HPV-pozytywny rak jamy ustnej - etiologia i czynniki ryzyka.

HPV oral infection is one of a etiological risk factors of oral and pharyngeal squamous cell carcinoma development. HPV-positive OSCC seems to have better prognostics and to be more susceptible to treatment than cancer with major a etiological factors being alcohol or tobacco. Therefore, qualifying a patient to an appropriate OSCC group is vital. The aim of this work is to present HPV infection risk factors, as well as the implications of such infection. This should facilitate creating awareness in this matter among the patients.Zakażenie wirusem HPV w jamie ustnej jest jednym z czynników etiologicznych rozwoju raka płaskonabłonkowego jamy ustnej (OSCC) oraz gardła środkowego. HPV (+) OSCC związany z obecnością zakażenia wirusem HPV w jamie ustnej wydaje się wiązać z lepszym rokowaniem i odpowiedzią na leczenie niż rak, którego głównymi czynnikami etiologicznymi są alkohol czy tytoń. Dlatego też bardzo istotna jest kwalifikacja pacjenta do odpowiedniej grupy. Celem tej pracy jest przedstawienie czynników ryzyka infekcji wirusem HPV oraz implikacji, jakie niesie ze sobą zakażenie. Wiedza ta ułatwi lekarzom zwiększanie świadomości pacjentów

Antecedent Hyperglycemia Is Associated With an Increased Risk of Neutropenic Infections During Bone Marrow Transplantation

OBJECTIVE—To use bone marrow transplantation (BMT) as a model for testing the association between hyperglycemia and infection

Purinergic signalling and immune cells

This review article provides a historical perspective on the role of purinergic signalling in the regulation of various subsets of immune cells from early discoveries to current understanding. It is now recognised that adenosine 5'-triphosphate (ATP) and other nucleotides are released from cells following stress or injury. They can act on virtually all subsets of immune cells through a spectrum of P2X ligand-gated ion channels and G protein-coupled P2Y receptors. Furthermore, ATP is rapidly degraded into adenosine by ectonucleotidases such as CD39 and CD73, and adenosine exerts additional regulatory effects through its own receptors. The resulting effect ranges from stimulation to tolerance depending on the amount and time courses of nucleotides released, and the balance between ATP and adenosine. This review identifies the various receptors involved in the different subsets of immune cells and their effects on the function of these cells

Purinergic signalling in B cells

Adenosine and adenosine triphosphate are involved in purinergic signaling which plays an important role in control of the immune system. Much data have been obtained regarding impact of purinergic signaling on dendritic cells, macrophages, monocytes and T lymphocytes, however less attention has been paid to purinergic regulation of B cells. This review summarizes present knowledge on ATP- and Ado-dependent signaling in B lymphocytes. Human B cells have been shown to express A1-AR, A2A-AR, A2B-AR and A3-AR and each subtype of P2 receptors. Surface of B cells exhibits two antagonistic ectoenzymatic pathways, one relies on constitutive secretion and resynthesis of ATP, while the second one depends on degradation of adenosine nucleotides to nucleosides and their subsequent degradation. Inactivated B cells remain under the suppressive impact of autocrine and paracrine Ado, whereas activated B lymphocytes increase ATP release and production. ATP protects B cells from Ado-induced suppression and exerts pro-inflammatory effect on the target tissues, and it is also involved in the IgM release. On the other hand, Ado synthesis is necessary for optimal development, implantation and maintenance of the plasmocyte population in bone marrow in the course of the primary immune response. Moreover, Ado plays an important role in immunoglobulin class switching, which is a key mechanism of humoral immune response. Disruption of purinergic signaling leads to severe disorders. Impairment of Ado metabolism is one of the factors responsible for common variable immunodeficiency. There are several lines of evidence that dysfunction of the immune system observed during diabetes may in part depend on disrupted ATP and Ado metabolism in the B cells

Purinergic signaling in B cells

Adenosine and adenosine triphosphate are involved in purinergic signaling which plays an important role in control of the immune system. Much data have been obtained regarding impact of purinergic signaling on dendritic cells, macrophages, monocytes and T lymphocytes, however less attention has been paid to purinergic regulation of B cells. This review summarizes present knowledge on ATP- and Ado-dependent signaling in B lymphocytes. Human B cells have been shown to express A1-AR, A2A-AR, A2B-AR and A3-AR and each subtype of P2 receptors. Surface of B cells exhibits two antagonistic ectoenzymatic pathways, one relies on constitutive secretion and resynthesis of ATP, while the second one depends on degradation of adenosine nucleotides to nucleosides and their subsequent degradation. Inactivated B cells remain under the suppressive impact of autocrine and paracrine Ado, whereas activated B lymphocytes increase ATP release and production. ATP protects B cells from Ado-induced suppression and exerts pro-inflammatory effect on the target tissues, and it is also involved in the IgM release. On the other hand, Ado synthesis is necessary for optimal development, implantation and maintenance of the plasmocyte population in bone marrow in the course of the primary immune response. Moreover, Ado plays an important role in immunoglobulin class switching, which is a key mechanism of humoral immune response. Disruption of purinergic signaling leads to severe disorders. Impairment of Ado metabolism is one of the factors responsible for common variable immunodeficiency. There are several lines of evidence that dysfunction of the immune system observed during diabetes may in part depend on disrupted ATP and Ado metabolism in the B cells

Overexpression of ID1 reverses the repression of human dental pulp stem cells differentiation induced by TWIST1 silencing

Multiple studies showed that the cessation of TWIST1 expression is the prerequisite for osteoblasts' maturation. However, recent reports revealed that the function of TWIST1 is different in the dental pulp stem cells (DPSCs), where a high level of TWIST1 expression promoted DPSCs' differentiation. The aim of the study was to investigate the impact of TWIST1 and ID1 on the differentiation process in the human DPSCs. Methods: TWIST1 and ID1 expression in the DSPCs was modulated by lentivirus transduction. Genes expression was assessed with qRT-PCR. The proteins level was evaluated by Western blot. The DPSCs differentiation was assessed with the proliferation, alkaline phosphatase (ALP) activity, and calcium concentration assays. Results: TWIST1 silencing suppressed the expression of ID1 and both the early and late markers of odontoblasts' differentiation detected at the transcript and protein level. The forced overexpression of ID1 increased the expression of the late markers of odontoblasts differentiation but diminished the expression of the early markers. DPCSs with the silenced TWIST1 and subsequent ID1 overexpression displayed an increase in the expression of the late markers of odontoblasts differentiation. Cells with silenced TWIST1 and overexpressing ID1 had increased activity of ALP, higher calcium concentration and decreased proliferation rate. The high level of ID1 expression might be a critical factor stimulating DPSCs differentiation and it might compensate the repressed differentiation of DPSCs caused by TWIST1 silencing. Conclusion: The mutual correlation between the expression level of TWIST1 and ID1 might be a critical factor driving the process of the human odontoblasts' differentiation

Overexpression of ID1 reverses the repression of human dental pulp stem cells differentiation induced by TWIST1 silencing

Multiple studies showed that the cessation of TWIST1 expression is the prerequisite for osteoblasts' maturation. However, recent reports revealed that the function of TWIST1 is different in the dental pulp stem cells (DPSCs), where a high level of TWIST1 expression promoted DPSCs' differentiation. The aim of the study was to investigate the impact of TWIST1 and ID1 on the differentiation process in the human DPSCs. Methods: TWIST1 and ID1 expression in the DSPCs was modulated by lentivirus transduction. Genes expression was assessed with qRT-PCR. The proteins level was evaluated by Western blot. The DPSCs differentiation was assessed with the proliferation, alkaline phosphatase (ALP) activity, and calcium concentration assays. Results: TWIST1 silencing suppressed the expression of ID1 and both the early and late markers of odontoblasts' differentiation detected at the transcript and protein level. The forced overexpression of ID1 increased the expression of the late markers of odontoblasts differentiation but diminished the expression of the early markers. DPCSs with the silenced TWIST1 and subsequent ID1 overexpression displayed an increase in the expression of the late markers of odontoblasts differentiation. Cells with silenced TWIST1 and overexpressing ID1 had increased activity of ALP, higher calcium concentration and decreased proliferation rate. The high level of ID1 expression might be a critical factor stimulating DPSCs differentiation and it might compensate the repressed differentiation of DPSCs caused by TWIST1 silencing. Conclusion: The mutual correlation between the expression level of TWIST1 and ID1 might be a critical factor driving the process of the human odontoblasts' differentiation

The Level of TWIST1 expression determines the response of colon cancer cells to mitogen-activated protein kinases inhibitors

Background/Aim: Currently, it has been proposed that combination of 5-fluorouracil (5FU) with inhibitors of the mitogen-activated protein kinases (MAPKs) signaling pathway might enhance the efficacy of 5FU-based chemotherapy in colon cancer. Our study aimed to investigate an impact of TWIST1 silencing on the sensitivity of cancer cells to 5FU and selected MAPK inhibitors. Materials and Methods: The suppression of TWIST1 expression in human colon cancer HT29 and HCT116 cell lines was achieved by transduction with lentiviral vector carrying the TWIST1 silencing sequence (pLL3.7-sh TWIST1). The statistical calculation was performed with analysis of variance or Dunnett's test for comparison to control group. Paired Student's t-test was performed when two groups were analyzed. Results: Suppression of TWIST1 reduced the proliferation rate of colon cancer cells and enhanced their sensitivity to 5FU and MAPKs inhibitors. The sensitivity of HT29 cells to examined compounds was more dependent on TWIST1 expression level compared to HCT116 cells. The most noticeable effect of TWIST1 suppression on sensitivity of both colon cancer cell lines to combined treatment of 5FU and the MAPKs inhibitors was observed for inhibitors of p38α/β and JNK1-3. We also noted that the suppression of TWIST1 significantly sensitized both cell lines to combined treatment of 5FU and Rac inhibitor. Conclusions: Our observations point to TWIST1 expression level as a marker of colon cancer sensitivity to combined treatment of 5FU and MAPKs inhibitors