2,754 research outputs found
Cancer Immunotherapy in Diffuse Large B-Cell Lymphoma
Remarkable progress has been made in the field of cancer immunotherapy in the past few years. Immunotherapy has become a standard treatment option for patients with various cancers, including melanoma, lymphoma, and carcinomas of the lungs, kidneys, bladder, and head and neck. Promising immunotherapy approaches, such as chimeric antigen receptor (CAR) T cell therapy and therapeutic blockade of immune checkpoints, in particular cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 pathway (PD-1/PD-L1), have boosted the development of new therapeutic regimens for patients with cancer. Immunotherapeutic strategies for diffuse large B-cell lymphoma (DLBCL) include monoclonal anti-CD20 antibody (rituximab), monoclonal anti-PD-1 antibodies (nivolumab and pembrolizumab), monoclonal anti-PD-L1 antibodies (avelumab, durvalumab, and atezolizumab) and chimeric antigen receptor (CAR) T cell therapy. In this review, we outline the latest highlights and progress in using immunotherapy to treat patients with DLBCL, with a focus on the therapeutic blockade of PD-1/PD-L1 and CAR T cell therapy in DLBCL. We also discuss current clinical trials of PD-1/PD-L1 and CAR T cell therapy and review the challenges and opportunities of using immunotherapy for the treatment of DLBCL
MicroRNAs associated to single drug components of R-CHOP identifies diffuse large B-cell lymphoma patients with poor outcome and adds prognostic value to the international prognostic index
Prevalence of bortezomib-resistant constitutive NF-kappaB activity in mantle cell lymphoma
<p>Abstract</p> <p>Background</p> <p>The proteasome inhibitor bortezomib can inhibit activation of the transcription factor NF-κB, a mechanism implicated in its anti-neoplastic effects observed in mantle cell lymphoma (MCL). However, NF-κB can be activated through many distinct mechanisms, including proteasome independent pathways. While MCL cells have been shown to harbor constitutive NF-κB activity, what fraction of this activity in primary MCL samples is sensitive or resistant to inhibition by bortezomib remains unclear.</p> <p>Results</p> <p>Proteasome activity in the EBV-negative MCL cell lines Jeko-1 and Rec-1 is inhibited by greater than 80% after exposure to 20 nM bortezomib for 4 hours. This treatment decreased NF-κB activity in Jeko-1 cells, but failed to do so in Rec-1 cells when assessed by electrophoretic mobility shift assay (EMSA). Concurrently, Rec-1 cells were more resistant to the cytotoxic effects of bortezomib than Jeko-1 cells. Consistent with a proteasome inhibitor resistant pathway of activation described in mouse B-lymphoma cells (WEHI231) and a breast carcinoma cell line (MDA-MB-468), the bortezomib-resistant NF-κB activity in Rec-1 cells is inhibited by calcium chelators, calmodulin inhibitors, and perillyl alcohol, a monoterpene capable of blocking L-type calcium channels. Importantly, the combination of perillyl alcohol and bortezomib is synergistic in eliciting Rec-1 cell cytotoxicity. The relevance of these results is illuminated by the additional finding that a considerable fraction of primary MCL samples (8 out of 10) displayed bortezomib-resistant constitutive NF-κB activity.</p> <p>Conclusion</p> <p>Our findings show that bortezomib-resistant NF-κB activity is frequently observed in MCL samples and suggest that this activity may be relevant to MCL biology as well as serve as a potential therapeutic target.</p
Mutant p53 as an Antigen in Cancer Immunotherapy
The p53 tumor suppressor plays a pivotal role in cancer and infectious disease. Many oncology treatments are now calling on immunotherapy approaches, and scores of studies have investigated the role of p53 antibodies in cancer diagnosis and therapy. This review summarizes the current knowledge from the preliminary evidence that suggests a potential role of p53 as an antigen in the adaptive immune response and as a key monitor of the innate immune system, thereby speculating on the idea that mutant p53 antigens serve as a druggable targets in immunotherapy. Except in a few cases, the vast majority of published work on p53 antibodies in cancer patients use wild-type p53 as the antigen to detect these antibodies and it is unclear whether they can recognize p53 mutants carried by cancer patients at all. We envision that an antibody targeting a specific mutant p53 will be effective therapeutically against a cancer carrying the exact same mutant p53. To corroborate such a possibility, a recent study showed that a T cell receptor-like (TCLR) antibody, initially made for a wild-type antigen, was capable of discriminating between mutant p53 and wild-type p53, specifically killing more cancer cells expressing mutant p53 than wild-type p53 in vitro and inhibiting the tumour growth of mice injected with mutant p53 cancer cells than mice with wild-type p53 cancer cells. Thus, novel antibodies targeting mutant p53, but not the wild-type isoform, should be pursued in preclinical and clinical studies.</p
Sequential sampling for predators in cotton
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Dysregulation of Cell Survival in Diffuse Large B Cell Lymphoma: Mechanisms and Therapeutic Targets
Diffuse large B cell lymphoma (DLBCL) is the most common type of lymphoma worldwide, representing 30–40% of non-Hodgkin lymphomas, and is clinically aggressive. Although more than half of patients with DLBCL are cured by using standard first-line immunochemotherapy, the remaining patients are refractory to the first-line therapy or relapse after complete remission and these patients require novel therapeutic approaches. Understanding the pathogenesis of DLBCL is essential for identifying therapeutic targets to tackle this disease. Cell survival dysregulation, a hallmark of cancer, is a characteristic feature of DLBCL. Intrinsic signaling aberrations, tumor microenvironment dysfunction, and viral factors can all contribute to the cell survival dysregulation in DLBCL. In recent years, several novel drugs that target abnormal cell survival pathways, have been developed and tested in clinical trials of patients with DLBCL. In this review, we discuss cell survival dysregulation, the underlying mechanisms, and how to target abnormal cell survival therapeutically in DLBCL patients
Detection of Vibrationally Excited CO in IRC+10216
Using the Submillimeter Array we have detected the J=3-2 and 2-1 rotational
transitions from within the first vibrationally excited state of CO toward the
extreme carbon star IRC+10216 (CW Leo). The emission remains spatially
unresolved with an angular resolution of ~2" and, given that the lines
originate from energy levels that are ~3100 K above the ground state, almost
certainly originates from a much smaller (~10^{14} cm) sized region close to
the stellar photosphere. Thermal excitation of the lines requires a gas density
of ~10^{9} cm^{-3}, about an order of magnitude higher than the expected gas
density based previous infrared observations and models of the inner dust shell
of IRC+10216.Comment: Accepted for publication in ApJ Letter
IRC+10216's Innermost Envelope -- The eSMA's View
We used the Extended Submillimeter Array (eSMA) in its most extended
configuration to investigate the innermost (within a radius of 290 R* from the
star) circumstellar envelope (CSE) of IRC+10216. We imaged the CSE using HCN
and other molecular lines with a beam size of 0."22 x 0."46, deeply into the
very inner edge (15 R*) of the envelope where the expansion velocity is only 3
km/s. The excitation mechanism of hot HCN and KCl maser lines is discussed. HCN
maser components are spatially resolved for the first time on an astronomical
object. We identified two discrete regions in the envelope: a region with a
radius of . 15 R*, where molecular species have just formed and the gas has
begun to be accelerated (region I) and a shell region (region II) with a radius
of 23 R* and a thickness of 15 R*, whose expansion velocity has reached up to
13 km/s, nearly the terminal velocity of 15 km/s. The SiS line detected
in region I shows a large expansion velocity of 16 km/s due to strong wing
components, indicating that the emission may arise from a shock region in the
innermost envelope. In region II, the P.A. of the most copious mass loss
direction was found to be 120 +/- 10 degrees, which may correspond to the
equatorial direction of the star. Region II contains a torus-like feature.
These two regions may have emerged due to significant differences in the size
distributions of the dust particles in the two regions.Comment: 26 pages, 8 figures, accepted for publication in The Astrophysical
Journal. Please find the pdf at
http://www.submm.caltech.edu/~hs/astroph/0904.0280.pdf and the ps file at
http://www.submm.caltech.edu/~hs/astroph/0904.0280.p
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