Pannexin-1 channels promote CD8+ T cell effector and memory responses through distinct intracellular pathways.

Sensing of extracellular metabolites controls CD8+ T cell function. Their accumulation can occur through export by specialized molecules, such as the release channel Pannexin-1 (Panx1). Whether Panx1 controls CD8+ T cell immune responses to antigen, however, has not been previously addressed. Here, we report that T cell-specific Panx1 is needed for CD8+ T cell responses to viral infections and cancer. We found that CD8-specific Panx1 favors memory CD8+ T cell survival primarily through ATP export and induction of mitochondrial metabolism. CD8-specific Panx1 is also crucial for the effector expansion of CD8+ T cells, however this regulation occurs independently of eATP. Instead, our results suggest a connection between Panx1-induced extracellular lactate accumulation and the complete activation of effector CD8+ T cells. In summary, Panx1 regulates effector and memory CD8+ T cells through export of distinct metabolites and by engaging different metabolic and signaling pathways.

P2RX7 Enhances Tumor Control by CD8+ T Cells in Adoptive Cell Therapy.

Expression of the purinergic receptor P2RX7 by CD8+ T cells promotes the generation of memory populations following acute infections. However, data suggest that P2RX7 may limit the efficacy of antitumor responses. Herein, we show that P2RX7 is beneficial for optimal melanoma control in a mouse CD8+ T-cell adoptive transfer model. Tumor-specific P2rx7-/- CD8+ T cells exhibited impaired mitochondrial maintenance and function but did not display signs of overt exhaustion early in the antitumor response. However, as the tumor burden increased, the relative frequency of P2RX7-deficient CD8+ T cells declined within the tumor; this correlated with reduced proliferation, increased apoptosis, and mitochondrial dysfunction. Extending these studies, we found that the transient in vitro stimulation of P2RX7 using the ATP analogue BzATP led to enhanced B16 melanoma control by CD8+ T cells. These findings are in keeping with the concept that extracellular ATP (eATP) sensing by P2RX7 on CD8+ T cells is required for their ability to efficiently eliminate tumors by promoting mitochondrial fitness and underscore the potential for P2RX7 stimulation as a novel therapeutic treatment to enhance tumor immunotherapy.

68Ga-Prostate-specific membrane antigen (PSMA) positron emission tomography (pet) in prostate cancer: a systematic review and meta-analysis

ABSTRACT Introduction: Prostate cancer (PC) is the second most commonly diagnosed cancer in males. 68Ga-PSMA PET/CT, a non-invasive diagnostic tool to evaluate PC with prostate-specific membrane antigen (PSMA) expression, has emerged as a more accurate alternative to assess disease staging. We aimed to identify predictors of positive 68Ga-PSMA PET and the accuracy of this technique. Materials and methods: Diagnostic accuracy cross-sectional study with prospective and retrospective approaches. We performed a comprehensive literature search on PubMed, Cochrane Library, and Embase database in search of studies including PC patients submitted to radical prostatectomy or radiotherapy with curative intent and presented biochemical recurrence following ASTRO 1996 criteria. A total of 35 studies involving 3910 patients submitted to 68-Ga-PSMA PET were included and independently assessed by two authors: 8 studies on diagnosis, four on staging, and 23 studies on restaging purposes. The significance level was α=0.05. Results: pooled sensitivity and specificity were 0.90 (0.86-0.93) and 0.90 (0.82-0.96), respectively, for diagnostic purposes; as for staging, pooled sensitivity and specificity were 0.93 (0.86-0.98) and 0.96 (0.92-0.99), respectively. In the restaging scenario, pooled sensitivity and specificity were 0.76 (0.74-0.78) and 0.45 (0.27-0.58), respectively, considering the identification of prostate cancer in each described situation. We also obtained specificity and sensitivity results for PSA subdivisions. Conclusion: 68Ga-PSMA PET provides higher sensitivity and specificity than traditional imaging for prostate cancer.

Influência de substâncias irrigadoras endodônticas na microdureza da dentina radicular: revisão integrativa / Influence of endodontic irrigation substances on the microdurity of the radicular dentin: integrative review

As soluções de irrigação são essenciais como auxiliares na limpeza e desinfecção do sistema de canais radiculares (SCR). Entretanto, essas substâncias químicas podem gerar alterações na composição da dentina. Assim, o presente estudo teve como objetivo avaliar, por meio de uma revisão integrativa, os efeitos do hipoclorito de sódio (NaOCl) a 1%; 2,5%; 3%; 5%; 5,25%; 6% e 17%; digluconato de clorexidina (CHX) a 2% e EDTA 2,5%; 5%; 15% e 17% sobre a microdureza da dentina do canal radicular após sua utilização como solução irrigadora. Foi realizada uma revisão integrativa nas bases de dados: PubMed, Cochrane e Lilacs, utilizando-se os seguintes descritores em inglês: "irrigating solutions"; "chelaling agentes"; "dentin microhardness"; "EDTA"; "sodium hypochlorite"; "chlorhexidine gluconate". Foi utilizado o conector "and" associando dentin microhardness aos outros descritores. Critérios de inclusão: Artigos científicos na área da odontologia, escritos em inglês e português que aborda o tema "As soluções de hipoclorito de sódio (NaOCl), digluconato de clorexidina (CHX) e EDTA influenciam na microdureza da dentina radicular?''. Critérios de exclusão: artigos repetidos em mais de uma base de dados, livros, teses de doutorado, dissertações de mestrado, resumos e trabalhos publicados em congresso. Fortes evidências indicam que o hipoclorito de sódio, digluconato de clorexidina e EDTA influenciam na microdureza da dentina radicular, quando utilizadas como solução irrigadora durante o tratamento endodôntico... (AU)

Irrigation solutions are essential as an aid in cleaning and disinfecting the root canal system (SCR). However, these chemicals can cause changes in the composition of dentin. Thus, the present study aimed to evaluate, through an integrative review, the effects of 1% sodium hypochlorite (NaOCl); 2.5%; 3%; 5%; 5.25%; 6% and 17%; 2% chlorhexidine digluconate (CHX) and 2.5% EDTA; 5%; 15% and 17% on the microhardness of root canal dentin after its use as an irrigating solution. An integrative review was carried out in the databases: PubMed, Cochrane and Lilacs, using the following descriptors in English: "irrigating solutions"; "chelaling agents"; "dentin microhardness"; "EDTA"; "sodium hypochlorite"; "chlorhexidine gluconate". The "and" connector was used, associating dentin microhardness with other descriptors. Inclusion criteria: Scientific articles in the field of dentistry, written in English and Portuguese that address the topic "Do solutions of sodium hypochlorite (NaOCl), chlorhexidine gluconate (CHX) and EDTA influence the microhardness of root dentin?". Exclusion criteria: articles repeated in more than one database, books, doctoral theses, master's dissertations, abstracts and papers published in congress. Strong evidence indicates that sodium hypochlorite, chlorhexidine gluconate and EDTA influence the microhardness of root dentin when used as an irrigating solution during endodontic treatment... (AU)

68Ga-Prostate-specific membrane antigen (psma) positron emission tomography (pet) in prostate cancer: a systematic review and meta-analysis.

INTRODUCTION: Prostate cancer (PC) is the second most commonly diagnosed cancer in males. 68Ga-PSMA PET/CT, a non-invasive diagnostic tool to evaluate PC with prostate-specific membrane antigen (PSMA) expression, has emerged as a more accurate alternative to assess disease staging. We aimed to identify predictors of positive 68Ga-PSMA PET and the accuracy of this technique. MATERIALS AND METHODS: Diagnostic accuracy cross-sectional study with prospective and retrospective approaches. We performed a comprehensive literature search on PubMed, Cochrane Library, and Embase database in search of studies including PC patients submitted to radical prostatectomy or radiotherapy with curative intent and presented biochemical recurrence following ASTRO 1996 criteria. A total of 35 studies involving 3910 patients submitted to 68-Ga-PSMA PET were included and independently assessed by two authors: 8 studies on diagnosis, four on staging, and 23 studies on restaging purposes. The significance level was α=0.05. RESULTS: pooled sensitivity and specificity were 0.90 (0.86-0.93) and 0.90 (0.82-0.96), respectively, for diagnostic purposes; as for staging, pooled sensitivity and specificity were 0.93 (0.86-0.98) and 0.96 (0.92-0.99), respectively. In the restaging scenario, pooled sensitivity and specificity were 0.76 (0.74-0.78) and 0.45 (0.27-0.58), respectively, considering the identification of prostate cancer in each described situation. We also obtained specificity and sensitivity results for PSA subdivisions. CONCLUSION: 68Ga-PSMA PET provides higher sensitivity and specificity than traditional imaging for prostate cancer.

Can positron emission mammography help to identify clinically significant breast cancer in women with suspicious calcifications on mammography?

OBJECTIVE: To evaluate the diagnostic accuracy of positron emission mammography (PEM) for identifying malignant lesions in patients with suspicious microcalcifications detected on mammography. METHODS: A prospective, single-centre study that evaluated 40 patients with suspicious calcifications at mammography and indication for percutaneous or surgical biopsy, with mean age of 56.4 years (range: 28-81 years). Patients who agreed to participate in the study underwent PEM with 18F-fluorodeoxyglucose before the final histological evaluation. PEM findings were compared with mammography and histological findings. RESULTS: Most calcifications (n = 34; 85.0 %) were classified as BIRADS 4. On histology, there were 25 (62.5 %) benign and 15 (37.5 %) malignant lesions, including 11 (27.5 %) ductal carcinoma in situ (DCIS) and 4 (10 %) invasive carcinomas. On subjective analysis, PEM was positive in 15 cases (37.5 %) and most of these cases (n = 14; 93.3 %) were confirmed as malignant on histology. There was one false-positive result, which corresponded to a fibroadenoma, and one false negative, which corresponded to an intermediate-grade DCIS. PEM had a sensitivity of 93.3 %, specificity of 96.0 % and accuracy of 95 %. CONCLUSION: PEM was able to identify all invasive carcinomas and high-grade DCIS (nuclear grade 3) in the presented sample, suggesting that this method may be useful for further evaluation of patients with suspected microcalcifications. KEY POINTS: • Many patients with suspicious microcalcifications at mammography have benign results at biopsy. • PEM may help to identify invasive carcinomas and high-grade DCIS. • Management of patients with suspicious calcifications can be improved.