Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Kidney tumors represent a wide scale of histological observations. However, only angiomyolipoma can be recognised preoperatively from results of the graphical examination. Other types can be recognised only on the bases of histological examination. Completely benign tumor is oncocytoma (it represents about 5% of all kidney tumors). Angiomyolipoma (2%) is also benign, though some case reports describing its malign transformation has been published. Angiomyolipoma under 4 cm can be only monitored, the larger tumors should be resected or selectively embolised the arterial blood supply to prevent spontaneous rupture. From the group of benign tumors only cystic nephroma can be diagnosed more often (up to 1%). One of the criteria for diagnosing the renal cortical adenoma is its size under 5 mm. That is why any adenoma, which could be diagnosed by means of graphical examination and therefore clinically significant does not exist. Most of tumors are malign epithelial tumors--renal carcinomas (RC). The are classified according Heidelberg classification into 5 elementary types: clear cell, papillary, chromophobe, originating form collecting ducts and not classifiable. Clear cell (conventional) renal carcinoma (CRC) comes most often (70 to 80%), its malign potential rise with increased size of tumor and with the gradient. Five-year survival is achieved in 30-50%. Granular form of CRC carcinoma (7% of all CRC) is the equivalent of poorly differentiated PRC and it has an adverse prognosis. In contrary, the cystic form of CRC (about 6%) in benign. Papillary form of RC has the five-year survival in 84%, malignant are only tumors poorly differentiated. These are tumors with extensive necroses, which brings a fragile consistency and they can be distinguished by graphical examination. Chromophobe type of RC (5%) has the five-year survival in 90%. Poor prognosis has its sarcomatoid form, which can originate from any RC, but most frequently it is derived from the chromophobe type. The form originating from collecting ducts is highly infrequent and very malignant with the five-year survival in 20% only. The unclassified form of RC (3-5%) includes tumors not suiting to the criteria of the previous RC. Other primary renal malignant tumors (sarcomas, Wilms' tumor of adults, medullar carcinoma, carcinoid) are very rare. Comparatively frequent are metastases of other tumors (namely that of lung carcinoma) and renal impairment in leukemia, which are complication not often met by urologist.
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PMID:[Histologic classification of kidney tumors for clinical practice in adults]. 1150 85

Using differential display-polymerase chain reaction, we identified a novel gene sequence, designated solid tumor-associated gene 1 (STAG1), that is upregulated in renal cell carcinoma (RCC). The full-length cDNA (4839 bp) encompassed the recently reported androgen-regulated prostatic cDNA PMEPA1, and so we refer to this gene as STAG1/PMEPA1. Two STAG1/PMEPA1 mRNA transcripts of approximately 2.7 and 5 kb, with identical coding regions but variant 3' untranslated regions, were predominantly expressed in normal prostate tissue and at lower levels in the ovary. The expression of this gene was upregulated in 87% of RCC samples and also was upregulated in stomach and rectal adenocarcinomas. In contrast, STAG1/PMEPA1 expression was barely detectable in leukemia and lymphoma samples. Analysis of expressed sequence tag databases showed that STAG1/PMEPA1 also was expressed in pancreatic, endometrial, and prostatic adenocarcinomas. The STAG1/PMEPA1 cDNA encodes a 287-amino-acid protein containing a putative transmembrane domain and motifs that suggest that it may bind src homology 3- and tryptophan tryptophan domain-containing proteins. This protein shows 67% identity to the protein encoded by the chromosome 18 open reading frame 1 gene. Translation of STAG1/PMEPA1 mRNA in vitro showed two products of 36 and 39 kDa, respectively, suggesting that translation may initiate at more than one site. Comparison to genomic clones showed that STAG1/PMEPA1 was located on chromosome 20q13 between microsatellite markers D20S183 and D20S173 and spanned four exons and three introns. The upregulation of this gene in several solid tumors indicated that it may play an important role in tumorigenesis.
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PMID:Characterization of a novel gene, STAG1/PMEPA1, upregulated in renal cell carcinoma and other solid tumors. 1156 75

Allogeneic stem cell transplantation has emerged as a potentially curative form of immunotherapy for patients with hematological malignancies that are resistant to conventional chemo/radiotherapy. Donor T cell populations targeting allogeneic minor histocompatibility antigens expressed on the patient's malignant cells are felt to be the driving force of the graft-versus-leukemia reaction, although to date only a handful of these antigens have been fully characterized. Recent data from experimental animal models and limited clinical data in humans suggest that graft-versus-tumor effects, analogous to the graft-versus-leukemia reaction, may be generated against malignancies of epithelial origin. This article reviews the results of a pilot trial demonstrating graft-versus-renal cell carcinoma effects following nonmyeloablative stem cell transplantation, highlighting the potential of allogeneic immunotherapy for treating cancer.
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PMID:Nonmyeloablative blood stem cell transplantation as adoptive allogeneic immunotherapy for metastatic renal cell carcinoma. 1164 4

Clinically effective cancer immunotherapy has been sought for more than 100 years and has been recently applied most successfully in strategies that passively deliver immune effectors such as monoclonal antibodies (anti-CD20 for lymphoma and anti-HER2/neu for breast cancer), donor lymphocyte infusions in chronic myelongenous leukemia and non-myeloablative allogeneic peripheral blood progenitor transplants for renal cell carcinoma. There is mounting enthusiasm for strategies employing active stimulation of antitumour immune responses. These include vaccines based on tumour antigen proteins and peptides, autologous, allogeneic or gene-modified tumour cells, dendritic cells and antigen-encoding viral vector constructs. Indeed, randomised Phase III clinical trials of autologous tumour cell vaccines for colorectal cancer demonstrated an improvement in disease free survival and a trend toward improved overall survival [1]. Despite these preliminary successes, it is clear that the many strategies under development cannot all be evaluated for survival benefit in large clinical trials that require many years, patients and resources to complete. This highlights the need to develop intermediate markers to help prioritise which agents to test in prospective randomised Phase III trials.
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PMID:Surrogate markers of response to cancer immunotherapy. 1172 26

Pentostatin (2prime prime or minute-deoxycoformycin, dCF) is a product of the fermentation of Streptomyces antibioticus. It is a tight-binding inhibitor of adenosine deaminase (ADA), an enzyme essential in cellular metabolism of purines. Children with congenital absence of ADA suffer from atrophy of lymphoid tissues and severe combined immune deficiency (SCID) syndrome. It was speculated that pentostatin would be lymphocytotoxic, and this proved to be the case, promoting its investigation in lymphoid neoplasms. It was anticipated that pentostatin would be most active in neoplasms with high intracellular concentrations of ADA---e.g., acute lymphocytic leukemia (ALL), particularly its T cell variety. Although pentostatin proved to be active in ALL, large doses were required and toxic effects outweighted therapeutic benefits. By contrast, pentostatin proved to be exceptionally active in hairy cell leukemia (HCL), a B cell neoplasm with low intracellular concentrations of ADA. Pentostatin has since been shown to possess activity in chronic lymphocytic leukemia, prolymphocytic leukemia, cutaneous T cell lymphomas, adult T cell lymphoma-leukemia, and low-grade non-Hodgkin's lymphomas. It potentiates the activity of vidarabine against viruses and against the cells of acute myeloid leukemia. Pentostatin is inactive in melanoma and renal carcinoma, but has not been adequately evaluated in other solid tumors. The toxic effects of pentostatin include renal failure, central nervous system (CNS) depression, immunosuppression, keratoconjunctivitis, and opportunistic infections. In the absence of pre-existing bone marrow compromise, pentostatin produces only mild myelosuppression. Aside from its use as an antineoplastic agent, pentostatin has potential applications as an immunosuppresive drug, as an antiviral agent, as an antimalarial compound, and in the protection of cells of the CNS from damage induced by ischemia and anoxia.
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PMID:Pentostatin (2prime prime or minute-Deoxycoformycin): Clinical Pharmacology, Role In Cancer Chemotherapy, and Future Prospects. 1184 52

Allogeneic hematopoietic stem cell transplantation (HSCT) is the most effective treatment for selected hematological malignancies. Its curative potential is largely mediated by an immune-mediated destruction of malignant cells by donor lymphocytes termed graft-versus-leukemia (GVL) effect. However, because of its toxicity, conventional allogeneic HSCT is restricted to younger and fitter patients. These observations led several groups to set up new (less toxic) transplant protocols (nonmyeloablative stem cell transplantation or NMSCT) based on a two-step approach: first, the use of immunosuppressive (but nonmyeloablative) preparative regimens providing sufficient immunosuppression to achieve engraftment of allogeneic hematopoietic stem cells and, in a second step, destruction of malignant cells by the GVL effect. Preliminary results showed that NMSCT were feasible with a relatively low transplant-related mortality (TRM), even in patients older than 65 years. In addition, strong antitumor responses were observed in several hematological malignancies as well as in some patients with renal cell carcinoma. After discussing the mechanisms and efficacy of the GVL effect as well as the rationale for NMSCT strategies, this article reviews the first results of ongoing clinical trials. Innovative modalities that may permit amplification of the GVL effect while minimizing the risk of GVHD are discussed. Because the benefits of NMSCT over alternative forms of treatment remain to be demonstrated, this strategy should be restricted to patients included in clinical trials.
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PMID:Nonmyeloablative allogeneic hematopoietic stem cell transplantation. 1198 97

The potent immunomodulatory, antiproliferative and antiviral properties of interferons (IFNs), together with their availability in large amounts thanks to the recombinant DNA technique, have resulted in their widespread clinical use in a variety of viral and nonviral proliferative disorders. In dermato-oncology, IFNs have been used primarily in melanoma, but also in nonmelanoma skin cancer, such as squamous and basal cell carcinomas, Kaposi sarcomas and lymphomas. Trials with IFNs have been performed in patients with melanoma in an adjuvant setting (stage II and III) and in metastatic disease (stage IV). While the response rates with IFNs as single agents in stage IV disease usually do not exceed 15%, the use of adjuvant IFNs has been claimed to increase disease-free survival (stage II), or even overall survival (stage III), in low- or high-dose regimens, respectively; the latter, however, involved numerous side-effects and were beset with lack of compliance and acceptance, as well as being very costly. Pegylated IFN (PEG-IFN) is a form of recombinant human IFN that has been chemically modified by the covalent attachment of a branched metoxpolyethylene glycol moiety. Pharmacogenetic and pharmacodynamic data obtained in animal and in phase I studies have indicated that PEG-IFN injected once a week has the potential to be superior in efficacy to human IFN injected three times a week. The safety profiles of PEG-IFN and IFN are comparable in healthy volunteers and in chronic hepatitis C (CHC) patients. PEG-IFN is currently being evaluated for the treatment of CHC, renal cell carcinoma, chronic myelogenous leukaemia, and malignant melanoma, the last in both stage IV and stage III disease.
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PMID:Perspectives of pegylated interferon use in dermatological oncology. 1207 10

Recent clinical trials in melanoma and leukemia have demonstrated potential for increased survival time and improved remission when histamine dihydrochloride is added to cytokine monotherapy. In the present study, the pharmacokinetics of subcutaneous histamine (1 mg) in 21 healthy subjects and 12 melanoma patients was determined via model-dependent methods. Drug-drug interactions with subcutaneous interleukin-2 (1.1 mg) were evaluated in a combined cohort of patients with melanoma (n = 8) or renal cell carcinoma (n = 4). Histamine dihydrochloride administered over 10 minutes in healthy subjects peaked at 18 minutes (Cmax 38 nmol/L), attained a distribution volume of 59 L, and was eliminated at 6%/min. The results were similar in a 20-minute infusion in melanoma patients. No gender effects were observed (p > 0.05). Interleukin-2 injected either 10 minutes prior to or 10 minutes following histamine dihydrochloride had no effect on histamine kinetics. Histamine dihydrochloride administered 10 minutes prior to injection of interleukin-2 also had no effect on interleukin-2 kinetics. Maximal concentration of interleukin-2 (2,442 pg/ml) occurred at 2.5 hours with an elimination half-life of 1.7 hours, area under the curve (AUC) of 15,746 pg x h/ml, and volume of distribution and plasma clearance of 194 L and 74 L/h, respectively. However, interleukin-2 Cmax (1,758 pg/ml) and AUC (12,448 pg x h/ml) were reduced when histamine dihydrochloride was infused 10 minutes following interleukin-2, likely due to the pharmacodynamic effects of histamine, including increased heart rate and reduced blood pressure. It is concluded that histamine dihydrochloride and interleukin-2 can be safely coadministered with minimal interaction.
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PMID:Pharmacokinetics of histamine dihydrochloride in healthy volunteers and cancer patients: implications for combined immunotherapy with interleukin-2. 1209 44

Recombinant retroviral vectors are still the most common gene delivery vehicles for gene therapy purposes, especially for construction of genetically modified tumor vaccines (GMTV). However, these vehicles are characterized by relatively low titre and in the case of many tumor cell lines, low transduction efficiency. We constructed bicistronic retroviral vector pseudotypes of amphotropic murine leukemia virus (A-MuLV) and gibbon ape leukemia virus (GaLV), encoding enhanced green fluorescent protein (EGFP) as a rapid and easily detectable reporter gene. Transduction of five different human melanoma and four renal carcinoma cell lines by these two virus pseudotypes revealed differences in transduction efficiency, which wase markedly lower for the renal carcinoma cell lines. Stimulation of retroviral receptor expression (PiT1 and PiT2) by phosphate depletion induced a limited increase of receptor mRNA levels, but did not improve the gene transfer efficiency. In contrast, simultaneous transduction with both vector pseudotypes markedly increased the transduction efficiency, compared to GaLV or A-MuLV alone. The same effect could be achieved by several repeated exposures of target cells to fresh vector preparation. Overexpression of GaLV receptor (PiT1) in target cells significantly increased the transduction rate and enabled retrovirus mediated gene transfer into the cells which normally are not transducible by GaLV pseudotypes. We demonstrated that, using different transduction strategies, the relatively inefficient, widely used retroviral vector systems could be significantly improved.
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PMID:Expression of PiT1 and PiT2 retroviral receptors and transduction efficiency of tumor cells. 1236 74

Nonablative hematopoietic cell transplantation (HCT) is becoming a preferred treatment for those recipients in whom the potential toxicity risk of standard ablative allogeneic therapy may be unacceptable. Graft-versus-malignancy effects may be generated against epithelial malignancies which are similar to the graft-versus-leukemia activity that is well documented in human hematological malignancies. Renal cell carcinoma has been shown to be responsive to immunotherapy with recombinant human cytokines and may be an ideal model for exploring this novel therapy. Clinical investigations have demonstrated regression of metastatic renal cell carcinoma occurs in some patients following nonablative allogeneic HCT. However, graft-versus-host disease remains a significant toxicity of nonablative transplantation, and further investigations are warranted to further evaluate this promising approach and to improve its safety.
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PMID:Nonablative hematopoietic cell transplantation for the treatment of metastatic renal cell carcinoma. 1247 72


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