Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The management of gastrointestinal stromal tumors, usually defined as c-KIT-positive mesenchymal neoplasias, has evolved very rapidly in the last five years. Imatinib mesylate (Glivec(R)) is the standard treatment in unresectable or metastatic gastrointestinal stromal tumors. Imatinib should be given until development of intolerance or progressive disease. It is not uncommon for gastrointestinal stromal tumors to become larger during the early post-treatment phase and conventional response to treatment criteria in solid tumors have a limited value for evaluation the efficiency of imatinib in this period. FDG-PET has proven to be highly sensitive in detecting early response tumor. A 53-year old woman was diagnosed of relapsed gastrointestinal stromal tumor 18 months after adyuvant imatinib mesylate finished. Imatinib was started and 72 hours later the tumor showed a decrease of fluorodeoxyglucose F18 uptake on positron emission tomography scan.
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PMID:[Utility of FDG-PET for early evaluation of efficiency of imatinib mesylate (Glivec) in the treatment of gastrointestinal stromal tumors]. 1738 36

Designated radiopharmaceuticals labelled with the prominent positron-emitter (18)F can be defined as molecular imaging probes for the examination of cardiovascular diseases at the cellular and subcellular level. Such molecular imaging agents representing radioindicators or radiotracers offer the opportunity to non-invasively trace their path and fate in the living organism by the scintigraphic technique, positron emission tomography (PET). The glucose analogue [(18)F]FDG is a widespread PET tracer and one of the earliest examples of a PET molecular imaging probe feasible to in vivo visualise glucose utilisation by a metabolic trapping mechanism. This short review is focussed on selected established (18)F-labelled PET tracers as well as (18)F-labelled radioligands in development that show the potential of being probes for the in vivo molecular imaging of proteins relevant in cardiovascular diseases such as receptors (i.e. beta-Adrenoceptors), transporters (i.e. NET and VMAT) and proteases (i.e. MMPs).
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PMID:(18)F-labelled cardiac PET tracers: selected probes for the molecular imaging of transporters, receptors and proteases. 1832 69

A 60-year-old woman was admitted to the hospital with left thigh pain. She had undergone mastectomy and axillary lymph node dissection for right breast cancer (T3N2M0) five years and two months earlier. The pathological diagnosis then was invasive ductal carcinoma with axillaryly mph node metastases. Hormone receptors and HER2 status were negative and positive (3+), respectively. The patient received adjuvant chemotherapy and radiotherapy, but bone metastases appeared 18 months after surgery. Although trastuzumab-combination chemotherapy with taxane and/or capecitabine was given, bone metastases in thoracic vertebra resulted in incomplete paralysis in both legs. She underwent thoraco-lumbar vertebral fixation 10 months before admission. A PET/CT revealed multiple bone metastases in the left femur as well as vertebrae, and CEA rose markedly. She received radiotherapy and trastuzumab monotherapy in addition to bisphosphonate. Temporarily, CEA decreased, but because recurrence nests were recognized in the supraclavicle and mediastinum after the eight-month treatment, trastuzumab monotherapy was followed by trastuzumab plus vinorelbine combined therapy. This regimen markedly reduced CEA after three months, but it rose again over the following three months. As S-1-combined therapy was not effective, trastuzumab+gemcitabine (1 g/week and two weeks on/one week off) combined therapy was started. CEA decreased markedly after 4 cycles, and FDG accumulation in the recurrence region was markedly improved. The adverse event during this treatment was minor, and PS was sufficiently maintained. These results suggest that trastuzumab plus gemcitabine combination therapy is effective for HER2-positive metastatic breast cancer.
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PMID:[A case of HER2-positive metastatic breast cancer responding to trastuzumab plus gemcitabine combination therapy]. 1840 45

cis-Dichlorodiamminoplatinum (II) (cisplatin) has demonstrated extraordinary activities against a variety of solid tumors. However, the clinical efficacy is contrasted by its toxicity profile. To reduce the toxicity and enhance the circulation time of cisplatin, core-shell structure nanoparticles were prepared from block copolymer of methoxy poly(ethylene glycol)-polycaprolactone (mPEG-PCL). Cisplatin was incorporated into the nanoparticles with high encapsulation efficiency more than 75%. Controlled release of cisplatin was observed in a sustained manner. In vitro cytotoxicity studies proved the efficacy of cisplatin-loaded nanoparticles against BGC823 and H(22) cells in a dose and time-dependent manner. Furthermore, intratumoral administration was applied to improve the tumor-targeted delivery in the in vivo evaluation. Compared with free cisplatin, cisplatin-loaded nanoparticles exhibited superior antitumor effect by delaying tumor growth when delivered intratumorally, while no significant improvement was observed when they were administrated intraperitoneally. Positron emission tomography/computed tomography (PET/CT) imaging was utilized for the first time to detect the declined (18)F-labeled 2-fluoro-2-deoxy-d-glucose ((18)F-FDG) uptake of the tumor in mice receiving cisplatin-loaded nanoparticles intratumorally. These results suggest that polymeric nanoparticles with core-shell structures are promising for further studies as drug delivery carriers, and intratumoral delivery of drug-loaded nanoparticles could be a probable clinically useful therapeutic regimen.
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PMID:Superior antitumor efficiency of cisplatin-loaded nanoparticles by intratumoral delivery with decreased tumor metabolism rate. 1863 74

It has been suggested that a high EGFR gene copy number may be an indicator of good response to EGFR tyrosine kinase inhibitor therapy and a marker of poor prognosis in NSCLC. However, imaging features related to EGFR gene copy number status in adenocarcinoma are still unknown. We therefore retrospectively analyzed CT, FDG-PET, and histopathologic slides of surgical resected lung adenocarcinoma in 132 patients. Tumor characteristics on preoperative chest-CT, such as, GGO proportions, tumor diameters, and cavitation; FDG-PET SUV(max); and histopathologically determined differentiation degrees and tumor subtypes were evaluated. EGFR gene copy number status was categorized as FISH-positive or -negative. FISH-positivity was found in 53 patients (40.2%) and was significantly more frequent in tumors with a SUV(max)>7.0 (P=0.007). Furthermore, FISH-negativity was found to be more frequent in tumors with a GGO>50% (P=0.023) and diameter <15.5mm (P=0.006) on CT, or a well-differentiated histopathology (P=0.002). Moreover, the frequency of FISH-positivity increased as SUV(max) increased (P=0.0008) and as the proportion of GGO decreased (P=0.01). SUV(max)>7.0 was an independent predictor of FISH-positive results (odds ratio, 3.941; 95% CI, 1.691-9.182; P=0.01). In conclusion, a high SUV(max) on FDG-PET was significantly related to FISH-positive results. A high proportion of GGO, small tumor diameter on CT, and a well-differentiated histopathology were more frequent in FISH-negative adenocarcinomas.
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PMID:EGFR gene copy number in adenocarcinoma of the lung by FISH analysis: investigation of significantly related factors on CT, FDG-PET, and histopathology. 1881 24

The large use of target therapies in the treatment of gastrointestinal stromal tumors (GISTs) highlighted the urgency to integrate new molecular imaging technologies, to develop new criteria for tumor response evaluation and to reach a more comprehensive definition of the molecular target. These aspects, which come from clinical experiences, are not considered enough in preclinical research studies which aim to evaluate the efficacy of new drugs or new combination of drugs with molecular target. We developed a xenograft animal model GIST882 using nude mice. We evaluated both the molecular and functional characterization of the tumor mass. The mutational analysis of KIT receptor of the GIST882 cell lines and tumor mass showed a mutation on exon 13 that was still present after in vivo cell growth. The glucose metabolism and cell proliferation was evaluated with a small animal PET using both FDG and FLT. The experimental development of new therapies for GIST treatment requires sophisticated animal models in order to represent the tumor molecular heterogeneity already demonstrated in the clinical setting and in order to evaluate the efficacy of the treatment also considering the inhibition of tumor metabolism, and not only considering the change in size of tumors. This approach of cancer research on GISTs is crucial and essential for innovative perspectives that could cross over to other types of cancer.
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PMID:Advances in preclinical therapeutics development using small animal imaging and molecular analyses: the gastrointestinal stromal tumors model. 1922 18

The head-and-neck squamous-cell carcinomas (HNSCC) represent in order of frequency the fourth leading cause of cancer deaths among men in France. The term HNSCC includes various anatomopathological and clinical entities with different evolution patterns. For this reason, it is necessary to identify prognostic and predictive factors able to help in the choice of the treatment. The clinical factors with a prognostic value are the tumor location, the tumor size and the lymph node status. The degree of differentiation is the most important histologic factor. More recently, the identification of molecular factors has opened the way to new therapies. Thus, the overexpression of EGFR is associated with a poor prognosis. Its inhibition improves the survival of patients. p53 mutations and cyclin D1 amplification are actually subject to intensive research. The tumors associated with HPV infection are distinguishable by a better prognosis. 18-alpha-FDG positron emission tomography emerges as a useful tool for the therapeutic evaluation. The evolution of surgical techniques, the development of induction chemotherapy regimen or concurrent ones with radiotherapy and new techniques of conformal irradiation also results in a better locoregional control.
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PMID:[Prognosis and predictive factors in head-and-neck cancers]. 1935 12

O-(2-[(18)F]fluoroethyl)-L-tyrosine ([(18)F]FET) is one of the first (18)F-labeled amino acids for imaging amino acid metabolism in tumors. This tracer overcomes the disadvantages of [(18)F]fluorodeoxyglucose, [(18)F]FDG, and [(11)C]methionine, [(11)C]MET. Nevertheless, the various synthetic methods providing (18)F[FET] exhibit a big disadvantage concerning the necessity of two purification steps during the synthesis including HPLC purification, which causes difficulties in the automation, moderate yields, and long synthesis times >60 min. A new approach for the synthesis of [(18)F]FET is developed starting from 2-bromoethyl triflate as precursor. After optimization of the synthesis parameters including the distillation step of [(18)F]-FCH(2)CH(2)Br combined with the final purification of [(18)F]FET using a simple solid phase extraction instead of an HPLC run the synthesis [(18)F]FET could be significantly simplified, shortened, and improved. The radiochemical yield (RCY) was about 45% (not decay corrected and calculated relative to [(18)F]F(-) activity that was delivered from the cyclotron). Synthesis time was only 35 min from the end of bombardment (EOB) and the radiochemical purity was >99% at the end of synthesis (EOS). Thus, this simplified synthesis for [(18)F]FET offers a very good option for routine clinical use.
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PMID:New approach for the synthesis of [18F]fluoroethyltyrosine for cancer imaging: simple, fast, and high yielding automated synthesis. 1980 77

ERBB2/neu and Notch signaling are known to be deregulated in many human cancers. However, pathway cross-talk and dependencies are not well understood. In this study, we use an ERBB2-transgenic mouse model of breast cancer (neuT) to show that Notch signaling plays a critical role in tumor maintenance. Inhibition of the Notch pathway with a gamma-secretase inhibitor (GSI) decreased both the Notch and the mammalian target of rapamycin/AKT pathways. Antitumor activity resulting from GSI treatment was associated with decreased cell proliferation as measured by Ki67 and decreased expression of glucose transporter Glut1. Positron emission tomography (PET) imaging showed that the functional consequences of decreased Glut1 translated to reduced glucose uptake and correlated with antitumor effects as measured by micro-computed tomography imaging. The decrease of Glut1 in neuT tumors was also observed in several human breast cancer cell lines following GSI treatment. We provide evidence that approximately 27% of ERBB2-positive human breast cancer specimens display high expression of HES1, phospho-S6RP, and GLUT1. Together, these results suggest that pathways downstream of Notch signaling are, at least in part, responsible for promoting tumor growth in neuT and also active in both neuT and a subset of human breast cancers. These findings suggest that GSI may provide therapeutic benefit to a subset of ERBB2-positive breast cancers and that [(18)F]FDG-PET imaging may be useful in monitoring clinical response.
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PMID:Downregulation of Notch pathway by a gamma-secretase inhibitor attenuates AKT/mammalian target of rapamycin signaling and glucose uptake in an ERBB2 transgenic breast cancer model. 2019 67

A 56-year-old female visited our department due to bleeding from a mass in her left breast in November 2007. There was a tumor (diameter, 5 cm) accompanied by ulcer formation and fixation to the pectoral muscle, centering on the left breast Carea. CT examination showed multiple lung metastasis and liver metastasis. Core needle biopsy demonstrated scirrhous carcinoma. The tumor was positive for ER and strongly positive for HER2. After 4 courses of FEC100, 10 courses of trastuzumab / docetaxel combination therapy were performed for a total of 30 weeks. After the therapy, the breast tumor decreased in size, and the lung and liver metastatic lesions disappeared, showing a partial response (PR). FDG-PET examination revealed no abnormal accumulation. In February 2009, left mastectomy was performed. Pathological examination revealed Grade 2b and only a slight residue of cancer cells. This patient with advanced breast cancer accompanied by distant metastasis responded to trastuzumab/docetaxel combination therapy.
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PMID:[Efficacy of FEC and trastuzumab/docetaxel combination therapy for metastatic breast cancer]. 2033 92


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