Extracellular Vesicle and Particle Biomarkers Define Multiple Human Cancers.

There is an unmet clinical need for improved tissue and liquid biopsy tools for cancer detection. We investigated the proteomic profile of extracellular vesicles and particles (EVPs) in 426 human samples from tissue explants (TEs), plasma, and other bodily fluids. Among traditional exosome markers, CD9, HSPA8, ALIX, and HSP90AB1 represent pan-EVP markers, while ACTB, MSN, and RAP1B are novel pan-EVP markers. To confirm that EVPs are ideal diagnostic tools, we analyzed proteomes of TE- (n = 151) and plasma-derived (n = 120) EVPs. Comparison of TE EVPs identified proteins (e.g., VCAN, TNC, and THBS2) that distinguish tumors from normal tissues with 90% sensitivity/94% specificity. Machine-learning classification of plasma-derived EVP cargo, including immunoglobulins, revealed 95% sensitivity/90% specificity in detecting cancer. Finally, we defined a panel of tumor-type-specific EVP proteins in TEs and plasma, which can classify tumors of unknown primary origin. Thus, EVP proteins can serve as reliable biomarkers for cancer detection and determining cancer type.

Ethnic inequalities in involuntary admission under the Mental Health Act: an exploration of mediation effects of clinical care prior to the first admission.

BACKGROUND: Studies show ethnic inequalities in rates of involuntary admission and types of clinical care (such as psychological therapies). However, few studies have investigated if there is a relationship between clinical care practices and ethnic inequalities in involuntary admission. AIMS: This study investigated the impact of ethnicity and clinical care on involuntary admission and the potential mediation effects of prior clinical care. METHOD: In this retrospective cohort study, we used data from the electronic records of the South London and Maudsley NHS Foundation Trust and identified patients with a first hospital admission between January 2008 and May 2021. Logistic regression and mediation analyses were used to investigate the association between ethnicity and involuntary admission, and whether clinical care, in the 12 months preceding admission, mediates the association. RESULTS: Compared with White British people, higher odds of involuntary admission were observed among 10 of 14 minority ethnic groups; with more than twice the odds observed among people of Asian Chinese, of Asian Bangladeshi and of any Black background. There were some ethnic differences in clinical care prior to admission, but these had a minimal impact on the inequalities in involuntary admission. More out-patient appointments and home treatment were associated with higher odds of involuntary admission, whereas psychological therapies and having a care plan were associated with reduced odds of involuntary admission. CONCLUSIONS: Ethnic inequalities in involuntary admission persist after accounting for potential mediating effects of several types and frequencies of clinical care. Promoting access to psychological therapies and ensuring that care plans are in place may reduce involuntary admissions.

First assessment of atmospheric pollution by trace elements and particulate matter after a severe collapse of a tailings dam, Minas Gerais, Brazil: An insight into biomonitoring with Tillandsia usneoides and a public health dataset.

In this study, samples of bromeliad Tillandsia usneoides (n = 70) were transplanted and exposed for 15 and 45 days in 35 outdoor residential areas in Brumadinho (Minas Gerais state, Brazil) after one of the most severe mining dam collapses in the world. Trace elements aluminum (Al), arsenic (As), chromium (Cr), copper (Cu), iron (Fe), mercury (Hg), manganese (Mn), nickel (Ni) and zinc (Zn) were quantified by atomic absorption spectrometry. Scanning electron microscope generated surface images of T. usneoides fragments and particulate matter (PM2.5, PM10 and PM > 10). Aluminum, Fe and Mn stood out from the other elements reflecting the regional geological background. Median concentrations in mg kg-1 increased (p < 0.05) between 15 and 45 days for Cr (0.75), Cu (1.23), Fe (474) and Mn (38.1), while Hg (0.18) was higher at 15 days. The exposed-to-control ratio revealed that As and Hg increased 18.1 and 9.4-fold, respectively, not showing a pattern associated only with the most impacted sites. The PM analysis points to a possible influence of the prevailing west wind on the increase of total particles, PM2.5 and PM10 in transplant sites located to the east. Brazilian public health dataset revealed increase in cases of some cardiovascular and respiratory diseases/symptoms in Brumadinho in the year of the dam collapse (1.38 cases per 1000 inhabitants), while Belo Horizonte capital and its metropolitan region recorded 0.97 and 0.37 cases, respectively. Although many studies have been carried out to assess the consequences of the tailings dam failure, until now atmospheric pollution had not yet been evaluated. Furthermore, based on our exploratory analysis of human health dataset, epidemiological studies are required to verify possible risk factors associated with the increase in hospital admissions in the study area.

Happiness of Older Adults in Haemodialysis: Findings from a Comparative Study.

Happiness is related to longevity and better health; nevertheless, there is a lack of knowledge about the construct, understood as subjective well-being (SWB), of older adults undergoing hemodialysis. This cross-sectional study investigated the extent to which hemodialysis treatment affects the SWB of older adults, compared to non-dialysis older adults. Regarding this, a total of 126 participants have interviewed: all the older adults in the hemodialysis service, 42 patients, from a city in Brazil, and 84 older adults from the Community, age- and gender-matched, predominantly men (64.3%), aged between 60 and 81 years. Participants respond to pattern questionnaires about SWB (life satisfaction, positive affect, negative affect), depressive symptoms, sociodemographic characteristics, and physical health status. Analysis of variance presented in hemodialysis had no effect on SWB and depressive symptoms. Furthermore, participants in the hemodialysis had fewer years of schooling, and those in the community presented more diseases. The high number of illnesses and low educational level demonstrate effects on SWB, as well the length of hemodialysis is negatively associated with SWB. Therefore, hemodialysis by itself does not make older adults unhappier and depressive, but some variables depending on the socioeconomical status and length of treatment are associated with depression and worst SWB.

Ethnic disparities in clozapine prescription for service-users with schizophrenia-spectrum disorders: a systematic review.

Clozapine is the only licenced medication for treating treatment-resistant schizophrenia. Previous studies have suggested unequal rates of clozapine treatment by ethnicity among individuals with schizophrenia-spectrum disorders. One previous review has investigated this topic but was restricted to studies from the USA. This current review aims to synthesise the international literature regarding ethnic disparities in clozapine prescription amongst individuals with schizophrenia-spectrum disorders. We searched CINAHL, PubMed, Medline, Embase, APA PsycINFO and Open Grey and reviewed studies reporting on the proportion of service-users prescribed clozapine separately for different ethnic groups, in individuals with a primary diagnosis of schizophrenia or any schizophrenia-spectrum disorders. A narrative synthesis was conducted to integrate information from included studies. The review was registered in PROSPERO (Number: CRD42020221731). From 24 studies, there is strong, consistent evidence that Black and Hispanic service-users in the UK and the USA are significantly less likely to receive clozapine than White/Caucasian service-users after controlling for multiple demographic and clinical potential confounders. In New Zealand, Maori service-users were reported to be more likely to receive clozapine than those of White/European ethnicity. There is mixed evidence regarding Asian service-users in the UK. The mentioned disparities were observed in studies with TRS and non-TRS cohorts. The results imply that access to clozapine treatment varies among ethnic groups. These findings raise an ethical concern as they suggest a compromise of the standards of care in schizophrenia treatment practices. Interventions are needed to reduce clozapine prescribing disparities among ethnic communities.

Neutrophil extracellular traps (NETs) modulate inflammatory profile in obese humans and mice: adipose tissue role on NETs levels.

BACKGROUND: Neutrophil extracellular traps (NETs) are a recently discovered neutrophil defense mechanism which modulates several inflammatory conditions contributing to metabolic profile alterations. Therefore, the present study aimed to evaluate the production of NETs in obese patients and mice, verifying the possible mechanisms associated with the release of NETs by the adipose tissue. METHODS AND RESULTS: The present study investigated NETs production in human adipose tissue and also showing the neutrophils using intravital microscopy in mouse epididymal adipose tissue. Blood and white adipose tissues were obtained from eutrophic and obese individuals and from mice. Lipid, glycemic and leukocyte profiles were evaluated, as well as the levels of NETs and its markers. Bioinformatics and proteomics analyses were performed and the identified key proteins were measured. The main findings showed that the inflammatory markers interleukin-8 (IL-8), heat shock protein 90 (HSP90) and the E1 heat shock protein family (HSPE1) can be modulated by the NETs levels in obesity. Obesity has also been associated with increased cholesterol, glucose intolerance, ionic calcium and NETs. We also observed an increase in catalase and a decreased superoxide dismutase activity. Bioinformatics and proteomics analyses revealed that IL-8, HSP90 and HSPE1 were associated with obesity, inflammation and NETs release. CONCLUSIONS: In conclusion, the present study shows an increase in NETs production during obesity associated with important inflammatory markers in adipose.

Glycemic response, satiety, gastric secretions and emptying after bread consumption with water, tea or lemon juice: a randomized crossover intervention using MRI.

PURPOSE: Numerous studies, including our previous work with lemon juice, have reported that low-pH meals reduce the glycemic response to starchy foods. However, the underlying mechanism is not yet understood. Tea, for its polyphenol content, has also been investigated. The main objective of this research was to concurrently study gastric emptying, appetite perceptions and glycemic responses to bread consumed with water, tea, or lemon juice. METHODS: In this randomized, crossover intervention, ten participants consumed equal portions of bread (100 g) with 250 mL of water, water-diluted lemon juice, or black tea at breakfast. Gastric volumes, blood glucose concentrations and appetite perceptions were alternately assessed over 180 min using magnetic resonance imaging, the finger-prick method and visual analogue scales, respectively. RESULTS: Compared to water, lemon juice led to a 1.5 fold increase of the volume of gastric contents, 30 min after the meal (454.0 ± 18.6 vs. 298.4 ± 19.5 mL, [Formula: see text] ± SEM P < 0.00001). Gastric emptying was also 1.5 times faster (P < 0.01). Conversely, lemon juice elicited a lower glycemic response than water (blood glucose concentrations at t = 55 min were 35% lower, P = 0.039). Tea had no effect. Changes in appetite perceptions and gastric volumes correlated well, but with no significant differences between the meals. CONCLUSIONS: Lemon juice lowered the glycemic response and increased both gastric secretions and emptying rate. The results are compatible with the hypothesis that the reduction of the glycemic response is mainly due to the interruption of starch hydrolysis via the acid-inhibition of salivary α-amylase. TRIAL REGISTRATION NUMBER: NCT03265392, August 29, 2017.

Ethnic inequalities in clozapine use among people with treatment-resistant schizophrenia: a retrospective cohort study using data from electronic clinical records.

PURPOSE: Clozapine is the most effective intervention for treatment-resistant schizophrenia (TRS). Several studies report ethnic disparities in clozapine treatment. However, few studies restrict analyses to TRS cohorts alone or address confounding by benign ethnic neutropenia. This study investigates ethnic equity in access to clozapine treatment for people with treatment-resistant schizophrenia spectrum disorder. METHODS: A retrospective cohort study, using information from 11 years of clinical records (2007-2017) from the South London and Maudsley NHS Trust. We identified a cohort of service-users with TRS using a validated algorithm. We investigated associations between ethnicity and clozapine treatment, adjusting for sociodemographic factors, psychiatric multi-morbidity, substance misuse, neutropenia, and service-use. RESULTS: Among 2239 cases of TRS, Black service-users were less likely to be receive clozapine compared with White British service-users after adjusting for confounders (Black African aOR = 0.49, 95% CI [0.33, 0.74], p = 0.001; Black Caribbean aOR = 0.64, 95% CI [0.43, 0.93], p = 0.019; Black British aOR = 0.61, 95% CI [0.41, 0.91], p = 0.016). It was additionally observed that neutropenia was not related to treatment with clozapine. Also, a detention under the Mental Health Act was negatively associated clozapine receipt, suggesting people with TRS who were detained are less likely to be treated with clozapine. CONCLUSION: Black service-users with TRS were less likely to receive clozapine than White British service-users. Considering the protective effect of treatment with clozapine, these inequities may place Black service-users at higher risk for hospital admissions and mortality.

Clozapine treatment and risk of COVID-19 infection: retrospective cohort study.

BACKGROUND: Clozapine, an antipsychotic with unique efficacy in treatment-resistant psychosis, is associated with increased susceptibility to infection, including pneumonia. AIMS: To investigate associations between clozapine treatment and increased risk of COVID-19 infection in patients with schizophrenia-spectrum disorders who are receiving antipsychotic medications in a geographically defined population in London, UK. METHOD: Using information from South London and Maudsley NHS Foundation Trust (SLAM) clinical records, via the Clinical Record Interactive Search system, we identified 6309 individuals who had an ICD-10 diagnosis of schizophrenia-spectrum disorders and were taking antipsychotics at the time of the COVID-19 pandemic onset in the UK. People who were on clozapine treatment were compared with those on any other antipsychotic treatment for risk of contracting COVID-19 between 1 March and 18 May 2020. We tested associations between clozapine treatment and COVID-19 infection, adjusting for gender, age, ethnicity, body mass index (BMI), smoking status and SLAM service use. RESULTS: Of 6309 participants, 102 tested positive for COVID-19. Individuals who were on clozapine had increased risk of COVID-19 infection compared with those who were on other antipsychotic medication (unadjusted hazard ratio HR = 2.62, 95% CI 1.73-3.96), which was attenuated after adjusting for potential confounders, including clinical contact (adjusted HR = 1.76, 95% CI 1.14-2.72). CONCLUSIONS: These findings provide support for the hypothesis that clozapine treatment is associated with an increased risk of COVID-19 infection. Further research will be needed in other samples to confirm this association. Potential clinical implications are discussed.

Physical exercise, obesity, inflammation and neutrophil extracellular traps (NETs): a review with bioinformatics analysis.

Neutrophil extracellular traps (NETs) represent an innate organism defense mechanism characterized by neutrophil release of intracellular material to capture any aggressor agent. Elevated NETs release is associated with increased inflammatory response and related diseases, such as obesity. Chronic physical training is one of the main strategies to treat and prevent obesity. The relationship between physical training and NETs is still under study. The present review, followed by a bioinformatics analysis, demonstrates the meaningful connection between physical exercise, obesity, and NETs. The bioinformatics indicated TNF-α as a leading gene after the ontological analysis followed by positive-interleukin-6 regulation, chemokines, and inflammatory response regulation. The main results pointed to a relevant regulatory effect of physical training on NETs release, indicating physical exercise as a possible therapeutic target on modulating NETs and inflammation.

Acute oral treatment with resveratrol and Lactococcus Lactis Subsp. Lactis decrease body weight and improve liver proinflammatory markers in C57BL/6 mice.

The present study aimed to evaluate the effects of resveratrol, a nutraceutical polyphenol, and Lactococcus lactis (bacteria probiotic), on metabolic parameters and hepatic proinflammatory markers expression. C57BL/6 mice were divided into 4 groups: Standard (ST), Lactococcus lactis (LL), Resveratrol (RSV), and Lactococcus lactis plus resveratrol (LL + RSV). Lactococcus lactis and resveratrol were administered by orogastric gavage. Blood parameters were assessed (total cholesterol, triglycerides, ALT and AST). IL-6 mRNA expression was evaluated by Real-time PCR and TNF-α protein expression was assessed by immunohistochemistry. The main findings showed that resveratrol and Lactococcus lactis association decreased body weight, aspartate aminotransferase and total cholesterol levels. LL and LL + RSV decreased triglycerides levels and IL-6 and TNF-α expression. These results open a perspective of using resveratrol and Lactococcus lactis to improve metabolic parameters and Lactococcus lactis in preventing inflammation and the hepatic diseases development.

Lemon juice, but not tea, reduces the glycemic response to bread in healthy volunteers: a randomized crossover trial.

PURPOSE: The inhibition of enzymes that hydrolyze starch during digestion could constitute an opportunity to slow down the release, and ultimately the uptake, of starch-derived glucose. Simple dietary approaches consisting in pairing starch-rich foods with beverages that have the capacity to inhibit such enzymes could be an effective and easily implementable strategy. The objective of this work was to test the impact of black tea and lemon juice on the glycemic response to bread and subsequent energy intake in healthy adults. METHODS: A randomized crossover study was conducted with equal portions of bread (100 g) and 250 ml of water, black tea or lemon juice. Capillary blood glucose concentrations were monitored during 180 min using the finger-prick method. Ad libitum energy intake was assessed 3 h later. RESULTS: Tea had no effect on the glycemic response. Lemon juice significantly lowered the mean blood glucose concentration peak by 30% (p < 0.01) and delayed it more than 35 min (78 vs. 41 min with water, p < 0.0001). None of the tested beverages had an effect on ad libitum energy intake. CONCLUSION: These results are in agreement with previous in vitro studies showing that lowering the pH of a meal can slow down starch digestion through premature inhibition of salivary α-amylase. Furthermore, the effect of lemon juice was similar to what has been repeatedly observed with vinegar and other acidic foods. Including acidic beverages or foods in starchy meals thus appears to be a simple and effective strategy to reduce their glycemic impact.

Very Late Onset of Obsessive-Compulsive Disorder: Case Report and Review of Published Cases in Those More Than 60 Years Old.

ABSTRACT: It is widely agreed that obsessive-compulsive disorder (OCD) is less common among the elderly. However, several studies suggest that a third peak of OCD onset may occur after the age of 65. The onset of OCD in the elderly is unusual and mostly related to nonpsychiatric diagnoses. Nonetheless, some reports have documented late-onset OCD in older adults with no detection of cerebral abnormalities. Such differences in age of onset may be associated with phenotypical differences in disease severity, comorbidity, and treatment response across patients. In this report, we describe the case of late-onset OCD in an 80-year old man with no specific focal brain structural abnormality. The report could improve awareness of the disorder in the elderly and contribute to a better identification of clinical characteristics and additional risk factors of OCD.

Effect of Dexamethasone on Days Alive and Ventilator-Free in Patients With Moderate or Severe Acute Respiratory Distress Syndrome and COVID-19: The CoDEX Randomized Clinical Trial.

Importance: Acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19) is associated with substantial mortality and use of health care resources. Dexamethasone use might attenuate lung injury in these patients. Objective: To determine whether intravenous dexamethasone increases the number of ventilator-free days among patients with COVID-19-associated ARDS. Design, Setting, and Participants: Multicenter, randomized, open-label, clinical trial conducted in 41 intensive care units (ICUs) in Brazil. Patients with COVID-19 and moderate to severe ARDS, according to the Berlin definition, were enrolled from April 17 to June 23, 2020. Final follow-up was completed on July 21, 2020. The trial was stopped early following publication of a related study before reaching the planned sample size of 350 patients. Interventions: Twenty mg of dexamethasone intravenously daily for 5 days, 10 mg of dexamethasone daily for 5 days or until ICU discharge, plus standard care (n =151) or standard care alone (n = 148). Main Outcomes and Measures: The primary outcome was ventilator-free days during the first 28 days, defined as being alive and free from mechanical ventilation. Secondary outcomes were all-cause mortality at 28 days, clinical status of patients at day 15 using a 6-point ordinal scale (ranging from 1, not hospitalized to 6, death), ICU-free days during the first 28 days, mechanical ventilation duration at 28 days, and Sequential Organ Failure Assessment (SOFA) scores (range, 0-24, with higher scores indicating greater organ dysfunction) at 48 hours, 72 hours, and 7 days. Results: A total of 299 patients (mean [SD] age, 61 [14] years; 37% women) were enrolled and all completed follow-up. Patients randomized to the dexamethasone group had a mean 6.6 ventilator-free days (95% CI, 5.0-8.2) during the first 28 days vs 4.0 ventilator-free days (95% CI, 2.9-5.4) in the standard care group (difference, 2.26; 95% CI, 0.2-4.38; P = .04). At 7 days, patients in the dexamethasone group had a mean SOFA score of 6.1 (95% CI, 5.5-6.7) vs 7.5 (95% CI, 6.9-8.1) in the standard care group (difference, -1.16; 95% CI, -1.94 to -0.38; P = .004). There was no significant difference in the prespecified secondary outcomes of all-cause mortality at 28 days, ICU-free days during the first 28 days, mechanical ventilation duration at 28 days, or the 6-point ordinal scale at 15 days. Thirty-three patients (21.9%) in the dexamethasone group vs 43 (29.1%) in the standard care group experienced secondary infections, 47 (31.1%) vs 42 (28.3%) needed insulin for glucose control, and 5 (3.3%) vs 9 (6.1%) experienced other serious adverse events. Conclusions and Relevance: Among patients with COVID-19 and moderate or severe ARDS, use of intravenous dexamethasone plus standard care compared with standard care alone resulted in a statistically significant increase in the number of ventilator-free days (days alive and free of mechanical ventilation) over 28 days. Trial Registration: ClinicalTrials.gov Identifier: NCT04327401.

Probing the O-glycoproteome of gastric cancer cell lines for biomarker discovery.

Circulating O-glycoproteins shed from cancer cells represent important serum biomarkers for diagnostic and prognostic purposes. We have recently shown that selective detection of cancer-associated aberrant glycoforms of circulating O-glycoprotein biomarkers can increase specificity of cancer biomarker assays. However, the current knowledge of secreted and circulating O-glycoproteins is limited. Here, we used the COSMC KO "SimpleCell" (SC) strategy to characterize the O-glycoproteome of two gastric cancer SimpleCell lines (AGS, MKN45) as well as a gastric cell line (KATO III) which naturally expresses at least partially truncated O-glycans. Overall, we identified 499 O-glycoproteins and 1236 O-glycosites in gastric cancer SimpleCells, and a total 47 O-glycoproteins and 73 O-glycosites in the KATO III cell line. We next modified the glycoproteomic strategy to apply it to pools of sera from gastric cancer and healthy individuals to identify circulating O-glycoproteins with the STn glycoform. We identified 37 O-glycoproteins in the pool of cancer sera, and only nine of these were also found in sera from healthy individuals. Two identified candidate O-glycoprotein biomarkers (CD44 and GalNAc-T5) circulating with the STn glycoform were further validated as being expressed in gastric cancer tissue. A proximity ligation assay was used to show that CD44 was expressed with the STn glycoform in gastric cancer tissues. The study provides a discovery strategy for aberrantly glycosylated O-glycoproteins and a set of O-glycoprotein candidates with biomarker potential in gastric cancer.

Resilience in the face of peer victimisation and discrimination: The who, when and why in five patterns of adjustment.

Victimisation has a negative effect on psychosocial functioning. Based on the resilience theory, and with a sample of 2975 Portuguese students, the present study aims to: i) identify patterns of adjustment in the face of peer victimisation and perceptions of discrimination; ii) explore the association between the patterns of adjustment and the characteristics of participants (the who) and of the victimisation (the when and why). Cluster analysis revealed five patterns of adjustment: Unchallenged; Externally Maladjusted; Internally Maladjusted; Resilient, and At-Risk. The results suggest that there is no complete resilience in the face of social victimisation. Group differences were found regarding: i) gender, type of course, sexual orientation, ethnicity, nationality, parental educational level and religious beliefs; ii) the age at which peer victimisation was more frequent, and; iii) the motives underlying discrimination. Globally considered, peer victimisation is representative of the wider cultural environment and interventions should also target social prejudices.

Helicobacter pylori chronic infection and mucosal inflammation switches the human gastric glycosylation pathways.

Helicobacter pylori exploits host glycoconjugates to colonize the gastric niche. Infection can persist for decades promoting chronic inflammation, and in a subset of individuals lesions can silently progress to cancer. This study shows that H. pylori chronic infection and gastric tissue inflammation result in a remodeling of the gastric glycophenotype with increased expression of sialyl-Lewis a/x antigens due to transcriptional up-regulation of the B3GNT5, B3GALT5, and FUT3 genes. We observed that H. pylori infected individuals present a marked gastric local pro-inflammatory signature with significantly higher TNF-α levels and demonstrated that TNF-induced activation of the NF-kappaB pathway results in B3GNT5 transcriptional up-regulation. Furthermore, we show that this gastric glycosylation shift, characterized by increased sialylation patterns, favors SabA-mediated H. pylori attachment to human inflamed gastric mucosa. This study provides novel clinically relevant insights into the regulatory mechanisms underlying H. pylori modulation of host glycosylation machinery, and phenotypic alterations crucial for life-long infection. Moreover, the biosynthetic pathways here identified as responsible for gastric mucosa increased sialylation, in response to H. pylori infection, can be exploited as drug targets for hindering bacteria adhesion and counteract the infection chronicity.

Glycoengineered cell models for the characterization of cancer O-glycoproteome: an innovative strategy for biomarker discovery.

Glycosylation is one of the most abundant forms of protein posttranslational modification. O-glycosylation is a major type of protein glycosylation, comprising different types and structures expressed in several physiologic and pathologic conditions. The understanding of protein attachment site and glycan structure is of the utmost importance for the clarification of the role glycosylation plays in normal cells and in pathological conditions. Neoplastic transformation frequently shows the expression of immature truncated O-glycans. These aberrantly expressed O-glycans have been shown to induce oncogenic properties and can be detected in premalignant lesions, meaning that they are an important source of biomarkers. This article addresses the recent application of genetically engineered cancer cell models to produce simplified homogenous O-glycans allowing the characterization of cancer cells O-glycoproteomes, using advanced mass spectrometry methods and the identification of potential cancer-specific O-glycosylation sites. This article will also discuss possible applications of these biomarkers in the cancer field.

Therapy-induced enrichment of putative lung cancer stem-like cells.

Tumour drug resistance is a major issue in the management of lung cancer patients as almost all lung tumours are either intrinsically resistant or quickly develop acquired resistance to chemotherapeutic drugs. Cancer drug resistance has recently been linked, at least in part, to the existence of cancer stem-like cells (CSLCs), a small sub-population of cells within the tumour that possess stem-like properties. CSLCs are often isolated by fluorescence activated cell sorting (FACS) according to the expression of certain stem-like cell membrane markers. Conflicting results regarding the specificity of particular stem cell surface markers for isolating CSLCs have, however, been recently reported. Therefore, alternative strategies enabling the identification and study of CSLCs should be considered, particularly in tumour types where appropriate stem cell markers are not well established and validated, like in lung cancer. In this article, we review data indicating therapy-selection as a valid approach for putative lung CSLCs enrichment. We believe that this strategy would be determinant for correctly assessing and characterising the sub-populations of CSLCs that are able to survive chemo or radiotherapy regimens and, at the same time, also have the ability to recapitulate and sustain tumour growth. Using therapy-induced enrichment of CSLCs may, therefore, prove to be an extremely useful method for studying CSLCs and provide new clues regarding potential therapeutic targets for their efficient elimination, which will undoubtedly play a decisive role in improving lung cancer patients' survival.

Neoadjuvant chemotherapy with six cycles of carboplatin and paclitaxel in advanced ovarian cancer patients unsuitable for primary surgery: Safety and effectiveness.

OBJECTIVE: Three cycles of neoadjuvant chemotherapy (NACT) followed by interval debulking (ID) surgery is an alternative for patients with advanced ovarian cancer unresectable disease. This study aimed to determine the efficacy and safety of six cycles of NACT followed by cytoreduction. METHODS: Retrospective analysis of all patients with advanced epithelial ovarian cancer, tubal carcinoma, or primary peritoneal carcinoma treated with platinum based NACT between January 2008 and February 2012. RESULTS: Eighty-two patients underwent NACT; 78% and 18.2% had extensive stage IIIC or IV disease at diagnosis, respectively. Their median age was 60 years (41-82). On histology, serous adenocarcinoma was found in 90.2%. Patients did not receive chemotherapy after debulking surgery. 35.4% suffered grade 3/4 toxicity; the most commonly observed toxicities were hematologic and nausea. After NACT, 23.1% experienced clinical complete response, 57.4% partial response, and 12.1% disease progression. Complete resection of all macroscopic and microscopic disease (R0) was performed in 63.7%. Surgical complications were uncommon; however, four (6.2%) patients needed a second procedure due to operative complications and 18 (27.3%) needed blood transfusion after debulking. Over a median follow-up period of 19.2 months, median overall survival and chemotherapy-free interval were 37.5 months (confidence interval not reached) and 16 months, respectively. CONCLUSION: Six cycles of neoadjuvant carboplatin and paclitaxel was safe and effective and did not increase perioperative or postoperative complications in patients with stage IIIC/IV disease who were unsuitable for optimal PDS. The overall survival of this cohort was higher than that of those treated with ID surgery.