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)

In patients of ovarian cancer combined with multiple pulmonary nodules, the diagnosis of metastatic ovarian cancer is always considered. However, benign pulmonary conditions can be discovered instead. An 80-year-old female presented with a rapidly growing ovarian mass, elevated serum CA-125, and multiple pulmonary varying-sized nodular lesions. The pretreatment workup of her lung lesions failed to show a malignant cell, and it also failed to show any evidence of tuberculosis or other infectious diseases. After surgery, her disease was allotted to 'stage IV' epithelial ovarian cancer and adjuvant cytotoxic chemotherapy was then used. However, her sputum culture showed positive growth of Mycobacterium tuberculosis 4 weeks later. For fear of reactivation of pulmonary tuberculosis, the anticancer cytotoxic chemotherapy was postponed and the antituberculous treatment was given instead. After 6-month course of antituberculous therapy, no active lung lesion was detectable. In conclusion, infectious or inflammatory conditions can mimic metastatic disease and therefore add to the difficulty of stage determination. We recommend that there must be positive cytologic or pathologic results of lung lesions to allot a case of ovarian cancer to stage IV. Furthermore, whenever pulmonary lesions are seen on imaging, the possibility of diagnoses other than metastatic ovarian cancer should always be considered.
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PMID:Early-stage ovarian carcinoma combined with pulmonary tuberculosis mimicking advanced ovarian cancer: a case report. 1536 Dec 16

Despite advances in our understanding of tumour immunology there is no therapy of proven survival benefit for advanced melanoma. Nevertheless, disease progression is slow in a small proportion of patients with metastatic melanoma, suggesting a contribution to outcome from host factors. Recent data have indicated the importance of the heat shock protein receptor CD91 in immune responses to, and progression of, infectious disease. Here we investigate the relationship between CD91 expression and outcome in malignancy. Rare melanoma patients were recruited with advanced disease that was progressing unusually slowly. CD91 expression on their monocytes was compared with control patients with more typical rapidly advancing metastatic disease. Th1 and Th2 cytokines, as well as innate and adaptive immune subsets, were also measured in the two groups. A significant increase in median CD91 expression levels was observed in slow progressors (P = 0.006). There were no differences in other immune subset markers or inflammatory cytokines. The ability of CD91 to internalize and cross-present tumour antigens through the major histocompatibility complex class I pathway may maintain CD8-positive cytotoxic T cell responses and contribute to slow progression of advanced melanoma.
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PMID:The common heat shock protein receptor CD91 is up-regulated on monocytes of advanced melanoma slow progressors. 1549 42

Liver resection combined with the resection and reconstruction of the vena cava represents the only potential curative therapy for malignant hepatic tumors with invasion of the vena cava. We performed a liver resection with segmental replacement of the retrohepatic vena cava by synthetic grafts in 29 patients. In three cases, the additional presence of central involvement of all three hepatic veins required ex situ tumor resection. Four patients underwent a simultaneous exstirpation of the primary tumor (kidney or suprarenals). The remaining hepatic veins were reimplanted into the graft in three cases, and in two cases the renal veins were reimplanted. There was no perioperative mortality. A distal arteriovenous fistula was not applied. Five patients revealed postoperative transient liver insufficiency, requiring temporary dialysis in three cases. Two of these patients developed a transient multiorgan failure with the need of mechanical ventilation. 18 patients died during the course of follow-up, 17 of these cases due to recurrent metastases of the primary disease. Infection or thrombosis of the prosthetic vascular graft have not been observed. Beside tumor exstirpation, extended liver resection and concomitant vena cava replacement may prevent embolism as well as the obstruction of the vena cava with lower extremity swelling and the possibility of developing a Budd Chiari syndrome. We were able to achieve a long-term survival for surgically treated patients even in cases with advanced tumor stages.
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PMID:[Resection and reconstruction of the retrohepatic vena cava in combination with liver resections]. 1584 51

We report a case of rectal adenocarcinoma in a 9-year-old boy, which took the form of a second malignant neoplasm following treatment for an early childhood malignancy. The abdominal complaints were for a long time interpreted as an infectious disease. At the time of diagnosis of the rectal carcinoma, the tumor had already progressed to the stage of metastatic disease. Therapy consisted of deep anterior rectal resection and regional arterial chemotherapy for liver metastases. The child died 18 months after the diagnosis of rectal carcinoma. As survival for childhood tumors improves, rare second malignant neoplasms will become increasingly common in children and adolescents. This phenomenon emphasizes the need for continued clinical surveillance of patients who have been treated with chemotherapy or irradiation for childhood tumors. The increased risk of second malignant neoplasms and an early onset of adult-type tumors has to be considered.
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PMID:Adenocarcinoma of the rectum in childhood following chemotherapy and radiotherapy for a rhabdomyosarcoma--a case report. 1599 18

We reported earlier that IL-1beta, an NF-kappaB-regulated cytokine, was made by intestinal epithelial cells during detachment-induced apoptosis (anoikis) and that IL-1 was antiapoptotic for detached cells. Since surviving anoikis is a prerequisite for cancer progression and metastases, we are further exploring the link between anoikis and cytokines. Here we determined that multiple genes are expressed following detachment including a number of NF-kappaB-regulated products and therefore aimed to determine whether NF-kappaB signalling plays any role in regulating apoptosis. Using Western blotting, we detected that IkappaBalpha becomes phosphorylated immediately following detachment and that levels of phospho-IkappaBalpha peaked within 20 min. Phosphorylation of IkappaBalpha was followed by Rel A (p65) nuclear translocation. Increased NF-kappaB activity following detachment was confirmed using the detection of NF-kappaB-promoted luciferase gene expression delivered by adenovirus infection. Infection of cells with adenovirus expressing a super-repressor IkappaBalpha protein and pharmacological inhibitors of NF-kappaB resulted in the failure to phosphorylate IkappaBalpha, a more rapid activation of caspases and earlier apoptosis. We also detected that IkappaB kinase alpha (IKKalpha) and not IKKbeta became phosphorylated following detachment. Since IKKalpha is activated by NF-kappaB-inducing kinase (NIK), we overexpressed native NIK using an adenovirus vector that resulted in enhanced phospho-IkappaBalpha and nuclear p65 in detached cells compared to control detached cells but did not result in a significantly greater number of cells surviving to 24 h. We conclude that detachment directly activates NF-kappaB, which, in addition to launching an inflammatory cytokine wave, contributes to a delay in apoptosis in intestinal epithelial cells.
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PMID:Activation of NF-kappaB following detachment delays apoptosis in intestinal epithelial cells. 1600 76

Targeted antiangiogenic gene therapy is an attractive approach to treat metastatic cancer. However, the relative paucity of the receptors of the commonly used adenovirus serotype 5 in endothelial cells as compared with liver cells undermines the use of this vector for targeting the endothelial cells in tumors. To overcome this problem, we analyzed the ability of a hybrid Ad5/35 virus, where the serotype 5 fiber has been replaced with the fiber from serotype 35, to target tumor vasculature. Infection of human umbilical vein endothelial cells (HUVECs) with Ad5/35 at MOI 120 infected 100% of cells. In contrast, infection with Ad5 at the same MOI infected only 10% HUVECs. Ad5/35 was even more effective in transducing human aortic endothelial cells (HAECs), as infection with Ad5/35 at MOI 3.6 was sufficient to transduce 95% of cells. Gene expression analyses demonstrated that infection of HUVECs and HAECs with Ad5/35 resulted in between 1 and 3 orders of magnitude higher gene expression than infection with Ad5. Furthermore, various liver-derived cells were less infectable with Ad5/35 than Ad5, indicating a favorable toxicity profile for this virus. In a rat colon carcinoma tumor model, Ad5 was located mainly in the liver parenchyma after hepatic artery administration. In contrast, Ad5/35 was found only in the angiogenesis-rich border region of the tumor. Double immunostaining revealed that Ad5/35 colocalized with CD31 and Flk-1 positive endothelial cells. These results indicate that Ad5/35 may be useful in anticancer strategies targeting tumor endothelial cells.
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PMID:Efficient infection of tumor endothelial cells by a capsid-modified adenovirus. 1610 61

Limitations of current viral-based gene therapies for malignant tumors include lack of cancer-specific targeting and insufficient tumor delivery. To ameliorate these problems and develop a truly effective adenovirus gene-based therapy for cancer, we constructed a conditionally replication competent adenovirus (CRCA) manifesting the unique properties of tumor-specific virus replication in combination with production of a cancer-selective cytotoxic cytokine, melanoma differentiation associated gene-7/interleukin-24 (mda-7/IL-24), which embodies potent bystander antitumor activity. Cancer cell selective tropism was ensured by engineering the expression of the adenoviral E1A protein, necessary for viral replication, under the control of a minimal promoter region of progression elevated gene-3 (PEG-3), which functions selectively in diverse cancer cells with minimal activity in normal cells. In the E3 region of this CRCA, we introduced the mda-7/IL-24 gene, thereby mediating robust production of this cytokine as a function of adenovirus replication. Infection of this CRCA (designated Ad.PEG-E1A-mda-7) in normal mammary epithelial cells and breast cancer cells confirmed cancer cell selective adenoviral replication, mda-7/IL-24 expression, growth inhibition, and apoptosis induction. Injecting Ad.PEG-E1A-mda-7 into human breast cancer xenografts in athymic nude mice completely eradicated not only the primary tumor but also distant tumors (established on the opposite flank of the animal) thereby implementing a cure. This dual cancer-specific targeting strategy provides an effective approach for treating breast and other human neoplasms with the potential for eradicating both primary tumors and metastatic disease. Additionally, these studies support the potential use of mda-7/IL-24 in the therapy of malignant cancers.
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PMID:Dual cancer-specific targeting strategy cures primary and distant breast carcinomas in nude mice. 1617 3

Pancreatic cancer is an aggressive neoplasm with no current viable, effective treatment options. In the majority of cases, at first diagnosis, pancreatic cancer has already become metastatic so that conventional treatment regimens provide minimal, if any, clinical benefit in prolonging life or ameliorating the negative prognosis of this disease. These harsh realities underscore the need for developing improved treatment paradigms for this cancer, with gene therapy and immunotherapy currently being evaluated as potential therapeutic options. We currently describe an adenovirus-based therapy for successfully managing pancreatic cancer, the cancer terminator virus (CTV), which is founded on targeted induction of viral replication from a cancer-specific progression elevated gene-3 (PEG-3) promoter (PEG-Prom) and immune modulation by IFN-gamma. The PEG-Prom functions selectively in cancer cells of diverse lineages compared with their normal cellular counterparts. In the CTV, the PEG-Prom drives expression of the adenoviral early region 1A (E1A) gene, necessary for virus replication, with IFN-gamma simultaneously being expressed from the E3 region. Infection of normal cells and pancreatic cancer cells with the CTV confirmed cancer cell-selective adenoviral replication, robust IFN-gamma production coupled with virus replication, growth inhibition, and apoptosis induction. Infection of established pancreatic tumors in nude mice with the CTV promoted viral replication, IFN-gamma production, and activation of antitumor immunity resulting in complete eradication of both primary and distant tumors, curing animals of disease. The CTV provides a novel reagent for treating pancreatic and other human cancers with potential for eliminating both primary tumors and metastatic disease.
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PMID:Targeted virus replication plus immunotherapy eradicates primary and distant pancreatic tumors in nude mice. 1620 80

Surgery for pathological fracture of long tubular bones associated with metastatic cancer was given to 77 patients (1993-2000): segmental resection with endoprosthetic replacement - 26; intramedullary osteosynthesis - 17; perosseous extrafocal osteosynthesis - 34. No intraoperative complication was reported. Infection-related postoperative complications, mainly in perosseous osteosynthesis, developed in 5 (7%). All patients were self-sufficient on days 3-10 after operation.
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PMID:[Surgical treatment for pathologic fractures of long tubular bones in metastatic cancer]. 1627 7

Comprehensive bowel examination results from the combined use of T2-weighted single-shot and breath hold T1-weighted gradient echo, minus/plus fat suppression, and gadolinium-enhanced 3D gradient echo (3D VIBE, T1 FAME, 3D THRIVE). Gadolinium-enhanced imaging should be performed dynamically, but the venous 60- to 90-second delayed phase images with fat suppression are generally the most valuable. Removal of fat signal for detection of enhancing normal and abnormal structures is critical. Newly available True-FISP (FIESTA, BFFE) sequences obtained in the 2D form can be very helpful in delineation of bowel wall pathology and overall bowel anatomy, particularly when combined with a water-based intraluminal distending agent. Advantages include rapid acquisition, high signal-to-noise, and motion insensitivity. Generalized protocol for comprehensive evaluation of the entire abdomen and pelvis can be used for the following bowel indications: type and severity of inflammatory bowel disease (IBD); identifying enteric abscesses and fistulae; preoperative staging of malignant neoplasms, including rectal carcinoma; differentiating postoperative and radiation therapy changes from recurrent carcinoma; follow-up evaluation of metastases response to localized ablative or systemic chemotherapy. For improved visualization of bowel wall in dedicated examinations, bowel distension should be achieved using either orally or rectally delivered contrast agents to produce either bright or dark lumen. We have found 2D True-FISP without fat suppression superior to 3D True-FISP and to single-shot echo-train sequences to provide a T2-weighted image of bowel morphology. Strengths include: performed without fat suppression results in the very dark bowel wall being sandwiched between intermediate high signal fat adjacent to bowel serosa, and very high lumen signal from water-distending agent; 2D True-FISP provides motion insensitivity that is lost if 3D is used; True-FISP produces better edge sharpness than single-shot echo-train, higher contrast, and resists flow void artifacts commonly seen with single-shot echo-train imaging combined with a water distending agent. Drawbacks of this technique include: artifacts related to extreme sensitivity to field inhomogeneity, including air-soft tissue interfaces at the patient skin surface, and from retained bowel gas; retained bowel gas is dark against dark bowel wall, impairing bowel wall assessment; and True-FISP does not provide sensitivity for edema, which is superior on single-shot echo-train imaging. Small/large bowel indications for MRI include: inflammatory bowel disease, infectious disease including abscess evaluation or for appendicitis, inflammatory conditions including ischemia, and partial obstruction, malnutrition, and neoplasm search.
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PMID:Magnetic resonance imaging of the gastrointestinal tract. 1631 98


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