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:2.7.10.1 (ERK)
95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Loco-regionally advanced esophageal cancer is a lethal disease with poor outcomes despite aggressive multimodality therapy. The appropriate management of these patients is contentious and no single standard of care has been defined. Literature suggests that preoperative chemoradiotherapy may be superior to preoperative chemotherapy. Recently, several developments have impacted the care of these patients. The 2010 AJCC TNM staging system now recognizes the biologic heterogeneity of the disease and stages adenocarcinoma and squamous cell carcinoma separately. Studies suggest potentially less toxic chemotherapeutic agents including oxaliplatin may be useful in the management of this disease. FDG-PET imaging appears to have prognostic value and may predict for pathologic response. In addition, several trials have explored inhibition of the ErbB1 (EGFR) and ErbB2 (Her2) receptors. The monoclonal antibody trastuzumab appears to extend survival for patients with metastatic gastric and gastroesophageal junction adenocarcinoma and is under investigation for use in patients with loco-regionally advanced disease.
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PMID:Current developments in the management of locally advanced esophageal cancer. 2254 59

The use of positron imaging agents such as FDG, MET, and FLT is expected to lead the way for novel applications toward efficient malignancy grading and treatment of gliomas. In this study, the usefulness of FDG, MET and FLT-PET images was retrospectively reviewed by comparing their histopathological findings. FDG, MET, and FLT-PET were performed in 27 patients with WHO grade IV, 15 patients with WHO grade III, and 12 patients with WHO grade II during 5.5 years. The resulting PET images were compared by measuring SUVs and T/N ratios (tumor to normal tissue ratios). Although there were no significant differences in FDG-PET, there were significant differences in the T/N ratios in the MET-PET between WHO grades II and IV and in the FLT-PET between the WHO grades III and IV. In glioblastoma patients, the SUVs of the areas depicted by MRI in the MET-PET were different from those SUVs in the FLT-PET. Importantly, the areas with high SUVs in both MET-PET and FLT-PET were also high in Ki-67 index and were histologically highly malignant. PET imaging is a noninvasive modality that is useful in determining a tumor area for removal as well as improving preoperative diagnosis for gliomas.
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PMID:Usefulness of FDG, MET and FLT-PET studies for the management of human gliomas. 2257 90

Imatinib mesylate is a tyrosine kinase inhibitor of c-KIT and PDGFRA. Imatinib mesylate is an effective drug that can be used as a first-choice agent for treatment of GISTs. Prior to treatment, molecular diagnosis of c-KIT or PDGFRA is necessary; however, in some types of GISTs, it is impossible to obtain a sufficient amount of specimen for diagnosis. An inoperable or marginally resectable GIST in a 79-year-old female was difficult to be diagnosed at a molecular pathological level, and hence, exploratory treatment was initiated using imatinib combined with (18)FDG-PET evaluation at 1-month intervals. PET imaging indicated a positive response, and so we continued imatinib treatment in an NAC setting for 4 months. As a result, curative resection of the entire tumor was successfully performed with organ preservation and minimally invasive surgery. (18)FDG-PET evaluation at 1-month intervals is beneficial for GISTs that are difficult to be diagnosed histopathologically.
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PMID:(18)FDG-PET at 1-Month Intervals Is a Better Predictive Marker for GISTs That Are Difficult to Be Diagnosed Histopathologically: A Case Report. 2260 44

Through a comprehensive review of the current literature, the present article investigates several aspects of low grade astrocytomas (LGA), including prognostic factors, treatment strategies and follow-up regimes. LGA are in general relatively slow-growing primary brain tumours, but they have a very heterogeneous clinical behaviour. Several factors affect prognosis, and these include age, histological subtype, and Karnofsky Performance Score (KPS) prior to surgery. Furthermore, a number of different molecular genetic alterations have been shown to affect both the prognosis as well as the course of disease. The current literature seems to support the idea that treatment with radical tumour resection, where possible, yields better long term outcome for patients with LGA. However, adjuvant therapy is often necessary. Administering early postoperative radiotherapy to patients with partially resected LGA yields a longer period of progression-free survival, whereas patients with radically resected tumours should receive radiotherapy at the time of progression. Regarding chemotherapy, we found evidence to suggest that patients respond to both temozolomide (TMZ) and the combination of procarbazine, lomustine and vincristine (PCV). However, the response rates in patients receiving PCV seem superior to those of patients receiving TMZ. In follow-up PET scans, the tracers (18)F-FDG and MET provide high sensitivities for detection of new suspicious lesions and these tracers are furthermore effective in discriminating between tumour progression and radiation necrosis. The research into biomarkers is currently limited with regards to their applications in LGA diagnostics, and therefore further studies including larger patient populations are needed.
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PMID:Current treatment of low grade astrocytoma: a review. 2281 18

PET-CT scan has demonstrated to be very effective in lung cancer diagnosis and staging, but lung cancer has multiple ways of presentation, which can lead to an error in diagnosis imaging and a delay on the beginning of specific treatment. We present a case of a 77-year-old man with an initial PET-CT scan showing high 18F-FDG intake, suggesting a bilateral pneumonia, who was finally diagnosed of an EGFR-mutant lung adenocarcinoma. EGFR-activating mutation allowed us to start treatment with the oral tyrosin kinase inhibitor Gefitinib, obtaining a rapid and sustained response. Histological confirmation of imaging findings is always necessary to avoid diagnostic errors.
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PMID:EGFR-Mutant Lung Adenocarcinoma Mimicking a Pneumonia. 2295 91

GIST is driven by a gain-of-function mutation either in the KIT or PDGFRA gene. Atpresent , advanced and/or metastatic GIST is primarily treated by medical therapy of imatinib and sunitinib, both of which are re-imbursed by the government in Japan. Tumor responses are usually evaluated by contrast-enhanced CT scan with RECIST criteria, which cannot always predict patients with long SD showing similar prognostic effects to CR or PR. For early detection of drug activities, Choi's criteria with enhanced CT scan, as well as FDG-PET(or PET-CT), are considered to be useful. Choi's criteria also works for the early detection of resistance. When resistance and/or unmanagable adverse events are observed, early switching of drugs without any delay is recommended if there is another line of treatment.
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PMID:[Responses to treatment and switching tyrosine kinase inhibitors in gastrointestinal stromal tumor(GIST)]. 2299 68

The peripheral T-cell lymphomas represent about 15% to 20% of non-Hodgkin lymphomas and are marked by clinical and pathologic heterogeneity. The most common T-cell entities include peripheral T-cell lymphoma, not otherwise specified, angioimmunoblastic T-cell lymphoma, and anaplastic large cell lymphoma anaplastic lymphoma kinase-negative, which account for approximately 60% of T-cell lymphoma cases. Because of the rarity of T-cell lymphomas and lack of randomized prospective studies, treatment for these diseases is not well defined. Current treatment strategies draw from data from phase II studies, retrospective analyses, and personal experience. For fit patients who can tolerate treatment with curative intent, we treat peripheral T-cell lymphoma, not otherwise specified, angioimmunoblastic T-cell lymphoma, and anaplastic large cell lymphoma anaplastic lymphoma kinase-negative similarly with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)-based induction therapy followed by consolidation with autologous stem cell transplant. Given the marked differences in histology, biology, and clinical presentation for these diseases, it is likely that they should be approached differently. Furthermore, prognostic factors and degree of chemosensitivity as measured by FDG-PET (fluorodeoxyglucose positron emission tomography) should likely be used to guide patients along different treatment pathways. We have a long way to go toward perfecting the treatment for T-cell lymphoma. We believe that a uniform treatment approach for patients with aggressive T-cell lymphoma is not appropriate; however, we do not yet have enough data to support an individualized approach to treatment. Clinical and biologic prognostic factors, degree of chemosensitivity as measured by FDG-PET, and histology should all likely have a role in directing patients along different treatment pathways, but prospective studies are needed to confirm this.
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PMID:Should patients with aggressive peripheral T-cell lymphoma all be treated the same?: no... well yes, ...but maybe not for long. 2300 50

Noninvasive imaging methodologies are needed to assess treatment responses to novel molecular targeting approaches for the treatment of squamous cell carcinoma of the head and neck (SCCHN). Computer tomography and magnetic resonance imaging do not effectively distinguish tumors from fibrotic tissue commonly associated with SCCHN tumors. Positron emission tomography (PET) offers functional non-invasive imaging of tumors. We determined the uptake of the PET tracers 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) and 3'-[(18)F]Fluoro-3'-deoxythymidine ([(18)F]FLT) in several SCCHN xenograft models. In addition, we evaluated the utility of [(18)F]FLT microPET imaging in monitoring treatment response to an EGFR antisense approach targeted therapy that has shown safety and efficacy in a phase I trial. Two of the 3 SCCHN xenograft models tested demonstrated no appreciable uptake or retention of [(18)F]FDG, but consistent accumulation of [(18)F]FLT. The third tumor xenograft SCCHN model (Cal33) demonstrated variable uptake of both tracers. SCCHN xenografts (1483) treated with EGFR antisense gene therapy decreased tumor volumes in 4/6 mice. Reduced uptake of [(18)F]FLT was observed in tumors that responded to epidermal growth factor antisense (EGFRAS) gene therapy compared to non-responding tumors or tumors treated with control sense plasmid DNA. These findings indicate that [(18)F]FLT PET imaging may be useful in monitoring SCCHN response to molecular targeted therapies, while [(18)F]FDG uptake in SCCHN xenografts may not be reflective of the level of metabolic activity characteristic of human SCCHN tumors.
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PMID:Utility of 3'-[(18)F]fluoro-3'-deoxythymidine as a PET tracer to monitor response to gene therapy in a xenograft model of head and neck carcinoma. 2334 98

We previously reported that (18)F-fluorodeoxyglucose positron emission tomography scan (FDG-PET) is almost universally positive in patients with T cell lymphoma. In the present analysis we examined the impact of FDG-PET on the initial staging of peripheral T cell lymphomas (PTCLs), and the prognostic value of interim FDG-PET. This retrospective analysis identified patients with mature T or natural killer (NK) lymphomas who had PET scans as part of initial staging or staging at relapse [(n = 95) (staging cohort)] in the PTCL database at Memorial Sloan-Kettering Cancer Center. A subset of these patients had repeat PET for interim restaging during initial therapy with curative intent [(n = 50) (interim restaging cohort)]. The frequency of specific T cell histologies included in this analysis were: PTCL not otherwise specified (NOS) (n = 35); angioimmunoblastic T cell lymphoma (AITL) (n = 17); anaplastic large cell lymphoma (ALCL), ALK-1+ (n = 11) and ALK-1- (n = 12); adult T cell lymphoma/leukemia (ATLL) (n = 7); NK/T cell lymphoma (NKTCL) (n = 10); and enteropathy-associated T cell lymphoma (EATL) (n = 3). In the staging cohort, 77 patients were newly diagnosed, and 18 had relapsed disease. Pretreatment FDG-PET was positive in 96% of patients. PET identified additional disease sites in 47/95 patients (50%) when added to conventional staging. Most frequently identified additional sites were: other nodal (n = 24); bone (n = 10); skin (n = 8); nasopharynx (n = 4); spleen (n = 3); and lung (n = 2). However, FDG-PET modified computed tomography (CT)-based staging in only 5/95 patients (5.2%): two patients were upstaged and three patients were downstaged. FDG-PET-based staging did not alter planned treatment for any patient. Interim restaging with PET was performed after a median of 4 cycles of chemotherapy. In this cohort, treatment regimens included cyclophosphamide, doxorubicin, vincristine and prednisone CHOP (n = 19); CHOP/ifosfamide, carboplatin and etoposide (ICE) (n = 26); and other (n = 7). Subsequently, 29 patients were consolidated with either autologous (n = 22) or allogeneic (n = 7) stem cell transplant. After a median follow-up of 3.4 years for surviving patients, those with negative interim PET had superior progression-free survival (PFS) compared to patients with positive interim PET (p = 0.03). There were no differences in overall survival (OS). In PTCL, FDG-PET commonly identifies additional sites of disease but infrequently impacts CT-based staging and does not influence therapy. Interim FDG-PET may predict for PFS. FDG-PET should be integrated into prospective trials to confirm these findings.
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PMID:18F-fluorodeoxyglucose positron emission tomography in the staging and prognosis of T cell lymphoma. 2336 41

A 55-year-old Caucasian woman with lung adenocarcinoma stage IV presented with repeated relapse after treatment with cytotoxic chemotherapy (carboplatin, gemcitabine, docetaxel, pemetrexed) and targeted agents (erlotinib, cetuximab, sunitinib). Comprehensive molecular diagnostics (EGFR-, ALK-, RAS-, BRAF-, PIK3CA-, HER2- and DDR2-aberrations) were performed and failed initially to detect any driver mutation. While the patient suffered from rapid deterioration of her general condition, in particular from progressive dyspnea due to lung metastases, we implemented screening for RET- and ROS1 translocations into our molecular diagnostic program based on recent reports of these new molecular subgroups in lung adenocarcinoma. On retesting the patient's tumor sample was found to harbor a ROS1-translocation. The patient was subsequently treated with crizotinib and experienced a pronounced clinical improvement corresponding to a complete metabolic response in (18)F-FDG-PET and a good and confirmed partial response in CT (RECIST 1.1). Our case exemplifies the need for rapid implementation of newly discovered rare genetic lung cancer subtypes in routine molecular diagnostics.
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PMID:Complete metabolic response in a patient with repeatedly relapsed non-small cell lung cancer harboring ROS1 gene rearrangement after treatment with crizotinib. 2355 10


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