Asymptomatic stage I sarcoidosis complicated by pulmonary tuberculosis: a case report

<p>Abstract</p> <p>Introduction</p> <p>Sarcoidosis is a multisystem granulomatous disorder characterized pathologically by the presence of non-caseating granulomas in involved tissues. Depressed cellular immunity predisposes patients to infections with certain intracellular organisms, mostly fungi, <it>Mycobacterium tuberculosis </it>and <it>Nocardia </it>species. As these infections are mainly insidious and difficult to differentiate from the underlying disease, a possible misdiagnosis may lead to fatal complications for the patient.</p> <p>Case presentation</p> <p>We present a case of a 67-year-old woman with undiagnosed asymptomatic stage I sarcoidosis for at least 8 years before her admission and a 1-month history of fever, exertional dyspnea and dry cough, in whom pulmonary tuberculosis was documented.</p> <p>Conclusion</p> <p>This case highlights the need for great vigilance among physicians in order to rule out any possible infection before establishing the diagnosis of sarcoidosis.</p

In vitro and in vivo analysis of RTK inhibitor efficacy and identification of its novel targets in glioblastomas

Treatment for glioblastoma consists of radiotherapy and temozolomide-based chemotherapy. However, virtually all patients recur, leading to a fatal outcome. Receptor tyrosine kinase (RTK)-targeted therapy has been the focus of attention in novel treatment options for these patients. Here, we compared the efficacy of imatinib, sunitinib, and cediranib in glioblastoma models. In the present work, the biologic effect of the drugs was screened by viability, cell cycle, apoptosis, migration, and invasion in vitro assays or in vivo by chick chorioallantoic membrane assay. Intracellular signaling was assessed by Western blot and the RTK targets were identified using phospho-RTK arrays. The amplified status of KIT, PDGFRA, and VEGFR2 genes was assessed by quantitative polymerase chain reaction. In a panel of 10 glioblastoma cell lines, we showed that cediranib was the most potent. In addition, cediranib and sunitinib synergistically sensitize the cells to temozolomide. Cediranib efficacy was shown to associate with higher cytostatic and unique cytotoxic effects in vitro and both antitumoral and antiangiogenic activity in vivo, which could associate with its great capacity to inhibit mitogen-activated protein kinase (MAPK) and AKT pathways. The molecular status of KIT, PDGFRA, and VEGFR2 did not predict glioblastoma cell responsiveness to any of the RTK inhibitors. Importantly, phospho-RTK arrays revealed novel targets for cediranib and sunitinib therapy. In conclusion, the novel targets found may be of value as future biomarkers for therapy response in glioblastoma and lead to the rational selection of patients for effective molecular targeted treatment.This work was funded by Fundacao para a Ciencia e Tecnologia (FCT, Portugal; Project PTDC/SAU-TOX/114549/2009) and by Pfizer/Sociedade de Ciencias Medicas de Lisboa with the award "Research in Oncology Diseases, Prof. Francisco Gentil." Olga Martinho is a recipient of a PhD fellowship (SFRH/BD/36463/2007), and Vera Miranda-Goncalves is a recipient of a research fellowship (SFRH/BI/33503/2008), both from FCT. Andre Lopes Carvalho has a Brazilian National Council for Scientific and Technological Development Scholarship (CNPq, 313181/2009-8)

Response to sunitinib in combination with proton beam radiation in a patient with chondrosarcoma: a case report

<p>Abstract</p> <p>Introduction</p> <p>Chondrosarcoma is well-known to be primarily resistant to conventional radiation and chemotherapy.</p> <p>Case presentation</p> <p>We present the case of a 32-year-old Caucasian man with clear cell chondrosarcoma who presented with symptomatic recurrence in his pelvis and metastases to his skull and lungs. Our patient underwent systemic therapy with sunitinib and then consolidation with proton beam radiation to his symptomatic site. He achieved complete symptomatic relief with a significantly improved performance status and had an almost complete and durable metabolic response on fluorine-18-fluorodeoxyglucose positron emission tomography.</p> <p>Conclusions</p> <p>Our findings have important clinical implications and suggest novel clinical trials for this difficult to treat disease.</p

Breakfast habits and differences regarding abdominal obesity in a cross-sectional study in Spanish adults: The ANIBES study

Background: Previous studies have indicated that breakfast has a protective effect against obesity. The aim of this study was to describe the breakfast habits of the Spanish adult population and to assess the possible association between breakfast frequency and the presence of abdominal obesity, in a cross-sectional analysis of the ANIBES Study. Methods: A representative sample of 1655 Spanish adults (aged 39±12 y; (mean±sd)) from the ANIBES Study was investigated. The final field work was carried out from mid-September to November (three months) 2013. Collected data included a dietary data collected by a 3-days food record, and health, socioeconomic, physical activity and anthropometric (weight, height and waist circumference) data. Abdominal obesity was defined as having a waist-to-height ratio ≥0.5. The adults were also classified into three groups based on the number of days they ate breakfast (never (0/3 days), sometimes (1-2/3 days) and always (3/3 days)). Logistic regression analyses were used to evaluate the association between breakfast and abdominal obesity. Results: In total, 3.6% of adults skipped breakfast and 14.1% ate breakfast sometimes. Having always breakfast was negatively associated with abdominal obesity [OR = 0.738 (0.558–0.975) p = 0.033]. The odds of abdominal obesity after full adjustment (age, gender, and educational and activity level) were 1.5 times higher for those who skipped breakfast when compared to those who always have breakfast. By correcting the model considered for other variables, the odds among smokers decreased when they have breakfast sometimes [OR = 0.032 (0.003–0.387) p = 0.007] and always [OR = 0.023 (0.002–0.270) p = 0.003] comparing with smokers who skip breakfast. Conclusion: Breakfast frequency could be negatively associated with abdominal obesity, especially among smokers.ANIBES Study was financially supported by Coca Cola Iberia through an agreement with the Spanish Nutrition Foundation (FEN)

Melanoma: A model for testing new agents in combination therapies

Treatment for both early and advanced melanoma has changed little since the introduction of interferon and IL-2 in the early 1990s. Recent data from trials testing targeted agents or immune modulators suggest the promise of new strategies to treat patients with advanced melanoma. These include a new generation of B-RAF inhibitors with greater selectivity for the mutant protein, c-Kit inhibitors, anti-angiogenesis agents, the immune modulators anti-CTLA4, anti-PD-1, and anti-CD40, and adoptive cellular therapies. The high success rate of mutant B-RAF and c-Kit inhibitors relies on the selection of patients with corresponding mutations. However, although response rates with small molecule inhibitors are high, most are not durable. Moreover, for a large subset of patients, reliable predictive biomarkers especially for immunologic modulators have not yet been identified. Progress may also depend on identifying additional molecular targets, which in turn depends upon a better understanding of the mechanisms leading to response or resistance. More challenging but equally important will be understanding how to optimize the treatment of individual patients using these active agents sequentially or in combination with each other, with other experimental treatment, or with traditional anticancer modalities such as chemotherapy, radiation, or surgery. Compared to the standard approach of developing new single agents for licensing in advanced disease, the identification and validation of patient specific and multi-modality treatments will require increased involvement by several stakeholders in designing trials aimed at identifying, even in early stages of drug development, the most effective way to use molecularly guided approaches to treat tumors as they evolve over time

Deep sequencing of gastric carcinoma reveals somatic mutations relevant to personalized medicine

<p>Abstract</p> <p>Background</p> <p>Globally, gastric cancer is the second most common cause of cancer-related death, with the majority of the health burden borne by economically less-developed countries.</p> <p>Methods</p> <p>Here, we report a genetic characterization of 50 gastric adenocarcinoma samples, using affymetrix SNP arrays and Illumina mRNA expression arrays as well as Illumina sequencing of the coding regions of 384 genes belonging to various pathways known to be altered in other cancers.</p> <p>Results</p> <p>Genetic alterations were observed in the WNT, Hedgehog, cell cycle, DNA damage and epithelial-to-mesenchymal-transition pathways.</p> <p>Conclusions</p> <p>The data suggests targeted therapies approved or in clinical development for gastric carcinoma would be of benefit to ~22% of the patients studied. In addition, the novel mutations detected here, are likely to influence clinical response and suggest new targets for drug discovery.</p

Chemical Biology Drug Sensitivity Screen Identifies Sunitinib as Synergistic Agent with Disulfiram in Prostate Cancer Cells

Peer reviewe

Prevalence of chlamydia pneumoniae in greek patients with acute exacerbation of chronic obstructive pulmonary disease

Η οξεία λοίμωξη από C. pneumoniae έχει ενοχοποιηθεί ως αιτιολογικός παράγοντας στα επεισόδια παροξύνσεων της ΧΑΠ. Παράλληλα αντικείμενο έρευνας αποτελεί η πιθανή σχέση της χρόνιας λοίμωξης από C. pneumoniae με την εξέλιξη της ΧΑΠ. Στη παρούσα εργασία μελετηθήκαν 150 ασθενείς με παρόξυνση ΧΑΠ (128 άνδρες, μέση ηλικία 70.3±10.4 έτη, μέση τιμή FEV1 41.6±15.8 % της προβλεπόμενης τιμής) κατά την περίοδο Σεπτέμβριος του 2004-Σεπτέμβριος του 2008. Από όλους τους ασθενείς λήφθηκε δείγμα αίματος 5 ml κατά την εισαγωγή τους (δείγμα οξείας φάσεως) και 30 μέρες μετά από αυτή (δείγμα αναρρώσεως). Σε όλους τους ασθενείς υπολογίστηκε η παρουσία αντισωμάτων κατά των C. pneumoniae με τη μέθοδο του MIF και την ανοσοενζυμική μέθοδο ELISA. Υπολογίστηκε ο επιπολασμός της οξείας, παλαιάς και χρόνιας λοίμωξης από C. pneumoniae με τη μέθοδο του MIF. Παράλληλα εκτιμήθηκε ο επιπολασμός της οξείας και παλαιάς λοίμωξης από C. pneumoniae με την ELISA. Δείγμα αίματος 5 ml λήφθηκε από 100 υγιείς μάρτυρες (ομάδα ελέγχου) κατά την ίδια χρονική περίοδο και υπολογίστηκε η παρουσία αντισωμάτων κατά των C. pneumoniae με την μέθοδο του MIF. Εκτιμήθηκε το ποσοστό της παλαιάς και χρόνιας λοίμωξης από C. pneumoniae στην ομάδα ελέγχου. Σε 12 ασθενείς (8%) διαγνώστηκε οξεία λοίμωξη από C. pneumoniae. Σε 9 ασθενείς (6%) έγινε διάγνωση οξείας λοίμωξης από C. pneumoniae και με τις δύο ορολογικές μεθόδους. Σε τρεις ασθενείς (25%) με οξεία λοίμωξη από C. pneumoniae απομονώθηκε μικροβιακό παθογόνο στις καλλιέργειες πτυέλων. Χρησιμοποιώντας την μέθοδο του MIF ως μέθοδο αναφοράς η ευαισθησία, ειδικότητα, θετική και αρνητική διαγνωστική αξία της ELISA για την διάγνωση οξείας λοίμωξης από C. pneumoniae ήταν 81.8%, 99%, 90% και 98.6% αντίστοιχα. Ογδονταέξι ασθενείς (62.3%) και 24 υγιείς μάρτυρες (24%) είχαν ορολογικά ευρήματα παλαιάς λοίμωξης από C. pneumoniae με τη μέθοδο του MIF (p=0.00). Με βάση τα αποτελέσματα της ELISA 50 ασθενείς (36.2%) πληρούσαν τα ορολογικά κριτήρια για παλαιά λοίμωξη από C. pneumoniae σε σχέση με 86 ασθενείς (62.3%) που ήταν οροθετικοί με τον MIF (p=0.00). Χρησιμοποιώντας την μέθοδο του MIF ως μέθοδο αναφοράς η ευαισθησία, ειδικότητα, θετική και αρνητική διαγνωστική αξία της ELISA για την διάγνωση της παλαιάς λοίμωξης από C. pneumoniae στην ομάδα των ασθενών με ΧΑΠ ήταν 53.5%, 90.4%, 90.2% και 54% αντίστοιχα. Τριανταέξι ασθενείς (26%) και πέντε υγιείς μάρτυρες (5%) είχαν ορολογικά ευρήματα χρόνιας λοίμωξης από C. pneumoniae (p=0.00). Όταν οι ασθενείς χωρίστηκαν σε τρεις ομάδες έτσι ώστε να διερευνηθεί η πιθανή συσχέτιση της χρόνιας λοίμωξης από C. pneumoniae με τη βαρύτητα της νόσου (FEV1 ? 50%, 30% £ FEV1 <50% και FEV1 < 30%), παρουσιάστηκε στατιστικά σημαντική συσχέτιση μεταξύ των δύο αυτών παραμέτρων (p=0.01). Τα C. pneumoniae αποτελούν ένα λοιμώδη παράγοντα ο οποίος παρουσιάζει μικρή συσχέτιση με τα επεισόδια παροξύνσεων των Ελλήνων ασθενών με ΧΑΠ. Η οξεία λοίμωξη από C. pneumoniae μπορεί να συνυπάρχει με λοιμώξεις από άλλα μικροβιακά παθογόνα. Η ανοσοενζυμική μέθοδος ELISA που χρησιμοποιήθηκε στην παρούσα μελέτη παρουσίασε αξιόλογα αποτελέσματα σε σχέση με τον MIF όσον αφορά τη διάγνωση της οξείας λοίμωξης από C. pneumoniae αλλά όχι της παλαιάς λοίμωξης. Τόσο η παλαιά όσο και η χρόνια λοίμωξη από C. pneumoniae ήταν πιο συχνές σε στατιστικά σημαντικό βαθμό στην ομάδα των ασθενών με ΧΑΠ σε σύγκριση με την ομάδα ελέγχου, κάτι το οποίο πιθανότατα οφείλεται στη διαταραχή των προστατευτικών μηχανισμών άμυνας των ασθενών αυτών όσον αφορά λοιμώξεις του αναπνευστικού συστήματος. Το γεγονός ότι η χρόνια λοίμωξη από C. pneumoniae ήταν πιο συχνή στους ασθενείς με βαρύτερη νόσο αποτελεί ένα εύρημα το οποίo χρήζει περαιτέρω διερεύνησης για τον πιθανό ρόλο της χρόνιας λοίμωξης από αυτό το παθογόνο στην εξέλιξη της ΧΑΠ