Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 34-year-old female who had received left hemi-thyroidectomy because of carcinoma of the thyroid complained of progressive deafness 5 years postoperatively. A red pulsating tumor was found in her mid-ear; it was removed incompletely. The tumor was diagnosed as a glomus jugulare tumor. The patient died at age 47 due to tumor progression. Autopsy revealed a temporal bone tumor with brain invasion; histological examination confirmed it to be a metastasis from the thyroid carcinoma. Clinical and histological details of this rare case are reported and the relevant literature is reviewed.
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PMID:[A case of thyroid carcinoma with temporal bone metastasis]. 632 84

Vestibular schwannomas (VS) are among the most common benign tumors of the central nervous system. Bilateral VS are the hallmark of neurofibromatosis type II, commonly leading to complete deafness and cranial nerve deficits as a result of tumor progression or treatment with surgery or radiation. Effective medical therapies are needed to address tumor progression and treatment-related morbidity. This article reviews the standard therapies for VS, summarizes the molecular biology of these tumors, and describes potential targets for chemotherapeutic agents. The article also defines and recommends the use of specific clinical end points in future drug trials, describes previous and current experience with anti-VEGF and anti-EGFR agents, and delineates areas of future research.
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PMID:Chemotherapy: present and future. 2248 28

Shp2 is a positive regulator for Erk activation downstream of receptor tyrosine kinases for growth factors. It has been controversial how Shp2 induces Erk activation. We here demonstrate that EphA2 is responsible for Shp2-mediated Erk activation by phosphorylating Tyr542 and Tyr580 of Shp2 in the cells stimulated with growth factors. In NMuMG mammary epithelial cells stimulated with hepatocyte growth factor (HGF), HGF-dependent Erk phosphorylation was prolonged only in the presence of EphA2. This Erk activation paralleled the phosphorylation of Tyr542/580 of Shp2 and the association of Grb2 with Shp2, suggesting the positive signal involving Grb2 signal to activate Ras-Erk pathway. Immunohistochemical studies of mammary cancer specimens revealed that the cancer progression was associated with both Tyr580 phosphorylation of Shp2 and increased expression of EphA2, which were also correlated with increased Erk phosphorylation. Overexpression of either Shp2Thr468Met (a phosphatase-defective mutant found in Lentigines, Electrocardiographic abnormalities, Ocular hypertelorism, Pulmonary stenosis, Abnormal genitalia, Retardation of growth and sensorineural Deafness (LEOPARD) syndrome) or Shp2Asn308Asp (a phosphatase-active mutant found in Noonan syndrome) with EphA2 exhibited comparable activation of Erk and stronger activation than wild-type Shp2, suggesting the phosphatase-independent Erk activation. Expression of Shp2Thr468Met with Tyr542/580Phe mutations resulted in the suppression of Erk activation. Phosphatase-active and -inactive, and wild-type Shp2s bound equally to Grb2, suggesting that phosphorylation of Tyr542/580 of Shp2 was essential but not sufficient for Shp2-mediated Erk activation. We found that Gab1 (Grb2-associated binder 1) was involved in the mutant Shp2-mediated Erk activation. Zebrafish injected with Shp2Thr468Met mRNA showed cardiac edema, whereas those depleted of EphA2b showed less phenotype, suggesting that EphA2 might partly account for the phenotype of LEOPARD syndrome. Collectively, tyrosine phosphorylation of Shp2 by EphA2 contributes to the phosphatase-independent Shp2-mediated activation of Erk and might be involved in Shp2-associated diseases.
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PMID:Involvement of EphA2-mediated tyrosine phosphorylation of Shp2 in Shp2-regulated activation of extracellular signal-regulated kinase. 2331 28

This review describes the current state of knowledge of the Raph blood group system, which consists of a single antigen, MER2. MER2 was initially classified as a high-incidence antigen in the 901 series of blood groups, formerly known as 901011, but was reclassified as an antigen in the Raph blood group system in 2004. There have been six reports of human alloantibodies to MER2. Three of the subjects were found to have a stop codon in the CD151 gene, which encodes a member of the tetraspanin family of proteins. These three individuals had nephropathy and deafness, and two of the three, who are siblings, also had skin lesions and P-thalassemia minor. The fourth subject had missense mutation c.533G>A (p.Argl78His). Subjects 5 and 6 shared missense mutation c.511C>T (p.Argl71Cys) as well as a synonymous single-nucleotide mutation (c.579A>G) and had no clinical features. Although the CD151 protein is critical to cell- to-cell interactions and cell signaling and is implicated in cancer progression, the significance in transfusion medicine is limited to one report of a hemolytic transfusion reaction in Subject 5.
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PMID:Raph blood group system. 2523 43

Increasing numbers of patients with vestibular schwannoma (VS) have been treated with focused-beam stereotactic radiation treatment (SRT) including Gamma knife, CyberKnife, X-knife, Novalis, or proton beam therapy. The purpose of this study was to document the incidence of tumor regrowth or symptoms that worsened or first developed following SRT and to discuss surgical strategies for patients who have failed SRT for VS. A consecutive series of 39 patients with SRT failed VS were surgically treated. Clinical symptoms, tumor regrowth at follow-up, intraoperative findings, and surgical outcome were evaluated. There were 15 males and 24 females with a mean age of 51.8 years. Thirty-six patients (92.3%) demonstrated steady tumor growth after SRT. Two (5.1%) patients with slight increase of the mass underwent surgical resection because of development of unbearable facial pain. Symptoms that worsened or newly developed following SRT in this series were deafness (41%), dizziness (35.9%), facial numbness (25.6%), tinnitus (20.5%), facial nerve palsy (7.7%), and facial pain (7.7%). Intraoperative findings demonstrated fibrous changes of the tumor mass, cyst formation, and brownish-yellow or purple discoloration of the tumor capsule. Severe adhesions between the tumor capsule and cranial nerves, vessels, and the brainstem were observed in 69.2%. Additionally, the facial nerve was more fragile and irritable in all cases. Gross total resection (GTR) was achieved in 33.3% of patients, near-total resection (NTR) in 35.9%, and subtotal resection (STR) in 30.8% of patients. New facial nerve palsy was seen in seven patients (19.4%) postoperatively. Our findings suggest that patients with VS who fail SRT with either tumor progression or worsening of clinical symptoms will have an increased rate of adhesions to the neurovascular structures and may have radiation-influenced neuromalacia. Salvage surgery of radiation-failed tumors is more difficult and will have a higher risk of postoperative complications. Radical total resection may not be feasible, and conservative modality of subtotal resection needs to be considered to avoid new neurologic deficits.
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PMID:Surgical management of vestibular schwannomas after failed radiation treatment. 2678 33

The efficacy of radiosurgery for neurofibromatosis type 2 (NF2)-associated vestibular schwannoma (VS) remains debatable. We retrospectively analyzed radiosurgical outcomes for NF2-associated VS compared to sporadic VS using our database of 422 consecutive VS patients. Twenty-five patients with 30 NF2-associated VSs with a mean follow-up of 121 months were identified. NF2-associated VSs exhibited excellent tumor control (10-year cumulative rate, 92% vs. 92% in sporadic VSs; p = 0.945) and worse overall survival (73% vs. 97%; p = 0.005), mainly due to tumor progression other than the treated VSs. The presence of NF2 was not associated with failed tumor control via multivariate Cox proportional hazard analyses. No difference in radiation-induced adverse events (RAEs) was confirmed between cohorts, and prescription dose (hazard ratio 8.30, 95% confidence interval 3.19-21.62, p < 0.001) was confirmed as a risk for cranial nerve injuries via multivariate analysis. Further analysis after propensity score matching using age, volume, and sex as covariates showed that NF2-associated VSs exhibited excellent local control (100% vs. 93%; p = 0.240) and worse overall survival (67% vs. 100%; p = 0.002) with no significant difference in RAEs. Excellent long-term tumor control and minimal invasiveness may make radiosurgery a favorable therapeutic option for NF2 patients with small to medium VS, preferably with non-functional hearing or deafness in combination with postoperative tumor growth or progressive non-operated tumors, or with functional hearing by patients' wish.
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PMID:Long-Term Outcomes of Stereotactic Radiosurgery for Vestibular Schwannoma Associated with Neurofibromatosis Type 2 in Comparison to Sporadic Schwannoma. 3159 25