Targeting multidrug resistance protein 1 (mdr1) potentiates smac-mimetic therapy to kill leukemic stem cells and overcome resistance in acute myeloid leukemia

Acute myeloid leukemia (AML) is an aggressive disease with a current 5-year survival rate of only ∼25%, therefore development of effective treatments towards resistant AML is urgently needed. Potential mechanisms of therapy resistance include overexpression of members of the inhibitor of apoptosis protein (IAP) family. Natural IAP antagonists such as second-mitochondria-derived activator of ca spases (Smac) exist, leading to the pharmaceutical development of Smac-mimetics (SMs). The clinical SM birinapant has been trialed in AML and solid cancers, as well as in hepatitis B virus (HBV), with variable and limited success.
Source: Experimental Hematology - Category: Hematology Authors: Tags: 3100 Source Type: research

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AbstractBackgroundPrevious studies have identified that patients withEGFR mutations tend to have better responses to targeted therapy, as well as chemotherapy; however, the effect of genetic alterations in terms of radiotherapy (RT) ‐related outcomes has not been fully assessed. We studied the impact of common non‐small cell lung cancer (NSCLC) genetic alterations (EGFR,ALK andKRAS) in relation to objective response rate (ORR) to RT in patients with brain metastases.MethodsFrom 2009 –2015, 153 patients with an available genotyping status were treated with whole‐brain irradiation (WBI) before receiving systemic ...
Source: Thoracic Cancer - Category: Cancer & Oncology Authors: Tags: ORIGINAL ARTICLE Source Type: research
ConclusionsEndostar delivered by CIV with CCRT may be a better option than IV in terms of potential survival and safety for unresectable stage III NSCLC.Key pointsSignificant findings of the study Endostar delivered by continuous intravenous pumping might achieve more favorable survival over intravenous injection and reduce adverse hematological reactions in patients with unresectable stage III NSCLC treated with Endostar combined with CCRT.What this study adds The administration route of recombinant human endostatin is also one key factor for survival and safety to consider when treating patients with unresectable stage III NSCLC.
Source: Thoracic Cancer - Category: Cancer & Oncology Authors: Tags: ORIGINAL ARTICLE Source Type: research
ConclusionsThe use of osimertinib immediately after nivolumab significantly increased the frequency of grade 3 or higher hepatotoxicity in patients with advanced NSCLC harboringEGFR mutation acquired T790M resistance.
Source: Thoracic Cancer - Category: Cancer & Oncology Authors: Tags: ORIGINAL ARTICLE Source Type: research
Date: Tuesday, 04 21, 2020; Speaker: Kapil Bharti, Ph.D., Head of the Ocular and Stem Cell Translational Research Section , National Eye Institute; Building 10; Lipsett Amphitheatre ; Videocast Event
Source: NIH Calendar of Events - Category: American Health Source Type: events
To gain a better understanding of the factors that govern in vivo cellular recognition, artificial glycoproteins are created as biomimetic probes to study the influence of specific glycan assemblies to biodistribution. The principle aim of this Review is to present pioneering research that has driven artificial glycoprotein ‐based targeting and subsequent adaptations with potential therapeutic applications. AbstractAkin to a cellular “fingerprint,” the glycocalyx is a glycan‐enriched cellular coating that plays a crucial role in mediating cell‐to‐cell interactions. To gain a better understanding of the ...
Source: Small - Category: Nanotechnology Authors: Tags: Review Source Type: research
In this study, biogenic nanoparticles are obtained directly from lipoaspirate, an easily accessible and abundant source of biological material. Compared to ADSC‐EVs, lipoaspirate nanoparticles (Lipo‐NPs) take less time to process (hours compared to months) and cost less t o produce (clinical‐grade cell culture facilities are not required). The physicochemical characteristics and anti‐inflammatory properties of Lipo‐NPs are evaluated and compared to those of patient‐matched ADSC‐EVs. Moreover, guanabenz loading in Lipo‐NPs is evaluated for enhanced anti‐ inflammatory effects. Apolipoprotein E and glyceroli...
Source: Small - Category: Nanotechnology Authors: Tags: Full Paper Source Type: research
L-GILZ binds and inhibits nuclear factor κB nuclear translocation in undifferentiated thyroid cancer cells. J Chemother. 2020 Feb 18;:1-5 Authors: Marchetti MC, Cannarile L, Ronchetti S, Delfino DV, Riccardi C, Ayroldi E Abstract Proto-oncogene mutations and abnormal activation of mitogen-activated protein kinase (MAPK) signalling are recurrently found in thyroid cancers. Some thyroid neoplasms respond to drugs that inhibit MAPK pathway activation. Previously, we showed that pharmacological inhibition of MAPK in thyroid cancer cells inhibits cell proliferation and upregulates L-GILZ (long glucoco...
Source: Journal of Chemotherapy - Category: Cancer & Oncology Tags: J Chemother Source Type: research
Authors: Maruta M, Miyoshi T, Matsuo N, Yamashina T, Irie K, Tsuruta M, Tsukada H, Tsuruyama M, Nagano M, Hiraki Y Abstract We administered FOLFOX (oxaliplatin (L-OHP) plus infusional 5-fluorouracil (5-FU) and leucovorin) to an hemodialysis (HD) patient with advanced gastric cancer (AGC), and investigated pharmacokinetics (PKs) and dialyzability of L-OHP. The patient was a 54-year-old Japanese man with a diagnosis of inoperable AGC. FOLFOX was instituted 3 h prior to the start of a 4 h HD period with the L-OHP and 5-FU doses reduced by 50% for the first cycle, and 30% reduced dose was administered for...
Source: Journal of Chemotherapy - Category: Cancer & Oncology Tags: J Chemother Source Type: research
CONCLUSIONS: Despite the retrospective nature of the observations and the low number of enrolled patients, the application of MRgRT in LACC appears to be safe and feasible with a favorable toxicity profile and response rates comparable to gold standard, supporting the setup of larger prospective studies to investigate the potentialities of this new technology. PMID: 32066345 [PubMed - as supplied by publisher]
Source: Tumori - Category: Cancer & Oncology Tags: Tumori Source Type: research
CONCLUSIONS: Cancer diagnosis should always be considered in patients with unprovoked thrombosis and, if NSCLC is diagnosed, genetic alterations should be always sought after. A possible relation between venous thromboembolism and oncogenic drivers, particularly for ALK translocations, has been hypothesized. Similarly to ALK-positive NSCLC, ROS1 rearranged disease has been associated with an increased thromboembolic risk. Further studies are needed to better evaluate this relation and to evaluate the potential benefit of a prophylactic anticoagulating treatment in this subset of patients. PMID: 32066344 [PubMed - as supplied by publisher]
Source: Tumori - Category: Cancer & Oncology Tags: Tumori Source Type: research
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