Carlos E. Bueso-Ramos

Bio: Carlos E. Bueso-Ramos is an academic researcher from University of Texas MD Anderson Cancer Center. The author has contributed to research in topics: Myeloid leukemia & Leukemia. The author has an hindex of 63, co-authored 474 publications receiving 18846 citations.

MicroRNAs in body fluids—the mix of hormones and biomarkers

Abstract: Since the discovery of microRNAs (miRNAs), the study of these small noncoding RNAs has steadily increased and more than 10,000 papers have already been published. The great interest in miRNAs reflects their central role in gene-expression regulation and the implication of miRNA-specific aberrant expression in the pathogenesis of cancer, cardiac, immune-related and other diseases. Another avenue of current research is the study of circulating miRNAs in serum, plasma, and other body fluids--miRNAs may act not only within cells, but also at other sites within the body. The presence of miRNAs in body fluids may represent a gold mine of noninvasive biomarkers in cancer. Since deregulated miRNA expression is an early event in tumorigenesis, measuring circulating miRNA levels may also be useful for early cancer detection, which can contribute greatly to the success of treatment. In this Review, we discuss the role of fluid-expressed miRNAs as reliable cancer biomarkers and treatment-response predictors as well as potential new patient selection criteria for clinical trials. In addition, we explore the concept that miRNAs could function as hormones.

Curcumin Suppresses the Paclitaxel-Induced Nuclear Factor-κB Pathway in Breast Cancer Cells and Inhibits Lung Metastasis of Human Breast Cancer in Nude Mice

Abstract: Currently, there is no effective therapy for metastatic breast cancer after surgery, radiation, and chemotherapy have been used against the primary tumor. Because curcumin suppresses nuclear factor-kappaB (NF-kappaB) activation and most chemotherapeutic agents activate NF-kappaB that mediates cell survival, proliferation, invasion, and metastasis, we hypothesized that curcumin would potentiate the effect of chemotherapy in advanced breast cancer and inhibit lung metastasis. We tested this hypothesis using paclitaxel (Taxol)-resistant breast cancer cells and a human breast cancer xenograft model. As examined by electrophoretic mobility gel shift assay, paclitaxel activated NF-kappaB in breast cancer cells and curcumin inhibited it; this inhibition was mediated through inhibition of IkappaBalpha kinase activation and IkappaBalpha phosphorylation and degradation. Curcumin also suppressed the paclitaxel-induced expression of antiapoptotic (XIAP, IAP-1, IAP-2, Bcl-2, and Bcl-xL), proliferative (cyclooxygenase 2, c-Myc, and cyclin D1), and metastatic proteins (vascular endothelial growth factor, matrix metalloproteinase-9, and intercellular adhesion molecule-1). It also enhanced apoptosis. In a human breast cancer xenograft model, dietary administration of curcumin significantly decreased the incidence of breast cancer metastasis to the lung and suppressed the expression of NF-kappaB, cyclooxygenase 2, and matrix metalloproteinase-9. Overall, our results indicate that curcumin, which is a pharmacologically safe compound, has a therapeutic potential in preventing breast cancer metastasis possibly through suppression of NF-kappaB and NF-kappaB-regulated gene products.

Long-term follow-up results of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (Hyper-CVAD), a dose-intensive regimen, in adult acute lymphocytic leukemia

Abstract: Background Modern intensive chemotherapy regimens have improved the prognosis for patients with adult acute lymphocytic leukemia (ALL). With these regimens, the complete response rates are now reported to be > 80%, and the long-term survival rates range from 30% to 45%. The current analysis updated the long-term results with the original hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (Hyper-CVAD) program, with a median follow-up time of 63 months. Methods Between 1992 and 2000, 288 patients were treated with Hyper-CVAD. The median age of the patients was 40 years, and 59 patients (20%) were > or = age 60 years. The incidence of Philadelphia chromosome (Ph)-positive ALL was 17%, and the incidence of of T-cell ALL was 13%. Results A complete response (CR) was achieved in 92% of patients. The induction mortality rate was 5% (2% if the patient's age was or = 60 years). With a median follow-up time of 63 months, the 5-year survival rate was 38% and the 5-year CR duration rate was 38%. Multivariate analysis of prognostic factors for CR duration identified the following adverse factors: age > or = 45 years, leukocytosis > or = 50 x 10(9)/L, poor performance status (an Eastern Cooperative Oncology Group score of 3-4), Ph-positive disease, French-American-British L2 morphology, > 1 course to achieve CR, and Day 14 bone marrow blasts > 5%. Patients were divided into low-risk (risk score 0-1; 37%), intermediate risk (risk score 2-3; 36%), and poor-risk groups (risk score > or = 4; 27%) with 5-year CR duration rates of 52%, 37%, and 10%, respectively. Conclusions Compared with the previous VAD regimens, Hyper-CVAD was associated with significantly better CR rates, CR duration, and survival. The long-term follow-up results of Hyper-CVAD were favorable. Comparison of Hyper-CVAD with other established adult ALL regimens is warranted.

Chemoimmunotherapy with hyper-CVAD plus rituximab for the treatment of adult Burkitt and Burkitt-type lymphoma or acute lymphoblastic leukemia

Abstract: Background Adult Burkitt-type lymphoma (BL) and acute lymphoblastic leukemia (B-ALL) are rare entities composing 1% to 5% of non-Hodgkin lymphomas NHL) or ALL. Prognosis of BL and B-ALL has been poor with conventional NHL or ALL regimens, but has improved with dose-intensive regimens. Methods To evaluate the addition of rituximab, a CD20 monoclonal antibody, to intensive chemotherapy in adults with BL or B-ALL, 31 patients with newly diagnosed BL or B-ALL received the hyper-fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD) regimen with rituximab. Their median age was 46 years; 29% were 60 years or older. Rituximab 375 mg/m(2) was given on Days 1 and 11 of hyper-CVAD courses and on Days 1 and 8 of methotrexate and cytarabine courses. Results Complete remission (complete response [CR]) was achieved in 24 of 28 (86%) evaluable patients; 3 had a partial response, and 1 had resistant disease. There were no induction deaths. The 3-year overall survival (OS), event-free survival, and disease-free survival rates were 89%, 80%, and 88%, respectively. Nine elderly patients achieved CR with all of them in continuous CR (except 1 death in CR from infection), with a 3-year OS rate of 89%. Multivariate analysis of current and historical (those treated with hyper-CVAD alone) groups identified age and treatment with rituximab as favorable factors. Conclusions The addition of rituximab to hyper-CVAD may improve outcome in adult BL or B-ALL, particularly in elderly patients.

I and i

Abstract: There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality. Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

Cancer chemoprevention with dietary phytochemicals

Abstract: Chemoprevention refers to the use of agents to inhibit, reverse or retard tumorigenesis. Numerous phytochemicals derived from edible plants have been reported to interfere with a specific stage of the carcinogenic process. Many mechanisms have been shown to account for the anticarcinogenic actions of dietary constituents, but attention has recently been focused on intracellular-signalling cascades as common molecular targets for various chemopreventive phytochemicals.

Patterns of Somatic Mutation in Human Cancer Genomes

Abstract: AACR Centennial Conference: Translational Cancer Medicine-- Nov 4-8, 2007; Singapore PL02-05 All cancers are due to abnormalities in DNA. The availability of the human genome sequence has led to the proposal that resequencing of cancer genomes will reveal the full complement of somatic mutations and hence all the cancer genes. To explore the nature of the information that will be derived from cancer genome sequencing we have sequenced the coding exons of the family of 518 protein kinases, ~1.3Mb DNA per cancer sample, in 210 cancers of diverse histological types. Despite the screen being directed toward the coding regions of a gene family that has previously been strongly implicated in oncogenesis, the results indicate that the majority of somatic mutations detected are “passengers”. There is considerable variation in the number and pattern of these mutations between individual cancers, indicating substantial diversity of processes of molecular evolution between cancers. The imprints of exogenous mutagenic exposures, mutagenic treatment regimes and DNA repair defects can all be seen in the distinctive mutational signatures of individual cancers. This systematic mutation screen and others have previously yielded a number of cancer genes that are frequently mutated in one or more cancer types and which are now anticancer drug targets (for example BRAF , PIK3CA , and EGFR ). However, detailed analyses of the data from our screen additionally suggest that there exist a large number of additional “driver” mutations which are distributed across a substantial number of genes. It therefore appears that cells may be able to utilise mutations in a large repertoire of potential cancer genes to acquire the neoplastic phenotype. However, many of these genes are employed only infrequently. These findings may have implications for future anticancer drug development.