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

Metabolic imaging with positron emission tomography (PET) provides, in neuro-oncology, information complementary to that provided by anatomic imaging obtained with CT-scanner or MRI. Only a few publications have yet reported its use in oligodendroglial tumors. These findings and partial results obtained in ongoing work, suggest some preliminary conclusions: 11C-MET (L-methyl-methionine) is a more appropriate tracer than 18F-FDG (fluoro-deoxy-glucose), in terms of both specificity and sensitivity, for the assessment of patients with this category of tumor. PET/MET allows differentiation between grade II and grade III oligodendrogliomas; better targeting for stereotactic biopsy; more accurate assessment of the post-operative residual tumor; identification of progression from low-grade to anaplastic grade during the disease course; differentiation between recurrence and a post-radiation processes. PET/MET allows, to some extent, prediction of response to radiotherapy; and, probably, to chemotherapy.
 ...
PMID:[Metabolic imaging for supratentorial oligodendrogliomas]. 1629 75

A-64-year-old woman, who had been treated with augmentation mammaplasty 40 years ago, came to our hospital complaining of left breast pain. The mass was ill-defined, located in the upper outer quadrant area of her breast, and was 2 cm in diameter. MRI examination showed that the tumor had a spiculation and an irregular edge. There were no regional lymph nodes in her axilla and supra-subscapular. The diagnosis was Class IV by the fine needle aspiration biopsy cytology. We diagnosed the left breast cancer being in T2N0M0, Stage IIA, then we carried out Bt (Auchincloss method) and Sentinel lymph node biopsy (SLNB). There were metastatic cancer cells in the sentinel lymph node. So, we added level II lymph nodes dissection. The histological diagnosis was papillotubular carcinoma, f+, n+ (8/11). The endocrine receptor status of the tumor was ER+, PgR+ and the HER2/neu score was 0. There was paraffinoma in the non-cancer area. We dosed 6 cycles of FEC chemotherapy (CPA 800 mg, EPI 80 mg, 5-FU 750 mg/body x 1 cycle). We recognized no side effects of the chemotherapy for the patient.
 ...
PMID:[A case of breast cancer detected by MRI mammography after Hollywood syndrome]. 1631 41

The large majority of gastrointestinal stromal tumors (GIST) can be diagnosed on the basis of KIT immunoreactivity. However, some atypical tumors show weak or negative KIT expression. We studied the imaging characteristics of atypical GIST, reviewing CT and MRI findings in ten patients (eight men, two women; mean age 59 years) with atypical GIST. Radiological studies were evaluated by two radiologists by consensus and included CT and MR imaging in all patients. Pathological diagnoses were made from surgery and confirmed by the polymerase-chain reaction (PCR) to amplify both exons of the c-kit gene and PDGFRA gene. The CT and MR examinations revealed a heterogeneous mass of the stomach containing cystic regions and soft tissue elements in all cases. All lesions were extraluminal masses and had an exophytic epicenter. On T1-weighted MR images soft tissue elements of the tumors were of homogeneously low- (n=3) or iso-signal intensity (n=7) compared with the liver parenchyma. On fast spin-echo T2-weighted MR images soft tissue elements of all tumors showed cystic regions of significantly high signal intensity interspersed with septumlike structures of low signal intensity. All lesions exhibited homogeneously (n=4) or heterogeneously (n=6) mild to moderate enhancement of soft tissue elements. Despite the relatively small number of patients CT and MRI findings of atypical GIST are a submucosal mass with soft tissue elements and cystic regions.
 ...
PMID:CT and MRI findings in KIT-weak or KIT-negative atypical gastrointestinal stromal tumors. 1639 44

Leptomeningeal carcinomatosis represents a rare manifestation of metastatic breast cancer (MBC). A 39-year-old female presenting with HER2-overexpressing MBC and suffering from meningeal carcinomatosis was treated with the humanized antibody trastuzumab directed to HER2 by intrathecal administration. The patient was diagnosed with HER2-overexpressing stage III breast cancer in December 2003. In August 2004, the patient developed a singular intracerebral metastasis which was resected by neurosurgery followed by whole-brain radiotherapy. Since MRI and cerebrospinal fluid (CSF) analyses indicated meningeal carcinomatosis, the patient was commenced on trastuzumab (6 mg/kg q3w) and capecitabine (2.500 mg/m2 d1-14, q3w). Prompted by clinical deterioration, 5 repeated doses of intrathecal methotrexate (15 mg/dose) were administered, yet without clinical improvement. There is initial evidence that trastuzumab does not reach an adequate concentration in CSF after intravenous application. Nevertheless, infiltration of trastuzumab into CSF is facilitated under conditions of an impaired blood-brain barrier, as it is known for meningeal carcinomatosis. For patients with leptomeningeal disease, intrathecal application of trastuzumab may provide an interesting therapeutical approach for patients with HER2 overexpressing metastatic breast cancer. Therefore, an Ommaya reservoir for intrathecal treatment with trastuzumab was placed surgically and intrathecal therapy was begun with escalating doses of trastuzumab (5-20 mg), which proved to be effective and well tolerated by the patient. Within 2 weeks after treatment, the patients' condition improved significantly and cell counts in CSF obtained from the Ommaya reservoir remained low for 11 months after first diagnosis of meningeal carcinomatosis when clinical symptoms and MRI indicated progression of meningeal and cerebral disease.
 ...
PMID:Application of intrathecal trastuzumab (Herceptintrade mark) for treatment of meningeal carcinomatosis in HER2-overexpressing metastatic breast cancer. 1659 13

Mutations in KAL1 and FGFR1 cause Kallmann syndrome (KS), whereas mutations in the GNRHR and GPR54 genes cause idiopathic hypogonadotropic hypogonadism with normal olfaction (nIHH). Mixed pedigrees containing both KS and nIHH have also been described; however, the genetic cause of these rare cases is unknown. We examined the FGFR1 gene in seven nIHH subjects who either belonged to a mixed pedigree (n = 5) or who had associated midline defects (n = 2). Heterozygous FGFR1 mutations were found in three of seven unrelated nIHH probands with normal MRI of the olfactory system: (i) G237S in an nIHH female and a KS brother; (ii) (P722H and N724K) in an nIHH male missing two teeth and his mother with isolated hyposmia; and (iii) Q680X in a nIHH male with cleft lip/palate and missing teeth, his brother with nIHH, and his father with delayed puberty. We show that these mutations lead to receptor loss-of-function. The Q680X leads to an inactive FGFR1, which lacks a major portion of the tyrosine kinase domain (TKD). The G237S mutation inhibits proper folding of D2 of the FGFR1 and likely leads to the loss of cell-surface expression of FGFR1. In contrast, the (P722H and N724K) double mutation causes structural perturbations in TKD, reducing the catalytic activity of TKD. We conclude that loss-of-function mutations in FGFR1 cause nIHH with normal MRI of the olfactory system. These mutations also account for some of the mixed pedigrees, thus challenging the current idea that KS and nIHH are distinct entities.
 ...
PMID:Mutations in fibroblast growth factor receptor 1 cause both Kallmann syndrome and normosmic idiopathic hypogonadotropic hypogonadism. 1660 36

This study prospectively evaluates the outcomes at a minimum 4-year follow-up after PCL reconstruction using quadruple hamstring tendon autograft with an arthroscopic double fixation technique. During 1996-1999, hamstring tendon autograft graft has been used in 57 patients. Data from 52 patients who had been followed up completely were analyzed. All patients suffered from a grade 3 or higher grade of posterior drawer test and posterior sag sign with MRI image confirmation. Twelve knees had combined posterior and posterolateral instability, which were simultaneously reconstructed. Clinical assessments included Lysholm knee score, International Knee Documentation Committee (IKDC) scores, KT-1000 instrumented test, thigh muscle assessment, and radiographic evaluation. The mean Lysholm score was 54 (40-65) and 91 (65-100) points (P<0.01) before and after surgery. Thirty (58%) patients could return to moderate or strenuous activity. The evaluation of AP translation has been performed with KT-1000. The average posterior displacement measured with KT-1000 was 11.69+/-2.01 mm preoperatively and 3.45+/-2.04 mm postoperatively. Forty-two (81%) patients demonstrated ligament laxity of less than 5 mm. Forty-two (81%) patients were rated as normal or nearly normal based on IKDC scores. Forty-six (88%) patients achieved a minimum of 80% recovery of extensor strength and 44 (85%) patients achieved a minimum of 80% recovery of flexor strength. Statistically significant differences existed in thigh girth, extensor strength, and flexor strength before and after reconstruction. Arthroscopic reconstruction for PCL with four-strand hamstring tendon graft produced satisfactory results. The semitendinosus and gracilis tendon graft is adequate in graft size, technically easier to perform and more reproducible, and had a satisfactory result.
 ...
PMID:Arthroscopic posterior cruciate ligament reconstruction with hamstring tendon autograft: results with a minimum 4-year follow-up. 1681 85

Antibody-based anticancer agents are promising chemotherapeutic agents. Among these agents, Herceptin (trastuzumab), a humanized anti-human epidermal growth factor receptor 2 (HER2/c-erbB2) monoclonal antibody, has been used successfully in patients with breast cancer. However, in patients with brain metastasis, the blood-brain barrier limits its use, and a different delivery method is needed to treat these patients. Here, we report that Herceptin can be delivered locally and noninvasively into the mouse central nervous system through the blood-brain barrier under image guidance by using an MRI-guided focused ultrasound blood-brain barrier disruption technique. The amount of Herceptin delivered to the target tissue was correlated with the extent of the MRI-monitored barrier opening, making it possible to estimate indirectly the amount of Herceptin delivered. Histological changes attributable to this procedure were minimal. This method may represent a powerful technique for the delivery of macromolecular agents such as antibodies to treat patients with diseases of the central nervous system.
 ...
PMID:Noninvasive localized delivery of Herceptin to the mouse brain by MRI-guided focused ultrasound-induced blood-brain barrier disruption. 1686 82

Apert syndrome was diagnosed in a newborn with typical facial and digital features whose only detected prenatal abnormality had been agenesis of the corpus callosum. This prompted a review of the central nervous system findings in all cases of Apert syndrome treated at the Craniofacial Center Boston Children's Hospital between 1978 and 2004. Two of 30 patients with Apert syndrome had prenatal identification of mild dilatation of the lateral cerebral ventricles and complete agenesis of the corpus callosum (ACC) documented with both ultrasound and MRI. Both had the common S252W mutation of FGFR2. Though cranial and orbital malformations typical of Apert were eventually seen in these fetuses in the third-trimester, even in retrospect, these were not detectable at mid second-trimester, ultrasound screening for congenital malformations. Hand malformations also went undetected in the second-trimester despite extensive imaging by experienced radiologists. We conclude that prenatal ultrasonographic identification of mild ventriculomegaly or ACC should stimulate a careful search for features of Apert syndrome and prompt follow-up imaging to look for bony abnormalities that have later onset. Prenatal molecular testing for Apert mutations should be considered in cases of mild ventriculomegaly and ACC.
 ...
PMID:Apert syndrome: what prenatal radiographic findings should prompt its consideration? 1690 98

Catecholamine-secreting metastatic carcinoid should be considered in differential diagnosis of malignant pheochromocytoma. Paroxysmal functioning or hormonally silent gastroenteropancreatic neuroendocrine tumors (GEP NETs) require repeat biochemical measurements and sensitive anatomic and functional imaging studies overlapping those for malignant pheochromocytoma. This report presents clinical, laboratory, and radiologic findings in a patient presenting with heart rate variability; vasoactive headaches reactive to ethanol, tyramine and tryptophan; labile blood pressure; diaphoresis; diarrhea; abdominal pain; unexplained pancreatitis; joint pain; and paroxysmal flushing with pallor. GI studies (including endoscopic ultrasound) and multiple imaging modalities (including 2D CT, MRI with gadolinium, [18]FDG PET/CT, [123I]MIBG, and SRS [111In]Octreotide [OctreoScan]) were not diagnostic. 24-h BP, Holter and 30-day cardiac event monitors plus urinary biochemical studies consistently suggested catecholamine-synthesizing NET. NIH plasma metanephrines studies and [6]-[18F]Fluorodopamine PET ruled out malignant pheochromocytoma (pheo). Repeated studies showed persistently abnormal GEP NET biomarkers and urinary catecholamines. Capsule endoscopy revealed suspicious submucosal lesions throughout the small intestine. Dual-phase 64-slice multidetector computed tomography (MDCT) with 3D volumetric reconstruction of the abdomen and pelvis revealed multiple diffuse liver metastases and three extrahepatic lesions consistent with metastatic carcinoid. In combination, intensive biochemical testing repeated over time, dual-phase 64-slice MDCT with 3D image reconstruction and volume-rendering (VR) technique, and advanced radionuclide imaging are required to detect NETs' sporadic or paroxysmal functioning, rule out extra-adrenal pheochromocytoma, and localize and characterize metastatic carcinoid. If pheochromocytoma is ruled out, yet symptoms and biochemical markers for catecholamine excess are present, then carcinoid and other amine-precursor-uptake decarboxylation (APUD) tumors must remain in the differential diagnosis.
 ...
PMID:Catecholamine-secreting metastatic carcinoid as differential diagnosis in pheochromocytoma: clinical, laboratory, and imaging clues in the search for the lurking neuroendocrine tumor (NET). 1710 73

Pheochromocytoma (PHEO) is considered to be a rare cause of hypertension. However, if left untreated, PHEOs may lead to fatal hypertensive crises during anesthesia and other stresses. The diagnosis of PHEO is therefore extremely important. A 24-hour blood pressure (BP) pattern per se might be of some diagnostic value due to frequently observed higher BP variability as well as an attenuated night-time BP decrease. So far, germline mutations in five genes have been identified to be responsible for familial PHEOs: the von Hippel-Lindau gene, which causes von Hippel-Lindau syndrome, the RET gene leading to multiple endocrine neoplasia type 2, the neurofibromatosis type 1 gene, which is associated with von Recklinghausen's disease and the genes encoding the B and D subunits of mitochondrial succinate dehydrogenase (SDHB, SDHD), which are associated with familial paragangliomas and PHEOs. Genetic analysis should be offered to those patients with confirmed PHEO who are 50 years old or younger. Plasma-free metanephrines or urinary fractionated metanephrines seem to have higher diagnostic values compared to plasma or urinary catecholamines for the biochemical diagnosis of PHEO. Imaging with (123)I-metaiodobenzylguanidine or (18)F-fluorodopamine PET, if available, are in addition to CT/MRI useful for the detection of multifocal/extra-adrenal forms. Appropriate pharmacologic treatment with subsequent laparoscopic extirpation of PHEO is usually successful in benign forms. There is, however, no convincingly effective mode of treatment in malignant PHEOs.
 ...
PMID:Recent advances in the diagnosis and treatment of pheochromocytoma. 1711 41


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>