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)

Genetic modification of primary tumor cells by gene transfer is of major interest to study the role of specific genes in the biology of a given malignancy and to modify tumor cells for therapeutic use. Multiple myeloma (MM) is a low-proliferating cancer, with often less than 1% of the cells in the S phase of the cell cycle. As primary myeloma cells are notoriously difficult to transduce, we conducted a comparison of various viral vectors, known to integrate the transgene of interest into the target genome, for their ability to stably promote the expression of an enhanced green fluorescent protein (EGFP) transgene. We compared three murine leukemia virus-based vectors, differing only in their viral envelope, a human immunodeficiency virus (HIV)-based vector pseudotyped with the vesicular stomatitis virus glycoprotein (VSV-G), and an adeno-associated virus type 2 vector. Transduction characteristics of these vectors were evaluated in human myeloma cell lines and in primary myeloma cells. Unequivocally, we observed that the VSV-G/HIV vector was the most efficient vector for transducing the cell lines and the only one able to transduce primary myeloma cells reproducibly. The mean percentage of transduced primary myeloma cells was 43.6% (range, 16.3-77.6%), with one round of infection at a low multiplicity of infection, including MM cell samples with less than 1% of cells in the S phase. A quantitative polymerase chain reaction assay demonstrated that this more efficient EGFP expression was associated with a higher GFP copy number in the targeted cell. We propose that lentiviral vectors should be used for transduction of nonproliferating primary tumor cells such as myeloma cells.
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PMID:Comparison of murine leukemia virus, human immunodeficiency virus, and adeno-associated virus vectors for gene transfer in multiple myeloma: lentiviral vectors demonstrate a striking capacity to transduce low-proliferating primary tumor cells. 1467 Jan 24

The relatively low efficiency of target cell transduction and variations in the stability of transgene expression by retroviral vectors based on the Moloney murine leukemia virus (MoMLV) are major impediments to the use of such vectors in cancer gene therapy approaches. The present study was designed to investigate the stability and efficiency of transgene expression in human lung and breast cancer cell lines transduced with vectors based on human immunodeficiency virus type 1 (HIV-1) in vitro and in vivo in nude mouse models of metastasis. H460 lung carcinoma cells and MDA-MB-231 breast carcinoma cells were transduced with lentiviral vectors encoding enhanced green fluorescent protein (EGFP) and beta-galactosidase (beta-Gal), respectively. Transduced H460 cells were administered to nude mice by either intravenous or subcutaneous injection and MDA-MB-231 cells were implanted orthotopically into the mammary fat pad of such mice to induce primary tumor and metastatic lung tumor formation. High-level EGFP expression was maintained in transduced H460 cells in metastatic lung nodules for up to 6 weeks and transgene expression in vitro persisted for at least 23 days after retrieval of EGFP-positive H460 cells from the lungs of tumor-bearing mice and subsequent cultivation in vitro. Likewise, beta-Gal expression levels in metastatic MDA-MB-231 cells in lungs remained high for up to 11 weeks. Southern blot analyses carried out with DNA from lung nodules showed that proviral DNAs in H460 cells were maintained stably over many cell generations and during subsequent reimplantation in vivo. However, molecular analyses revealed variations in transgene copy numbers and expression levels among individual lung clones. These results demonstrate the usefulness of HIV-1-based lentiviral vectors for sustained and stable transgene expression in human lung and breast cancer cell lines in vitro and in vivo.
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PMID:Stable transgene expression in tumors and metastases after transduction with lentiviral vectors based on human immunodeficiency virus type 1. 1514 75

Clear cell sarcoma of soft tissue (CCSST), also known as malignant melanoma of soft parts, represents a rare lesion of the musculoskeletal system usually affecting adolescents and young adults. CCSST is typified by a chromosomal t(12;22)(q13;q12) translocation resulting in a fusion between the Ewing sarcoma gene (EWSR1) and activating transcription factor 1 (ATF1), of which the activity in nontransformed cells is regulated by cyclic AMP. Our aim was to identify critical differentially expressed genes in CCSST tumor cells in comparison with other solid tumors affecting children and young adults to better understand signaling pathways regulating specific features of the development and progression of this tumor entity. We applied Affymetrix Human Genome U95Av2 oligonucleotide microarrays representing approximately 12,000 genes to generate the expression profiles of the CCSST cell lines GG-62, DTC-1, KAO, MST2, MST3, and Su-CC-S1 in comparison with 8 neuroblastoma, 7 Ewing tumor, and 6 osteosarcoma cell lines. Subsequent hierarchical clustering of microarray data clearly separated all four of the tumor types from each other and identified differentially expressed transcripts, which are characteristically up-regulated in CCSST. Statistical analysis revealed a group of 331 probe sets, representing approximately 300 significant (P < 0.001) differentially regulated genes, which clearly discriminated between the CCSST and other tumor samples. Besides genes that were already known to be highly expressed in CCSST, like S100A11 (S100 protein) or MITF (microphthalmia-associated transcription factor), this group shows an obvious portion of genes that are involved in cyclic AMP response or regulation, in pigmentation processes, or in neuronal structure and signaling. Comparison with other expression profile analyses on neuroectodermal childhood tumors confirms the high robustness of this strategy to characterize tumor entities based on their gene expression. We found the avian erythroblastic leukemia viral oncogene homologue 3 (ERBB3) to be one of the most dramatically up-regulated genes in CCSST. Quantitative real-time PCR and Northern blot analysis verified the mRNA abundance and confirmed the absence of the inhibitory transcript variant of this gene. The protein product of the member of the epidermal growth factor receptor family ERBB3 could be shown to be highly present in all of the CCSST cell lines investigated, as well as in 18 of 20 primary tumor biopsies. In conclusion, our data demonstrate new aspects of the phenotype and the biological behavior of CCSST and reveal ERBB3 to be a useful diagnostic marker.
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PMID:Expression profiling of t(12;22) positive clear cell sarcoma of soft tissue cell lines reveals characteristic up-regulation of potential new marker genes including ERBB3. 1515 91

The primary tumors that typically cause carcinomatous meningitis include lung cancer, breast cancer, leukemia, lymphoma and melanoma. A variety of neurological signs and symptoms can be seen depending on the extent and location of the meningeal metastasis. Once the diagnosis of carcinomatous meningitis is confirmed, the search for the primary tumor can be a challenge and at times may require extensive radiographic or even surgical evaluation to obtain specimen for pathological confirmation. Here we report a patient who presented with bilateral cranial nerve VIII and cerebellar symptoms, and was diagnosed with carcinomatous meningitis. Only after an exploratory laporatomy did it become clear that the initial symptoms were related to a metastatic gallbladder carcinoma.
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PMID:Carcinomatous meningitis as the presenting manifestation of gallbladder carcinoma: case report and review of the literature. 1552 9

Radiation exposure, known to cause DNA damage, may be a potential source of field cancerization of the upper aerodigestive tract. Radiotherapy for head and neck cancers has been examined as a possible risk factor for second primary cancers, but the results have been equivocal. We evaluated the impact of therapeutic radiation for oral cancer on the risk of second primary cancers with data from the Surveillance, Epidemiology, and End Results (SEER) program for 1973-1999. Among 30,221 first primary oral squamous cell carcinoma patients, 6163 (20.4%) patients developed a second primary cancer, 5042 of which were metachronous. Patients treated with radiation only (RR=1.64, 95%CI=1.18-2.29) or radiation with surgery (RR=1.49, 95%CI=1.07, 2.06) had elevated risks of developing a second primary tumor, whereas patients treated with surgery only did not appear to be at increased risk (RR=1.28, 95%CI=0.93, 1.76). Consistent with an expected latent period between radiation exposure and tumor occurrence, radiation became a risk factor after 10 years of follow-up for solid cancers of the oral cavity (RR=2.8, 95%CI=1.5, 5.2), pharynx (RR=5.9, 95%CI=1.7, 20.7), esophagus (RR=3.9, 95%CI=1.1, 13.4) and lung (RR=1.5, 95%CI=1.0, 2.4), and after 1-5 years of follow-up for second primary leukemia (RR=2.5, 95%CI=1.0, 6.7). Radiotherapy for oral cancer appears to be a risk factor for second primary tumors. Further studies that account for chemotherapy and examine frequency and duration of radiotherapy would be of interest in confirming the observed association.
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PMID:Radiotherapy for oral cancer as a risk factor for second primary cancers. 1576 94

B-cell chronic lymphocytic leukemia (B-CLL) remains an incurable disease that requires innovative new approaches to improve therapeutic outcome. Honokiol is a natural product known to possess potent antineoplastic and antiangiogenic properties. We examined whether honokiol can overcome apoptotic resistance in primary tumor cells derived from B-CLL patients. Honokiol induced caspase-dependent cell death in all of the B-CLL cells examined and was more toxic toward B-CLL cells than to normal mononuclear cells, suggesting greater susceptibility of the malignant cells. Honokiol-induced apoptosis was characterized by the activation of caspase-3, -8, and -9 and cleavage of poly(adenosine diphosphate-ribose) polymerase (PARP). Exposure of B-CLL cells to honokiol resulted in up-regulation of Bcl2-associated protein (Bax) and down-regulation of the expression of the key survival protein myeloid-cell leukemia sequence 1 (Mcl-1), which is associated with response to treatment in B-CLL patients. In addition, B-CLL cells pretreated with interleukin-4 (IL-4), a cytokine known to support B-CLL survival, underwent apoptosis when subsequently incubated with honokiol, indicating that honokiol could also overcome the prosurvival effects of IL-4. Furthermore, honokiol enhanced cytotoxicity induced by fludarabine, cladribine, or chlorambucil. These data indicate that honokiol is a potent inducer of apoptosis in B-CLL cells and should be examined for further clinical application either as a single agent or in combination with other anticancer agents.
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PMID:The natural product honokiol induces caspase-dependent apoptosis in B-cell chronic lymphocytic leukemia (B-CLL) cells. 1580 33

Primary penile carcinoma is one of the rarest male genital tract tumors. We rarely encounter this malignancy in Turkey because circumcision is routinely performed as a part of the Islamic tradition. Despite the medical paradox that the penis is rarely affected by metastases, approximately 300 cases have been reported in the literature. The primary lesion is almost 75% of pelvic origin; genitourinary or rectosigmoid primaries and penile metastasis from extrapelvic primaries constitute 25% of other primaries. Furthermore, isolated metastatic penile carcinomas are exceptionally rare. The rarity of the event prompted this study, which describes 10 cases of metastatic tumors of the penis including 7 cases with transitional cell carcinoma of the bladder, and in 1 case each of squamous cell carcinoma of the lung, adenocarcinoma of the prostate and leukemia. The main characteristics of the primary tumor are described, along with the diagnosis, treatment and the outcome of patients.
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PMID:Penile metastasis from other malignancies. A study of ten cases and review of the literature. 1649 10

We performed retrospectively study on 136 thoracoscopies done in our clinic in the period January 2000 and December 2004. We reviewed 136 thoracoscopies, 71 patients were male and 65 were female (mean age 58.4 years). Straw colored effusions were present in 78 cases (57%) and hemorrhagic in 58 cases (43%). The surgical procedure consist in diagnostic of thoracoscopy with drainage of pleural effusion, multiply pleural biopsy, pleurodesis and continuous pleural drainage. In our study, the talc powder (5g) was successfully as sclerosing agent. The primary tumor was: lung-63 (46%), breast-26 (19%), mesothelioma-21 (15.5%), stomach-3, ovarian-3, prostate-3, colon-2, lymphoma-1, leukemia-2, plasmocytoma-1 and unknown primary tumor in 11 cases (8%). Adverse effects included-chest pain-35 cases (25%), fever-20 cases (15%), empyema-6 cases (4.5%), prolonged air leak-5 cases (4%), pulmonary infection-2 cases, acute respiratory failure-1 case, malignant invasion of scar-1 patient. For statistical analysis, the success of talc pleurodesis was defined as the absence of pleural fluid on the follow-up chest radiographs. Pleurodesis was successful in 125 cases (92%) of the patients after 1 month-follow-up. Thoracoscopic talc pleurodesis is a safe, economical and effective treatment for malignant pleural effusion.
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PMID:[Thoracoscopic pleurodesis in malignant pleural effusions]. 1661 48

The importance of cancer stem cells (CSCs) in tumor-initiation has been firmly established in leukemia and recently reported for a variety of solid tumors. However, the role of CSCs in multistage cancer progression, particularly with respect to metastasis, has not been well-defined. Cancer metastasis requires the seeding and successful colonization of specialized CSCs at distant organs. The biology of normal stem cells and CSCs share remarkable similarities and may have important implications when applied to the study of cancer metastasis. Furthermore, overlapping sets of molecules and pathways have recently been identified to regulate both stem cell migration and cancer metastasis. These molecules constitute a complex network of cellular interactions that facilitate both the initiation of the pre-metastasis niche by the primary tumor and the formation of a nurturing organ microenvironment for migrating CSCs. In this review, we surveyed the recent advances in this dynamic field and propose a unified model of cancer progression in which CSCs assume a central role in both tumorigenesis and metastasis. Better understanding of CSCs as a fundamental component of the metastatic cascade will lead to novel therapeutic strategies against metastatic cancer.
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PMID:Beyond tumorigenesis: cancer stem cells in metastasis. 1717 81

Along with a brief review of the literature, we report the clinicopathologic features of 12 cases of extramammary malignancies metastatic to the breast. Histological diagnoses of the primary tumor were as follows: non-Hodgkin diffuse large B-cell lymphoma (3 patients), acute mycloid leukemia (3 patients), serous papillary adenocarcinoma, well-differentiated adenocarcinoma, squamous cell carcinoma, undifferentiated neoplasm, mesothelioma, and melanoma. The most common mammographic finding was a well-circumscribed mass with increased density but without speculation, calcifications or other signs that characterize the majority of primary carcinomas. Ultrasound revealed well-circumscribed masses without retrotumor acoustic shadowing. The interval between diagnosis of primary cancer and the appearance of breast metastasis ranged from 0 to 108 months (mean: 17, median: 1). Survival after the detection of the breast metastases ranged from 0.2 to 144 months (mean: 23, median: 9.5). In conclusion, metastasis can mimic either benign disease or primary malignancy and is often an unexpected diagnosis in a patient presenting with a breast mass. Thus, an accurate diagnosis is important to avoid unnecessary mutilating surgery. These masses generally indicate disseminated metastatic disease, with a very poor survival rate.
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PMID:Metastases to the breast from extramammary malignancies: a clinicopathologic study of 12 cases. 1721 43


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