A Phase 3 Randomized Clinical Trial of Chemotherapy With or Without Algenpantucel-L (HyperAcute-Pancreas) Immunotherapy in Subjects With Borderline Resectable or Locally Advanced Unresectable Pancreatic Cancer.

OBJECTIVES: To compare the efficacy and safety of algenpantucel-L [HyperAcute-Pancreas algenpantucel-L (HAPa); IND# 12311] immunotherapy combined with standard of care (SOC) chemotherapy and chemoradiation to SOC chemotherapy and chemoradiation therapy alone in patients with borderline resectable or locally advanced pancreatic ductal adenocarcinoma (PDAC). SUMMARY BACKGROUND DATA: To date, immunotherapy has not been shown to benefit patients with borderline resectable or locally advanced unresectable PDAC. HAPa is a cancer vaccine consisting of allogeneic pancreatic cancer cells engineered to express the murine α(1,3)GT gene. METHODS: A multicenter, phase 3, open label, randomized (1:1) trial of patients with borderline resectable or locally advanced unresectable PDAC. Patients received neoadjuvant SOC chemotherapy (FOLFIRINOX or gemcitabine/nab-paclitaxel) followed by chemoradiation (standard group) or the same standard neoadjuvant regimen combined with HAPa immunotherapy (experimental group). The primary outcome was overall survival. RESULTS: Between May 2013 and December 2015, 303 patients were randomized from 32 sites. Median (interquartile range) overall survival was 14.9 (12.2-17.8) months in the standard group (N = 158) and 14.3 (12.6-16.3) months in the experimental group (N = 145) [hazard ratio (HR) 1.02, 95% confidence intervals 0.66-1.58; P = 0.98]. Median progression-free survival was 13.4 months in the standard group and 12.4 months in the experimental group (HR 1.33, 95% confidence intervals 0.72-1.78; P = 0.59). Grade 3 or higher adverse events occurred in 105 of 140 patients (75%) in the standard group and in 115 of 142 patients (81%) in the experimental group (P > 0.05). CONCLUSIONS: Algenpantucel-L immunotherapy did not improve survival in patients with borderline resectable or locally advanced unresectable PDAC receiving SOC neoadjuvant chemotherapy and chemoradiation. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01836432.

High-added value co-products obtained from pecan nut (Carya illinoinensis) using a green extraction technology.

Abstract: The aqueous (AF) and solid (SF) fractions obtained as co-products in the aqueous extraction of pecan nut oil assisted by Alcalase® were evaluated. In the AF, the degree of protein hydrolysis (DH) and the electrophoretic profile of protein hydrolysates, phenolic compounds, and antioxidant capacity (reducing potential of the hydrophilic compounds, RPHC, 2,2-diphenyl-1-picrylhydrazyl, DPPH; and inhibition of lipid peroxidation) were determined. The proximate composition and microstructure were evaluated in SF. The results indicated a DH of 3.9%. The sample treated with the enzyme (ET) showed a molecular weight of proteins lower than 15 kDa. The ET showed higher content of phenolics (726.3 mg GAE/100 g) and antioxidant capacity higher than the sample without enzymatic treatment. The SF showed a residual lipid content rich in oleic and linoleic acids. Furthermore, changes in the proximate composition and the microstructure were observed. The results indicate the potentiality of hydrolyzed fractions for application in food.

Leaf proteome comparison of two GM common bean varieties and their non-GM counterparts by principal component analysis.

BACKGROUND: A genetically modified (GM) common bean event, namely Embrapa 5.1, was approved for commercialization in Brazil. The present work aimed to use principal component analysis (PCA) to compare the proteomic profile of this GM common bean and its non-GM counterpart. RESULTS: Seedlings from four Brazilian common bean varieties were grown under controlled environmental conditions. Leaf proteomic profiles were analyzed by two-dimensional gel electrophoresis (2DE). First, a comparison among 12 gels from four common bean varieties was performed by PCA using volume percentage of 198 matched spots, presented in all gels. The first two principal components (PC) accounted for 46.8% of total variation. Two groups were clearly separated by the first component: Pérola and GM Pérola from Pontal and GM Pontal. Secondly, another comparison among six gels from the same variety GM and its non-GM counterpart was performed by PCA; in this case it was possible to distinguish GM and non-GM. CONCLUSION: Separation between leaf proteomic profile of GM common bean variety and its counterpart was observed only when they were compared in pairs. These results showed higher similarity between GM variety and its counterpart than between two common bean varieties. PCA is a useful tool to compare proteomes of GM and non-GM plant varieties.

[Prevalence of Chlamydia trachomatis infection and factors with the risk of acquiring sexually transmitted infections in college students]. / Prevalencia de la infección por Chlamydia trachomatis y factores de riesgo de infecciones transmisibles sexualmente en estudiantes universitarios.

Chlamydia trachomatis genital infection is nowadays considered one of the most frequent causes of sexually transmitted infections (STI) in the world, mainly affecting the group of young people under 25 years old. The aim of this study was to determine the prevalence of C. trachomatis infection in newly admitted students to Universidad Nacional del Sur, Bahía Blanca, Argentina, and to evaluate the risk factors to acquire STI. For that purpose, 204 young college students with a mean age of 19 were involved in this study. Each participant delivered a sample of first-void urine and completed a questionnaire which was then submitted anonymously. The research for C. trachomatis was done on 114 valid samples through a technique of DNA amplification, whose molecular target was the gene ompA. Four cases of infection by C. trachomatis were detected with a prevalence of 3.5%. The risks factors associated to the infection were a history of 7 or more partners since the start of sexual activity and contact with a new sexual partner in the last 4 months. The prevalence of such infection reflects a moderate circulation of this microorganism in the studied population. This fact, along with some aspects shown by the questionnaire results, would characterize a population having a low risk profile for acquiring STIs. However, some other information obtained from the questionnaires gave some opposite evidence, which would alert us on the need of keeping watch, raising awareness and implementing preventive actions in this population.

Advanced glycation end product (AGE) targeting antibody SIWA318H is efficacious in preclinical models for pancreatic cancer.

SIWA318H is a novel monoclonal antibody that selectively targets an advanced glycation end product biomarker found in damaged/dysfunctional cells exhibiting (a) aerobic glycolysis, and (b) oxidative stress. Cells with this biomarker are dysfunctional and are associated with stresses and/or damages relating to aging, cancer and other disease processes. In this study, we evaluated the biological effects and antitumor activity of SIWA318H in preclinical models for pancreatic cancer. SIWA318H binds to pancreatic cancer cells and cancer-associated fibroblasts, as well as tumor xenografts derived from pancreatic cancer patients. Furthermore, SIWA318H induced significant antibody-dependent cell-mediated cytotoxicity (ADCC) against pancreatic cancer cells. In a humanized CD34+ NSG mouse xenograft model for pancreatic cancer, tumors in mice treated with SIWA318H grew significantly slower compared to those in control mice (p < 0.001). After 3 weeks of treatment with SIWA318H, the tumor growth was suppressed by 68.8% and 61.5% for the high and low dose regimens, respectively, when compared to the isotype antibody control (ANOVA p < 0.002). Moreover, a significant increase in complete remission (CR) rate was observed in mice receiving the high dose (60%, p < 0.04) or low dose (77.8%, p < 0.02) of SIWA318H treatment compared with control mice (6.7%). Immunohistochemical analyses of the tumor tissues showed a significant decrease in senescent cells in the tumor microenvironment of SIWA318H treated mice compared to that of control treated mice (p < 0.05). These results provide compelling evidence that SIWA318H is a promising novel therapeutic against pancreatic cancer.

Treatment Response in First-Line Metastatic Pancreatic Ductal Adenocarcinoma Is Stratified By a Composite Index of Tumor Proliferation and CD8 T-Cell Infiltration.

PURPOSE: Determinants of treatment outcomes to chemotherapy-based regimens in metastatic pancreatic ductal adenocarcinoma (PDA) remain ill-defined. Our aim was to examine tissue-based correlates of treatment response and resistance using matched baseline and on-treatment biopsies collected from patients with PDA treated in the first-line metastatic setting. EXPERIMENTAL DESIGN: Patients with treatment-naïve metastatic PDA were enrolled in a Phase II trial (NCT02077881) investigating gemcitabine plus nab-paclitaxel in combination with indoximod, an orally administered small-molecule inhibitor of the IDO pathway. Baseline and on-treatment biopsies (week 8) of metastatic lesions (88% liver) were collected from a cohort of responders (N = 8) and non-responders (N = 8) based on RECIST v1.1 and examined by multiplex IHC and mRNA sequencing. RESULTS: Treatment altered the transcriptional profile of metastatic lesions with a decrease in tumor cell proliferation independent of treatment response. The antiproliferative response was seen in both basal and classical PDA subtypes. PDA subtype was not associated with survival outcomes; instead, genes involved in immune activation distinguished responders from non-responders. Tumor response was associated with an increase in CD3+ and CD8+ T-cell infiltrates into metastatic lesions. A composite of decreased tumor proliferation in response to treatment and increased CD8 T-cell infiltration in metastatic lesions identified responders and associated with a favorable survival outcome. CONCLUSIONS: Our findings suggest that inhibiting cancer cell proliferation alone in PDA is insufficient to produce tumor responses and support a role for tumor-extrinsic mechanisms, such as CD8+ T cells, which combine with the cancer cell proliferation index to define treatment outcomes.

Type I collagen and matrix metalloproteinase 1, 3 and 9 gene polymorphisms in the predisposition to pelvic organ prolapse.

AIM: To evaluate whether the presence of specific polymorphism in the gene promoter of collagen and some matrix metalloproteinases was associated with the risk of developing pelvic organ prolapse. METHODS: A case-control study was carried on 233 women: 137 were cases with ≥ stage II pelvic organ prolapse and 96 were matched controls without pelvic pathologies. Allele and genotype frequencies related to polymorphisms at the Sp1 site of type I collagen and some functional polymorphisms in the promoters of metalloproteinases-1, -3 and -9 have been compared between groups. It has been shown that these single-insertions/deletions polymorphisms located in the promoter region of the genes have a functional significance in the regulation of their transcriptional level and local expression. Genotypes were determined by polymerase chain reaction (PCR) amplification and sequence analysis. SPSS 14.0 software was used for data analysis. Probability values of <0.05 were considered statistically significant. RESULTS: No difference between groups was found in the genotype distribution polymorphisms for COL1A1, metalloproteinases-9 and -3, while the distribution of the polymorphism of metalloproteinases-1 was significantly increased in the cases when compared with controls (p = 0.04). CONCLUSIONS: Our findings suggest that the polymorphism of metalloproteinases-1 might have a role in mediating susceptibility to pelvic organ prolapse.

Differential Distribution and Activity Profile of Acylpeptide Hydrolase in the Rat Seminiferous Epithelium.

Acylpeptide hydrolase (APEH) is a serine protease involved in amino acid recycling from acylated peptides (exopeptidase activity) and degradation of oxidized proteins (endoproteinase activity). This enzyme is inhibited by dichlorvos (DDVP), an organophosphate compound used as an insecticide. The role of APEH in spermatogenesis has not been established; therefore, the aim of this study was to characterize the distribution and activity profile of APEH during this process. For this purpose, cryosections of male reproductive tissues (testis and epididymis) and isolated cells (Sertoli cells, germ cells, and spermatozoa) were obtained from adult rats in order to analyze the intracellular localization of APEH by indirect immunofluorescence. In addition, the catalytic activity profiles of APEH in the different male reproductive tissues and isolated cells were quantified. Our results show that APEH is homogeneously distributed in Sertoli cells and early germ cells (spermatocytes and round spermatids), but this pattern changes during spermiogenesis. Specifically, in elongated spermatids and spermatozoa, APEH was localized in the acrosome and the principal piece. The exopeptidase activity was higher in the germ cell pool, compared to sperm and Sertoli cells, while the endoproteinase activity in epididymal homogenates was higher compared to testis homogenates at 24 h of incubation. In isolated cells, this activity was increased in Sertoli and germ cell pools, compared to spermatozoa. Taken together, these results indicate that APEH is differentially distributed in the testicular epithelium and undergoes re-localization during spermiogenesis. A possible role of APEH as a component of a protection system against oxidative stress and during sperm capacitation is discussed.

Dermoscopic Aspects of Cutaneous Adverse Drug Reactions.

BACKGROUND: Little is known about the dermoscopic evaluation of cutaneous adverse drug reactions (CADRs). OBJECTIVES: To evaluate the dermoscopic patterns of CADRs and identify those associated with severe cutaneous adverse reactions to drugs (SCARDs). PATIENTS AND METHODS: Patients included in this study from May 2015 to April 2016 had presented with CADRs. CADR presentation and classification were based on standard criteria. SCARDs included Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), overlap SJS/TEN, drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP). The dermoscopic features of CADRs were described and compared according to the severity of the reactions. RESULTS: Sixty-nine patients were included. Sixteen patients (23.2%) presented SCARDs. The main dermoscopic findings in SJS, overlap SJS/TEN and TEN were black dots or necrotic areas (100%). Erosion [respectively, 4/6 (66.7%), 3/3 (100%) and 1/1 (100%)], necrotic borders [respectively, 4/6 (66.7%), 3/3 (100%) and 1/1, (100%)] and epidermal detachment [respectively, 5/6 (83.3%); 2/3 (66.7%) and 1/1 (100%)] were also common among these reactions. Erythema and purpuric dots were the main dermoscopic findings [respectively, 5/6 (83.3%) and 4/6 (66.7%)] in DRESS. In non-severe reactions, the most prevalent structures were erythema and purpura in exanthema [respectively, 31/33 (93.9%) and 24/33 (72.7%)] and erythema and vascular structures in urticarial reactions [respectively, 6/6 (100%) and 3/6 (50%)]. Black dots or necrotic areas, epidermal detachment, necrotic borders and erosion were highly associated with SCARDs (P < 0.001). CONCLUSIONS: Dermoscopy improves clinical recognition of SCARDs.

Phase II trial of the IDO pathway inhibitor indoximod plus pembrolizumab for the treatment of patients with advanced melanoma.

BACKGROUND: The indoleamine 2,3-dioxygenase (IDO) pathway is a key counter-regulatory mechanism that, in cancer, is exploited by tumors to evade antitumor immunity. Indoximod is a small-molecule IDO pathway inhibitor that reverses the immunosuppressive effects of low tryptophan (Trp) and high kynurenine (Kyn) that result from IDO activity. In this study, indoximod was used in combination with a checkpoint inhibitor (CPI) pembrolizumab for the treatment for advanced melanoma. METHODS: Patients with advanced melanoma were enrolled in a single-arm phase II clinical trial evaluating the addition of indoximod to standard of care CPI approved for melanoma. Investigators administered their choice of CPI including pembrolizumab (P), nivolumab (N), or ipilimumab (I). Indoximod was administered continuously (1200 mg orally two times per day), with concurrent CPI dosed per US Food and Drug Administration (FDA)-approved label. RESULTS: Between July 2014 and July 2017, 131 patients were enrolled. (P) was used more frequently (n=114, 87%) per investigator's choice. The efficacy evaluable population consisted of 89 patients from the phase II cohort with non-ocular melanoma who received indoximod combined with (P).The objective response rate (ORR) for the evaluable population was 51% with confirmed complete response of 20% and disease control rate of 70%. Median progression-free survival was 12.4 months (95% CI 6.4 to 24.9). The ORR for Programmed Death-Ligand 1 (PD-L1)-positive patients was 70% compared with 46% for PD-L1-negative patients. The combination was well tolerated, and side effects were similar to what was expected from single agent (P). CONCLUSION: In this study, the combination of indoximod and (P) was well tolerated and showed antitumor efficacy that is worth further evaluation in selected patients with advanced melanoma.

Quality of life and sexual, bladder, and intestinal dysfunctions after class III nerve-sparing and class II radical hysterectomies: a questionnaire-based study.

BACKGROUND: To compare quality of life and bladder, intestinal, and sexual dysfunctions in 2 groups of patients undergoing different types of radical hysterectomies (RHs). METHODS: Patients with cervical cancer who underwent RH have been enrolled in a questionnaire-based study. Quality of life (QoL) and bladder, intestinal, and sexual dysfunctions were evaluated with the Functional Assessment of Cancer Therapy-Cervix (FACT-Cx). Patients were grouped according to the type of RH: group 1, class II RH and group 2, class III nerve-sparing RH (NSRH). RESULTS: Of 157 women included in the study, 127 filled out the questionnaire. Overall, QoL score assessed with the FACT questionnaire did not differ significantly between the 2 groups. The FACT subscales assessing physical, functional, emotional, and social well-being did not differ significantly between the 2 groups, whereas the FACT-Cx subscales assessing disease-related symptoms in group 2 patients showed a significantly worse score (72 vs 66; P = 0.03). Evaluating singularly the 15 items of the Cx subscales assessing disease-related symptoms, we did not find any significant difference between the 2 groups, but only Cx1 ("I am bothered by discharge or bleeding from my vagina") was significantly worse in group 2 patients. At univariate analysis, we found that NSRH and adjuvant radiotherapy (RT) impact negatively on the FACT-Cx subscales regarding pelvic visceral function. However, at multivariate analysis, only adjuvant RT impact negatively. CONCLUSIONS: Patients submitted to class III NSRH did not present worse QoL and pelvic visceral dysfunctions when compared with class II RH. The RT seems to be a factor impacting negatively on bladder and sexual function.

Is there yet any place for reagent strips in diagnosing spontaneous bacterial peritonitis in cirrhotic patients? An accuracy and cost-effectiveness study in Brazil.

BACKGROUND: Diagnosis of spontaneous bacterial peritonitis (SBP) is currently based on ascitic cell counting, but there is a need for a more simple and rapid diagnostic tool. The objectives of this study are to evaluate the accuracy of reagent strips in diagnosing SBP and compare their costs with total and differential cell counts. PATIENTS AND METHODS: 71 cirrhotic in- and outpatients were consecutively included (159 samples). Spontaneous bacterial peritonitis was defined as neutrophil cells >or= 250/microL. The cutoff values for each reagent strip were defined by a receiver operating characteristic (ROC) curve. Sensitivity (S), Specificity (Sp), Positive and Negative Predictive Values (PPV and NPV), Accuracy (Ac) and cost-effectiveness (US$) in comparison to cell count exam were calculated. RESULTS: Spontaneous bacterial peritonitis was diagnosed in 17 patients (23.9%), 11 of them with positive culture (64.7%). The best cutoff points found in ROC curves were 1+ for Multistix 10 SG and ca. 75 for Choiceline 10 (Multistix 10 SG S = 80%, Sp = 98.5%, PPV = 90.9%, NPV = 96.2%, Ac = 95%; Choiceline 10 S = 76.9%, Sp = 97.7%, PPV = 87%, NPV = 95.6%, Ac = 94%). In terms of cost-effectiveness by cost/accuracy, cell count was 41.5, Multistix 10 SG 0.57, and Choiceline 10, 0.19 (P < 0.001). CONCLUSION: Reagent strips are a useful tool for diagnosing SBP in cirrhotic patients, but they have some limitations. Strips are especially indicated when total and differential cell counts are not quickly available or sometimes unavailable. They are also indicated as screening test in emergency rooms to anticipate the diagnosis of SBP and allow its early treatment. It's an interesting option in developing countries.

Methylprednisolone administration alters adenine nucleotide hydrolysis in rat blood serum.

The effect of methylprednisolone on the hydrolysis of adenine nucleotides by rat blood serum enzymes was studied. Adult male Wistar rats were submitted to three different treatments with synthetic steroid methylprednisolone: one dose of 50 mg/kg, i.p. (acute); or oral doses of 6 mg/kg dissolved in drinking water for 15 (sub-chronic) or 30 (chronic) days. Decreased ADP hydrolysis was observed after acute and sub-chronic treatments. Furthermore, ATP, ADP and AMP hydrolysis decreased after chronic treatment. These alterations may constitute one of the mechanisms that mediate the development of some of the side effects associated with corticosteroid use.

Effective treatment of preexisting melanoma with whole cell vaccines expressing alpha(1,3)-galactosyl epitopes.

The hyperacute immune response in humans is a potent mechanism of xenograft rejection mediated by complement-fixing natural antibodies recognizing alpha(1,3)-galactosyl epitopes (alphaGal) not present on human cells. We exploited this immune mechanism to create a whole cell cancer vaccine to treat melanoma tumors. B16 melanoma vaccines genetically engineered to express alphaGal epitopes (B16alphaGal) effectively treated preexisting s.c. and pulmonary alphaGal-negative melanoma (B16Null) tumors in the alpha(1,3)-galactosyltransferase knockout mouse model. T cells from mice vaccinated with B16alphaGal recognized B16Null melanoma cells measured by detection of intracellular tumor necrosis factor-alpha. We showed successful adoptive transfer of immunity to recipient mice bearing lung melanoma metastasis. Mice receiving lymphocytes from donors previously immunized with B16alphaGal had reduced pulmonary metastases. The transfer of lymphocytes from mice vaccinated with control vaccine had no effect in the pulmonary metastasis burden. This study unequivocally establishes for the first time efficacy in the treatment of preexisting melanoma tumors using whole cell vaccines expressing alphaGal epitopes. Vaccination with B16alphagal induced strong long-lasting cell-mediated antitumor immunity extended to B16Null. These data formed the basis for the testing of this therapeutic strategy in human clinical trials currently under way.

Comparison of Grain Proteome Profiles of Four Brazilian Common Bean (Phaseolus vulgaris L.) Cultivars.

Common bean (Phaseolus vulgaris L.) is a source of proteins for about one billion people worldwide. In Brazil, 'BRS Sublime', 'BRS Vereda', 'BRS Esteio', and 'BRS Estilo' cultivars were developed by Embrapa to offer high yield to farmers and excellent quality to final consumers. In this work, grain proteomes of these common bean cultivars were compared based on two-dimensional gel electrophoresis (2-DE) and tandem mass spectrometry (MS/MS). Principal component analysis (PCA) was applied to compare 349 matched spots in these cultivars proteomes, and all cultivars were clearly separated in PCA plot. Thirty-two differentially accumulated proteins were identified by MS. Storage proteins such as phaseolins, legumins, and lectins were the most abundant, and novel proteins were also identified. We have built a useful platform that could be used to analyze other Brazilian cultivars and genotypes of common beans.

Portación nasal de Staphylococcus aureus en trabajadores de la salud de dos hospitales de la ciudad de Bahía Blanca, Argentina / Staphylococcus aureus nasal carriage in health care workers at two hospitals in Bahía Blanca city, Argentina / Carreamento nasal de Staphylococcus aureus em profissionais da saúde de dois hospitais da cidade de Bahía Blanca, Argentina

Resumen La portación nasal de Staphylococcus aureus representa un riesgo considerable para infecciones tanto nosocomiales como comunitarias. El objetivo del trabajo fue investigar la prevalencia de portación nasal de S. aureus sensibles (SAMS) y resistentes a meticilina (SAMR) en trabajadores de la salud, determinar su asociación con factores epidemiológicos y sus patrones de resistencia a los antimicrobianos. Se tomaron 152 muestras nasales de personal de dos hospitales de la ciudad de Bahía Blanca (Argentina). Los aislados de S. aureus se identificaron por métodos convencionales y por el sistema automatizado BD PhoenixTM 100. La prevalencia de portación nasal de S. aureus fue de 32,2% y, de SAMR, de 12,2%. La frecuencia de portación en el personal de laboratorio (58,8%) resultó estadísticamente significativa. Los aislados fueron sensibles a trimetoprima-sulfametoxazol, cloranfenicol, rifampicina, fluoroquinolonas y vancomicina. Estos datos alertan sobre la necesidad de identificar portadores de S. aureus e implementar estrategias que controlen una potencial diseminación de estos microorganismos.

Abstract The nasal carriage of Staphylococcus aureus represents a considerable risk for both nosocomial and community infections. The objective of this work was to investigate the prevalence of nasal carriage of both methicilin-susceptible (MSSA) and methicillin-resistant S. aureus (MRSA) in health workers, to determine their association with epidemiological factors and their patterns of antimicrobial resistance. One hundred and fifty-two nasal samples were taken from personnel from two hospitals in the Bahía Blanca city (Argentina). The S. aureus isolates were identified by conventional methods and by the automated BD PhoenixTM 100 system. The prevalence of S. aureus nasal carriage was 32.2% and that of MRSA, 12.2%. The frequency of carrying deterin laboratory personnel was statistically significant (58.8%). The isolates were susceptible to trimethoprim-sulfamethoxazole, chloramphenicol, rifampin, fluoroquinolones and vancomycin. These data warn of the need to identify S. aureus carriers and implement strategies that control the potential spread of these microorganisms.

Resumo O carreamento nasal de Staphylococcus aureus representa um risco considerável para infecções tanto nosocomiais quanto comunitárias. O objetivo do trabalho foi investigar a prevalência de carreamento nasal de S. aureus sensíveis (SAMS) e resistentes à meticilina (SARM) em profissionais da saúde; determinar sua associação com fatores epidemiológicos e seus padrões de resistência aos antimicrobianos. Foram coletadas 152 amostras nasais de funcionários de dois hospitais da cidade de Bahía Blanca (Argentina). Os isolados de S. aureus foram identificados por métodos convencionais e pelo sistema automatizado BD PhoenixTM 100. A prevalência de carreamento nasal de S. aureus foi de 32,2% e a de SARM, de 12,2%. A frequência de carreamento no pessoal do laboratório foi estatisticamente significativa (58,8%). Os isolados foram sensíveis a trimetoprim-sulfametoxazol, cloranfenicol, rifampicina, fluoroquinolonas e vancomicina. Esses dados alertam para a necessidade de identificar portadores de S. aureus e implementar estratégias que controlem a propagação potencial desses microrganismos.

Pancreatic cancer: Update on immunotherapies and algenpantucel-L.

Pancreatic adenocarcinoma is notoriously lethal, and despite improvements in systemic chemotherapy approaches bringing survival rates for metastatic disease to almost 1 year, by 2030 it is expected to become the second leading cause of cancer death. Pancreatic cancer (PC) prognosis has been associated with both the presence of intratumoral helper and cytotoxic T lymphocytes, as well as humoral immune responses to tumor associated antigens like mesothelin. It is well described that the PC microenvironment is characterized by a fibroinflammatory and immunosuppressive stroma. On these premises several immune-targeted strategies have been developed to harness the adaptable immune system with a goal of improving survival with little toxicity. Cancer vaccines involve the administration of tumor-associated antigens with the goal of inducing an endogenous anti-tumor response. Among several strategies discussed, we will focus on the algenpantucel-L (HyperAcute™ Pancreas) immunotherapy. Algenpantucel-L is a whole cell immunotherapy consisting of irradiated allogeneic PC cells genetically engineered to express the murine enzyme α(1,3)-galactosyltransferase (αGT), which ultimately leads to hyperacute rejection with complement- and antibody-dependent cytotoxicity. While phase III data in the adjuvant treatment of pancreatic cancer are pending, phase II results have been encouraging, particularly for patients who demonstrated humoral immunologic responses. Novel strategies using immune checkpoint inhibitors, costimulatory antibodies, and combinations with cancer vaccines may overcome immunotolerance and improve treatment success.

Algenpantucel-L immunotherapy in pancreatic adenocarcinoma.

Pancreatic adenocarcinoma is the 4th leading cause of cancer death in the USA and the EU. A minority of patients presents with surgically resectable and potentially curable disease, but among these, 80% are destined to relapse and overall survival rates with adjuvant chemotherapy average 24 months. Immunotherapy is a promising therapeutic option and a potential paradigm shift in the treatment of patients with pancreatic cancer, and may be particularly effective when used early in the disease course to prevent metastatic spread. Algenpantucel-L (HyperAcute Pancreas, NewLink Genetics, Ames, IA, USA) is a whole-cell immunotherapy consisting of irradiated allogeneic pancreatic cancer cells genetically engineered to express the murine enzyme α-GT, which results in hyperacute rejection of the tumor cells with complement- and antibody-dependent cytotoxicity. Phase II clinical trial data has been encouraging, particularly for patients who demonstrated humoral immunologic responses. Here, we report preliminary results and biomarkers correlations with clinical activity of algenpantucel-L in pancreatic cancer.

High-efficiency lentiviral vector-mediated gene transfer into murine macrophages and activated splenic B lymphocytes.

The goal of the present report was to determine if lentiviral vectors could mediate gene transfer into murine terminally differentiated macrophages and mature B lymphocytes as a new strategy of gene delivery into professional antigen-presenting cells (APC). We demonstrated that nondividing tissue resident macrophages were efficiently transduced in vitro by lentiviral vectors. Gene transfer efficiencies of up to 90% were demonstrated using a green fluorescent protein (GFP) reporter gene-containing vector and expression was stable for the length of cell culture. Transduced macrophages were functionally competent, preserving their phagocytic activity, accessory cell function, interleukin (IL)-12 secretion, and nitric oxide (NO) production similar to control untransduced macrophages. Lentiviral vector mediated transduction of CD19(+) B cell blasts was demonstrated to be in the range of 60%-70% GFP-positive cells. These transduced cells retain the ability to upregulate CD80 and CD86 similar to control B cell cultures. In addition, we show that the human immunodeficiency virus type 1 (HIV-1) accessory proteins Nef, Vpr, Vif, and Vpu are not required for the transduction of both resident macrophages and activated B lymphoblasts. We conclude that HIV-1-based lentiviral vectors can mediate efficient gene transfer into primary murine macrophages and mature B lymphocytes.