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)

BACKGROUND: Surgical resection of hepatocellular carcinomas and metastases to the liver cannot always be performed, and systemic therapies for these entities are of limited value. The techniques of chemoembolization and hepatic artery infusion have been used for patients who are not candidates for surgery. METHODS: Chemoembolization uses percutaneous intra-arterial infusion of chemotherapeutic agents and embolic material. This provides longer contact of the agents with the tumor cells and induces ischemia. Hepatic arterial chemoinfusion uses the knowledge that hepatic cancers are supplied predominantly by the hepatic artery. RESULTS: Chemoembolization using Lipiodol, doxorubicin, and Gelfoam has promoted necrosis of unresectable hepatocellular tumors and may have prolonged patient survival. Hepatic arterial infusion with fluorinated pyrimidines produces more objective responses than systemic chemotherapy but probably does not alter survival. CONCLUSIONS: The nonsurgical treatments of chemoembolization and hepatic arterial infusion of chemotherapy have expanded our armamentarium to manage many primary and metastatic tumors in the liver. Additional approaches are needed.
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PMID:Regional Transcatheter Therapy of Hepatic Neoplasms. 1076 98

A major obstacle that limits the potential of human gene therapy is the inefficiency of gene delivery to appropriate sites in vivo. Previous studies demonstrated that the physiological surveillance function performed by von Willebrand factor (vWF) could be incorporated into retroviral vectors by molecular engineering of the MuLV ecotropic envelope (Env) protein. To advance the application of vWF targeting technology beyond laboratory animals, we prepared an extensive series of Env proteins bearing modified vWF-derived matrix-binding sequences and assembled these chimeric proteins into targeted vectors that are capable of transducing human cells. Initially, a dual envelope configuration was utilized, which required coexpression of a wild-type amphotropic Env. Subsequently, streamlined "escort" Env proteins were constructed wherein the inoperative receptor-binding domain of the targeting partner was replaced by the vWF-derived collagen-binding motif. Ultimately, an optimal construct was developed that exhibited properties of both extracellular matrix (ECM)-targeting and near wild-type amphotropic infectivity, and could be arrayed as a single envelope on a retroviral particle. On intraarterial instillation, enhanced focal transduction of neointimal cells (approximately 20%) was demonstrated in a rat model of balloon angioplasty. Moreover, transduction of tumor foci (approximately 1-3%) was detected after portal vein infusion of a matrix-targeted vector in a nude mouse model of liver metastasis. We conclude that the unique properties of these targeted injectable retroviral vectors would be suitable for improving therapeutic gene delivery in numerous clinical applications, including vascular restenosis, laser and other surgical procedures, orthopedic injuries, wound healing, ischemia, arthritis, inflammatory disease, and metastatic cancer.
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PMID:Molecular engineering of matrix-targeted retroviral vectors incorporating a surveillance function inherent in von Willebrand factor. 1081 Dec 27

Thirty-four patients suffering from various kinds of tumors, including metastasis, were treated by selective embolization with both spherical and cylindrical poly(2-hydroxyethyl methacrylate) [poly(HEMA)] particles and topical chemotherapy. Treatment of a patient with carcinoid metastases in the liver is discussed. Immediately after embolization, 5-fluorouracil, and later, doxorubicin and Lipiodol, were selectively infused into the tumorous tissue for approximately 1 week. Patient received four cycles of this infusion. Chemoembolization proceeded against the background of anticoagulant therapy using small doses of heparin or its low-molecular-weight analogue, dalteparin. This was followed by transcutaneous transhepatic portography and embolization. Finally, the tumor-feeding artery and portal vein were sealed by a hydrogel. After 1.5 months, the affected liver lobe was resected. Although 4 years from the beginning of treatment, the patient is still alive. Embolization with poly(HEMA) hydrogel particles in conjunction with an anticancer drug infusion via catheter is recommended as an efficient method of tumor treatment. The therapeutic effect has been shown to be a function of ischemia and slow local infusion of drug into the tumor, and systemic drug levels can be kept low.
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PMID:Targeted chemoembolization of tumors with poly(2-hydroxyethyl methacrylate) particles. 1082 17

Chemoembolization has become the preferred treatment for patients with inoperable, hypervascular hepatic malignancies in the Far East, but controversial elsewhere. In vivo microscopy in addition to other experimental procedures are used in this presentation to better understand the mechanisms involved in chemoembolization. In chemoembolization Lipiodol acts as a contrast material, a vehicle for chemotherapy and an embolic agent. Although not optimal, Lipiodol injected into the hepatic artery, traverses the peribiliary plexus to the portal veins resulting in a dual embolization. Chemoembolization creates ischemia, slows arterial flow and increases the contact time between the infusate and the neoplasms, increasing the tumor cell kill. However, the vascular occlusion also produces infarction and fibrosis compounding the already existing cirrhosis frequently associated with hepatocellular carcinoma. Lipiodol/ethanol (3:1) injected into the segmental or lobar hepatic artery supplying the neoplasm also gains access to the associated portal venous branches causing focal ablation. This preoperative approach is easier to perform than direct portal vein occlusion, with less parenchymal damage and comparable hypertrophy of the remnant liver frequently necessary for adequate hepatic function following resection. Polymer-drug conjugates, e.g. PG-TXL, have considerable potential for intra-arterial delivery especially with the dramatic increase in concentration of the drug in the tumor and its efficacy. Using in vivo microscopy especially with green fluorescent protein (GFP) gene as an efficient and non-toxic tumor cell marker, the events leading to hepatic metastases can be documented which will serve to better evaluate these varied techniques of chemoembolization.
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PMID:Hepatic chemoembolization: clinical and experimental correlation. 1092 54

The management of advanced digestive endocrine tumors is often challenging. Liver metastases are usually diffuse at the time of diagnosis, and surgical resection is rarely feasible. Objective response rates with systemic chemotherapy are disappointing. Arterial hypervascularization of most liver metastases from digestive endocrine tumors argues in favor of hepatic arterial chemoembolization (HACE). It is assumed that embolization-induced ischemia sensitizes tumor cells to cytotoxic drugs, whose tumor concentrations are increased by blood flow slowing down. The aims of HACE are: (1) to control otherwise untractable hormone-related symptoms, particularly the carcinoid syndrome (>50% urinary 5-HIAA decrease: 57-91%) and insulinoma-related life-threatening hypoglycemias; (2) to inhibit tumor growth (objective response rates: 33-80%; mean duration: 6-42.5 months), and (3) to improve patients' survival. The postembolization syndrome, usually mild and transient, is the commonest side effect. Major extrahepatic complications are rare. In conclusion, HACE seems to be an attractive alternative treatment for diffuse (unresectable) and progressive metastases confined to the liver in patients with digestive endocrine tumors, mainly following unsuccessful systemic chemotherapy. Further studies assessing the long-term results of HACE and comparing it to other treatments, particularly systemic chemotherapy, are needed.
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PMID:Hepatic arterial chemoembolization in the management of advanced digestive endocrine tumors. 1094 Jun 92

With adequate medical management the midgut carcinoid tumor generally is an indolent malignancy associated with substantial life expectancy and appreciable life quality, even in the presence of liver metastases and significant tumor burden. Abdominal complications may occur in this entity of carcinoids owing to entrapment of intestines and encasement of mesenteric vessels by mesenteric metastases and associated marked mesenteric fibrosis. This may be the cause of abdominal pain, disabling diarrhea, weight loss to the extent of malnutrition, and eventually the risk of death with acute or chronic intestinal obstruction or intestinal gangrene. Operative removal of the mesentericointestinal lesion is often indicated to prevent or treat these complications but may be technically difficult when mesenteric metastases extend in the vicinity of major vessels in the mesenteric root. At laparotomy 56 patients with advanced midgut carcinoids underwent removal of the mesenteric tumor with a method for preserving the mesenteric vessels. This was feasible by mobilizing and releasing the right colon and mesenteric root from posterior adhesions, identifying the mesenteric artery below the pancreas, and free-dissecting this artery on the tumor capsule in the mobilized mesentery. Dissection was successful even with tumors initially judged inoperable unless tumor growth completely surrounded the mesenteric vessels or extended retroperitoneally. One patient was subjected to distal intestinal artery bypass. Symptom relief was been substantial and often of long duration after mesenteric tumor removal in patients who prior to surgery often had threatening intestinal ischemia. Patients with advanced midgut carcinoids may benefit markedly from dissectional removal of mesenteric tumors, which (conceivably better than conventional wedge resection) preserves the length of the remaining intestine.
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PMID:Method for dissection of mesenteric metastases in mid-gut carcinoid tumors. 1103 14

A 57-year-old female patient with known cardiac disease developed a 4 to 6 week history of diarrhea, followed by onset of orthopnea and subsequent right-sided cardiac failure. On hospital admission she was found to have pure tricuspid regurgitation, without evidence of cardiac ischemia, pulmonary embolism, bacterial endocarditis or pericardial disease. A 24-hour urine collection for 5-HIAA was elevated, and a subsequent octreotide scan documented abnormal uptake in the pelvic cul-de-sac. Bilateral ovarian masses were found at laparotomy, which on pathological examination were found to be a benign left ovarian cystic teratoma, and a right carcinoid tumor of the ovary. This patient presented with systemic complaints of diarrhea, and orthopnea and right sided heart failure that on evaluation were ultimately found to be due to a unilateral primary carcinoid tumor of the ovary, which accounts for less than 0.1% of all ovarian carcinomas, and only 5% of all carcinoids. Treatment of this malignant carcinoid syndrome presentation consisted of debulking of the tumor and continuation of her diuretics and digoxin. Diarrhea and orthopnea ceased within 2 weeks after her oophorectomy. On evaluation 6 weeks and 6 months postoperatively, her cardiac function was stable, though unchanged. 5-HIAA levels were within normal limits, demonstrating the curative function of surgery in patients with unilateral ovarian carcinoid without evidence of metastases, as well as preserved cardiac function in otherwise stable patients.
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PMID:A case of diarrhea and orthopnea in a 57-year-old female. 1106 Oct 23

Hemorrhage and liver failure are the two greatest concerns for patients undergoing major liver resection. Inflow occlusion (Pringle maneuver) is often used to minimize blood loss, but hepatic ischemia results in an increased risk of postoperative hepatic dysfunction. We report our experience with the Harmonic Scalpel ultrasonically activated shears (UAS; Ethicon Endo-Surgery, Cincinnati, OH) and a vascular stapler for hepatic resection as technological advances that aid in minimizing blood loss and thereby reduce the need for inflow occlusion. We retrospectively reviewed liver resections performed from September 1997 through July 1998, in which the UAS and articulating vascular endoscopic linear cutting stapler were used. The vascular stapler was used to divide the appropriate portal vein branch and hepatic vein(s) before parenchymal transection. Parenchymal dissection was performed with UAS to a depth of approximately 2 to 3 cm, and the remainder of the liver parenchyma was divided by a clamp crush and clip and suture ligate technique. Patients underwent segmental resection (n = 12), lobectomy (n = 13), or extended lobectomy (n = 11). Resection was performed for metastatic disease, primary liver tumors, or benign disease in 21, 8, and 7 patients, respectively. A Pringle maneuver was performed in 7 of 36 patients (mean clamp time, 8 minutes). The median required intraoperative blood transfusion was 0 units of packed red blood cells. Major and minor complications occurred in 12 and 3 patients, respectively. Two deaths were related to pneumonia and abdominal infection. The vascular stapler safely and securely divides portal vein branches and hepatic veins. The UAS initiates parenchymal transection with minimal blood loss. These two technologies facilitate the surgeon's aim of liver resection without blood transfusion or Pringle maneuver.
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PMID:The role of the ultrasonically activated shears and vascular cutting stapler in hepatic resection. 1109 14

Arterial embolization of a malignant tumor is extremely rare. We report an unusual case of a young adult man who presented with acute lower limb ischemia and a mass in the right lung and left atrium. These clinical manifestations were the result of metastases and embolization from a germ cell tumor and were the first indication of malignancy in this patient. The importance of appropriate investigations in the subsequent treatment is stressed.
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PMID:Recurrent arterial embolization from a metastatic germ cell tumor invading the left atrium. 1115 44

Cathepsin D (CD) and cathepsin E are representative lysosomal and nonlysosomal aspartic proteinases, respectively, and play an important role in the degradation of proteins, the generation of bioactive proteins, antigen processing, etc. Recenty, several lines of evidence have suggested the involvement of these two enzymes in the execution of neuronal death pathways induced by aging, transient forebrain ischemia, and excessive stimulation of glutamate receptors with excitotoxins. CD has also been shown to mediate apoptosis induced by various stimuli and p53-dependent tumor suppression. To gain more insight into in vivo functions of CD, mice deficient in this enzyme were generated. The mutant animals showed a progressive atrophy of the intestinal mucosa, a massive destruction of lymphoid organs, and a profound accumulation of ceroid lipofuscin, and developed a phenotype resembling neuronal ceroid lipofucinosis, suggesting that CD is essential for proteolysis of proteins regulating cell growth and tissue homeostasis. It has also been shown that CD molecules secreted from human prostate carcinoma cells are responsible for the generation of angiostatin, a potent endogenous inhibitor of angiogenesis, suggesting its contribution to the prevention of tumor growth and angiogenesis-dependent growth of metastases. Interestingly, pro-CD from human breast carcinoma cells showed a significantly lower angiostatin-generating activity than that from prostate carcinoma cells. Since deglycosylated CD molecules from both carcinoma cells showed a low angiostatin-generating activity, this discrepancy appeared to be attributed to the difference in the carbohydrate structures of CD molecules between the two cell types and to contribute to their potency to prevent tumor growth and metastases.
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PMID:New functional aspects of cathepsin D and cathepsin E. 1121 63


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