Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a retrospective review of varicella-zoster (V-Z) Infections in adult cancer patients, 766 episodes of V-Z Infection were studied among 740 patients seen at a large comprehensive cancer center from 1972 to 1980. The highest risk of infection was present among patients with lymphoma and leukemia. The risk of dissemination of V-Z Infection was significantly associated with the presence of active tumor at the time of Infection. The site of the primary tumor correlated with the site of subsequent zoster Infection among patients with breast cancer, cancer of the respiratory tract, and gynecologic cancer. Pain attributable to V-Z Infection was present in a large majority of episodes. The median time from the completion of therapy to the onset of Infection was seven months for patients receiving radiotherapy and less than one month for those receiving chemotherapy. Various attributes of this study group were compared with those of previously studied cancer and noncancer populations.
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PMID:Varicella-zoster infection in adult cancer patients. A population study. 338 2

Infection with herpes simplex virus (HSV) enhances the growth of Lewis lung tumor (LLT). Infection with HSV-1 enhances as efficiently as HSV-2. A significant acceleration of primary tumor formation was obtained. In mice, lung metastases were increased in number and size above the controls. Enhancement occurred only with high doses of infectious virus and was also obtained only when the virus infection was at a site close to that of the tumor implantation. This finding, in addition to the lack of antigenicity of LLT, is interpreted as arguing against an immunologic mechanism of the phenomenon.
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PMID:Enhancement of Lewis lung carcinoma by the concomitant infection of the host with herpes simplex virus type 1 and type 2. 629 46

Twenty-one patients who underwent pelvic exenteration for primary (n = 8) or recurrent (n = 13) vulvar malignancy at the M. D. Anderson Cancer Center between 1956 and 1989 were evaluated. A posterior exenteration was performed in 12 patients, anterior exenteration was performed in 6, and total exenteration was performed in 3. In patients with primary tumors, radical vulvectomy and inguinal lymphadenectomy were also performed. The median patient age was 57 years. The mean tumor diameters were 5 cm (primary) and 4 cm (recurrent). Infections were the most frequent postoperative complications (n = 15), followed by pulmonary (n = 4) and cardiac problems (n = 3). There were no treatment-related deaths. Five patients required further surgery to correct late postoperative sequelae. Four of eight patients experienced recurrence after treatment of their primary tumor; the recurrences were local only (n = 1), in the inguinal area (n = 2), or local and in the pelvis (n = 1). Nine of the 13 patients treated for recurrent tumors developed a second recurrence; the second recurrences were all within the pelvis, although two also had a distant component. The 5-year survival rates were 70% for patients treated for primary disease and 38% for patients treated for recurrent disease. Pelvic exenteration is indicated for selected patients with advanced vulvar malignancy.
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PMID:Pelvic exenteration for primary and recurrent vulvar cancer. 762 6

To explore the potential of recombinant vectors based on recombinant adeno-associated virus (rAAV) for cancer vaccination, we investigated the transduction efficiency of rAAV into cancer cells ex vivo. Infection of human epithelial cancer cell lines with rAAV carrying reporter genes encoding beta-galactosidase (rAAV/LacZ) or luciferase (rAAV/Luc) resulted in high levels of reporter gene expression (>90% positive cells). In marked contrast, rAAV poorly transduced all murine tumor cell lines, as well as human hematopoietic cell lines. Either irradiation or adenovirus infection of tumor cells prior to rAAV infection induced a 10- to 100-fold increase of reporter gene expression. To determine the transduction efficiency of rAAV into primary cancer cells, freshly isolated, irradiated tumor cells from malignant melanoma and ovarian carcinoma patients were infected with rAAV/Luc, resulting in up to 6.9-fold higher levels of gene expression than in a HeLa tumor cell line. Time course experiments with freshly isolated tumor cells infected with rAAV/Luc showed maximal levels of luciferase expression between days 3 and 9 posttransduction. Simultaneous infection of primary tumor cells with up to three rAAV vectors containing genes encoding the immunostimulatory proteins B7-2 (CD86), p35 subunit of IL-12, and p40 subunit of IL-12 resulted in high expression of B7-2 in more than 90% of the tumor cells and in the secretion of high levels of IL-12. Taken together, our results demonstrate that rAAV efficiently transduces freshly isolated human, epithelial tumor cells and might therefore be a potent tool to produce improved, gene-modified cancer vaccines.
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PMID:Recombinant adeno-associated virus for the generation of autologous, gene-modified tumor vaccines: evidence for a high transduction efficiency into primary epithelial cancer cells. 960 16

Recombinant adenoviral vectors expressing u-PA, t-PA, PAI-1 and PAI-2 were employed to correlate the expression of components of the fibrinolytic system with the invasiveness of HT 1080 tumor cells. Migration through Transwell inserts in vitro in the presence of plasminogen was increased up to 22% by overexpression of u-PA, whereas t-PA had no effect. Gene transfer of PAI-1 or PAI-2 both reduced migration in a dose-dependent manner by up to 43% with PAI-1 and 29% with PAI-2. Two routes of gene transfer were used to alter metastasis of subcutaneously implanted HT 1080 cells expressing firefly luciferase in nude mice. Infection of cultured tumor cells with adenovirus expressing either PAI-1 or PAI-2 before implantation significantly reduced the incidence of lung metastasis by 60% compared with control virus. However, only PAI-2 reduced the incidence of lung and brain metastasis following liver gene transfer. Although PAI gene transfer by either route reduced primary tumor size, it had little effect on tumor vascularization or host survival. The migratory and metastatic phenotype of HT 1080 tumor cells is thus directly dependent on u-PA expression levels and can be altered by gene transfer of u-PA or plasminogen activator inhibitors.
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PMID:Reduction of tumor cell migration and metastasis by adenoviral gene transfer of plasminogen activator inhibitors. 1043 7

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

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

Infection of mice with the murine sarcoma virus (Moloney) markedly suppressed the humoral antibody response to sheep erythrocyte antigen injected 10 days after infection, when tumor size was maximal, and on day 26, when primary tumors had partially regressed. Humoral antibody response was also inhibited when antigen was injected at the time secondary tumors and metastases were evident. No significant suppression of humoral antibody was seen when mice were injected with sheep erythrocyte antigen 5 days after virus infection. Inhibition of the cellular immune response of murine sarcoma virus (Moloney)-infected mice, as measured by the increased survival time of skin grafts, was also determined. Mice that were infected 5 days prior to grafting demonstrated prolonged survival of grafts, suggesting a suppression of cellular immunity. These mice had a graft survival time 14 days greater than noninfected controls. No significant prolongation of graft survival was seen in mice grafted at the times of maximum primary tumor growth, of primary tumor regression, or when secondary tumors had appeared.
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PMID:Immunosuppression by murine sarcoma virus (Moloney). 1655 30

Interferon-gamma (IFN-gamma) is a proinflammatory cytokine that also acts as a potent immunomodulatory agent. In this study, a replication-deficient recombinant avian (fowlpox) virus was engineered to express the murine IFN-gamma gene (rF-MuIFN-gamma) with the rationale of delivering concentrated levels of the cytokine to a local tissue microenvironment. Subcutaneous (s.c.) rF-MuIFN-gamma administration resulted in IFN-gamma production that (1) was restricted to the tissue microenvironment of the injection site and (2) was biologically active, as evidenced by a significant increase of class I MHC expression levels in s.c. growing tumors following rF-MuIFN-gamma administration. Infection of a highly tumorigenic murine cell line, MC38, with rF-MuIFN-gamma functioned as an effective tumor cell-based vaccine by protecting mice from the formation of primary tumors and from subsequent tumor challenge. The cell-based vaccine was completely ineffective if mice were vaccinated with MC38 cells either pretreated with rIFN-gamma or infected with the wild-type fowlpox virus (FP-WT). Analysis of the regional lymph nodes draining the site of injection of the rF-MuIFN-gamma-based tumor cell vaccine revealed the presence of tumor-specific cell lysis (CTL) as well as a significant amount of lysis directed at natural killer (NK)-sensitive YAC-1 cells. Flow cytometric analyses coupled with functional assays confirmed the sustained presence of NK1.1(+) cells within those draining lymph nodes for up to 5 days after rF-MuIFN-gamma injection. Mice treated with NK cell-depleting antibodies prior to the injection of the rF-MuIFN-gamma-infected MC38 tumor cells were not protected from primary tumor growth; analysis of the lymph nodes draining the injection site in NK-depleted mice revealed an accompanying loss of the tumor-specific CTL activity. The findings provide evidence that NK cells, known for their contributions to host innate immunity, also provide immunoregulatory signals required for the development of an adaptive immune response, which, in turn, protected vaccinated mice against tumor growth.
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PMID:Targeted delivery of murine IFN-gamma using a recombinant fowlpox virus: NK cell recruitment to regional lymph nodes and priming of tumor-specific host immunity. 1827 3

Sarcoidosis is a granulomatous disease of unknown origin, with pulmonary findings in more than 90% of patients. Extrapulmonary involvement is common and all organs can be involved (especially lymph nodes, eyes, joints, central nervous system) but it is rare to find an isolated extrapulmonary disease (less than 10% of patients). Granulomatous inflammation of the spleen and the liver is common in patients with systemic sarcoidosis, while hepatosplenic enlargement is unusual and splenic involvement rare. We report two cases of systemic sarcoidosis, that onset with splenic and hepatosplenic disease, and one case with splenic sarcoidosis without pulmonary involvement. In the first case a 53-year-old woman with mild abdominal pain underwent sonography and CT, which revealed one hypoechoic/hypodense splenic lesion. Laboratory tests were normal. In order to exclude a lymphoma, splenectomy was performed: histology revealed a sarcoid granuloma. After surgery the patient was asymptomatic and now, after two years, disease is silent. The second case is a 66-year-old woman with a recent weight loss (8 kg in two months) and alterated liver function tests (AST 61 U/l, ALT 72 U/l, Alkaline phosphatase 748 U/l, g-GT 381 U/l). Since she had a familiar history of colon cancer, abdominal US scan, abdominal CT scan and MRI were performed and showed inter-aorto-caval lymphadenopathies and discreet multiple bilobar hepatic and splenic substitutive lesions, with no signs of primary tumor. Upper and lower GI endoscopy, full gynecological workup, complete set of tumor markers, bone marrow biopsy were performed. All resulted negative for neoplasia. Small pulmonary infiltrations were observed on chest-CT scan but cytology on BAL was normal. Infections were also excluded. An exploratory laparotomy showed whitish peritoneal, hepatic and splenic nodules. The histological exam revealed chronic granulomatous lesions typical for sarcoidosis. During a two-year follow-up after the splenectomy the patient feels well without any treatment. The third patient is a 32-year-old woman with mild epigastric pain after meals. Neck-thoracic CT, bone scintigraphy and upper GI endoscopy were negative. Abdominal US and MR showed splenomegaly with multiple splenic lesions. Splenectomy was performed and histological exam showed chronic granulomatous lesions typical for sarcoidosis. Further laboratory tests were normal, except for ACE (66 UI/l). After the surgery ACE became normal and now, three years later, the patient is still asymptomatic. We conclude that hepatosplenic involvement is less rare than it is thought. It is often oligosymptomatic or accompanied with unspecific manifestations and laboratory abnormalities. The diagnosis could be difficult; in fact typical laboratory findings of sarcoidosis such as ACE, lysozyme, calcium, were not diagnostic. Ultrasonography and CT were important but the diagnosis was established only with the histological examination of suspected lesions. This latter required to differentiate liver and/or spleen sarcoidosis from tuberculosis and other infections, primary biliary cirrhosis, metastasis or malignant lymphoma.
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PMID:Atypical sarcoidosis: case reports and review of the literature. 2138 7


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