Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Malignant lymphomas were observed in 38% (9 of 24) of simian immunodeficiency virus (SIV)-infected cynomolgus monkeys (Macaca fascicularis) 5 to 15 months after inoculation with SIV strain SMM3. Lymphomagenesis in the SIV-infected monkeys was not related directly to the SIV-infectious dose given. All SIV-infected animals developed severe immunodeficiency. No significant difference in immunodeficiency was observed between tumor-bearing and non-tumor-bearing animals. In contrast, no lymphomas were observed in a comparable group of HIV-2-infected monkeys, which did not develop immunodeficiency; nor did the noninfected control monkeys. All 9 SIV-related tumors were high-grade B-cell lymphoblastic or pleomorphic lymphomas with extranodal, disseminated growth. Most tumors showed marked infiltration by monocytes and CD8+ T lymphocytes. Occasional tumor infiltrating cells showed immunohistochemical reaction for SIV. The cells of two tumors were established in vitro and shown to be of B-cell phenotype. The tumor cell cultures showed no reverse transcriptase activity and no evidence of virus infection by electron microscopy. Our observations indicate that SIV-induced immunodeficiency in cynomolgus monkeys also mimics HIV infection and AIDS in humans with regard to increased lymphomagenesis and type of lymphomas.
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PMID:Malignant lymphomas in cynomolgus monkeys infected with simian immunodeficiency virus. 170 62

To determine the true incidence of abnormalities in bone marrow specimens from patients infected with human immunodeficiency virus (HIV) and the clinical significance of these abnormalities regarding their cause and their role in the production of hematologic complications, 216 bone marrow biopsies, aspirates, and/or imprint preparations from 178 patients who either were seropositive for HIV infection or met the Centers for Disease Control (CDC) criteria for acquired immunodeficiency syndrome (AIDS) were studied. Detailed morphologic review was performed in a blind fashion as to clinical status. Extensive clinical, therapeutic, and laboratory data were collected for each patient. Statistical analysis was performed to detect significant correlations between morphologic findings and clinical/therapeutic/laboratory features. Among the most common bone marrow findings were hypercellularity (53% of specimens), myelodysplasia (69%), evidence of reticuloendothelial (RE) iron blockade (65%), megaloblastic hematopoiesis (38%), fibrosis (20%), plasmacytosis (25%), lymphocytic aggregates (36%), and granulomas (13%). A number of statistically significant correlations between morphologic findings and clinical features were noted. No significant association was detected between any morphologic finding and therapy with a variety of drugs. In 7 of 14 (50%) patients found to have marrow involvement by malignant neoplasm, the bone marrow represented the initial site of diagnosis of the neoplasm. Most of the bone marrow abnormalities associated with HIV infection appear to be related directly to the infection or its complications and not to therapeutic intervention. In certain clinical situations, bone marrow examination continues to be useful in the management of patients infected with HIV.
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PMID:The bone marrow in human immunodeficiency virus (HIV)-related disease. Morphology and clinical correlation. 170 27

Pentoxifylline (Trental), used routinely for the treatment of intermittent claudication, has been shown previously to decrease the levels of tumor necrosis factors-alpha (TNF-alpha) RNA in cancer patients and to lead to a general improvement of well being. Increased TNF-alpha levels have been observed not only in cancer patients but also in cachectic patients with the acquired immunodeficiency syndrome (AIDS), and TNF-alpha is known to increase the expression of the human immunodeficiency virus type 1 (HIV-1) via activating its long terminal repeat (LTR). Moreover, TNF-alpha decreases the therapeutic efficacy of zidovudine (AZT). Here we show a significant decrease in HIV-1 replication by pentoxifylline in infected human peripheral blood mononuclear cells. The reduction was proportional to the downregulation of expression of a reporter gene, the bacterial gene for chloramphenicol acetyl transferase, linked to the HIV-1 LTR in human monocytoid cells. We conclude that patients with AIDS may benefit from pentoxifylline treatment because of its blockage of TNF-alpha-mediated HIV-1 upregulation, from increased efficacy of AZT, and also from improvement in TNF-alpha-induced cachexia.
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PMID:Pentoxifylline (Trental) decreases the replication of the human immunodeficiency virus type 1 in human peripheral blood mononuclear cells and in cultured T cells. 130 72

Two HIV-1 isolates were obtained from a patient receiving long-term treatment with zidovudine (ZDV). The in vitro sensitivity to ZDV triphosphate of the reverse transcriptase (RT) from both isolates appeared to be unchanged compared to that of the LAV-Bru HIV-1 reference strain. When isolates were grown in CEM cells (a T-lymphoblastoid tumor cell line) and their RT activity and core antigen (p24) production were determined, the level of p24 production compared to RT activity was high; in infected CEM cells treated with ZDV, RT activity was at background level while the p24 production was still significant, thus indicating a dissociation of RT activity and core antigen production.
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PMID:In vitro assays show a dissociation of reverse transcriptase activity and core antigen (p24) production in two HIV-1 isolates from a patient receiving long-term treatment with zidovudine (ZDV). 170 62

Interferon-alpha is an effective treatment for a subset of patients with AIDS-associated Kaposi's sarcoma. When given at high doses to patients who lack systemic signs, symptoms, and opportunistic infections associated with advanced HIV infection and who maintain some degree of cell-mediated immune function, tumor regression may be observed in a high proportion of patients. Although the addition of chemotherapy to IFN-alpha appears to confer no added benefits, the combination of IFN-alpha with zidovudine has induced high tumor response rates in preliminary studies, including responses in some patients considered unlikely to respond to IFN-alpha alone. IFN-alpha-induced tumor regression has also been associated with suppression of HIV, as measured by serum p24 antigen concentrations and peripheral blood virus cultures. Other biologic agents, including interferons beta and gamma, tumor necrosis factor, and IL-2, have also been tested, to a lesser extent, in patients with Kaposi's sarcoma. Although systemically administered IFN-beta and intralesional TNF injections have led to tumor regression in some cases, the role of these biologics has been incompletely defined. Additional studies of these agents in combination with nucleoside reverse transcriptase inhibitors such as zidovudine will be required to fully assess their role in the treatment of Kaposi's sarcoma and HIV infection. It can also be anticipated that newer biologic agents, which specifically inhibit the production or action of angiogenic factors believed to be involved in the genesis of Kaposi's sarcoma, will be studied in the near future.
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PMID:Interferon and other biologic agents for the treatment of Kaposi's sarcoma. 170 60

A new class of compounds, 9-[(2RS)-3-fluoro-2-phosphonylmethoxypropyl] [(RS)-FPMP] derivatives of purines, is described that has selective activity against a broad spectrum of retroviruses [including human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2)] but not other RNA or DNA viruses. This activity spectrum is completely different from that of the parental compounds, 9-[(2S)-3-hydroxy-2-phosphonylmethoxypropyl] [(S)-HPMP] derivatives of purines, which are active against a broad range of DNA viruses. The racemic (RS)-FPMP derivatives of adenine and 2,6-diaminopurine, termed (RS)-FPMPA and (RS)-FPMPDAP, respectively, are markedly more selective as in vitro antiretroviral agents than their 9-(2-phosphonylmethoxyethyl) (PME) counterparts, PMEA and PMEDAP. Also, (RS)-FPMPA and (RS)-FPMPDAP have a substantially higher therapeutic index in mice in inhibiting Moloney murine sarcoma virus-induced tumor formation and associated death and are markedly less inhibitory to human bone marrow cells than PMEA and PMEDAP. The diphosphate derivative of (RS)-FPMPA [(RS)-FPMPApp] is a potent and selective inhibitor of HIV-1 reverse transcriptase but not of HSV-1 DNA polymerase or DNA polymerase alpha. (RS)-FPMPApp, akin to PMEA diphosphate (PMEApp), acts as a DNA chain terminator. The DNA chain-terminating properties of PMEApp and (RS)-FPMPApp seem to be a prerequisite for acyclic nucleoside phosphonates to exhibit antiretrovirus (i.e., anti-HIV) activity.
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PMID:9-[(2RS)-3-fluoro-2-phosphonylmethoxypropyl] derivatives of purines: a class of highly selective antiretroviral agents in vitro and in vivo. 171 Dec 14

Different strains of HIV susceptible lymphoblastoid cells have been infected by HIV-1 and examined by means of 1H NMR spectroscopy at different times after infection, taking advantage of the presence of high resolution lipid signals from the plasma membrane of tumor cells. A transient decrease in intensity of fatty acid signals, originated by changes in membrane structure, has been observed early after viral infection. Marked alterations in membrane-dependent steps of phospholipid synthesis can also be inferred by the observed transient depression in peaks from choline-based metabolites. Spectral modifications deriving from changes in lipid metabolism are also produced both in infected cells a few days after infection and in permanently infected cells. 1H NMR can, therefore, monitor structural and metabolic effects induced by HIV infection.
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PMID:Interaction of HIV-1 with susceptible lymphoblastoid cells. 1H NMR studies. 171 16

In 1973 the observation was published that in patients who had received non specific blood transfusions before kidney transplantation graft survival was improved. An immunosuppressive effect of blood transfusion was suggested. Indeed, modulation on the cellular and humoral immunologic system has been demonstrated during the last decade. But this immunomodulation effect might worsen the prognosis after cancer surgery. Whereas in several experimental studies in animals the negative influence was confirmed, clinical investigations on the other hand are contradictive. In our retrospective study we analysed the follow-up of 273 patients (158 men, 115 women; average age 66 years) on which we had performed a curative resection of their colorectal carcinoma. 182 patients had received nonspecific random blood transfusions. The survival rate for patients with blood transfusions was significantly worse in comparison to the non-transfused group (43% versus 73%, respectively). Even when we subdivided our patients into tumor stage, differentiation and localisation, the negative influence of transfused blood was confirmed. We conclude that beside the risk of transmitting hepatitis or HIV the immunosuppressive effect is a strong argument to restrict the indication for blood transfusion.
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PMID:[Effect of perioperative allogenic blood transfusion on prognosis of colorectal cancer]. 175 10

A decrease in Natural Killer (NK) cell activity is a common feature of the immune dysfunction found in patients with HIV-induced acquired immune deficiency syndrome (AIDS). We and others have shown earlier that staphylococcal protein A (SpA) preparations enhance NK cell activity against tumor targets. The present study was aimed at exploring whether the decreased NK activity of lymphocytes from HIV seropositive subjects could be modulated or restored in vitro by SpA. Two types of HIV-seropositive subjects were studied: hemophiliac and non-hemophiliac; matched controls were chosen among hospital staff and HIV-seronegative hemophiliac volunteers. In vitro proliferation and interleukin-2(IL-2)/interferon gamma (IFN gamma) release in response to mitogens were also studied. NK cell responses of peripheral blood lymphocytes (PBL) of HIV-seropositives were lower than those of seronegatives. However, exposure of PBL from HIV-seropositive individuals to SpA boosted their NK cell responses against NK-resistant target cells of tumor origin. The decrease in NK activity could not be attributed to the low number of NK cells, since no significant difference in NK cell number was observed between HIV-seropositive individuals and controls. Mitogen-induced blastogenic responses were present in all four groups, as was the mitogen-induced IFN gamma release. We conclude that impaired NK activity and its boosting against NK-resistant targets after SpA induction is an important characteristic of lymphocytes of HIV-seropositive individuals regardless of the disease state and that this NK defect may not be irreversible.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differential staphylococcal protein A-induced enhancement of natural killer cell activity of lymphocytes from HIV-seropositive individuals. 176 53

We present an outline of the complex interplay of oxidants and antioxidants in infectious diseases in general, and in particular with reference to the HIV infection, and subsequent opportunistic infections. Viral and opportunistic infections may directly or indirectly cause an imbalance in prooxidant/antioxidant mechanisms and result in generation of increased steady state concentrations of reactive oxidants. In HIV patients a prooxidant state could lead to a self-perpetuation of infection via stimulated expression of genes carrying the virus genome, and subsequently to immunosuppression, and promotion of initiated cells to neoplastic growth.
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PMID:Oxidative imbalance in HIV infected patients. 176 17


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