1,721,073 research outputs found
Bortezomib inhibits T-cell function versus infective antigenic stimuli in a dose-dependent manner in vitro
No full textTumor dormancy as an alternative step in the development of chemoresistance and metastasis - clinical implications
No full textBackground: The ability of a tumor to become dormant in response to suboptimal conditions has recently been recognized as a key step in tumor progression. Tumor dormancy has been found to be implicated in several tumor types as the culprit of therapy resistance and metastasis development, the deadliest features of a cancer. Several lines of evidence indicate that the development of these traits may rely on the de-differentiation of committed tumor cells that regain stem-like properties during a dormant state. Presently, dormancy is classified into cell- and population-level, according to the preponderance of cellular mechanisms that keep tumor cells quiescent or to a balance between overall cell division and death, respectively. Cellular dormancy is characterized by autophagy, stress-tolerance signaling, microenvironmental cues and, of prime relevance, epigenetic modifications. It has been found that the epigenome alters during cellular quiescence, thus representing the driving force for short-term cancer progression. Population-level dormancy is characterized by processes that counteract proliferation, such as inappropriate blood supply and intense immune responses. The latter two mechanisms are not mutually exclusive and may affect tumor masses both simultaneously and subsequently. Conclusions: Overall, tumor dormancy may represent an additional step in the acquisition of cancer characteristics, and its comprehension may clarify both theoretical and practical aspects of cancer development. Clinically, only a deep understanding of dormancy may explain the course of tumor development in different patients, thus representing a process that may be targeted to prevent and/or treat advanced-stage cancers. That is especially the case for breast cancer, against which the mTOR inhibitor everolimus displays potent antitumor activity in patients with metastatic disease by impeding autophagy and tumor dormancy onset. Here we will also discuss other targeted therapies directed towards tumor dormancy onset, e.g. specific inhibitors of SFK and MEK, or aimed at keeping tumor cells dormant, e.g. prosaposin derivatives, that may shortly enter clinical assessment in breast, and possibly other cancer types
Association of PIM gene translocation and TELAML1 rearrangement., LEUKEMIA RESEARCH,vol. Leuk Res. 2007 Dec;31(12):1761-2
No full textFolic acid fortification and cancer risk
No full textRoger Bayston and colleagues1 state that, to the best of our knowledge, folic acid does not reduce colorectal cancer risk but neither does it increase it. Although the question surrounding this type of cancer is still debated, we want to underline the possibility that folic acid fortification could have many more beneficial effects than merely those on neural tube defects.
Lack of maternal folate supplementation has been associated with an increased risk of childhood leukaemia, possibly resulting from DNA hypomethylation and strand breakage.2 Susceptibility to some types of cancer has been linked to the methylation level of the gene encoding cyclin-dependent kinase inhibitor 2A (CDKN2A), and there seems to be an interesting association between folate concentrations and consequent hypermethylation of such genes.3
Decreased dietary folate has also been associated with epigenetic silencing of CDKN2A in solid tumours, and this relation has been shown to be modified by the MTHFR genotype, suggesting a mechanism of action of folate deficiency in cancer.4
The folate pathways that maintain cell homoeostasis and genomic integrity during cellular division could represent an essential step in our understanding of the biology of cancers. Additional experimental and clinical observations could help clarify the role of folate concentrations and methylation of genes such as CDKN2A in the homoeostasis of normal and malignant blood cells.
To avoid the risk of colon cancer, perhaps a genetic analysis of patients could be done to identify individuals with the MTHFR 677TT genotype, which could be the only condition in which high concentrations of folate might promote colon cancer development.5
We declare that we have no conflict of interest
Safety and Efficacy of Pegylated Liposomal Doxorubicin In Combination with Dexamethasone and Bortezomib (VMD) or Lenalidomide (RMD) In Multiple Myeloma Refractory/Relapsed Patients
No full textFludarabine, Bortezomib, Myocet and rituximab chemotherapy in relapsed and refractory mantle cell lymphoma
No full textAbstract
Based on the hypothesis that bortezomib may potentiate fludarabine activity by inhibiting DNA repair, we designed a phase I trial using this combination with rituximab in patients with relapsed and refractory indolent and mantle cell non-Hodgkin lymphoma. Twenty-four patients were enrolled. Non-Hodgkin lymphoma subtypes included 12 patients with follicular lymphoma, four with marginal zone lymphoma, three with lymphoplasmacytic lymphoma, three with mantle cell lymphoma and two with small lymphocytic/chronic lymphocytic leukaemia. Fludarabine and bortezomib were escalated in cohorts of three patients. Rituximab was added to the maximum tolerated dose of fludarabine and bortezomib and added significant dose-limiting myelosuppression. The maximum tolerated dose was fludarabine 25 mg/m(2) on days 1-3, bortezomib 1.3 mg/m(2) on days 1, 4, 8, 11, with rituximab 375 mg/m(2) on day 1 administered every 21 d. Clinical responses were observed in 11 patients, five of whom were refractory to their most recent treatment regimen. Six additional patients had stable disease for a median of 10 months (range 4-30+). Cumulative myelosuppression and neuropathy was observed. The combination of fludarabine, bortezomib, and rituximab appears to be an active regimen with manageable toxicity for relapsed NHL
Molecular Remission After VTD or TAD As Induction for Multiple Myeloma: Results with Two Different Methods of Analysis
No full textMatch unrelated bone marrow transplantation in a case of high risk myelodysplastic syndrome treated with azacitidine and concomitant 1alpha-25-dihydroxyvitamin D3, as differentiating agent.
No full textPegylated liposomal doxorubicin in combination with dexamethasone and bortezomib (VMD) or lenalidomide (RMD) in multiple myeloma pretreated patients
No full textBortezomib and liposomal doxorubicin are highly effective in obtaining the best possible response before autologous transplant for multiple myeloma
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