1,721,137 research outputs found
C and CX3C chemokines: Cell sources and physiopathological implications
No full textWithin the fascinating world of chemokines, C and CX3C chemokines have long been regarded as two minor components, even though they present unique features and show less redundancy than the other chemokine families. Nevertheless, the body of data on their expression and role in various inflammatory disorders has grown in the past few years. The C chemokine family is represented by two chemokines, XCL1/lymphotactin-alpha and XCL2/lymphotactin-beta, whereas the CX3C chemokine family contains only one member, called CX3CL1/ fractalkine. In this review, we present an overview on the structure, expression and signaling properties of these chemokines and their respective receptors and examine how they contribute to inflammation and the regulation of leukocyte trafficking, as well as their potential role in the pathophysiology of human inflammatory diseases. Taken together, these data expand the biological importance of C and CX3C chemokines from that of simple immune modulators to a much broader biological role, even though their precise commitment within the framework of immune responses has still to be determined
The Angiogenic Switch: Implications in the Regulation of Tumor Dormancy
No full textAngiogenesis plays an established role in the growth promotion of dormant micrometastasis, because blood vessels deliver oxygen and nutrients into the tumor microenvironment. A discrete event termed "the angiogenic switch" has been recognized as key in promoting the transition towards a clinically aggressive tumor. This concept generally describes a permanent change in the angiogenic capacity of the tumor sustained by genetic events occurring in cancer cells. Recent evidence, however, indicates that a transient angiogenic switch delivered by components of the tumor microenvironment can also convey tumorigenic properties to tumor cells. Why is the angiogenic switch so fundamental in the promotion of tumor growth? In addition to the recognized feeding function of blood vessels, there is accumulating evidence suggesting that endothelial cells - and perhaps other cellular components of the microenvironment - communicate both positive and negative signals to tumor cells. This cross-talk between heterogeneous cell types could turn out to be important in the regulation of cancer cells' behaviour. In this review, we discuss the possible implications of the angiogenic switch on our understanding of the regulation of tumor dormancy
In vitro lymphocyte response to the phytomitogens in untreated and treated patients with Hodgkin's disease.
No full textIn vitro lymphocyte response to phytohemagglutinins (PHA), concavalin A (Con A), and pokeweed mitogen (PW) was evaluated in untreated and treated patients with Hodgkin's disease (HD). The responding capacity to PHA was depressed, though not constantly, in the untreated patients compared with the response to lymphocytes from normal individuals. The depression was more evident, at group level, when the cells were stimulated with suboptimal concentrations of PHA. Radiotherapy constantly induced a strong decrease or a complete loss of the responding capacity of the cells which persisted at low levels for many months. Some years after the initial course of treatment, the response was clearly depressed, but it was better in patients in remission than during relapse. Splenectomy did not affect the responding capacity of the cells. The depressive effect induced by chemotherapy was apparently less marked and persistent than that of radiation. Con A- and PW-induced lymphocyte transformation usually paralleled the PHA-induced response. The depressed response to PHA was not due to an inhibitory activity of HD serum. Washed HD lymphocytes in fetal calf serum were not stimulated better than in autologous plasma, nor were HD sera able to depress the response of normal lymphocytes to PHA, Con A, PW, and PPD. Supernatants from HD lymphocytes cultured for 24 h without any stimulant, and extracts of these cells were also unable to affect the response of normal lymphocytes to PHA
“Il vizio di respirare”: rilevazioneepidemiologica sull’abitudine al fumo tra igiovani
No full textINTRODUZIONE: Dall’indagine ISS-Doxa sul fumo del 2010 emerge che nella fascia d’età dai 15-24 anni il 21.9% dei ragazzi è abituale fumatore. Per ridurre la diffusione del fumo nei soggetti adulti, è indispensabile ridurre il numero delle persone che iniziano a fumare in giovane età.
Secondo i dati della letteratura infatti le persone che non iniziano a fumare durante l’adolescenza, hanno una bassa probabilità di diventare un fumatore regolare in età adulta. Obiettivo dello studio è quello di valutare l’abitudine
al fumo di alunni delle classi medie e superiori ed i fattori che aumentano il rischio di incorrere in questo vizio.METODI: Nel corso dell’anno scolastico 2009-2010, hanno aderito al progetto
“Il vizio di respirare”, per la prevenzione del fumo di sigaretta nei giovani,
9 scuole medie inferiori e 7 istituti superiori della Provincia di Padova ed ha
coinvolto un numero complessivo di 1580 soggetti. E’stato somministrato
un questionario QAT (questionario sugli adolescenti ed il fumo) che mirava
ad indagare le condizioni demografiche, ambientali e sociali che inducono
il giovane ad iniziare a fumare.
RISULTATI: Dalla rilevazione emerge che il 31.1% del campione ha provato
almeno una volta a fumare ed il 16.6% è attualmente fumatore. Se
analizzato il dato per classe frequentata, si osserva che tra i soggetti di
prima media il 5.6% ha provato a fumare ed il 51.7% tra gli studenti di
prima superiore. Inoltre in prima media solo l’1% è attuale fumatore, ma
in prima superiore il 28.9% si dichiara fumatore abituale, tra questi il
53,9% è maschio e il 46.1% è femmina. Gli studenti fumatori delle
superiori dichiarano inoltre di aver iniziato a fumare in media 12.7 mesi
prima. La probabilità di essere fumatore alle superiori è del 3.6% se il
ragazzo non ha tra i migliori amici nessun fumatore, del 21.8% se ha un
amico fumatore, il 32.9% se due amici fumatori, il 61.5% se tre amici
fumatori, l’85.0% se tutti fumano. L’abitudine al fumo non è associata al
ruolo che il ragazzo ritiene di avere nel gruppo di amici o alla forza legame
del ragazzo con il gruppo è invece associato alle dimensioni e alle
caratteristiche del gruppo: maggiore probabilità di essere fumatori si
osserva nei soggetti che frequentano grandi gruppi e più contrari alle
regole. Nei ragazzi fumatori inoltre emerge come sia maggiore la percezione
delle quantità di sigarette fumate dall’insegnate che stimano di più e dai
propri genitori.
CONCLUSIONI: I dati confermano che già all’età di 13-14 anni il 28.9% dei ragazzi inizia ad essere fumatore abituale e che il contesto ambientale influenza il rischio della dipendenza
Ligand-driven activation of the notch pathway in T-ALL and solid tumors: Why Not(ch)?
No full textThe Notch pathway is an evolutionally conserved cell-cell interaction signalling system involved in several key aspects of cell life, ranging from differentiation and proliferation to apoptosis. As such, it plays an important role in development, homeostasis, angiogenesis and various diseases. Over-activation of the Notch pathway has often been reported in cancer, leading to a variety of effects including increased proliferation, protection from apoptosis and maintenance of cancer initiating cells. Additionally, this signalling pathway has also been involved in tumor angiogenesis. The clearest example of oncogenic Notch signalling is observed in T acute lymphoblastic leukemia (T-ALL), an aggressive neoplasm of immature T-cells, due to genetic alterations leading to ligand-independent increased Notch1 receptor signalling. In solid tumors, however, extrinsic regulation through canonical cell-cell interactions appears to drive activation of the pathway. We recently found that triggering of Notch3 signalling by DLL4 expressed on angiogenic endothelial cells promotes escape of T-ALL cells from tumor dormancy in a xenograft model. This observation discloses un unsuspected role for ligand-dependent regulation of Notch receptors in T-ALL cells, suggesting that blocking extrinsic Notch activation by anti-DLL4 or other ligand-targeted drugs could represent a novel therapeutic approach for this aggressive malignancy
DMET? (Drug-Metabolizing Enzymes and Transporters) microarray analysis of colorectal cancer patients with severe 5-fluorouracil-induced toxicity.
No full textPURPOSE: 5-fluorouracil (5-FU) has been widely used since the 1980s, and it remains the backbone of many chemotherapeutic combination regimens. However, its use is often limited by the occurrence of severe toxicity. Although several reports have shown the detrimental effect of some dihydropyrimidine dehydrogenase (DPYD) and thymidylate synthase (TYMS) gene polymorphisms in patients undergoing 5-FU-based treatment, they account for only a minority of toxicities.
METHODS: Looking for new candidate genetic variants associated with 5-FU-induced toxicity, we used the innovative genotyping microarray Affymetrix Drug-Metabolizing Enzymes and Transporters (DMET)TM Plus GeneChip that interrogates 1,936 genetic variants distributed in 231 genes involved in drug metabolism, excretion, and transport. To reduce variability, we analyzed samples from colorectal cancer patients who underwent fairly homogenous treatments (i.e., Machover or Folfox) and experienced G3 or G4 toxicity; control patients were matched for therapy and selected from those who did not disclose toxicity (G0-G1).
RESULTS: Pharmacogenetic genotyping showed no significant difference in DPYD and TYMS genetic variants distribution between cases and controls. However, other polymorphisms could account for 5-FU-induced toxicity, with the CHST1 rs9787901 and GSTM3 rs1799735 having the strongest association.
CONCLUSIONS: Although exploratory, this study suggests that genetic polymorphisms not directly related to 5-FU pharmacokinetics and pharmacodynamics are involved in 5-FU-induced toxicity. Our data also indicates DMETTM microarray as a valid approach to discover new genetic determinants influencing chemotherapy-induced toxicity
Spontaneous Invitro Production of Virus-specific Antibody By Lymphocytes From Hiv-infected Subjects
No full textIn vitro synthesis of IgG directed against HIV components was detected by ELISA and Western blot assay of lymphocyte culture supernatants. Lymphocytes from HIV-infected individuals spontaneously produced antibody against HIV proteins very early in culture, suggesting in vivo activation of HIV-specific antibody-forming cells. The frequency of circulating B cells spontaneously secreting HIV-specific IgG was very high in some cases, but spontaneous HIV-specific antibody synthesis was not accompanied by polyclonal reactivation of B-cell clones of different specificity. The pattern of specificity of the anti-HIV antibody produced in vitro did not reflect the serum pattern consistently. These findings indicate a new approach potentially useful for the study of the immunobiology of HIV infection. The possible implications of the in vitro production of HIV-specific antibody for the diagnosis, prognosis and clinical management of this infection are also discussed
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