2,754 research outputs found
The ambitious role of anti angiogenesis molecules: Turning a cold tumor into a hot one
In renal cancer emerging treatment options are becoming available and there is a strong need to combine therapies to reformulate and adjourn clinical practice. We here highlight and discuss the need to take advantage of the common immune targets to design combined strategies to increase clinical responses
"Some notes on the use of stare"
The complex series of semantic and syntactic functions borne by the Romance offshoots of lat. stare has been at times related to early developments already attested in Latin (cf. Bourciez 1956; Ribeiro 1958). The verbal form that we find in Latin, however, is consistently considered as a postural verb, i.e. stare ‘stand (on a erected position, on foot)’, (cf. Stengaard 1991; Pountain 1982).
Looking at things from a Latin perspective, after an analysis of an extensive collection of the occurrences from Plautus to Late Latin texts, it is possible to draw a diachronical sequence of meanings and functions. Far from being semantically static, stare displays profiles that extend from a verb that expresses absence of movement, to a plainly “situative” verb (i.e. pointing generically to the physical presence of an animate/inanimate entity in a certain place), to a durative verb referring to a temporal scope.
While a significantly wide range of semantic cores is attested already in the early Imperial period (Livy, Petronius) and continues in later authors (Augustinus, Ammianus, Peregrinatio Egeriae), more syntax-oriented phenomena can only sporadically be found in texts from different temporal stages, in occurrences where stare entwines with other lexical items having a predicative status or bearing an aspectual function (Valerius Flaccus, Tacitus, Script. Hist. Aug., Vulgata, Avienus). Possibly, some semantic features that seem to characterize a few uses of this verb (i.e. mainly the espression of transitory vs. inherent state or condition), could be related to aspects and features supposedly relevant in later Romance developments (cf., for ex., King 1991 for an analysis of the opposition sp. ser vs. estar).
The aim of this paper, thus, is to offer a brief description of the uses of stare within the Latin language; to search for a rationale of its diachronic evolution; and, tentatively, to draw parallels and to look for functional similarities between uses of this verb and later, Romance phenomena
CD137+ T-cells: protagonists of the immunotherapy revolution
The CD137 receptor is expressed by activated antigen-specific T-cells. CD137+ T-cells were identified inside TILs and PBMCs of different tumor types and have proven to be the naturally occurring antitumor effector cells, capable of expressing a wide variability in terms of TCR specificity against both shared and neoantigenic tumor-derived peptides. The aim of this review is thus summarizing and highlighting their role as drivers of patients’ immune responses in anticancer therapies as well as their potential role in future and current strategies of immunotherapy. The CD137 receptor (4-1BB, TNF RSF9) is an activation induced molecule expressed by antigen-specific T-cells. The engagement with its ligand, CD137L, is capable of increasing Tcell survival, proliferation, and cytokine production. This allowed to identify the CD137+ T-cells as the real tumor-specific activated T-cell population. In fact, these cells express various TCRs that are specific for a wide range of tumor-derived peptides, both shared and neoantigenic ones. Moreover, their prevalence in sites close to the tumor and their unicity in killing cancer cells both in vitro and in vivo, raised particular interest in studying their potential role in different strategies of immunotherapy. They indeed showed to be a reliable marker able to predict patient’s outcome to immune-based therapies as well as monitor their response. In addition, the possibility of isolating and expanding this population, turned promising in order to generate effector antitumor T-cells in the context of adoptive T-cell therapies. CD137-targeting monoclonal antibodies have already shown their antitumor efficacy in cancer patients and a number of clinical trials are thus ongoing to test their possible introduction in different combination approaches of immunotherapy. Finally, the intracellular domain of the CD137 receptor was introduced in the anti-CD19 CAR-T cells that were approved by FDA for the treatment of pediatric B-cell leukemia and refractory B-cell lymphoma
Rheumatoid factor: a novel determiner in cancer history
The possible interplay between autoimmunity and cancer is a topic that still needs to be deeply explored. Rheumatoid factors are autoantibodies that are able to bind the constant regions (Fc) of immunoglobulins class G (IgGs). In physiological conditions, their production is a transient event aimed at contributing to the elimination of pathogens as well as limiting a redundant immune response by facilitating the clearance of antibodies and immune complexes. Their production can become persistent in case of different chronic infections or diseases, being for instance a fundamental marker for the diagnosis and prognosis of rheumatoid arthritis. Their presence is also associated with aging. Some studies highlighted how elevated levels of rheumatoid factors (RFs) in the blood of patients are correlated with an increased cancer risk, tumor recurrence, and load and with a reduced response to anti-tumor immunotherapies. In line with their physiological roles, RFs showed in different works the ability to impair in vitro anti-cancer immune responses and effector functions, suggesting their potential immunosuppressive activity in the context of tumor immunity. Thus, the aim of this review is to investigate the emerging role of RFs as determiners of cancer faith
Anemia in Cardio-Renal Syndrome: clinical impact and pathophysiologic mechanisms
Anemia is a disease that is often associated with heart failure (HF) and renal
insufficiency (RI). This unfavorable triad of conditions has been called
Cardio-Renal-Anemia Syndrome (CRS). The association of HF, RI, and anemia is
poorly reported in multicenter clinical trials, so the pathophysiologic
mechanisms and treatment options need to be better defined. When CRS patients
develop anemia, a "perfect storm" often occurs: HF and RI cause anemia which will
worsen the first two conditions. Anemia appears to be the result of complex
interactions between cardiac performance, bone marrow homeostasis, renal
dysfunction, and various drug side effects. However, neurohormonal and
inflammatory activities play a key role in the beginning and progression of the
disease. As a consequence, endogenous erythropoietin activity dysfunction with
inadequate production and tissue resistance occurs. Despite the advances of
therapy in the neurohormonal activation blockade, mortality and hospitalization
in HF still remain unacceptably high, suggesting that specific comorbidity
treatments could have a significant positive prognostic impact. Anemia should be
recognized as one of the novel targets in HF treatmen
An overview of carbohydrate-based carbonic anhydrase inhibitors
Carbonic anhydrases (CAs) are metalloenzymes responsible for the reversible hydration of carbon dioxide to bicarbonate, a fundamental reaction involved in various physiological and pathological processes. In the last decades, CAs have been considered as important drug targets for different pathologies such as glaucoma, epilepsy and cancer. The design of potent and selective inhibitors has been an outstanding goal leading to the discovery of new drugs. Among the different strategies developed to date, the design of carbohydrate-based CA inhibitors (CAIs) has emerged as a versatile tool in order to selectively target CAs. The insertion of a glycosyl moiety as a hydrophilic tail in sulfonamide, sulfenamide, sulfamate or coumarin scaffolds allowed the discovery of many different series of sugar-based CAIs, with relevant inhibitory results. This review will focus on carbohydrate-based CAIs developed so far, classifying them in glycosidic and glycoconjugated inhibitors based on the conjugation chemistry adopted
Natriuretic peptides and NGAL in heart failure: does a link exist?
In recent years there has been growing interest in the development of new
diagnostic tools and particularly in laboratory tests for the identification of
heart failure (HF) patients. Because of the rise in HF occurrence, it is
necessary to use simple and reliable method to recognize those patients at risk
before the onset of the clinical symptoms. To date HF diagnosis remains
difficult: its symptoms and signs are often non specific as well as being poor
sensitive indicators for HF severity. Throughout the last 10 years published
literature has highlighted a boom in the use of biomarkers for HF. Both B-type
and N-terminal pro-B-type natriuretic peptides have demonstrated specific role in
heart failure diagnosis, as well as risk assessment. A single determination of
BNP at any time during the development of chronic heart failure (CHF) provides a
clinically useful tool to establish the outcome. Renal dysfunction is often
associated with heart failure and predicts adverse clinical outcomes. Many
studies have recently suggested the clinical use of serum neutrophil
gelatinase-associated lipocalin (NGAL) levels in patients admitted to the
hospital for acute HF can be used to estimate the risk of early worsening renal
function. This could be potentially applied in clinical practice for early
identification of renal dysfunction development in patients with HF. NGAL levels
appear also to predict renal dysfunction in patients with chronic HF and
preserved renal function. For all these reasons, BNP and NGAL are two emerging
tools useful for diagnosis and prognosis in HF. The combination of two laboratory
biomarkers could potentially identify patients with more elevated risks of both
cardiac hemodynamic impairment and kidney dysfunction
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