Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Brain metastases occur in 20-40% of patients with cancer and their frequency has increased over time. Lung, breast and skin (melanoma) are the commonest sources of brain metastases, and in up to 15% of patients the primary site remains unknown. After the introduction of MRI, multiple lesions have outnumbered single lesions. Contrast-enhanced MRI is the gold standard for the diagnosis. There are no pathognomonic features on CT or MRI that distinguish brain metastases from primary malignant brain tumors or nonneoplastic conditions: therefore a tissue diagnosis by biopsy should be always obtained in patients with unknown primary tumor before undergoing radiotherapy and/or chemotherapy. Some factors are prognostically important: a high Performance Status, a solitary brain metastasis, an absence of systemic metastases, a controlled primary tumor and a younger age. Based on these factors, subgroups of patients with different prognosis have been identified (RPA class I, II, III). Symptomatic therapy includes corticosteroids to reduce vasogenic cerebral edema and anticonvulsants to control seizures. In patients with newly diagnosed brain metastases prophylactic anticonvulsants should not be used routinely. The combination of surgery and whole-brain radiotherapy (WBRT) is superior to WBRT alone for the treatment of single brain metastasis in patients with limited or absent systemic disease and good neurological condition. Complete surgical resection allows a relief of intracranial hypertension, seizures and focal neurological deficits. Radiosurgery, alone or in conjunction with WBRT, yields results which are comparable to those reported after surgery followed by WBRT, provided that lesion's diameter does not exceed 3-3.5 cm. Radiosurgery offers the potential of treating patients with surgically inaccessible metastases. Still controversial is the need for WBRT after surgery or radiosurgery: local control seems better with the combined approach, but overall survival does not improve. Late neurotoxicity in long surviving patients after WBRT is not negligible; to avoid this complication patients with favorable prognostic factors must be treated with conventional schedules of RT, and monitoring of cognitive functions is important. WBRT alone is the treatment of choice in patients with single brain metastasis not amenable to surgery or radiosurgery, and with an active systemic disease, and in patients with multiple brain metastases. A small subgroup of these latter may benefit from surgery. The response rate of brain metastases to chemotherapy is similar to the response rate of the primary tumor and extracranial metastases, some tumor types being more chemosensitive (small cell lung carcinoma, breast carcinoma, germ cell tumors). New radiosensitizers and cytotoxic or cytostatic agents, and innovative technique of drug delivery are being investigated.
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PMID:Management of brain metastases. 1238 50

Cell adhesion to fibronectin results in formation of actin stress fibres and focal adhesions. In fibroblasts, this response requires two co-operative signals provided by interactions of the RGD sequence with alpha5beta1 integrin and the heparin-binding domain II (Hep II) domain with syndecan-4. Within Hep II, this activity was mapped to repeat III13 and to the peptide FN-C/H-V(WQPPRARITGY, repeat III14). We previously described that the synthetic heparin-binding peptide/III5 (HBP/III5) (WTPPRAQITGYRLTVGLTRR, repeat III5) binds heparin and mediates cell adhesion via chondroitin sulphate proteoglycans. We have now studied whether HBP/III5 co-operates with alpha5beta1 and drives a full cytoskeletal response in melanoma cells. SKMEL-178 cells attached and spread on the RGD-containing FNIII7-FNIII10 (FNIII7-10) fragment, but did not form stress fibres or focal adhesions. Co-immobilization of HBP/III5 with FNIII7-10 or adding soluble HBP/III5 to cells prespread on FNIII7-10, effectively induced these structures. Cell transfection with dominant-negative N19RhoA, a member of the small GTPase family, abolished the HBP/III5 effect. Both chondroitinase and heparitinase diminished focal adhesions, indicating that both types of proteoglycans bound HBP/III5 in melanoma cells. We have mapped the active sequence of HBP/III5 to YRLTVGLTRR, which is a novel sequence in fibronectin with focal-adhesion-promoting activity. The last two arginine (R) residues of this sequence are required for activity, since their replacement by alanine completely abrogated the HBP/III5 cytoskeletal effect. Moreover, this sequence is also active in the context of large fibronectin fragments. Our results establish that the Hep III region provides co-operative signals to alpha5beta1 for the progression of the cytoskeletal response and that these include activation of RhoA.
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PMID:A synthetic peptide from the heparin-binding domain III (repeats III4-5) of fibronectin promotes stress-fibre and focal-adhesion formation in melanoma cells. 1251 80

Health disparities are of continuing concern to the community of public health professionals. Despite concerted efforts on a number of fronts, little progress seems to have been made towards eliminating these disparities. This is due in part to a frame of reference that focuses on race and racism. While racism plays a role, continued focus on socially constructed racial groups will not lead to solutions to the problem. Humans are biological organisms and the presence of disease indicates a maladaptation between the individual human organism and its environment. Lumping together into a 'racial' group large numbers of individuals who share little in terms of phenotype, culture, and/or behavior inhibits reaching appropriate solutions. Progress will only be made when the issue of health disparities is reframed as one of phenotype/environmental mismatch. Such a frame crosscuts current racial groups. Health disparities such as hypertension, prostate cancer, low-birth-weight (LBW) infants, infant mortality, rickets, and melanoma are affected by the interactions of degree of pigmentation, amount of exposure to ultraviolet B (UVB) radiation, and levels of serum vitamin D. Reframing the problem of health disparities from one of race and racism to one of phenotype/environmental mismatch permits a solution to an otherwise intractable problem.
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PMID:Health disparities: reframing the problem. 1285 93

With the widespread diffusion of stereotactic radiosurgical procedures, GKR treatments have gained considerable momentum as a major therapeutic option for patients harboring primary or metastatic brain tumors. Present results in high grade gliomas indicate a potential palliative role of this technique. The overall low radiosensitivity of these oncotypes and their infiltrative nature-with the resulting problems in properly defining the tumor target-are still a major obstacle to further development of the approach. In this regard, useful contributions are expected from advances in molecular neurobiology and functional neuroimaging as shown by preliminary investigations with MR spectroscopy. Surgery maintains a dominant role in the therapeutic armamentarium for low grade gliomas. However, in unfavorable cases (unresectable tumors, recurrences), GKR seems to be an effective alternative to conventional radiochemotherapy. In grade 2 astrocytomas and specifically in grade 1 pilocytic forms, short-to-mid-term reported studies have documented encouraging 70 to 93% local tumor control rates, with minimal cerebral toxicity. Finally, during the last decade, GKR has become a primary treatment choice for patients harboring small-to-medium-size brain metastases, with reasonable life expectancy and no impending intracranial hypertension. Focal tumor responses are consistently elevated, even in the most radioresistant oncotypes (melanoma, renal carcinoma); median and actuarial survival rates are far better than with conventional radiation treatments and are comparable to those observed in accurately selected surgical-radiation series.
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PMID:The role of gamma knife radiosurgery in the treatment of primary and metastatic brain tumors. 1277 10

A 61-year-old Caucasian female presented with a 6-week history of dry persistent cough. She had no shortness of breath, chest pain, fever, chills, or weight loss. She had been diagnosed with melanoma on the left thigh 6 months earlier. It was a spindle cell variant, Clark's grade III, with maximal thickness of 0.5 mm. At the time of diagnosis of melanoma, there was no evidence of metastasis on chest radiographs or computed tomography (CT) of the abdomen and pelvis. Treatment of her melanoma was limited to surgical excision with no subsequent radiation or chemotherapy. Other significant past medical history included hypertension, hypothyroidism, and bilateral breast augmentation. She had a 40 pack-year history of smoking.
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PMID:Multiple lung nodules in a woman with a history of melanoma. 1466 85

Psoriasis is a chronic condition that shows variability in phenotype and severity. The disease can seriously compromise patients' quality of life, regardless of disease extent. Systemic treatment is indicated when lesional burden is extensive and/or frequently relapsing, and when quality of life is severely altered. Furthermore, surveys have indicated that patients are dissatisfied with their current topical or phototherapy. The efficacy of ciclosporin in the treatment of psoriasis is well established. However, widespread use of this drug has been limited by concerns over adverse effects, such as renal impairment, hypertension and the potential risk of malignancy. Data from many clinical trials designed to examine the efficacy and safety of long-term continuous and intermittent short-course (< 12 weeks) therapy are now available. Information from these studies has aided dermatologists in developing treatment guidelines. Intermittent short-course therapy is well tolerated, safe, and highly effective in sustaining disease control and promoting quality of life. Long-term continuous ciclosporin therapy may be useful in some patients with refractory psoriasis. If treatment guidelines are followed, the risk of nephrotoxicity and hypertension is low. Ciclosporin therapy is associated with an increased risk of non-melanoma skin cancer (mainly squamous cell carcinoma) when patients have been previously exposed to psoralen-ultraviolet A (PUVA). The incidence of non-skin malignancy shows no significant difference to that observed in the general population.
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PMID:The use of ciclosporin in psoriasis: a clinical review. 1511 40

BAY 43-9006 is an oral inhibitor of CRAF, wild-type BRAF, mutant V599E BRAF, vascular endothelial growth factor receptor (VEGFR) 2, VEGFR3, mVEGFR2, FLT-3, platelet-derived growth factor receptor, p38, and c-kit among other kinases. A Phase I study of BAY 43-9006 identified 400 mg orally twice daily as the recommended Phase II dose. The Phase II results of a study of BAY 43-9006 at 400 mg orally twice daily were particularly interesting in patients with renal cell carcinoma. Data from the first 41 patients with renal cell carcinoma showed that 30% of patients had stable disease (defined as between 25% reduction and 25% growth), 40% had responded (defined as >25% reduction), and 30% had progressed. Disease could be stabilized for periods in excess of a year. Some lesions became cystic and could actually enlarge while developing a low attenuation core. This phenomenon is recognized in the treatment of gastrointestinal stromal tumors with imatinib mesylate. The toxic effects of BAY 43-9006 were manageable and included hypertension, edema, diarrhea, hand and foot syndrome, rash, and hair loss where the rash involved the scalp. There was an impression of tachyphylaxis such that patients who required a dose reduction could be restored to full dose after a few months. A Phase III randomized, placebo-controlled trial of BAY 43-9006 has started for patients whose renal cell carcinoma has progressed within 6 months of immunotherapy. Combination studies with interferon, interleukin 2, bevacizumab, and chemotherapy are under consideration. The therapeutic targets of BAY 43-9006 in renal cell carcinoma remain unclear. Unlike melanoma, BRAF mutations have not been found in renal cell carcinoma. Other candidate targets include VEGFR2 and VEGFR3.
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PMID:Kinase inhibition with BAY 43-9006 in renal cell carcinoma. 1544 36

A non-enzymatic reaction between ketones or aldehydes and the amino groups of proteins contributes to the aging of proteins and to pathological complications of diabetes. Under hyperglycemic conditions in diabetes, this process begins with the conversion of reversible Schiff base adducts, and then to more stable, covalently-bound Amadori rearrangement products. Over a course of days to weeks, these early glycation products undergo further reactions and rearrangements to become irreversible crossed-linked, fluorescent protein derivatives termed advanced glycation end products (AGEs). Recent understanding of this process has confirmed that AGE-their receptor (RAGE) interaction-elicited oxidative stress generation was implicated in the pathogenesis of diabetic vascular complication, melanoma growth, expansion and metastasis. We have recently found that nifedipine, one of the most widely used dihydropyridine-based calcium antagonists (DHPs) for treatments of patients with angina pectoris and hypertension, inhibited RAGE overexpression in AGE-exposed endothelial cells by suppressing reactive oxygen species generation. Since RAGE is a signal-transducing receptor for AGEs and subsequently evokes inflammatory responses in various types of cells, thus eliciting angiogenesis and thrombogenesis, we hypothesize here that blockade of RAGE expression by nifedipine may have therapeutic potentials in treatment of patients with various AGE-related disorders. In this paper, we would like to propose the possible ways of testing our hypothesis. Does nifedipine treatment reduce the development and progression of diabetic vascular complications? If the answer is yes, is this beneficial effect of nifedipine superior than that of other DHPs with equihypotensive properties? Does nifedipine treatment decrease the incidence of melanoma and/or prolong the survival of patients with this devastating disorder? These prospective studies will provide further valuable information whether blockade by nifedipine of the AGE-RAGE signaling could be clinically relevant.
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PMID:Potential therapeutic implication of nifedipine, a dihydropyridine-based calcium antagonist, in advanced glycation end product (AGE)-related disorders. 1592 19

The goal of the donor evaluation is to ensure the suitability, safety and well being of the donor. In order to avoid important omissions, the evaluation of potential living kidney donors should be carried according to a protocol that includes a logical sequence of complementary explorations. Old age alone is not an absolute contraindication to donation but the evaluation should be more rigorous, because increased age may be associated with more post-operative complications after nephrectomy and renal function and long term graft survival could be shorter than the ones obtained from younger living donors. A body mass index of more than 35 kg/m2 should be an absolute contraindication to renal donation. Between 30 and 35 kg/m2 the donor evaluation should be more rigorous and it should be recommended to lose weight before nephrectomy. Hypertension is one of the most common reasons to declare a potential kidney donor unsuitable. Evidence of organ damage is an absolute contraindication to kidney donation. The donation is only reasonable when hypertension is well controlled with less than two drugs. To excluded diabetes mellitus all donors should have a fasting plasma glucose measurement. Diabetes mellitus is an absolute contraindication to living donation such as an impaired glucose tolerance or impaired fasting glucose with a family history of type 2 diabetes mellitus. Another contraindication to living donation is malignant disease, and the same standards should be adopted for cadaveric donors. The exceptions are low-grade non-melanoma skin cancer and carcinoma in situ of the uterine cervix. The presence of active infection usually precludes donation. It is very important to perform a routine test for viral infections. HIV, hepatitis B and C infection of the donor are usually a contraindication to living donor. CMV donor and recipient status should be taken into account before transplantation, and the recipients at risk for CMV disease should recieve prophylactic treatment according to the transplant unit policy.
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PMID:[Assessment of the living renal donor. Analysis of extra-renal pathology as a limitation for donation]. 1605 Apr 3

A case of primary leptomeningeal malignant melanoma localized in the cervical region in a 41-year-old woman is presented. The only clinical finding was intracranial hypertension with papilledema. A diagnosis of primary CNS melanoma was made after dermatological and ophthalmological consultations, ruled out a metastatic lesion. Primary leptomeningeal melanoma is an extremely rare spinal tumor. Its clinical presentation with signs of increased intracranial pressure but without cord symptoms is unusual. Clinical features of this case including the radiological and histologic findings are described. Diagnosis as well as management are discussed.
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PMID:Primary spinal melanoma with bilateral papilledema. 1620 28


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