Search results for "Heck"
showing 10 items of 682 documents
The TileCal Optical Multiplexer Board 9U
2011
Abstract TileCal is the hadronic calorimeter of the ATLAS experiment at LHC/CERN. The system contains roughly 10,000 channels of read-out electronics, whose signals are gathered and digitized in the front-end electronics and then transmitted to the counting room through two redundant optical links. Then, the data is received in the back-end system by the Optical Multiplexer Board (OMB) 9U which performs a CRC check to the redundant data to avoid Single Event Upsets errors. A real-time decision is taken on the event-to-event basis to transmit single data to the Read-Out Drivers (RODs) for processing. Due to the low dose level expected during the first years of operations in ATLAS it was deci…
Genetic and pharmacological modulation of DNA mismatch repair heterogeneous tumors promotes immune surveillance.
2023
Patients affected by colorectal cancer (CRC) with DNA mismatch repair deficiency (MMRd), often respond to immune checkpoint blockade therapies, while those with mismatch repair-proficient (MMRp) tumors generally do not. Interestingly, a subset of MMRp CRCs contains variable fractions of MMRd cells, but it is unknown how their presence impacts immune surveillance. We asked whether modulation of the MMRd fraction in MMR heterogeneous tumors acts as an endogenous cancer vaccine by promoting immune surveillance. To test this hypothesis, we use isogenic MMRp (Mlh1+/+) and MMRd (Mlh1-/-) mouse CRC cells. MMRp/MMRd cells mixed at different ratios are injected in immunocompetent mice and tumor reje…
Abstract 1993: Fishing for artemisinin-interacting proteins from human nasopharyngeal cancer cells
2012
Abstract Determining cellular target molecules of drugs by chemical proteomic techniques is complex and tedious. Most approaches rely on activity-based probe profiling and compound-centric chemical proteomics. The antimalarial artemisinin also exerts profound anti-cancer activity, but the mechanisms of action are incompletely understood. In the present study, we have identified artemisinin-interacting target proteins from human nasopharyngeal carcinoma cell line CNE1. Thereby, our approach overcomes usual problems in traditional fishing procedures, because the drug was attached to a polystyrene surface without further chemical modification. Using mass spectrometry we have identified 20 prot…
Ionizing radiation but not anticancer drugs causes cell cycle arrest and failure to activate the mitochondrial death pathway in MCF-7 breast carcinom…
2001
There is considerable evidence that ionizing radiation (IR) and chemotherapeutic drugs mediate apoptosis through the intrinsic death pathway via the release of mitochondrial cytochrome c and activation of caspases -9 and -3. Here we show that MCF-7 cells that lack caspase-3 undergo a caspase-dependent apoptotic cell death in the absence of DNA fragmentation and alpha-fodrin cleavage following treatment with etoposide or doxorubicin, but not after exposure to IR. Re-expression of caspase-3 restored DNA fragmentation and alpha-fodrin cleavage following drug treatment, but it did not alter the radiation-resistant phenotype of these cells. In contrast to the anticancer drugs, IR failed to induc…
Abstract 4662: Shikonin causes cancer cell death by inducing mitochondrial dysfunction
2012
Abstract Shikonin, a naturally occurring napthoquinone, has been used in herbal formulations for the treatment of several inflammatory diseases in Traditional Chinese Medicine since decades. In recent studies, shikonin revealed remarkable anticancer activities and thereby is a promising candidate for cancer chemotherapy. However, the underlying cellular mechanisms and targets of shikonin are still unknown. Here, we showed that shikonin indeed exhibits strong cytotoxic effects on a panel of 15 different cancer cell lines also containing multi-drug resistant cells. The strongest effects were obtained on U937 leukemia cells. To better understand the underlying mechanisms, we performed a whole …
Bortezomib: a new pro-apoptotic agent in cancer treatment.
2010
Bortezomib is a proteasome inhibitor. It targets the ubiquitin-proteasome pathway with subsequent inhibition of the degradation of proteins involved in cell cycle regulation and cancer cell survival. The best known molecular mechanism concerns the inhibition of IkappaB breakdown and the related stabilization of NFkappaB, thus preventing its translocation to the nucleus for the activation of downstream pathways. Bortezomib is the only drug in this class which has been approved for clinical use. It has shown an efficient antitumor effect in a phase III clinical trial (APEX) involving relapsed multiple myeloma patients. Response rate, time to progression and overall survival have been improved…
Abstract 6327: Artesunate reduces tumor growth and induces different kinds of cell death in docetaxel-resistant prostate carcinoma cells
2020
Abstract Introduction: Prostate carcinoma (PCa) is the most common cancer in men. The therapeutic effect of approved compounds, such as docetaxel, is limited due to the development of therapy resistance, making new treatment options essential. Artesunate (ART), used in Traditional Chinese Medicine, has shown anti-tumor activity in several tumor types. However, little is known about the efficacy of ART on therapy-resistant PCa. Therefore, the impact of ART on docetaxel-resistant PCa cells was investigated. Material and Methods: Parental (=sensitive) and docetaxel-resistant PCa cell lines, PC3, DU145, and LNCaP, were exposed to ART [1-100 µM] for 24, 48, or 72 hours. Cells not exposed to ART …
Abstract 1423: Shikonin impairs the growth of docetaxel-resistant prostate cancer cells by necroptosis
2021
Abstract Introduction: Prostate carcinoma (PCa) is the most common malignancy in men. Androgen-targeted therapy and chemotherapy are currently the treatment of choice for advanced stages. Due to resistance towards these therapies, prognosis remains poor and new treatment options are urgently required. Shikonin (SHI) from Traditional Chinese Medicine (TCM) might be promising, since it induces anti-tumor effects in different tumor entities. However, data on PCa are few, and data on resistant PCa are not existent. Material and Methods: Parental (=sensitive) and docetaxel-resistant PCa cell lines, PC3, DU145, LNCaP, and 22Rv1 were exposed to SHI [0.1 - 1.5 μM] for 24, 48, or 72 hours. Untreated…
Cyclin dependent kinase-1 (Cdk-1) inhibition as a novel therapeutic strategy against pancreatic ductal adenocarcinoma (pdac)
2021
Simple Summary Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers in humans, due to late diagnosis and limited treatment possibilities. Improved treatment for PDAC patients is warranted. Cyclin-dependent kinase 1 (CDK1) is a stimulator of cell cycle progression and its activity is regularly enhanced in pancreatic cancer cells. Therefore, CDK1 has been proposed as a novel drug target to treat patients with PDAC. This review describes the potential of CDK1 inhibition as a treatment for PDAC by outlining the molecular pathways influenced by CDK1 inhibition and new therapeutic strategies. Abstract The role of CDK1 in PDAC onset and development is two-fold. Firstly, since …
The impact of oophorectomy on survival from breast cancer in patients with CHEK2 mutations
2022
BACKGROUND: To estimate the impact of oophorectomy and other treatments on the survival of breast cancer patients with a CHEK2 mutation. METHODS: Women with Stage I–III breast cancer who were treated at 17 hospitals in Poland were tested for four founder mutations in the CHEK2 gene. 974 women (10%) were positive for a CHEK2 mutation. Control patients without a CHEK2 mutation were selected from a database of patients treated over the same time period. Information on treatments received and distant recurrences were retrieved from medical records. Treatments included chemotherapy, hormonal therapy (tamoxifen) and radiation therapy. Oophorectomies were performed for the treatment of breast canc…