Search results for "serine"

NUPR1 works against the metabolic stress-induced autophagy-associated cell death in pancreatic cancer cells.

2013

The incidence of pancreatic adenocarcinoma is increasing with more than 43,000 predicted new cases in the US and 65,000 in Europe this year. Pancreatic cancer patients have a short life expectancy with less than 3–4% 5-y survival, which results in an equivalent incidence and mortality rate. One of the major challenges in pancreatic cancer is the identification of pharmacological approaches that overcome the resistance of this cancer to therapy. Intensive research in the past decades has led to the classification of pancreatic cancers and the identification of the driver key genetic events. Despite the advances in understanding the molecular mechanisms responsible for pancreatic cancer patho…

Temsirolimus in mantle cell lymphoma and other non-Hodgkin lymphoma subtypes.

2009

Temsirolimus, an inhibitor of mammalian target of rapamycin (mTOR), has anti-tumor activity in patients with relapsed or refractory mantle cell lymphoma (MCL) and other mature lymphoid neoplasms. mTOR is an intracellular kinase that controls the mRNA translation of many proteins (eg, cyclin D1) that can act as oncogenes and contribute to lymphomagenesis. Characterized by overexpression of cyclin D1, MCL was identified as a disease that might be susceptible to mTOR inhibition. When single-agent temsirolimus was explored in two phase II studies for treatment of patients with relapsed or refractory MCL, it demonstrated anti-tumor activity, with overall response rates of 38% and 41%. Subsequent…

Thromboprophylaxis after renal transplantation and patient risk stratification: The case of mTOR inhibitors.

2020

Deregulation of the EGFR/PI3K/PTEN/Akt/mTORC1 pathway in breast cancer: possibilities for therapeutic intervention

2014

// Nicole M. Davis 1 , Melissa Sokolosky 1 , Kristin Stadelman 1 , Stephen L. Abrams 1 , Massimo Libra 2 , Saverio Candido 2 , Ferdinando Nicoletti 2 , Jerry Polesel 3 , Roberta Maestro 4 , Antonino D’Assoro 5 , Lyudmyla Drobot 6 , Dariusz Rakus 7 , Agnieszka Gizak 7 , Piotr Laidler 8 , Joanna Dulinska-Litewka 8 , Joerg Basecke 9 , Sanja Mijatovic 10 , Danijela Maksimovic-Ivanic 10 , Giuseppe Montalto 11,12 , Melchiorre Cervello 12 , Timothy L. Fitzgerald 13 , Zoya N. Demidenko 14 , Alberto M. Martelli 15 , Lucio Cocco 15 , Linda S. Steelman 1 and James A. McCubrey 1 1 Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University Greenville, NC 27858 USA 2 …

C172S Substitution in the Chloroplast-encoded Large Subunit Affects Stability and Stress-induced Turnover of Ribulose-1,5-bisphosphate Carboxylase/Ox…

1999

Previous work has indicated that the turnover of chloroplast ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco; EC 4.1.1. 39) may be controlled by the redox state of certain cysteine residues. To test this hypothesis, directed mutagenesis and chloroplast transformation were employed to create a C172S substitution in the Rubisco large subunit of the green alga Chlamydomonas reinhardtii. The C172S mutant strain was not substantially different from the wild type with respect to growth rate, and the purified mutant enzyme had a normal circular dichroism spectrum. However, the mutant enzyme was inactivated faster than the wild-type enzyme at 40 and 50 degrees C. In contrast, C172S mutant …

The design of artificial nestboxes for the study of secondary hole-nesting birds: A review of methodological inconsistencies and potential biases

2010

The widespread use of artificial nestboxes has led to significant advances in our knowledge of the ecology, behaviour and physiology of cavity nesting birds, especially small passerines. Nestboxes have made it easier to perform routine monitoring and experimental manipulation of eggs or nestlings, and also repeatedly to capture, identify and manipulate the parents. However, when comparing results across study sites the use of nestboxes may also introduce a potentially significant confounding variable in the form of differences in nestbox design amongst studies, such as their physical dimensions, placement height, and the way in which they are constructed and maintained. However, the use of …

In Vitro Evaluation of the Squaramide-Conjugated Fibroblast Activation Protein Inhibitor-Based Agents AAZTA5.SA.FAPi and DOTA.SA.FAPi

2021

Recently, the first squaramide-(SA) containing FAP inhibitor-derived radiotracers were introduced. DATA5m.SA.FAPi and DOTA.SA.FAPi with their non-radioactive complexes showed high affinity and selectivity for FAP. After a successful preclinical study with [68Ga]Ga-DOTA.SA.FAPi, the first patient studies were realized for both compounds. Here, we present a new squaramide-containing compound targeting FAP, based on the AAZTA5 chelator 1,4-bis-(carboxylmethyl)-6-[bis-(carboxymethyl)-amino-6-pentanoic-acid]-perhydro-1,4-diazepine. For this molecule (AAZTA5.SA.FAPi), complexation with radionuclides such as gallium-68, scandium-44, and lutetium-177 was investigated, and the in vitro properties of…

SYNTHESIS OF PYRROLO[3,2-H]QUINOLINONES WITH GOOD PHOTOCHEMOTHERAPEUTIC ACTIVITY AND NO DNA DAMAGE

2010

In the search for new photochemotherapeutic agents, a series of derivatives of the ring system pyrrolo[3,2-h]quinoline--bioisosters of the angular furocoumarin angelicin--were synthesized through a four-step synthetic approach, in reasonable overall yields. Eight of the synthesized derivatives showed a remarkable phototoxicity against a panel of four human tumor cell lines and a great dose UV-A dependence, reaching IC₅₀ values at submicromolar level. The mode of cellular death photoinduced by pyrrolo[3,2-h]quinolines was evaluated through a series of flow cytometric analysis and other tests were performed to clarify their mechanism of action.

Modulation of Hedgehog target gene expression by the Fused serine-threonine kinase in wing imaginal discs

1998

0925-4773 doi: DOI: 10.1016/S0925-4773(98)00130-0; The Fused (Fu) serine–threonine kinase and the Suppressor of fused (Su(fu)) product are part of the Hedgehog (Hh) signalling pathway both in embryos and in imaginal discs. In wing imaginal discs, the Hh signal induces Cubitus interruptus (Ci) accumulation and activates patched (ptc) and decapentaplegic (dpp) expression along the anterior/posterior (A/P) boundary. In this paper, we have examined the role of the Fu and Su(fu) proteins in the regulation of Hh target gene expression in wing imaginal discs, by using different classes of fu alleles and an amorphic Su(fu) mutation. We show that, at the A/P boundary, Fu kinase activity is involved …

Late infantile neuronal ceroid lipofuscinosis: Quantitative description of the clinical course in patients withCLN2 mutations

2002

We examined 26 individuals with clinical and electron microscopic signs of late infantile neuronal ceroid lipofuscinosis (LINCL). In 22 cases, we found both pathogenic alleles. Sixteen patients exclusively carried either one or a combination of the two common mutations R208X and IVS5-1G > C. In the remaining cases, four missense mutations could be detected, of which R127Q, N286S, and T353P represent novel, previously not described alleles. A clinical performance score was developed by rating motor, visual, and verbal functions and the incidence of cerebral seizures in 3-month intervals during the course of the disease. A Total Disability Score was derived by summing up the single scores for…