Home About us Contact
|
Home About us Contact | ||
|
|
||
Solid Cancers (solid + cancers)
Selected AbstractsExpression and mutational analysis of MET in human solid cancersGENES, CHROMOSOMES AND CANCER, Issue 12 2008Patrick C. Ma MET receptor tyrosine kinase and its ligand hepatocyte growth factor (HGF) regulate a variety of cellular functions, many of which can be dysregulated in human cancers. Activated MET signaling can lead to cell motility and scattering, angiogenesis, proliferation, branching morphogenesis, invasion, and eventual metastasis. We performed systematic analysis of the expression of the MET receptor and its ligand HGF in tumor tissue microarrays (TMA) from human solid cancers. Standard immunohistochemistry (IHC) and a computerized automated scoring system were used. DNA sequencing for MET mutations in both nonkinase and kinase domains was also performed. MET was differentially overexpressed in human solid cancers. The ligand HGF was widely expressed in both tumors, primarily intratumoral, and nonmalignant tissues. The MET/HGF likely is functional and may be activated in autocrine fashion in vivo. MET and stem cell factor (SCF) were found to be positively stained in the bronchioalevolar junctions of lung tumors. A number of novel mutations of MET were identified, particularly in the extracellular semaphorin domain and the juxtamembrane domain. MET-HGF pathway can be assayed in TMAs and is often overexpressed in a wide variety of human solid cancers. MET can be activated through overexpression, mutation, or autocrine signaling in malignant cells. Mutations in the nonkinase regions of MET might play an important role in tumorigenesis and tumor progression. MET would be an important therapeutic antitumor target to be inhibited, and in lung cancer, MET may represent a cancer early progenitor cell marker. © 2008 Wiley-Liss, Inc. [source] PIK3CA cancer mutations display gender and tissue specificity patterns,HUMAN MUTATION, Issue 2 2008Silvia Benvenuti Abstract The occurrence of oncogenic alleles can display striking tissue specificity. For example KRAS mutations are very frequent in pancreatic cancers but relatively rare in melanomas. The opposite is true for BRAF mutations. Somatic mutations in the gene encoding for the phosphatidylinositol 3-kinase (PI3KCA) catalytic subunit, PIK3CA, occur at high frequency in many solid cancers. We have examined whether PI3K oncogenic mutations (exons 9 and 20) might exhibit gender and/or tissue specificity. By examining large cohorts of breast and colorectal cancers affecting both men and women we found that the pattern of PIK3CA mutations is distinctive. In colorectal cancers, PIK3CA (but not KRAS, APC, or TP53) mutations display a gender bias occurring at higher frequencies in women. We also found that male breast cancers display PIK3CA mutations at an overall frequency similar to that observed in female breast tumors. In male breast cancers, however, PIK3CA mutations are found mainly in exon 20. We conclude that PI3KCA mutations affecting exons 9 and 20 display gender- and tissue-specific patterns, thus suggesting that the different amino acid changes could exert distinct functional effects on the oncogenic properties of this enzyme. Furthermore, we propose that sexual dimorphisms and tissue specific factors might directly or indirectly influence the occurrence of PI3KCA cancer alleles. Hum Mutat 29(2), 284,288, 2008. © 2007 Wiley-Liss, Inc. [source] New malignancies following childhood cancer in the United States, 1973,2002INTERNATIONAL JOURNAL OF CANCER, Issue 10 2007Peter D. Inskip Abstract The objectives of our study were to quantify risks for developing new malignancies among childhood cancer survivors, identify links between particular types of first and subsequent cancer, and evaluate the possible role of treatment. A cohort of 25,965 2-month survivors of childhood cancer diagnosed in the U.S. during 1973,2002 was identified and followed through SEER cancer registries. Observed-to-expected ratios (O/E) were calculated, and Poisson regression was used to compare risks among treatment groups. Childhood cancer survivors were at nearly 6-fold risk of developing a new cancer relative to the general population (O/E = 5.9, 95% CI: 5.4,6.5). Most common were subsequent primary cancers of the female breast, central nervous system, bone, thyroid gland and soft tissue, as well as cutaneous melanoma and acute non-lymphocytic leukemia (ANLL). The greatest risks of subsequent cancers occurred among patients diagnosed previously with Hodgkin lymphoma (HL), Ewing sarcoma, primitive neuroectodermal tumor, or retinoblastoma. Risk of subsequent solid cancers was higher among persons whose initial treatment for childhood cancer included radiotherapy, whereas the excess of subsequent ANLL was strongly related to chemotherapy. The O/E for subsequent ANLL increased with increasing calendar year of initial cancer diagnosis among survivors of cancers other than HL, most likely due to increasing use of leukemogenic drugs for solid cancers and non-Hodgkin lymphoma. Childhood cancer survivors are at markedly increased risk of developing a variety of new cancers relative to the general population, but the magnitude of excess risk and specific types of second cancer vary widely by type of first cancer. © 2007 Wiley-Liss, Inc. [source] Second malignancies among survivors of germ-cell testicular cancer: A pooled analysis between 13 cancer registriesINTERNATIONAL JOURNAL OF CANCER, Issue 3 2007Lorenzo Richiardi Abstract We investigated the risk of second malignancies among 29,511 survivors of germ-cell testicular cancer recorded in 13 cancer registries. Standardized incidence ratios (SIRs) were estimated comparing the observed numbers of second malignancies with the expected numbers obtained from sex-, age-, period- and population-specific incidence rates. Seminomas and nonseminomas, the 2 main histological groups of testicular cancer, were analyzed separately. During a median follow-up period of 8.3 years (0,35 years), we observed 1,811 second tumors, with a corresponding SIR of 1.65 (95% confidence interval (CI): 1.57,1.73). Statistically significant increased risks were found for fifteen cancer types, including SIRs of 2.0 or higher for cancers of the stomach, gallbladder and bile ducts, pancreas, bladder, kidney, thyroid, and for soft-tissue sarcoma, nonmelanoma skin cancer and myeloid leukemia. The SIR for myeloid leukemia was 2.39 (95% CI: 1.41,3.77) after seminomas, and 6.77 (95% CI: 4.14,10.5) after nonseminomas. It increased to 37.9 (95% CI: 18.9,67.8; based on 11 observed cases of leukemia) among nonseminoma patients diagnosed since 1990. SIRs for most solid cancers increased with follow-up duration, whereas they did not change with year of testicular cancer diagnosis. Among subjects diagnosed before 1980, 20 year survivors of seminoma had a cumulative risk of solid cancer of 9.6% (95% CI: 8.7,10.5%) vs. 6.5% expected, whereas 20 years survivors of nonseminoma had a risk of 5.0% (95% CI: 4.2,6.0%) vs. 3.1% expected. In conclusion, survivors of testicular cancers have an increased risk of several second primaries, where the effect of the treatment seems to play a major role. © 2006 Wiley-Liss, Inc. [source] REVIEW ARTICLE: Cancer stem cells and human malignant melanomaPIGMENT CELL & MELANOMA RESEARCH, Issue 1 2008Tobias Schatton Summary Cancer stem cells (CSC) have been identified in hematological malignancies and several solid cancers. Similar to physiological stem cells, CSC are capable of self-renewal and differentiation and have the potential for indefinite proliferation, a function through which they may cause tumor growth. Although conventional anti-cancer treatments might eradicate most malignant cells in a tumor, they are potentially ineffective against chemoresistant CSC, which may ultimately be responsible for recurrence and progression. Human malignant melanoma is a highly aggressive and drug-resistant cancer. Detection of tumor heterogeneity, undifferentiated molecular signatures, and increased tumorigenicity of melanoma subsets with embryonic-like differentiation plasticity strongly suggest the presence and involvement of malignant melanoma stem cells (MMSC) in the initiation and propagation of this malignancy. Here, we review these findings in the context of functional properties ascribed to melanocyte stem cells and CSC in other cancers. We discuss the association of deregulated signaling pathways, genomic instability, and vasculogenic mimicry phenomena observed in melanoma subpopulations in light of the CSC concept. We propose that a subset of MMSC may be responsible for melanoma therapy-resistance, tumor invasiveness, and neoplastic progression and that targeted abrogation of a MMSC compartment could therefore ultimately lead to stable remissions and perhaps cures of metastatic melanoma. [source] Cancer-associated pH-responsive tetracopolymeric micelles composed of poly(ethylene glycol)- b -poly(L -histidine)- b -poly(L -lactic acid)- b -poly(ethylene glycol)POLYMERS FOR ADVANCED TECHNOLOGIES, Issue 12 2008Kyung Taek Oh Abstract To create a novel vector for specifically delivering anticancer therapy to solid tumors, we used diafiltration to synthesize pH-sensitive polymeric micelles. The micelles, formed from a tetrablock copolymer [poly(ethylene glycol) -b -poly(L -histidine)- b -poly(L -lactic acid)- b -poly(ethylene glycol)] consisted of a hydrophobic poly(L -histidine) (polyHis) and poly(L -lactic acid) (PLA) core and a hydrophilic poly(ethylene glycol) (PEG) shell, in which we encapsulated the model anticancer drug doxorubicin (DOX). The robust micelles exhibited a critical micellar concentration (CMC) of 2.1,3.5,µg/ml and an average size of 65,80,nm pH 7.4. Importantly, they showed a pH-dependent micellar destabilization, due to the concurrent ionization of the polyHis and the rigidity of the PLA in the micellar core. In particular, the molecular weight of PLA block affected the ionization of the micellar core. Depending on the molecular weight of the PLA block, the micelles triggering released DOX at pH 6.8 (i.e. cancer acidic pH) or pH 6.4 (i.e. endosomal pH), making this system a useful tool for specifically treating solid cancers or delivering cytoplasmic cargo in vivo. Copyright © 2008 John Wiley & Sons, Ltd. [source] Progressive multifocal leukoencephalopathy: A national estimate of frequency in systemic lupus erythematosus and other rheumatic diseasesARTHRITIS & RHEUMATISM, Issue 12 2009Eamonn S. Molloy Objective Progressive multifocal leukoencephalopathy (PML) is a rare, typically fatal, central nervous system demyelinating disease that results from reactivation of the JC virus, which generally occurs in immunosuppressed hosts. The aim of this study was to generate a national estimate of the frequency of PML among patients with rheumatic diseases. Methods Data were obtained from the Nationwide Inpatient Sample database. This is a 20% sample of all hospital discharges, weighted to represent the entire US inpatient population. Data were analyzed for the years 1998,2005 inclusive, representing 297,797,180 hospital discharges. Cases of PML, systemic lupus erythematosus (SLE), and other rheumatic diseases were identified by diagnostic codes from the International Classification of Diseases, Ninth Revision, Clinical Modification. Results A total of 9,675 cases of PML were identified. The majority were associated with human immunodeficiency virus (HIV; 7,934 patients [82.00%]), hematologic cancers (813 patients [8.40%]), and solid cancers (274 patients [2.83%]). Among the rheumatic diseases, 43 cases of PML (0.44%) were associated with SLE, 24 (0.25%) with rheumatoid arthritis (RA), and 25 (0.26%) with other connective tissue diseases (CTDs). When patients with other potential risk factors for PML (HIV, malignancy, bone marrow or other organ transplantation) were excluded, the rates of PML per 100,000 discharges coded for SLE, RA, and other CTDs were 4, 0.4 and 2, respectively, compared with a rate of PML in the background population of 0.2/100,000 discharges. Conclusion This study was confined to hospitalized patients with rheumatic diseases, and it was also limited by the lack of information regarding immunosuppressive therapy. Nevertheless, the findings suggest that, although rare overall, PML occurs more commonly in SLE than in other rheumatic diseases. [source] Reversible encephalopathy following 5-fluorouracil-based chemotherapy in patients with dihydropyrimidine dehyrogenase deficiencyASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY, Issue 3 2009Dong Wook KIM 5-fluorouracil (5-FU) is one of the most frequently used chemotherapy agents for the treatment of a number of solid cancers. We report two patients with advanced gastric cancer who developed acute encephalopathy after receiving chemotherapy composed of 5-FU and oxaliplatin. One patient presented with altered consciousness and the other with generalized tonic clonic seizure. 5-FU-induced encephalopathy was suspected by clinical, radiological and electroencephalographic findings, and both patients had reduced expression of dihyropyrimidine dehydrogenase, the rate-limiting enzyme responsible for the catabolism of 5-FU. The neurological symptoms improved spontaneously, and did not recur in the following cycle of chemotherapy with the administration of a reduced dose of 5-FU. We suggest that the early recognition of this adverse event can reverse 5-FU-induced neurological symptoms and a dose reduction of the offending drug can prevent the recurrence of 5-FU induced encephalopathy. [source] | |||||||||||||