Minimal residual disease (MRD) monitoring has been used to identify early molecular relapse and predict clinical relapse in mantle cell lymphoma (MCL). Few published data exist in MCL on the ...performance of next-generation sequencing–based assay of immunoglobulin gene rearrangements for MRD assessment.
In a prospective clinical trial (NCT01484093) with intensive induction chemotherapy and autologous stem-cell transplantation, posttreatment peripheral blood samples were collected from 16 MCL patients and analyzed with an earlier version of the Adaptive Biotechnologies MRD assay.
Of the 7 patients whose disease remained in remission, the MRD test remained negative in 5 (71%). Of the 9 patients who experienced relapse, the MRD test was positive at least 3 months before relapse in 6 patients (67%) and positive at the time of relapse in 1 patient (11%). All patients with at least 2 positive MRD tests experienced relapse.
The next-generation sequencing–based MRD assay identified early molecular relapse, and we observed more sensitivity in the cellular (circulating leukocytes) versus acellular (plasma cell-free DNA) compartment. This observation may be due to availability of tumor target or a limitation of the assay.
Limited information exists in mantle cell lymphoma (MCL) on the performance of next-generation sequencing–based assay of immunoglobulin gene rearrangements for minimal residual disease (MRD) assessment. Posttreatment peripheral blood samples were collected from 16 MCL patients and analyzed with the Adaptive Biotechnologies MRD assay, which identified early molecular relapse. We observed more sensitivity in the cellular versus acellular compartment.
CDK4 inhibitors (CDK4/6i), such as palbociclib, ribociclib, and abemaciclib, are approved in combination with hormonal therapy as a front-line treatment for metastatic HR+, HER2- breast cancer. Their ...targets, CDK4 and CDK6, are cell-cycle regulatory proteins governing the G
-S phase transition across many tissue types. A key challenge remains to uncover biomarkers to identify those patients that may benefit from this class of drugs. Although CDK4/6i addition to estrogen modulation therapy essentially doubles the median progression-free survival, overall survival is not significantly increased. However, in reality only a subset of treated patients respond. Many patients exhibit primary resistance to CDK4/6 inhibition and do not derive any benefit from these agents, often switching to chemotherapy within 6 months. Some patients initially benefit from treatment, but later develop secondary resistance. This highlights the need for complementary or companion diagnostics to pinpoint patients who would respond. In addition, because CDK4 is a bona fide target in other tumor types where CDK4/6i therapy is currently in clinical trials, the lack of target identification may obscure benefit to a subset of patients there as well. This review summarizes the current status of CDK4/6i biomarker test development, both in clinical trials and at the bench, with particular attention paid to those which have a strong biological basis as well as supportive clinical data.
Boron deficiency in the soil is commonly found throughout the country, mainly in cerrado soils, making it extremely necessary to fertilize such a micronutrient. Therefore, this study aimed to ...evaluate the availability of boron in clay and sandy soils with different sources of borated fertilizers in soybean cultivation in the 2018/19 soybean harvest. The availability of boron was evaluated by the method with hot water extraction in a soil sample in different soil layers and at a different time of collection. The experiment was assembled in randomized blocks (DBC), with 5 treatments and 4 replications, as follows: split boric acid: twice, total boric acid: one application of the integral dose, Granulex ®️, Produbor®️ and control treatment Granulex provided higher B content in the soil in the 1st collection, in the 10-20 cm layer in cl In sandy soil, the different sources did not defer under the availability of B at all depths and collections. In general, clayey soils retain B more when compared to sandy soils
In the CNS, where Ca
2+ overload has been established as a mechanism contributing to neuronal damage associated with excitotoxicity, stroke and ischemia, there is interest in understanding the role ...of calpain inhibition in rescuing neurons from death. In these settings, the activation of large stores of latent calpain may rapidly lead to the demise of the neuron within hours. The activity of calpain is strictly regulated by calcium concentrations and interactions with calpastatin (endogenous calpain inhibitor). The interaction between calpains and calpastatin is calcium dependent, and little is known about the regulation of the neuronal calpain–calpastatin system in vivo. It has been postulated that calpastatin can be modulated by nerve growth factors (NGFs). We have demonstrated in vitro as well as in vivo a neuroprotective effect of the β
2-adrenoceptor agonist clenbuterol (CLN) mediated through an increased NGF expression. In this study we attempt to find out whether CLN is capable (1) of modulating proteolysis regulated by the calpain–calpastatin system and (2) of attenuating DNA-fragmentation induced by cerebral ischemia.
Rats received CLN daily for 1 week, were then subjected to ischemia and finally perfused at different times post-ischemia. The proteolytic activity of calpain was measured by the immunolocalisation of calpastatin and spectrin-breakdown products (SBP). The time course of apoptosis was assessed by terminal dUTP nick end-labeling (TUNEL)-staining. CLN reduced CA1-hippocampal cell damage by 23%, attenuated DNA-laddering and decreased proteolysis of spectrin by enhancing calpastatin activity. These results provide evidence that CLN is a potent neuroprotective substance, which through the enhancement of calpastatin synthesis attenuates the apoptotic machinery and modulates proteolysis.
In the CNS, where Ca(2+) overload has been established as a mechanism contributing to neuronal damage associated with excitotoxicity, stroke and ischemia, there is interest in understanding the role ...of calpain inhibition in rescuing neurons from death. In these settings, the activation of large stores of latent calpain may rapidly lead to the demise of the neuron within hours. The activity of calpain is strictly regulated by calcium concentrations and interactions with calpastatin (endogenous calpain inhibitor). The interaction between calpains and calpastatin is calcium dependent, and little is known about the regulation of the neuronal calpain-calpastatin system in vivo. It has been postulated that calpastatin can be modulated by nerve growth factors (NGFs). We have demonstrated in vitro as well as in vivo a neuroprotective effect of the beta(2)-adrenoceptor agonist clenbuterol (CLN) mediated through an increased NGF expression. In this study we attempt to find out whether CLN is capable (1) of modulating proteolysis regulated by the calpain-calpastatin system and (2) of attenuating DNA-fragmentation induced by cerebral ischemia. Rats received CLN daily for 1 week, were then subjected to ischemia and finally perfused at different times post-ischemia. The proteolytic activity of calpain was measured by the immunolocalisation of calpastatin and spectrin-breakdown products (SBP). The time course of apoptosis was assessed by terminal dUTP nick end-labeling (TUNEL)-staining. CLN reduced CA1-hippocampal cell damage by 23%, attenuated DNA-laddering and decreased proteolysis of spectrin by enhancing calpastatin activity. These results provide evidence that CLN is a potent neuroprotective substance, which through the enhancement of calpastatin synthesis attenuates the apoptotic machinery and modulates proteolysis.
The aim of this paper is to analyze the strategy adopted by French engineering schools facing the internationalization of knowledge and technological production, knowing that the foreign languages ...and cultures training participate to make students able to work in an international context. For this purpose the Council of Deans of French Engineering Schools and Universities of Technology (CDEFI) did an inquiry among 173 French graduated engineering schools. Even if the French accreditation board for engineering education (CTI) asks to the engineering schools to teach at least one mandatory language: English, the study has shown that the majority of the schools (62%) impose students to study a second compulsory language. A wide variety of foreign languages, mandatory or not, is offered by the schools. In total, 16 different foreign languages are offered. In addition to English which is mandatory in all schools, 92% of the schools offer Spanish classes, 92% offer German classes, 71% offer Chinese classes and 53% offer Japanese classes. A large majority of engineering schools includes at least one permanent foreign languages teacher position : teachers of English (91%), German (63%) and Spanish (62%).The study showed that 97% of the schools work to integrate more than one foreign language in the curriculum of engineering students. Half of them would add a new language in addition to its current offering. The language more frequently cited in this case was Portuguese (37%). In almost all cases (92%), the management team and the staff consider that the foreign languages' learning is very important for engineering students. Their primary motivation in the choice of a foreign language would be the project to go abroad. The study established a link between languages taught in the school and academic and research international partnerships. The most cited countries regarding students exchanges were Spain, or other Spanish-speaking countries, Germany, China and the United Kingdom, which correspond to the four most widely taught languages in engineering schools. However, for future partnerships, we clearly noticed that French engineering schools want to collaborate with Brazil and China. The schools interested in partnerships with those countries are making significant efforts to integrate Chinese and Portuguese courses in the curriculum. The paper draws up a complete panorama of the diversity of their implementation.
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