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

Last year, we reported that human papilloma virus type 16 genome (HPV 16 genome) was detected in a case (S.Y.) of bladder carcinoma in situ (bladder CIS) (Cancer Res., 1988). Since then, a number of bladder tumors other than CIS were searched for HPV genome. However, no HPV genome was detected in the bladder tumors. From the results, we consider that HPV may not have a relation with all types of bladder tumor but with only a part of it. In the current report, the case (S.Y.) is presented more precisely than before, in particular on the characteristic bladder lesion. The patient was a 40-year-old female with immunodeficiency and anemia who was referred from a hospital with a complaint of asymptomatic pyuria. Cystoscopic examination revealed a bladder tumor, well-demarcated, white and velvety lesion with slight elevation. On November 25, 1987, she underwent total cystectomy, resection of the anterior vaginal wall and of a part of vulval skin, and ileal conduit formation. Postoperative course was stormy because of bleeding from the wounds and thrombophlebitis in the right femoral vein. In spite of the episodes, she eventually recovered and was discharged 2 months later. However she was readmitted 9 months later due to severe anemia which was ascribed to acute myelogenous leukemia. She is now on cancer chemotherapy for leukemia.
 ...
PMID:[Bladder carcinoma in situ which harbored human papilloma virus. A case report]. 255 17

We report here sensitive and specific measurement of immune responses of patients with certain kinds of carcinoma toward the physically and chemically well defined T antigen isolated from healthy human erythrocytes. Over 90% of adenocarcinoma tissues tested possess T-specific immunoreactive structures as determined with human antisera, in contrast to healthy tissues and benign lesions. Adenocarcinoma patients recognize the carcinoma-associated T antigen as foreign. Delayed-type skin hypersensitivity reaction to T antigen (DTHR-T) was positive in all 25 lung adenocarcinoma patients tested, in 88% of 101 patients with ductal, in 43% of 30 patients with lobular or tubular breast carcinoma and in 9/9 patients with adenocarcinoma of body cavities. Patients of all Stages reacted positively. All 7 patients with small cell lung carcinoma and 3/5 with malignant melanoma had a positive DTHR-T. None of 17 patients with malignant brain tumors, leukemia or Hodgkin's disease, sarcoma or thyroid carcinoma reacted. The DTHR-T was specific in that all 77 healthy persons and 48/49 with other diseases, including 23/24 with non-cancer lung disease were negative; one patient with organizing interstitial pneumonitis was positive. This points to a possible source of false positive reactions. 91% of 149 patients with histologically benign breast disease had a negative DTHR-T; the histology of some of the positive ones was reexamined, 2 proved to have carcinoma in situ.
 ...
PMID:Patients' immune response to breast and lung carcinoma-associated Thomsen-Friedenreich (T) specificity. 617 52

A basis for differentiation therapy of leukemias is provided by knowledge of agents which induce specific lineage maturation. All-trans retinoic acid (RA) induces differentiation of HL60 cells to neutrophils and is used to treat acute promyelocytic leukemia. We observed that RA did not induced neutrophil differentiation in serum-free grown HL60 cells whereas 50 nM 1 alpha,25-dihydroxyvitamin D3 (D3) induced maximal monocyte differentiation. Increasing RA concentrations reduced the D3 concentration required for monocyte differentiation. Cells treated with 5 nM D3 showed little response, but differentiated maximally with 5 nM D3 and 10 nM RA. The D3 analogs MC903, EB1089 and KH1060 were more potent inducers of monocyte differentiation. The extent to which analog activity was increased after cotreatment with RA was inversely related to potency. Twenty-four hour treatment with 10 nM RA primed cells for response to 5 nM D3; the reverse sequence being ineffective. Priming with 10 nM RA, or subsequent treatment with D3 (5 nM), did not alter expression of mRNAs encoding receptors for D3 (VDR), RA (RAR alpha) or 9-CIS RA (RXR alpha, beta, gamma). That RA promotes both neutrophil and monocyte differentiation has implications for the use of RA and D3 in treatment of leukemias and provides insight into mechanisms whereby RAR, VDR and RXR facilitate monocyte differentiation.
Leukemia 1994 May
PMID:All-trans retinoic acid and 1 alpha,25-dihydroxyvitamin D3 co-operate to promote differentiation of the human promyeloid leukemia cell line HL60 to monocytes. 818 38

We have reported two JAK-signaling modulators, CIS (cytokine-inducible SH2 protein) and JAB (JAK2 binding protein), which are structurally related. Here we cloned three additional CIS family genes (CIS2, CIS3, and CIS4) on the basis of an expression sequence tag (EST) database search. We also found at least two additional candidates of this gene family in the database. These genes were induced by erythropoietin and granulocyte-macrophage colony stimulating factor in certain hematopoietic cell lines. The SH2 domain and a C-terminal 40 amino acid region, designated the CIS homology domain (CH domain), are highly conserved in this family, while the N-terminal regions of these proteins share little similarity. A yeast two-hybrid assay and in vitro and in vivo binding assays revealed that in addition to JAB, CIS3 bound to the JAK2 tyrosine kinase domain (JH1), although the interaction of CIS3 with the JAK2-JH1 domain was much weaker than that of JAB. Transient expression of JAB and CIS3, but not other CISs, strongly inhibited leukemia inhibitory factor (LIF)-induced STAT3-reporter gene activation in 293 cells. Furthermore, constitutive overexpression of JAB and CIS3 in M1 leukemia cells prevented LIF-induced differentiation and growth arrest. Although the physiological function remains to be investigated, CIS family genes could play a role in the negative regulation of cytokine signaling by interacting with specific targets.
 ...
PMID:Cloning and characterization of novel CIS family genes. 934 48

Four members (SOCS-1, SOCS-2, SOCS-3, and CIS) of a family of cytokine-inducible, negative regulators of cytokine receptor signaling have recently been identified. To address whether any of these genes are induced in response to growth hormone (GH), serum-starved 3T3-F442A fibroblasts were incubated with GH for various time points, and the expression of the SOCS gene family was analyzed by Northern blotting. GH stimulated the rapid, transient induction of SOCS-3 mRNA, peaking 30 min after the initiation of GH exposure and declining to basal levels by 2 h. Expression of the other SOCS genes (SOCS-1, SOCS-2, CIS) was also up-regulated by GH, although to a lesser extent than SOCS-3 and with differing kinetics. SOCS-3 expression was also strongly induced in 3T3-F442A cells treated with leukemia-inhibitory factor (LIF), with weaker induction of SOCS-1 and CIS being observed. The preferential induction of SOCS-3 mRNA was also observed in hepatic RNA isolated from the livers of mice that had received a single supraphysiological dose of GH intraperitoneally. Co-transfection studies revealed that constitutive expression of SOCS-1 and SOCS-3, but not SOCS-2 or CIS, blocked GH-induced transactivation of the GH-responsive serine protease inhibitor 2.1 gene promoter.
 ...
PMID:Growth hormone preferentially induces the rapid, transient expression of SOCS-3, a novel inhibitor of cytokine receptor signaling. 943 Jun 58

Fas (APO-1/CD95) is a cell surface receptor that mediates apoptosis when it reacts with Fas ligand (FasL) or Fas antibody. In this study, we analyzed Fas and FasL expression in normal esophageal mucosa and esophageal squamous cell carcinomas. Reverse transcriptase-PCR revealed that Fas, soluble Fas, and FasL were expressed in all eight esophageal squamous carcinoma cell lines analyzed. Furthermore, it was demonstrated that FasL expressed in esophageal carcinoma cells is functional because coculture experiments using FasL-expressing TE-15 esophageal carcinoma cells resulted in apoptosis of Jurkat T leukemia cells, which are sensitive to Fas-mediated apoptosis. Immunohistochemistry of Fas and FasL showed that they are constitutively expressed in normal esophageal mucosa, FasL being predominantly in the basal and suprabasal layers, whereas Fas is in more differentiated layers, i.e., rows of polyhedral cells of the intermediate layers and squamous cells forming the outer layers. In 18 of 19 invasive esophageal squamous cell carcinomas, FasL expression was found in >50% of tumor cells. In contrast, most tumors (15 of 19, 79%) either showed no Fas expression or showed expression in <5% of tumor cells. These alterations were already detected in dysplasia and carcinoma in situ. These results suggest that up-regulation of FasL and down-regulation of Fas expression are early and frequent events associated with the evolution of esophageal squamous cell carcinomas.
 ...
PMID:Up-regulation of Fas (APO-1/CD95) ligand and down-regulation of Fas expression in human esophageal cancer. 960 41

Isotype-switch variants can easily be detected in a significant proportion of multiple myeloma (MM) patients. The biological significance of these isotype-switch variants remains obscure. Therefore, we studied the appearance of these isotype-switch variants in two murine MM models, 5T2MM and 5T33MM, both of IgG isotype. With a MM-specific PCR assay we could detect isotype-switch variants in the bone marrow of both the 5T2MM and the 5T33MM bearing mice, reflecting again the close resemblance of this mouse model to the human MM. These isotype-switch variants were not found in an in vitro stroma-independent variant of the 5T33MM line. However, when this 5T33MMvitro line was injected into young syngeneic mice, isotype-switch variants appeared thereafter in the isolated tumour cells. These isotype-switch variants could only originate from the MM-IgG expressing cell since IgG subclones from the 5T33MMvitro line again gave rise to isotype-switch variants. The appearance of IgA cells can be explained by down-stream switching of IgG to IgA, while the emergence of IgM cells have to occur via trans-switching to the sister chromatid as the Cmu region is deleted from the CIS-chromosome. This study demonstrates that isotype-switch variants originate from the major tumour clone suggesting no role for the MM-IgM expressing cell as a pre-switch precursor MM cell. The appearance of isotype-switch variants should be considered as a rare but normal event now becoming visible due to the high number of clonal cells present in MM.
Leukemia 2001 Jul
PMID:Myeloma isotype-switch variants in the murine 5T myeloma model: evidence that myeloma IgM and IgA expressing subclones can originate from the IgG expressing tumour. 1145 84

Adult T-cell leukemia (ATL) is an aggressive malignancy that is associated with human T-cell lymphotropic virus I (HTLV-I) infection. HTLV-I transformed T-cell lines and fresh ATL cells are characterized by constitutive activation of the interleukin-2 receptor (IL-2R) signaling pathway however, the mechanism(s) responsible for constitutive IL-2R activation are unknown. To further examine the cause of this signaling pathway deregulation, we measured mRNA and protein expression levels by real-time PCR and Western blots, respectively, of four negative regulators of the IL-2R signaling pathway including src homology 2 (SH2)-containing phosphatase (SHP1), cytokine-inducible (CIS) SH2-containing protein, suppressor of cytokine signaling-1 (SOCS1) and protein inhibitor of activated signal transducer and activator of transcription 3 (STAT3) (PIAS3) in six HTLV-1 negative and seven HTLV-1 positive T-cell leukemia lines. The activation status of the JAK/STAT pathway was also examined. SHP1 mRNA and protein expression levels were selectively down regulated in all HTLV-1-infected transformed cell lines, while CIS, SOCS1, and PIAS3 protein expression were markedly but variably upregulated and the cells showed evidence of constitutive STAT3 activation. In acutely HTLV-1 infected primary CD4+ T-cells there was a gradual loss of SHP1 expression over 10 weeks in culture which correlated with progression from immortalization to transformation and loss of IL-2 dependence for growth. Two transformed cell lines that were established following HTLV-1 infection showed loss of SHP1 expression and overexpression of CIS, SOCS1, PIAS3. However, this overexpression was not adequate to block constitutive activation of the JAK/STAT pathway. Thus, multiple levels of IL-2 receptor signal deregulation are found in HTLV-1 transformed cells, which may be a result of early loss of SHP1 expression.
 ...
PMID:Down-regulation of SHP1 and up-regulation of negative regulators of JAK/STAT signaling in HTLV-1 transformed cell lines and freshly transformed human peripheral blood CD4+ T-cells. 1463 83

New oncogenes and tumor suppressor genes that play an important role in the pathogenesis of urothelial bladder carcinoma have been discovered. The objectives of this review were to summarize the most important oncogenes and tumor suppressor genes involved in urothelial carcinoma and to address their role in pathogenesis, their prognostic value, and their potential use as therapeutic targets. The collected data led the authors to propose a common pathway in which the fibroblastic growth factor receptor 3 (FGFR3) mutation seems to be the earliest genetic abnormality responsible for the transformation from normal tissue to atypia and dysplasia. Three different progression pathways were proposed: The first operative pathway is from dysplasia to superficial papillary pathologic Ta (pTa) tumors to pT1 tumors and, ultimately, to pT2 tumors with FGFR3 and tuberous sclerosis complex 1 (TSC1) the responsible genes. The second major operative pathway is from dysplasia, to carcinoma in situ, and to solid pT1 and pT2 tumors. The third pathway of progression is from dysplasia to papillary T1 and pT2 tumors. The genes involved in the last 2 pathways are the p53, serine threonine protein kinase 15 (STK15), triple-function domain (TRIO), fragile histidine triad (FHIT), p63 genes; and alterations of 20q and 5p, alterations of adhesions, angiogenesis, and matrix-remodeling gene products also are involved. Finally, murine leukemia viral oncogene homologue 1 (RAF1) and CD9 are involved in the progression from papillary pT1 tumors to pT2 tumors.
 ...
PMID:Genetic alterations in urothelial bladder carcinoma: an updated review. 1647 May 87

The expression of heme oxygenase-1 (HO-1), stress-related enzyme, is induced in leukaemia and some cancer tissues, but relatively little is known about the differential pattern of HO-1 expression and proliferation in premalignant lesions of the epithelial oral mucosa. The purpose of this study was to evaluate whether HO-1 expression and proliferation were increased in preneoplastic lesions compared to normal and oral cancer tissues. Immunohistochemical staining was used to examine the expression patterns of HO-1 and proliferating cell nuclear antigen (PCNA) in a series of normal mucosa and mild-to-severe cases of oral epithelial dysplasia (OED) and oral squamous cell carcinoma. Both HO-1 and PCNA are expressed in the basal cells of normal oral mucosa. In patients with OED and carcinoma in situ, immunostaining for PCNA and HO-1 was more intense, and gradually extended into the superficial layers of the mucosa. HO-1 and PCNA expression was correlated with the degree of epithelial dysplasia. Oral squamous cell carcinoma also showed elevated expression of HO-1, but this level was not higher than in severe OED or carcinoma in situ. These results suggest that the up-regulation of HO-1 in premalignant oral lesions is part of an early cytoprotection mechanism against carcinogenesis in the oral mucosa.
 ...
PMID:Upregulation of heme oxygenase-1 in oral epithelial dysplasias. 1827 47


1 2 Next >>