Protein glycosylation and tumor microenvironment alterations driving cancer hallmarks

Decades of research have disclosed a plethora of alterations in protein glycosylation that decisively impact in all stages of disease and ultimately contribute to more aggressive cell phenotypes. The biosynthesis of cancer-associated glycans and its reflection in the glycoproteome is driven by microenvironmental cues and these events act synergistically toward disease evolution. Such intricate crosstalk provides the molecular foundations for the activation of relevant oncogenic pathways and leads to functional alterations driving invasion and disease dissemination. However, it also provides an important source of relevant glyco(neo)epitopes holding tremendous potential for clinical intervention. Therefore, we highlight the transversal nature of glycans throughout the currently accepted cancer hallmarks, with emphasis on the crosstalk between glycans and the tumor microenvironment stromal components. Focus is also set on the pressing need to include glycans and glycoconjugates in comprehensive panomics models envisaging molecular-based precision medicine capable of improving patient care. We foresee that this may provide the necessary rationale for more comprehensive studies and molecular-based intervention.The authors wish to acknowledge the Portuguese Foundation for Science and Technology (FCT) for the human resources grants: PhD grant SFRH/BD/111242/2015 (AP), and FCT auxiliary researcher grant CEECIND/03186/2017 (JF). FCT is co-financed by European Social Fund (ESF) under Human Potential Operation Programme (POPH) from National Strategic Reference Framework (NSRF). The authors also acknowledge the Portuguese Oncology Institute of Porto Research Centre (CI-IPOP-29-2014; CI-IPOP-58-2015), the PhD Program in Biomedical Sciences of ICBAS-University of Porto, and the Early stage cancer treatment, driven by context of molecular imaging (ESTIMA) framework (NORTE-01-0145-FEDER-000027). The authors were also supported by the CANCER project (NORTE-01-0145-FEDER-000029) co-funded through the NORTE-45-2015-02

Drug repurposing opportunities in pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is considered one of the deadliest tumors worldwide. The diagnosis is often possible only in the latter stages of the disease, with patients already presenting an advanced or metastatic tumor. It is also one of the cancers with poorest prognosis, presenting a five-year survival rate of around 5%. Treatment of PDAC is still a major challenge, with cytotoxic chemotherapy remaining the basis of systemic therapy. However, no major advances have been made recently, and therapeutic options are limited and highly toxic. Thus, novel therapeutic options are urgently needed. Drug repurposing is a strategy for the development of novel treatments using approved or investigational drugs outside the scope of the original clinical indication. Since repurposed drugs have already completed several stages of the drug development process, a broad range of data is already available. Thus, when compared with de novo drug development, drug repurposing is timeefficient, inexpensive and has less risk of failure in future clinical trials. Several repurposing candidates have been investigated in the past years for the treatment of PDAC, as single agents or in combination with conventional chemotherapy. This review gives an overview of the main drugs that have been investigated as repurposing candidates, for the potential treatment of PDAC, in preclinical studies and clinical trials.Cristina P. R. Xavier was supported by the Fundação para a Ciência e Tecnologia (FCT) and Fundo Social Europeu (FSE), Portugal, through the post-doc grant SFRH/BPD/122871/2016. This research group is supported by FEDER-Fundo Europeu de Desenvolvimento Regional through COMPETE 2020 and by FCT-Foundation for Science and Technology in the framework of project POCI-01-0145-FEDER-030457 and project POCI-01-0145-FEDER- 016390:CANCEL STEM

Risk factors for oesophageal squamous cell carcinoma in Mozambique

Studies evaluating risk factors for the occurrence of oesophageal squamous cell carcinoma (ESCC) in high-risk regions might contribute to a better understanding of the oesophageal cancer aetiology and incidence variation worldwide. We aimed to quantify the association between alcohol, tobacco and dietary history, and the occurrence of ESCC in Mozambique. A case–control study was conducted at Maputo Central Hospital. Cases (n = 143) were patients with newly diagnosed oesophageal cancer recruited in the Gastroenterology Service. Controls (n = 212) were selected in the Orthopaedic Ward among subjects with pathologies related to trauma. Crude and adjusted odds ratios (ORs), and the corresponding 95% confidence intervals (CI) were computed using non-conditional logistic regression. The risk of ESCC was higher in older participants and lower in those with higher household income. Alcohol drinking (lifetime consumption ≥ 55.1 versus 0 kg ethanol: OR = 5.56; 95% CI: 2.43–12.73) and tobacco smoking (lifetime consumption ≥ 20 versus 0 pack/years: OR=7.26; 95% CI: 1.42–37.17) were associated with increased risk of ESCC. Tea (at least twice daily versus less than daily: OR = 5.09; 95% CI: 2.45–10.58) was also associated with the occurrence of ESCC. No significant differences were observed for fruit and vegetable and for smoked meat or fish consumption. Findings from this study show that in our sample, the occurrence of ESCC is strongly influenced by lifetime consumption of tobacco and alcohol, and with tea drinking. This highlights the importance of preventive measures based on the promotion of healthier lifestyles. Copyright: © the authors; licensee ecancermedicalscience

Target score—a proteomics data selection tool applied to esophageal cancer identifies glut1-sialyl tn glycoforms as biomarkers of cancer aggressiveness

Esophageal cancer (EC) is a life-threatening disease, demanding the discovery of new biomarkers and molecular targets for precision oncology. Aberrantly glycosylated proteins hold tremendous potential towards this objective. In the current study, a series of esophageal squamous cell carcinomas (ESCC) and EC-derived circulating tumor cells (CTCs) were screened by immunoassays for the sialyl-Tn (STn) antigen, a glycan rarely expressed in healthy tissues and widely observed in aggressive gastrointestinal cancers. An ESCC cell model was glycoengineered to express STn and characterized in relation to cell proliferation and invasion in vitro. STn was found to be widely present in ESCC (70% of tumors) and in CTCs in 20% of patients, being associated with general recurrence and reduced survival. Furthermore, STn expression in ESCC cells increased invasion in vitro, while reducing cancer cells proliferation. In parallel, an ESCC mass spectrometry-based proteomics dataset, obtained from the PRIDE database, was comprehensively interrogated for abnormally glycosylated proteins. Data integration with the Target Score, an algorithm developed in-house, pinpointed the glucose transporter type 1 (GLUT1) as a biomarker of poor prognosis. GLUT1-STn glycoproteoforms were latter identified in tumor tissues in patients facing worst prognosis. Furthermore, healthy human tissues analysis suggested that STn glycosylation provided cancer specificity to GLUT1. In conclusion, STn is a biomarker of worst prognosis in EC and GLUT1-STn glycoforms may be used to increase its specificity on the stratification and targeting of aggressive ESCC forms.The authors wish to acknowledge the Portuguese Foundation for Science and Technology (FCT) for the human resources grants: PhD grant SFRH/BD/111242/2015 (AP), SFRH/BD/146500/2019 (MRS), SFRH/BD/142479/2018 (JS), SFRH/BD/105355/2014 (RA) and FCT assistant researcher grant CEECIND/03186/2017 (JAF). FCT is co-financed by European Social Fund (ESF) under Human Potential Operation Programme (POPH) from National Strategic Reference Framework (NSRF). The authors also acknowledge FCT the funding for CI-IPOP research unit (PEst-OE/SAU/UI0776/201) and LAQV-REQUIMTE research unit (UIDB/50006/2020), the Portuguese Oncology Institute of Porto Research Centre (CI-IPOP-29-2016-2020; CI-IPOP-58-2016-2020; CI-IPOP-Proj.70-bolsa2019-GPTE) and PhD Program in Biomedical Sciences of ICBAS-University of Porto. The author also thanks “Early stage cancer treatment, driven by context of molecular imaging (ESTIMA)” framework (NORTE-01-0145-FEDER-000027) and IPO-Score (DSAIPA/DS/0042/2018) for financial support. This work was financed by FEDER—Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020—Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020 and by Portuguese funds through FCT/MCTES—Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior. The authors also acknowledge support from the Portuguese League against Cancer grant LPCC-NRN-2020 (DF)

Metal accumulation in the tissues and shells of the Rapanine Whelk Indothais gradata along an acidified estuarine gradient

Human ImpactsPoster presentation: P-74Acidification of estuaries results from microbial CO2 generation, acid sulphate groundwater discharge, and anthropogenic activities, in the context of weak buffering potential of hyposaline waters. The resulting acidification introduces an additional yet poorly studied factor influencing the ecology and distributions of biological populations and species. Furthermore, it has a complex influence on estuarine chemistry, including altering the speciation of metals and potentially their availability to the biotic component. With the aim of providing baseline information for metal accumulation in the shells and tissues of organisms inhabiting acidified turbid tropical Asian estuaries, we studied the rapanine whelk Indothais gradata from the mineral-acidified Sungai ...postprin

Origen, desarrollo, y descripción de los tipos de gallina "criolla" existentes en varios municipio del valle del cauca

Se plantean argumentos que respaldan la hipótesis de la existencia de la gallina doméstica en América del Sur antes de su descubrimiento. Con el establecimiento de colonias se introdujeron tipos europeos para el consumo de parte de la población. Se explica cómo se generó tecnología apropiada, produciéndose excedentes para exportar antes de 1950. Se comenta el fuerte cambio que sufre la gallina cultura en el Siglo XX con las primeras importaciones, creándose así una dependencia tecnológica. Se describen 11 tipos de gallina "criolla" que existen en el valle del Cauca, y se mencionan algunos ajustes fisiológicos y anatómicos que favorecen un mejor comportamiento de la gallina "criolla"; se discuten y proponen elementos para la creación de un banco de germoplasma con estas aves.There are arguments that favorate the hypotesis that the domestic hen lived in South America before its discovery. There was introduction of European types when the colonies settled. Through apropiate technology there was enough product for exports before 1950. Because of the first imports there was a strong change for the poultry production in the XX Century because of that a technological dependence was introduced. There are 11 diferent types of country hens in the Cauca Valley. Some phisiological and anatomical adjustements help a better development of the country hen in Colombia. This study proposes some elements to create a bank of germplasm with country hens

Human papillomavirus prevalence among women with cervical intraepithelial neoplasia III and invasive cervical cancer from Goiânia, Brazil

This study estimated the prevalence and distribution of human papillomavirus (HPV) types among women with cervical intraepithelial neoplasia (CIN) grade III and invasive cervical cancer from Goiás (Brazil Central Region). Seventy-four cases were analyzed and consisted of 18 CIN III, 48 squamous cell carcinomas, 4 adenocarcinomas, 1 adenosquamous carcinoma and 3 undifferentiated carcinomas. HPV-DNA sequences were examined in formalin-fixed and paraffin-embedded tissues using primers from L1 region GP5+/GP6+. Polymerase chain reaction products were typed with dot blot hybridization using probes for HPV 16, 18, 31, 33, 45, 54, 6/11, 42/43/44, 51/52, 56/58. The prevalence of HPV was estimated to be 76% (56/74). HPV 16 was the most frequently found type, followed by HPV 33, 18 and 31. The prevalence of untyped HPV was 6%; 79% percent of the squamous cell carcinoma cases and 61% percent of the CIN III were positive for HPV and the prevalence rate of HPV types was the same for the total number of cases. According to other studies, HPV type 16 is the most prevalent virus in all Brazilian regions, but there is variation regarding to other types. Type 18 is the second most prevalent HPV in North, Southeast and South Brazil regions and types 31 and 33 are the second most prevalent HPV in Northeast and Central Brazil, respectively