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)

Allogeneic stem cell transplantation has emerged as a potentially curative treatment modality for patients with hematological malignancies. The graft-versus-leukemia effect, an immune mechanism mediated by the donor immune system, is an important component of the therapeutic effect of allogeneic transplantation. Recent data from experimental animal models and from preliminary clinical experience suggest that a graft-versus-tumor effect, analogous to the graft-versus-leukemia effect, may be generated against solid tumors such as renal cell cancer, breast cancer, and other malignancies. The use of non-myeloablative, immunosuppressive conditioning regimens offers the opportunity to achieve a full-donor engraftment with reduced transplant-related complications and mortality, enabling also patients of advanced age and with co-morbidities to receive an allografting. Advanced renal cell cancer, an essentially incurable disease, has emerged from pilot studies as a disease susceptible to the graft-versus-tumor effect. Future studies will demonstrate if the tumor responses observed after allografting will translate into a clinically meaningful survival advantage. Other tumors in which tumor responses have been observed are: breast cancer, ovarian cancer, colorectal cancer, soft-tissue sarcoma, and others. Advanced melanoma may not be amenable to graft-versus-tumor effect. Future studies will point to the identification, isolation and cloning of target antigen(s) of graft-versus-tumor effect, to further reduce toxicities and to achieve a selective cell-mediated immunotherapy.
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PMID:Allogeneic stem cell transplantation for the treatment of advanced solid tumors. 1537 71

p73, the homologue of p53, is a nuclear protein whose ectopic expression, in p53+/+ and p53-/- cells, recapitulates the most well-characterized p53 effects, such as growth arrest, apoptosis and differentiation. Unlike p53, which is mutated in half of human cancers, p73 is rarely mutated. However, altered expression of the p73 gene has been reported in neuroblastoma, lung cancer, prostate cancer and renal cell carcinoma. To investigate the potential involvement of p73 in acute myeloid leukemias (AMLs), we analyzed 71 samples from AML patients for the expression pattern of N-terminal transactivation-p73alpha (TA-p73alpha), its spliced isoforms and N-terminal-deleted-p73 transcripts (DeltaN-p73). We detected p73 gene expression in AML irrespective of FAB (French-American-British) subtypes. Notably, the analysis of DeltaN-p73 expression, which has been reported to inactivate both p53 and p73 antitumor effects, revealed a rather peculiar pattern. In fact, DeltaN-p73 transcript and protein were detectable in 27/28 (96.4%) cases of M0, M1, M2, M4, M5 and M6 AML and in 13/41 (31.7%) cases of PML-RARalpha-positive M3 AML (P<0.01). Thus, the distinct gene expression profile of p73 further supports the notion that acute promyelocytic leukemia is a biologically different subset of AML.
Leukemia 2004 Nov
PMID:Analysis of p73 expression pattern in acute myeloid leukemias: lack of DeltaN-p73 expression is a frequent feature of acute promyelocytic leukemia. 1538 38

This report summarises the epidemiological evidence on the association between tobacco smoking and cancer, which was reviewed by an international group of scientists convened by IARC. Studies published since the 1986 IARC Monograph on "Tobacco smoking" provide sufficient evidence to establish a causal association between cigarette smoking and cancer of the nasal cavities and paranasal sinuses, nasopharynx, stomach, liver, kidney (renal cell carcinoma) and uterine cervix, and for adenocarcinoma of the oesophagus and myeloid leukaemia. These sites add to the previously established list of cancers causally associated with cigarette smoking, namely cancer of the lung, oral cavity, pharynx, larynx, oesophagus, pancreas, urinary bladder and renal pelvis. Other forms of tobacco smoking, such as cigars, pipes and bidis, also increase risk for cancer, including cancer of the lung and parts of the upper aerodigestive tract. A meta-analysis of over 50 studies on involuntary smoking among never smokers showed a consistent and statistically significant association between exposure to environmental tobacco smoke and lung cancer risk. Smoking is currently responsible for a third of all cancer deaths in many Western countries. It has been estimated that every other smoker will be killed by tobacco.
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PMID:Tobacco smoking and cancer: a brief review of recent epidemiological evidence. 1555 76

Two cell lines that exemplify erythropoietin (EPO) receptor-positive tumors, human renal carcinoma cell lines RCC and the myelomonocytic leukemia cell line U937, were investigated for the apoptosis-modulatory potential of EPO. Cells cultured in the presence of EPO exhibited an elevated apoptotic response to cancer chemotherapeutic agents such as daunorubicin (Dauno) and vinblastine (VBL). Chemosensitization by EPO did not involve an increase in p53 activation, yet correlated with enhanced Bax/Bak-dependent mitochondrial membrane perturbation and caspase maturation. In vitro monotherapy with Dauno or VBL induced the degradation of IkappaBalpha, provoked the translocation of NF-kappaB p65/50 to the nucleus and stimulated the expression of an NF-kappaB-activatable reporter gene. All these signs of NF-kappaB activation were perturbed in the presence of EPO. Inhibition of JAK2, one of the receptor-proximal elements of EPO-mediated signal transduction, greatly diminished the EPO-mediated chemosensitization and NF-kappaB inhibition. EPO lost its death-facilitating effects in the presence of an NF-kappaB inhibitor, underscoring the cause-effect relationship between EPO-mediated chemosensitization and NF-kappaB inhibition. Altogether, these results suggest that, at least in a specific subset of tumors, EPO receptor agonists can prevent activation of the NF-kappaB pathway, thereby enhancing the propensity of EPO receptor-positive tumor cells to undergo apoptosis.
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PMID:Chemosensitization by erythropoietin through inhibition of the NF-kappaB rescue pathway. 1558 Feb 99

The tumor suppressor PTEN is mutated in a high percentage of human cancers, and is implicated in pathways regulating cell growth, proliferation, survival, and migration. Despite significant advances, our understanding of its mechanisms of action remains incomplete. We have used a high-throughput proteomic immunoblotting approach to identify proteins whose expression levels are modulated by PTEN. Out of over 800 proteins screened, 22 proteins showed significant changes in expression. Five proteins that exhibited two-fold or greater changes in expression level were further characterized. AKAP121 and G3BP expression was reduced, while dihydrofolate reductase (DHFR), Rap1 and RCC1 expression was elevated in response to PTEN expression in a PTEN-null T-cell leukemia line. The phosphatase activity of PTEN was required for these effects. However, direct inhibition of PI-3 Kinase could mimic PTEN in modulating expression of DHFR, G3BP, Rap1 and RCC1, but not AKAP121. Real-time PCR showed that the effects of PTEN were primarily post-transcriptional, and would not have been revealed by mRNA-based screens. We conclude from these data that PTEN can modulate the expression level of a number of different proteins. The identified proteins have the potential to serve as previously unrecognized effectors of PTEN, and suggest the existence of additional complexity in the modes by which PTEN can regulate cellular biology.
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PMID:Modulation of specific protein expression levels by PTEN: identification of AKAP121, DHFR, G3BP, Rap1, and RCC1 as potential targets of PTEN. 1578 28

Adoptive T cell therapy of renal cell carcinoma (RCC) is limited by the difficulty in generating sufficient numbers of RCC-reactive T cells in vitro. To circumvent this problem, we cloned T cell receptor (TCR) alpha and beta chains from a tumor-infiltrating lymphocyte clone specific for an RCC tumor antigen and transferred the TCR into human T cell lines and primary T lymphocytes. Efficient TCR expression in primary T lymphocytes was obtained only with a mouse myeloproliferative sarcoma virus (MPSV)-based retroviral vector, not with a Moloney murine leukemia virus (MLV)-based vector, although both viral supernatants were similar in titer, as shown by analysis of copy number integration in transduced T cells. Reverse transcription-polymerase chain reaction analysis revealed a higher amount of TCR-encoding transcripts when T cells were transduced with the MPSV vector in comparison with the MLV vector, indicating that high TCR expression levels can be achieved by appropriate cis-regulatory vector elements. The biological activity of the transferred TCR was shown by specific lysis of RCC cells ((51)Cr release assay) and by interferon gamma and tumor necrosis factor alpha release (enzyme-linked immunosorbent assay) in an antigen-specific and HLA-A*0201-restricted fashion. Comparison of the redirected T lymphocytes with the original tumor-infiltrating lymphocyte clone revealed similar killing and cytokine secretion capabilities. The functional activity of TCR-redirected T lymphocytes was stable over time. The results demonstrate that use of an optimized retroviral vector yielded a high TCR transduction efficiency and stable and high TCR expression in primary human T lymphocytes and redirected their specificity toward RCC cells.
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PMID:Redirecting human T lymphocytes toward renal cell carcinoma specificity by retroviral transfer of T cell receptor genes. 1600 62

Non-myeloablative allogenic peripheral blood stem cell transplantation (mini-transplant) is becoming a preferred treatment for those recipients in whom the potential toxicity risk of standard ablative allogeneic therapy may be acceptable. Graft-versus-tumor effect may be generated against epithelial malignancies that are similar to the graft-versus-leukemia activity 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 advanced renal cell carcinoma occurs in some patients following non-myeloablative allogenic peripheral blood stem cell transplantation. However, graft-versus-host disease remains a significant toxicity of nonablative transplantation, and directions for further study include the identification of the definitive tumor antigens involved in the graft-versus-tumor effect and means of selecting those patients who will benefit the most from this promising approach with due regard to improve its safety.
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PMID:[Non-myeloablative allogenic peripheral blood stem cell transplantation for treatment of advanced renal cell carcinoma]. 1616 64

Breast cancer is the leading cause of death from cancer in women. The metastatic involvement of the breast from nonmammary neoplasms is a relatively rare condition. Female patients are affected five to six times more frequently than male patients. We present seven patients with metastasis in the breast from extramammary tumors. Females seemed to be more frequently affected (6 women and 1 man) and included a wide range of ages (17-70 years old). All female patients had suspicious-looking abnormalities (B1-RADS 4) or lesions highly suspicious of malignancy (BI-RADS 5) in the mammography, without a confirmative fine needle aspiration cytology. The primary malignancies were equally distributed between non-hematological (1 renal adenocarcinoma, 1 melanoma, 1 leiomyosarcoma) and hematological (1 non-Hodgkin's, 2 Hodgkin's lymphomas and 1 leukemia). Treatment is therefore modified, taking into consideration the treatment and prognosis of the primary disease.
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PMID:Metastatic disease in the breast from nonmammary neoplasms. 1628 77

This study was undertaken to characterize preclinical cytotoxic interactions for human malignancies between the multikinase inhibitor sorafenib (BAY 43-9006) and proteasome inhibitors bortezomib or MG132. Multiple tumor cell lines of varying histiotypes, including A549 (lung adenocarcinoma), 786-O (renal cell carcinoma), HeLa (cervical carcinoma), MDA-MB-231 (breast), K562 (chronic myelogenous leukemia), Jurkat (acute T-cell leukemia), MEC-2 (B-chronic lymphocytic leukemia), and U251 and D37 (glioma), as well as cells derived from primary human glioma tumors that are likely a more clinically relevant model were treated with sorafenib or bortezomib alone or in combination. Sorafenib and bortezomib synergistically induced a marked increase in mitochondrial injury and apoptosis, reflected by cytochrome c release, caspase-3 cleavage, and poly(ADP-ribose) polymerase degradation in a broad range of solid tumor and leukemia cell lines. These findings were accompanied by several biochemical changes, including decreased phosphorylation of vascular endothelial growth factor receptor-2, platelet-derived growth factor receptor-beta, and Akt and increased phosphorylation of stress-related c-Jun NH2-terminal kinase (JNK). Inhibition of Akt was required for synergism, as a constitutively active Akt protected cells against apoptosis induced by the combination. Alternatively, the JNK inhibitor SP600125 could also protect cells from apoptosis induced by the combination, indicating that both inhibition of Akt and activation of JNK were required for the synergism. These findings show that sorafenib interacts synergistically with bortezomib to induce apoptosis in a broad spectrum of neoplastic cell lines and show an important role for the Akt and JNK pathways in mediating synergism. Further clinical development of this combination seems warranted.
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PMID:Cytotoxic synergy between the multikinase inhibitor sorafenib and the proteasome inhibitor bortezomib in vitro: induction of apoptosis through Akt and c-Jun NH2-terminal kinase pathways. 1698 72

Extramedullary manifestations of acute myeloid leukemia (AML) are rare and commonly involve one tissue. We report of a cutaneous acute myelomonocytic leukemia infiltrating the kidney next to the skin. A 61-year-old female patient with complex karyotype cutaneous AML FAB M4 underwent abdominal computed tomography scans. A lesion in her left kidney appeared suspicious of renal carcinoma as confirmed by histology. However, fluorescence in situ hybridization cytogenetics revealed a chromosome 11q23 abnormality in the nephrectomy specimen, which also appeared in the leukemic blasts of skin and bone marrow. Closer histomorphologic workup revealed an infiltration of the kidney with leukemia. This case report illustrates how modern diagnostic procedures can help to reveal rare sites of disease.
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PMID:Cytogenetics detects infiltrations of a primary cutaneous acute myeloid leukemia to the kidney. 1720 19


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