Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Multiple cysts and benign cystadenomas of the pancreas have been documented occasionally in von Hippel-Lindau syndrome (HLS); however, the malignant involvement of the pancreas in HLS is very rare. We report a case of HLS in which metastatic tumors from renal cell carcinoma (RCC) coexisted with multiple cysts in the pancreas. A 22-year-old woman with a history of HLS had undergone a partial resection of the left kidney for RCC 3 years earlier, at which time a solid mass in the pancreatic tail and multiple pancreatic cysts were also incidentally detected by computed tomography. Over the following 3 years, the mass enlarged slightly, thus raising suspicions that it might be a primary neoplasm of the pancreas. She was referred to the Department of Surgery and Surgical Basic Science to undergo surgery. In addition to the tumor in the pancreatic tail, however, further tumors in the pancreatic head were also disclosed by preoperative celiac arteriography and intraoperative palpation and ultrasonography. A distal pancreatectomy was performed, because the enucleation of all the tumors in the pancreatic head was technically impossible and because the patient declined a total pancreatectomy. A histologic examination of the mass in the pancreatic tail revealed metastatic RCC. This case emphasizes that metastatic disease should be included in the differential diagnosis when evaluating the pancreas in a patient with HLS.
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PMID:Pancreatic lesions in von Hippel-Lindau syndrome: the coexistence of metastatic tumors from renal cell carcinoma and multiple cysts. 1079 74

A variety of pediatric renal masses may be differentiated from Wilms tumor on the basis of their clinical and imaging features. Wilms tumor is distinguished by vascular invasion and displacement of structures and is bilateral in approximately 10% of cases. Nephroblastomatosis occurs most often in neonates and is characterized by multiple bilateral subcapsular masses, often associated with Wilms tumors. Renal cell carcinoma is unusual in children except in association with von Hippel-Lindau syndrome and typically occurs in the 2nd decade. Mesoblastic nephroma is the primary consideration in a neonate with a solid renal mass. Multilocular cystic renal tumor is suggested by a large mass with multiple cysts and little solid tissue. Clear cell sarcoma is distinguished by frequent skeletal metastases, and rhabdoid tumor is distinguished by its association with brain neoplasms. Angiomyolipoma frequently contains fat and is associated with tuberous sclerosis. Renal medullary carcinoma occurs in patients with sickle cell trait or hemoglobin SC disease and manifests as an infiltrative mass with metastases. Ossifying renal tumor of infancy is differentiated from mesoblastic nephroma by the presence of ossified elements. Metanephric adenoma lacks specific features but is always well defined. Renal lymphoma is characterized by multiple homogeneous masses, often with associated adenopathy.
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PMID:Pediatric renal masses: Wilms tumor and beyond. 1111 13

An acidic extracellular pH is a fundamental property of the malignant phenotype. In von Hippel-Lindau (VHL)-defective tumors the cell surface transmembrane carbonic anhydrase (CA) CA9 and CA12 genes are overexpressed because of the absence of pVHL. We hypothesized that these enzymes might be involved in maintaining the extracellular acidic pH in tumors, thereby providing a conducive environment for tumor growth and spread. Using Northern blot analysis and immunostaining with specific antibodies we analyzed the expression of CA9 and CA12 genes and their products in a large sample of cancer cell lines, fresh and archival tumor specimens, and normal human tissues. Expression was also analyzed in cultured cells under hypoxic conditions. Expression of CA IX and CA XII in normal adult tissues was detected only in highly specialized cells and for most tissues their expression did not overlap. Analysis of RNA samples isolated from 87 cancer cell lines and 18 tumors revealed high-to-moderate levels of expression of CA9 and CA12 in multiple cancers. Immunohistochemistry revealed high-to-moderate expression of these enzymes in various normal tissues and multiple common epithelial tumor types. The immunostaining was seen predominantly on the cell surface membrane. The expression of both genes was markedly induced under hypoxic conditions in tumors and cultured tumor cells. We conclude that the cell surface trans-membrane carbonic anhydrases CA IX and CA XII are overexpressed in many tumors suggesting that this is a common feature of cancer cells that may be required for tumor progression. These enzymes may contribute to the tumor microenvironment by maintaining extracellular acidic pH and helping cancer cells grow and metastasize. Our studies show an important causal link between hypoxia, extracellular acidification, and induction or enhanced expression of these enzymes in human tumors.
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PMID:Expression of hypoxia-inducible cell-surface transmembrane carbonic anhydrases in human cancer. 1123 39

Uveal melanoma is the most common form of primary eye cancer. Monosomy 3, which is an unusual finding in tumors but is present in approximately 50% of uveal melanomas, is significantly correlated with metastatic disease. To obtain positional information on putative tumor suppressor genes on this chromosome, we have investigated tumors from 333 patients by comparative genomic hybridization, microsatellite analysis, or conventional karyotype analysis. A partial deletion of the long arm was found in eight tumors, and the smallest region of deletion overlap (SRO) spans 3q24-q26. We found six tumors with a partial deletion of the short arm and were able to define a second SRO of about 2.5 Mb in 3p25. This SRO does not overlap with the VHL gene. Our finding suggests a role for two tumor suppressor genes in metastasizing uveal melanoma and may explain the loss of an entire chromosome 3 in these tumors.
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PMID:Partial deletions of the long and short arm of chromosome 3 point to two tumor suppressor genes in uveal melanoma. 1130 5

A rare case of familial Hippel-Lindau disease, which is an autosomal dominant disorder with inherited susceptibility to various forms of cancer, is reported in a 46-year-old father and his sons. The father complained of a malignant hypernephroma, which metastasized in the upper jaw 6 months later. As in this patient, renal cell carcinomas are fatal and are exhibited at an early age. Consequentially, patients with familial von Hippel-Lindau disease exhibiting cases of renal cell carcinoma should be examined very carefully in the head and neck region to detect and treat metastases as early as possible.
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PMID:Inheritance of Hippel-Lindau disease: a rare case of maxillary bone metastasis. 1131 6

We present a case report of von Hippel-Lindau disease associated with renal cell carcinoma and bilateral cystadenoma of the epididymis. A 26-year-old man appeared with painless tumors of the bilateral scrotal contents. Ultrasonography and other radiographic examinations including computed tomographic scan and dripinfusion pyelography showed multiocular tumors in the bilateral epididymis and a right renal tumor 3 cm in diameter. The tumors of the bilateral epididymis were surgically resected and of the right renal tumor enucleated. Histopathological examination revealed cystadenoma of the epididymis and renal cell carcinoma (clear cell carcinoma, G1, pT1a). He has not received adjuvant therapy, and is doing well with no evidence of metastatic disease 2 years after surgery.
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PMID:[Von Hippel-Lindau disease associated with renal cell carcinoma and bilateral cystadenoma of the epididymis: a case report]. 1141 Nov 1

For several reasons, chromosome 3p is thought to be involved in the pathogenesis of sporadic endocrine pancreatic tumours (EPTs): von Hippel-Lindau's disease (VHL gene at 3p25.5) is associated with EPTs; 3p is frequently involved in solid human tumours; and comparative genomic hybridization has identified frequent losses at 3p in EPTs. This study investigated 99 benign and malignant tumours, including 20 metastases, from 82 patients, by microsatellite loss of heterozygosity (LOH) analysis and fluorescence in situ hybridization (FISH) in order to evaluate the importance of chromosome 3p deletions in the molecular pathogenesis and biological behaviour of EPTs, to elaborate a common region of deletion, and to narrow down putative tumour suppressor gene loci. Allelic losses of 3p were found in 58/99 (58.6%) of tumours in 45/82 (54.9%) patients; analysis of seven microsatellite markers (3p26-p21) revealed a common region of LOH at 3p25.3-p23. The LOH frequency was significantly higher in malignant than in benign neoplasms (70.2% versus 28.0%; p=0.001). In addition, a strong correlation was found between the loss of alleles on chromosome 3p and clinically metastatic disease (LOH of 73.7% in metastasizing versus 41.5% in non-metastasizing tumours; p=0.008). EPTs from these patients showed a tendency towards losing large parts or the entire short arm of chromosome 3 with tumour progression. Furthermore, FISH analysis revealed complete loss of chromosome 3 in ten out of 37 EPTs (27%). These results indicate that a putative tumour suppressor gene at 3p25.3-p23 may play a role in the oncogenesis of sporadic EPTs and that losses of larger centromeric regions are associated with metastatic progression.
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PMID:Deletion at 3p25.3-p23 is frequently encountered in endocrine pancreatic tumours and is associated with metastatic progression. 1152 53

Von Hippel-Lindau (VHL) disease is an autosomal, dominant inherited tumour syndrome with an estimated prevalence of 2-3 per 100,000 persons. A germline mutation in the VHL gene predisposes carriers to tumours in multiple organs. These tumours may include haemangioblastoma in the retina and central nervous system (CNS), renal cell carcinoma, phaeochromocytoma, islet cell tumours of the pancreas, and endolymphatic sac tumours, as well as cysts and cystadenoma in the kidney, pancreas, epididymis and broad ligament. Penetrance of VHL disease is high, most carriers of a VHL germline mutation develop one or more tumours by the age of 60 years. The most common symptoms include: loss of vision, raised intracranial pressure, neurological deficits, paroxysmal raised blood pressure and local pain. At present, metastases from renal cell carcinoma and neurological complications from cerebellar haemangioblastoma are the most common causes of death. However, it is anticipated that intensive radiological and clinical monitoring, and advanced operation techniques will reduce both morbidity and mortality in patients with VHL disease.
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PMID:Clinical management of Von Hippel-Lindau (VHL) disease. 1170 42

Metastatic renal cell cancer remains a disease which is difficult to treat medically. Prognosis often depends more on intrinsic disease features than on treatment choices. In this review, we examine novel therapies and scientific directions surrounding the RCC treatment problem. Reports relating chromosomal aberrations and of comparative gene expression analyses relating to RCC, are reviewed briefly. The central role of the von Hippel Lindau protein in clear cell RCC pathogenesis is evident. The limited contribution of conventional cytotoxic chemotherapy is mentioned. Some clinically applied agents whose clinical results are highlighted include 5-FU, retinoids, thalidomide, razoxane and IL-12. Features of the pathophysiology of von Hippel Lindau protein are described, with attention to potential novel therapies targeting HIF-1alpha, VEGF, TGF-beta1 and TGF-alpha pathways. Immunotherapy is being explored in many angles. Most basic are cytokine therapies incorporating new IL-2 and IFN-alpha schedules. Newer cytokine-based drugs include pegylated forms and IL-12. Allogeneic mini-transplantation has generated much interest. Tumour-associated antigens are being used to direct therapy using both identified and non-identified epitopes. A variety of tumour-cell vaccine and dendritic-cell vaccine clinical approaches are discussed. Finally, nephrectomy for known metastatic disease has been demonstrated to be helpful in retrospective and now prospective trials. Resection of metastases is also discussed. We are optimistic that the further clinical development among these novel therapies will improve the outlook for metastatic RCC.
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PMID:Novel therapies for renal cell carcinoma. 1177 33

Here we report tumor-to-tumor metastases identified in two patients with von Hippel-Lindau (VHL) disease. The first patient had bilateral renal carcinomas and multiple cerebellar hemangioblastomas, and the second patient had a renal carcinoma and multiple hemangioblastomas in the retina, cerebellum and spinal cord. A cerebellar lesion from the first patient and a spinal lesion from the second patient contained two distinct components. The inner part of these tumors consisted of a nested mass of polygonal clear cells that expressed cytokeratin and epithelial membrane antigen, while the outer part of the tumors showed proliferation of capillaries and intervening foamy stromal cells that were negative for cytokeratin and epithelial membrane antigen. The tumors were thus considered to be hemangioblastomas complicated by metastatic lesions of renal cell carcinoma of clear cell type. These cases indicate that tumor-to-tumor metastasis should be considered when hemangioblastoma contains a clear cell carcinoma component in the setting of VHL disease, and that immunohistochemical staining for cytokeratin and epithelial membrane antigen is useful for the diagnosis.
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PMID:Metastasis of renal cell carcinoma to central nervous system hemangioblastoma in two patients with von Hippel-Lindau disease. 1184 68


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