a searchable data base. Interactive, rules-based forms were designed for structured data entry. The web-based forms have been customized for the clinical staff who enter the data. The forms have been tested by oncologists and their office assistants. Modules have been added to upload images and add legends, metadata, and code classifications such as ICD and CPT. Other features include a search interface and a permission system that controls user access. Oncologists enter detailed information during a patient's visit to the clinic. The electronic forms capture diagnoses, stage and history, which includes social, family, and medical history. A time map provides a graphical summary of a patient's record. Visualization of complex clinical information with intuitive navigation increases clarity while retaining the detail necessary for clinical information. Customized data entry forms and automatic coding speed the workflow. The system can potentially interface with multi-institutional data-sharing systems such as Cancer Bioinformatics Grid (CaBig).
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PMID:Structured data system for a breast cancer medical record. 1938 Sep 60

In this study, we show that degradable particles of a hydrophobic polymer can effectively deliver drugs to tumors after i.v. administration. Free-standing nanoparticles with diameters of 100-300 nm were successfully fabricated from highly hydrophobic, biodegradable poly(omega-pentadecalactone-co-butylene-co-succinate) (PPBS) copolyesters. PPBS copolymers with various compositions (20-80 mol% PDL unit contents) were synthesized via copolymerization of omega-pentadecalactone (PDL), diethyl succinate (DES), and 1,4-butanediol (BD) using Candida antarctica lipase B (CALB) as the catalyst. Camptothecin (CPT, 12-22%) was loaded into PPBS nanoparticles with high encapsulation efficiency (up to 96%) using a modified oil-in-water single emulsion technique. The CPT-loaded nanoparticles had a zeta potential of about -10 mV. PPBS particles were non-toxic in cell culture. Upon encapsulation, the active lactone form of CPT was remarkably stabilized and no lactone-to-carboxylate structural conversion was observed for CPT-loaded PPBS nanoparticles incubated in both phosphate-buffered saline (PBS, pH=7.4) and DMEM medium for at least 24 h. In PBS at 37 degrees C, CPT-loaded PPBS nanoparticles showed a low burst CPT release (20-30%) within the first 24 h followed by a sustained, essentially complete, release of the remaining drug over the subsequent 40 days. Compared to free CPT, CPT-loaded PPBS nanoparticles showed a significant enhancement of cellular uptake, higher cytotoxicity against Lewis lung carcinoma and 9L cell lines in vitro, a longer circulation time, and substantially better antitumor efficacy in vivo. These results demonstrate the potential of PPBS nanoparticles as long-term stable and effective drug delivery systems in cancer therapy.
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PMID:Poly(omega-pentadecalactone-co-butylene-co-succinate) nanoparticles as biodegradable carriers for camptothecin delivery. 1963 18

cAMP-dependent, PKA-independent effects on cell proliferation are mediated by cAMP binding to EPAC and activation of Rap signaling. In this report, we employed the analogue 8-CPT-2-O-Me-cAMP to study binding to EPAC and subsequent activation of B-Raf/ERK and mTOR signaling in human cancer cells. This compound significantly stimulated DNA synthesis, protein synthesis, and cellular proliferation of human 1-LN prostate cancer cells. By study of phosphorylation-dependent activation, we demonstrate that EPAC-mediated cellular effects require activation of the B-Raf/ERK and mTOR signaling cascades. RNAi directed against EPAC gene expression as well as inhibitors of ERK, PI 3-kinase, and mTOR were employed to further demonstrate the role of these pathways in regulating prostate cancer cell proliferation. These studies were then extended to several other human prostate cancer cell lines and melanoma cells with comparable results. We conclude that B-Raf/ERK and mTOR signaling play an essential role in cAMP-dependent, but PKA-independent, proliferation of cancer cells.
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PMID:Epac1-induced cellular proliferation in prostate cancer cells is mediated by B-Raf/ERK and mTOR signaling cascades. 1972 49

Extracellular adenosine-induced apoptosis of CW2 human colonic cancer cells by activating caspase-3, -8 and -9, and the effect was enhanced by adding EHNA, an adenosine deaminase inhibitor. Adenosine-induced CW2 cell death was inhibited by 8-CPT, an A(1) adenosine receptor inhibitor, but otherwise 2-chloroadenosine, an A(1) adenosine receptor agonist, and MDL-12330A, an inhibitor of adenylate cyclase, mimicked the adenosine effect. For mice inoculated with CW2 cells, intraperitoneal injection with adenosine reduced tumor growth and more prominent reduction was obtained with co-injection with EHNA. Adenosine, thus, suppresses CW2 human colonic cancer growth by inducing apoptosis as mediated via A(1) adenosine receptors.
Cancer Lett 2010 Apr 28
PMID:Adenosine suppresses CW2 human colonic cancer growth by inducing apoptosis via A(1) adenosine receptors. 1982 92

PURPOSE: Fatty acid synthase (FASN) is overexpressed in human breast carcinoma. The natural polyphenol (-)-epigallocatechin-3-gallate blocks in vitro FASN activity and leads to apoptosis in breast cancer cells without any effects on carnitine palmitoyltransferase-1 (CPT-1) activity, and in vivo, does not decrease body weight. We synthesized a panel of new polyphenolic compounds and tested their effects on breast cancer models. EXPERIMENTAL DESIGN: We evaluated the in vitro effects of the compounds on breast cancer cell growth (SK-Br3, MCF-7, and MDA-MB-231), apoptosis [as assessed by cleavage of poly(ADP-ribose) polymerase], cell signaling (HER2, ERK1/2, and AKT), and fatty acid metabolism enzymes (FASN and CPT-1). In vivo, we have evaluated their antitumor activity and their effect on body weight in a mice model of BT474 breast cancer cells. RESULTS: Two compounds potently inhibited FASN activity and showed high cytotoxicity. Moreover, the compounds induced apoptosis and caused a marked decrease in the active forms of HER2, AKT, and ERK1/2 proteins. Interestingly, the compounds did not stimulate CPT-1 activity in vitro. We show evidence that one of the FASN inhibitors blocked the growth of BT474 breast cancer xenografts and did not induce weight loss in vivo. CONCLUSIONS: The synthesized polyphenolic compounds represent a novel class of FASN inhibitors, with in vitro and in vivo anticancer activity, that do not exhibit cross-activation of beta-oxidation and do not induce weight loss in animals. One of the compounds blocked the growth of breast cancer xenografts. These FASN inhibitors may represent new agents for breast cancer treatment. (Clin Cancer Res 2009;15(24):7608-15).
Clin Cancer Res 2009 Dec 15
PMID:Novel Inhibitors of Fatty Acid Synthase with Anticancer Activity. 2000 54

Acetyl-CoA carboxylases (ACC) are rate-limiting enzymes in de novo fatty acid synthesis, catalyzing ATP-dependent carboxylation of acetyl-CoA to form malonyl-CoA. Malonyl-CoA is a critical bi-functional molecule, i.e., a substrate of fatty acid synthase (FAS) for acyl chain elongation (fatty acid synthesis) and an inhibitor of carnitine palmitoyltransferase I (CPT-I) for fatty acid beta-oxidation. Two ACC isoforms have been identified in mammals, i.e. ACC-alpha (ACCA, also termed ACC1) and ACC-beta (ACCB, also designated ACC2). ACC has long been used as a target for the management of metabolic diseases, such as obesity and metabolic syndrome, and various inhibitors have been developed in clinical trials. Recently, ACCA up-regulation has been recognized in multiple human cancers, promoting lipogenesis to meet the need of cancer cells for rapid growth and proliferation. Therefore, ACCA might be effective as a potent target for cancer intervention, and the inhibitors developed for the treatment of metabolic diseases would be potential therapeutic agents for cancer therapy. This review summarizes our recent findings and updates the current understanding of the ACCA with focus on cancer research.
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PMID:Acetyl-CoA carboxylase-a as a novel target for cancer therapy. 2003 65

Tuberous sclerosis complex 1 (TSC1) inhibits mammalian target of rapamycin (mTOR), a central promotor of cell growth and proliferation. The protein product of the TSC1 gene, hamartin (referred to as TSC1) is known to interact with Polo-like kinase 1 (Plk1) in a cell cycle regulated, phosphorylation-dependent manner. We hypothesized that the p53 target gene, Plk2, is a tumor suppressor, mediating its tumor suppressor function through interactions with TSC1 that facilitate TSC1/2 restraint of mTOR under hypoxic stress. We found that human lung tumor cells deficient in Plk2 grew larger than control tumors, and that Plk2 interacts with endogenous TSC1 protein. Additionally, C-terminal Plk2-GST fusion protein bound both TSC1 and TSC2 proteins. TSC1 levels were elevated in response to Adriamycin and cells transiently overexpressing Plk2 demonstrated decreased phosphorylation of the downstream target of mTOR, ribosomal protein p70S6 kinase during hypoxia. Plk2 levels were inversely correlated with cytoplasmic p70S6K phosphorylation. Plk2 levels did not increase in response to DNA damage (Adriamycin, CPT -11) when HCT 116 and H460 cells were exposed to hypoxia. TSC1-deficient mouse embryonic fibroblasts with TSC1 added back demonstrated decreased S6K phosphorylation, which was further decreased when Plk2 was transiently overexpressed. Interestingly, under normoxia, Plk2 deficient tumor cells demonstrated increased apoptosis in response to various chemotherapeutic agents including CPT -11 but increased resistance to apoptotic death after CPT-11 treatment under hypoxia, and tumor xenografts comprised of these Plk2-deficient cells were resistant to CPT -11. Our results point to a novel Plk2-TSC1 interaction with effects on mTOR signaling during hypoxia, and tumor growth that may enable targeting Plk2 signaling in cancer therapy.
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PMID:The p53 target Plk2 interacts with TSC proteins impacting mTOR signaling, tumor growth and chemosensitivity under hypoxic conditions. 2005 36

A series of novel 9-benzylideneamino derivatives of homocamptothecin were synthesized via Friedlaender cyclization from our obtained intermediate 5. All the compounds were evaluated for in vitro cytotoxicity against three cancer cell lines (A549, LOVO and MDA-MB-435). Most of these derivatives possessed potent growth inhibitory effect on all the tested cell lines and four compounds (6d, 6f, 6i, 6k) showed higher inhibitory activities with the IC50 values of 2.3 nM-9.8 nM against breast cancer cell than topotecan. As compared to CPT, compound 6f revealed higher topoisomerase I inhibitory activity.
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PMID:Synthesis and evaluation of 9-benzylideneamino derivatives of homocamptothecin as potent inhibitors of DNA topoisomerase I. 2020 23

Gastric adenosquamous carcinoma is known as an infrequent histological cancer with a poor prognosis. A 69-year-old man was revealed to have gastric squamous carcinoma on the gastric body remote from esophagus (cT4 cN3, cStage IV). A curative operation was impossible so he was treated with systemic chemotherapy using S-1+docetaxel. After 1 course, we changed to second-line chemotherapy combining CPT-11+CDDP because of heterochronic multiple hepatic metastases. PET-CT and CT findings after 5 courses of second-line therapy showed reduced primary tumor and metastatic lesions. The curative operation was performed based on the effective response with downstaging. The final histological diagnosis showed gastric adenosquamous carcinoma. The adjuvant chemotherapy of CPT-11 was continued without relapse for almost 2 years.
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PMID:[A case of gastric adenosquamous carcinoma successfully treated with second-line chemotherapy (CPT-11 and CDDP)]. 2071 91


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