Sarcopenia measured by tomography as a predictor of morbidity and mortality in thoracic surgery, a retrospective cohort study.

BACKGROUND: Sarcopenia has been identified as a risk factor for perioperative adverse events. Several studies have shown that tomographic assessment of muscle mass can be an appropriate indicator of sarcopenia associated with morbidity and mortality. The aim of the study was to determine the association between height-adjusted area of ​​the pectoral and erector spinae muscles (haPMA and haESA) and perioperative morbidity and mortality in thoracic surgery. METHODS: Retrospective cohort study. Measurement of muscle areas was performed by tomography. The outcomes were 30-day mortality and postoperative morbidity. The discriminative capacity of the muscle areas was evaluated with an analysis of ROC curves and the Youden index was used to establish a cut-off point. The raw morbidity and mortality risk was determined and adjusted for potential confounders. RESULTS: A total of 509 patients taken to thoracic surgery were included. The incidence of 30-day mortality was 7.3%. An association was found between muscle areas and 30-day mortality and pneumonia, with adequate discriminative power for mortality (AUC 0.68 for haPMA and 0.67 for haESA). An haPMA less than 10 and haESA less than 8.5 cm2/m2 were identified as a risk factor for 30-day mortality with an adjusted OR of 2.34 (95%CI 1.03-5.15) and 2.22 (95%CI 1.10-6.04) respectively. CONCLUSIONS: Sarcopenia, defined as low muscle area in the pectoral and erector spinae muscles, is associated with increased morbidity and mortality in patients undergoing thoracic surgery.

SNAI1-expressing fibroblasts and derived-extracellular matrix as mediators of drug resistance in colorectal cancer patients.

Resistance to antitumor treatments is one of the most important problems faced by clinicians in the management of colorectal cancer (CRC) patients. Cancer-Associated Fibroblasts (CAFs) are the main producers and remodelers of the extracellular matrix (ECM), which is directly involved in drug resistance mechanisms. Primary Normal Fibroblasts (NFs) and CAFs and cell lines (fibroblasts and tumor cells), were used to generate ECM and to identify its role in the oxaliplatin and cetuximab chemoresistance processes of CRC cells mediated by SNAI1-expressing fibroblasts. Matrices generated by Snai1 KO MEFs (Knockout Mouse Embryonic Fibroblasts) confer less resistance on oxaliplatin and cetuximab than wild-type MEF-derived matrices. Similarly, matrices derived from CAFs cause greater survival of colorectal cancer cells than NF-derived matrices, in a similar way to Snai1 expression levels. In addition, Snail1 expression in fibroblasts regulates drug resistance and metabolism gene expression in tumor cells mediated by ECM. Finally, a series of 531 patients (TCGA) with CRC was used to assess the role of SNAI1 expression in patients' prognosis indicating an association between tumor SNAI1 expression and overall survival in colon cancer patients but not in rectal cancer patients. SNAI1 expression in CRC cancer patients, together with in vitro experimentation, suggests the possible use of SNAI1 expression in tumor-associated fibroblasts as a predictive biomarker of response to oxaliplatin and cetuximab treatments in patients with CRC.

Properties of the avocado oil extracted using centrifugation and ultrasound-assisted methods.

The aim of this work was to evaluate the technologies effect of cold extraction by centrifugation (CE) and ultrasound-assisted (US-CE) methods without adding water, on the avocado oil yield, nutritional composition, physicochemical characteristics, oxidative stability (oxidation temperature and time, besides activation energy) and accelerated shelf life regarding hexane extraction (control). The US-CE improved the physicochemical properties such as acidity, peroxides, and iodine indexes regarding CE and Control. US-CE improved the yield, nutritional quality of fatty acids, oxidative stability, shelf life, and ω-6/ω-3 ratio regarding CE. Furthermore, US-CE improved the ratio yield/time extraction of the oil and increased the oxidation temperature regarding control. The main advantage of oils extracted using CE and US-CE concerning control was higher oxidative stability. The most representative polyunsaturated fatty acids identified in all treatments were γ-linolenic and conjugated α-linolenic acids. α-linolenic acid was only detected in US-CE and control. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10068-021-00940-w.

Sentinel lymph node biopsy procedure in squamous vulvar cancer. 10 years follow-up analysis. / Biopsia selectiva de ganglio centinela en el carcinoma escamoso de vulva. Análisis de seguimiento a 10 años.

AIM: Application of sentinel lymph node biopsy (SLNB) procedure in early-stage vulvar cancer and analysis of results, recurrences and complications. MATERIAL AND METHODS: 40 patients with vulvar cancer and SLNB between 2008 and 2018 were retrospectively reviewed. During the surgical procedure the inguinofemoral lymph nodes were checked with a gamma probe to identify the sentinel nodes that were removed and referred for intraoperative pathological assessment. Subsequently, long-term patient follow-up was performed with analysis of complications, relapse and mortality. RESULTS: 40 patients (mean age: 72 years [47-86], the overall detection rate per patient was 95% and a total of 129 Sentinel Lymph Nodes (SLNs) were removed (3.22 SLN/patient). In 3 out of 25 patients with lateral tumour lesions drainage was bilateral and in 2 out of 15 with midline lesions drainage was unilateral. On lymphoscintigraphy, 16 out of 40 had bilateral drainage and 24 unilateral. A total of 119 SLN- and 10 SLN+ were obtained, in 8 out of 10 an inguinofemoral lymphadenectomy was performed. In the SLN- group, one case of lymphatic blockage and one false negative were included. In 12 out of 40 patients there were post-surgical complications, 4 of them lymphoedemas. In the median follow-up (40 months), 6 out of 10 with SLN+ (40% mortality) and 7 out of 30 SLN- (16% mortality) had recurrences. CONCLUSIONS: SLNB in vulvar cancer is the technique of choice for correct staging and locoregional therapy. Correct clinical lymph node staging is important before surgery in order to avoid potential blockage drainages which could induce a false negative SLN.

Significant differences in access to tests and treatments for multiple myeloma between public and private systems in Latin America. Results of a Latin American survey. GELAMM (Grupo de Estudio Latino Americano de Mieloma Múltiple).

The incidence of multiple myeloma (MM) has increased in the last 20 years, particularly in middle and low-middle income countries. Access to diagnostic and prognostic tests and the availability of effective care is highly variable globally. Latin America represents 10% of the world population, distributed in countries of varied size, population, and socio-economic development. In the last decade, great improvements have been made in the diagnosis and treatment of MM. Applying these advances in real life is a challenge in our region. Local data regarding MM standards of care and outcomes are limited. A survey was carried out among hematologists from 15 Latin American countries to describe access to MM diagnostic and prognostic tests and the availability of effective care options. This study provides real-world data for MM in our region, highlighting striking differences between public and private access to essential analyses and therapeutic options.

Increased renal damage in hypocomplementemic patients with ANCA-associated vasculitis: retrospective cohort study.

INTRODUCTION: The complement system has an important role in the pathogenesis of vasculitis associated with antineutrophilic cytoplasmic antibody (AAV) mainly at the level of the kidneys because patients with complement deposits on the glomerular basal membrane present more aggressive disease compared with those with pauci-immune vasculitis. AIM: To analyze the association of hypocomplementemia with the clinical manifestations, laboratory data, renal histology, progress to renal insufficiency, and mortality of patients with AAV. METHODS: Retrospective cohort study (2000-2007) included 93 patients with AAV. Hypocomplementemia is defined as having C3 values lower than 80 mg/dL or C4 values below 15 mg/dL. Demographic, statistical, clinical, hematological, serological, and histopathological characteristics of all the patients with and without diagnosis of hypocomplementemia were compared. In order to evaluate variable independence, a logistic regression analysis was used. RESULTS: Ninety-three patients were studied of whom 63 (67.7%) had complement dosage at the moment of AAV diagnosis. Seven patients (11.1%) presented hypocomplementemia and a greater kidney involvement compared with normocomplementemic patients. Thirty renal biopsies were analyzed and 4 (13.3%) showed immunocomplex (IC) or complement deposits by an immunofluorescence test (IFT). Patients with "non-pauci-immune" AAV also presented terminal chronic renal disease (TCRD). CONCLUSION: There is an association between low complement and the degree of renal damage in patients with AAV. Patients with renal biopsies confirming IC and/or complement deposits showed more aggressive renal disease. Key Points • The complement system has an important role in the pathogenesis of vasculitis associated to antineutrophilic cytoplasmic antibody. • The studies in murine models confirming the complement activation by alternative pathway and particularly the receptor C5a (C5aR) is necessary for the development of glomerulonefritis. • Complement deposit observed in the renal biopsies of patients diagnosed with AAV was correlated to greater kidney damage, greater proteinuria and major disease activity compared to patients diagnosed with typical pauci-immune vasculitis. • The presence of hypocomplementemia at the onset of the disease was also associated with a greater organ involvement, poor prognosis and greater mortality.

Phase I dose-escalation study of copanlisib in combination with gemcitabine or cisplatin plus gemcitabine in patients with advanced cancer.

BACKGROUND: Copanlisib is a pan-class I phosphatidylinositol 3-kinase (PI3K) inhibitor with predominant PI3K-α/δ activity that has demonstrated clinical activity and manageable safety when administered as monotherapy in a phase II study. Combination therapy may overcome compensatory signalling that could occur with PI3K pathway inhibition, resulting in enhanced inhibitory activity, and preclinical studies of copanlisib with gemcitabine have demonstrated potent anti-tumour activity in vivo. METHODS: A phase I, open-label, dose-escalation study to evaluate the safety, tolerability and recommended phase II dose (RP2D) of copanlisib with gemcitabine or with cisplatin plus gemcitabine (CisGem) in patients with advanced malignancies, including an expansion cohort in patients with biliary tract cancer (BTC) at the RP2D of copanlisib plus CisGem. Copanlisib and gemcitabine were administered on days 1, 8 and 15 of a 28-day cycle; maximum tolerated dose (MTD) and RP2D of copanlisib were determined. Copanlisib plus CisGem was administered on days 1 and 8 of a 21-day cycle; pharmacokinetics and biomarkers were assessed. RESULTS: Fifty patients received treatment as follows: dose-escalation cohorts, n=16; copanlisib plus CisGem cohort, n=14; and BTC expansion cohort, n=20. Copanlisib 0.8 mg kg-1 plus gemcitabine was the MTD and RP2D for both combinations. Common treatment-emergent adverse events included nausea (86%), hyperglycaemia (80%) and decreased platelet count (80%). Copanlisib exposure displayed a dose-proportional increase. No differences were observed upon co-administration of CisGem. Response rates were as follows: copanlisib plus gemcitabine, 6.3% (one partial response in a patient with peritoneal carcinoma); copanlisib plus CisGem, 12% (one complete response and three partial responses all in patients with BTC (response rate 17.4% in patients with BTC)). Mutations were detected in PIK3CA (1 out of 43), KRAS (10 out of 43) and BRAF (2 out of 22), with phosphate and tensin homologue protein loss in 41% (12 out of 29). CONCLUSIONS: Copanlisib plus CisGem demonstrated a manageable safety profile, favourable pharmacokinetics, and potentially promising clinical response.

Fibroelastic pseudotumor elastofibroma dorsi detected by 18F-FDG PET/CT scan and by postherapy radioiodine SPECT/CT. / Seudotumor fibroelástico elastofibroma dorsi detectado por 18F-FDG PET/TC y por 131I SPECT/TC posterapia.

Radioiodine uptake in the thyroid tissue, metastasis of differentiated thyroid cancer (DTC), and in other tissues, depends on the expression of sodium-iodide symporter (NIS). Vascular permeability, effusions, inflammation, and other mechanisms may also play a role in the accumulation of radioactive iodine. A 63-year-old woman underwent radioiodine therapy, as well as a post-therapy whole-body scan, as she was suspected of having lung metastasis from thyroid carcinoma. The scan not only showed uptake at the lung metastasis but also a faint diffuse bilateral uptake in the posterior thorax. On SPECT/CT this uptake was located in a known Elastofibroma Dorsi (ED) previously diagnosed by contrast CT and viewed in a FDG PET/CT. The radioiodine uptake in ED, especially if typical, is not a diagnostic problem in SPECT/CT study, but can be misleading in a study limited to a few planar images, particularly if the uptake occurs asymmetrically, or ED is located in a unsuspected area.

Phase II study of copanlisib, a PI3K inhibitor, in relapsed or refractory, indolent or aggressive lymphoma.

BACKGROUND: Copanlisib is a pan-class I phosphatidylinositol 3-kinase inhibitor with predominant activity against the α- and δ-isoforms. PATIENTS AND METHODS: This phase II study evaluated the response rate of copanlisib administered intravenously on days 1, 8, and 15 of a 28-day cycle, in patients with indolent or aggressive malignant lymphoma. Archival tumor tissues were used for immunohistochemistry, gene-expression profiling, and mutation analysis. RESULTS: Thirty-three patients with indolent lymphoma and 51 with aggressive lymphoma received copanlisib. Follicular lymphoma (48.5%) and peripheral T-cell lymphoma (33.3%) were the most common histologic subtypes. Most patients (78.6%) had received prior rituximab and 54.8% were rituximab-refractory. Median duration of treatment was 23 and 8 weeks in the indolent and aggressive cohorts, respectively (overall range 2-138). Eighty patients were evaluated for efficacy. The objective response rate was 43.7% (14/32) in the indolent cohort and 27.1% (13/48) in the aggressive cohort; median progression-free survival was 294 days (range 0-874) and 70 days (range 0-897), respectively; median duration of response was 390 days (range 0-825) and 166 days (range 0-786), respectively. Common adverse events included hyperglycemia (57.1%; grade ≥3, 23.8%), hypertension (54.8%; grade ≥3, 40.5%), and diarrhea (40.5%; grade ≥3, 4.8%), all generally manageable. Neutropenia occurred in 28.6% of patients (grade 4, 11.9%). Molecular analyses showed enhanced antitumor activity in tumors with upregulated phosphatidylinositol 3-kinase pathway gene expression. CONCLUSION: Intravenous copanlisib demonstrated promising efficacy and manageable toxicity in heavily pretreated patients with various subtypes of indolent and aggressive malignant lymphoma. Subtype-specific studies of copanlisib in patients with follicular, peripheral T-cell, and mantle cell lymphomas are ongoing. This trial is registered with ClinicalTrials.gov number NCT01660451 (Part A).

First-in-human phase I study of copanlisib (BAY 80-6946), an intravenous pan-class I phosphatidylinositol 3-kinase inhibitor, in patients with advanced solid tumors and non-Hodgkin's lymphomas.

BACKGROUND: To evaluate the safety, tolerability, pharmacokinetics, and maximum tolerated dose (MTD) of copanlisib, a phosphatidylinositol 3-kinase inhibitor, in patients with advanced solid tumors or non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Phase I dose-escalation study including patients with advanced solid tumors or NHL, and a cohort of patients with type 2 diabetes mellitus. Patients received three weekly intravenous infusions of copanlisib per 28-day cycle over the dose range 0.1-1.2 mg/kg. Plasma copanlisib levels were analyzed for pharmacokinetics. Biomarker analysis included PIK3CA, KRAS, BRAF, and PTEN mutational status and PTEN immunohistochemistry. Whole-body [(18)F]-fluorodeoxyglucose positron emission tomography ((18)FDG-PET) was carried out at baseline and following the first dose to assess early pharmacodynamic effects. Plasma glucose and insulin levels were evaluated serially. RESULTS: Fifty-seven patients received treatment. The MTD was 0.8 mg/kg copanlisib. The most frequent treatment-related adverse events were nausea and transient hyperglycemia. Copanlisib exposure was dose-proportional with no accumulation; peak exposure positively correlated with transient hyperglycemia post-infusion. Sixteen of 20 patients treated at the MTD had reduced (18)FDG-PET uptake; 7 (33%) had a reduction >25%. One patient achieved a complete response (CR; endometrial carcinoma exhibiting both PIK3CA and PTEN mutations and complete PTEN loss) and two had a partial response (PR; both metastatic breast cancer). Among the nine NHL patients, all six with follicular lymphoma (FL) responded (one CR and five PRs) and one patient with diffuse large B-cell lymphoma had a PR by investigator assessment; two patients with FL who achieved CR (per post hoc independent radiologic review) were on treatment >3 years. CONCLUSION: Copanlisib, dosed intermittently on days 1, 8, and 15 of a 28-day cycle, was well tolerated and the MTD was determined to be 0.8 mg/kg. Copanlisib exhibited dose-proportional pharmacokinetics and promising anti-tumor activity, particularly in patients with NHL. CLINICALTRIALSGOV: NCT00962611; https://clinicaltrials.gov/ct2/show/NCT00962611.

Twist1-induced activation of human fibroblasts promotes matrix stiffness by upregulating palladin and collagen α1(VI).

The transcription factor Twist1 is involved in the epithelial-mesenchymal transition and contributes to cancer metastasis through mostly unknown mechanisms. In colorectal cancer, Twist1 expression is mainly restricted to the tumor stroma. We found that human fibroblast cell lines stably transfected with Twist1 acquired characteristics of activated cancer-associated fibroblasts (CAFs), such as hyperproliferation, an increased ability to migrate and an alignment of the actin cytoskeleton. Further, Twist1-activated fibroblasts promoted increased matrix stiffness. Using quantitative proteomics, we identified palladin and collagen α1(VI) as two major mediators of the Twist1 effects in fibroblast cell lines. Co-immunoprecipitation studies indicated that palladin and Twist1 interact within the nucleus, suggesting that palladin could act as a transcription regulator. Palladin was found to be more relevant for the cellular biomechanical properties, orientation and polarity, and collagen α1(VI) for the migration and invasion capacity, of Twist1-activated fibroblasts. Both palladin and collagen α1(VI) were observed to be overexpressed in colorectal CAFs and to be associated with poor colorectal cancer patient survival and relapse prediction. Our results demonstrate that Twist1-expressing fibroblasts mimic the properties of CAFs present at the tumor invasive front, which likely explains the prometastatic activities of Twist1. Twist1 appears to require both palladin and collagen α1(VI) as downstream effectors for its prometastatic effects, which could be future therapeutic targets in cancer metastasis.

Frailty Across Age Groups.

BACKGROUND: The implementation of an aging biomarker into clinical practice is under debate. The Frailty Index is a model of deficit accumulation and has shown to accurately capture frailty in older adults, thus bridging biological with clinical practice. OBJECTIVES: To describe the association of socio-demographic characteristics and the Frailty Index in different age groups (from 20 to over one hundred years) in a representative sample of Mexican subjects. DESIGN: Cross-sectional analysis. SETTING: Nationwide and population-representative survey. PARTICIPANTS: Adults 20-years and older interviewed during the last Mexican National Health and Nutrition Survey (2012). MEASUREMENTS: A 30-item Frailty Index following standard construction was developed. Multi-level regression models were performed to test the associations of the Frailty Index with multiple socio-demographic characteristics across age groups. RESULTS: A total of 29,504 subjects was analyzed. The 30-item Frailty Index showed the highest scores in the older age groups, especially in women. No sociodemographic variable was associated with the Frailty Index in all the studied age groups. However, employment, economic income, and smoking status were more consistently found across age groups. CONCLUSIONS: To our knowledge, this is the first report describing the Frailty Index in a representative large sample of a Latin American country. Increasing age and gender were closely associated with a higher score.

E2f3 in tumor macrophages promotes lung metastasis.

The Rb-E2F axis is an important pathway involved in cell-cycle control that is deregulated in a number of cancers. E2f transcription factors have distinct roles in the control of cell proliferation, cell survival and differentiation in a variety of tissues. We have previously shown that E2fs are important downstream targets of a CSF-1 signaling cascade involved in myeloid development. In cancer, tumor-associated macrophages (TAMs) are recruited to the tumor stroma in response to cytokines secreted by tumor cells, and are believed to facilitate tumor cell invasion and metastasis. Using the MMTV-Polyoma Middle T antigen (PyMT) mouse model of human ductal carcinoma, we show that the specific ablation of E2f3 in TAMs, but not in tumor epithelial cells, attenuates lung metastasis without affecting primary tumor growth. Histological analysis and gene expression profiling suggest that E2f3 does not impact the proliferation or survival of TAMs, but rather controls a novel gene expression signature associated with cytoskeleton rearrangements, cell migration and adhesion. This E2f3 TAM gene expression signature was sufficient to predict cancer recurrence and overall survival of estrogen receptor (ER)-positive breast cancer patients. Interestingly, we find that E2f3b but not E2f3a levels are elevated in TAMs from PyMT mammary glands relative to controls, suggesting a differential role for these isoforms in metastasis. In summary, these findings identify E2f3 as a key transcription factor in TAMs, which influences the tumor microenvironment and tumor cell metastasis.

The emerging role of Snail1 in the tumor stroma.

The transcription factor Snail1 leads to the epithelial-mesenchymal transition by repressing the adherent and tight junctions in epithelial cells. This process is related to an increase of cell migratory and mesenchymal properties during both embryonic development and tumor progression. Although Snail1 expression is very limited in adult animals, emerging evidence has placed Snail at the forefront of medical science. As a transcriptional repressor, Snail1 confers cancer stem cell-like traits on tumor cells and promotes drug resistance, tumor recurrence and metastasis. In this review, we summarize recent reports that suggest the pro-tumorigenic roles of Snail1 expression in tumor stroma. The crosstalk between tumor and stromal cells mediated by Snail1 regulates paracrine communication, pro-tumorigenic abilities of cancer cells, extracellular matrix characteristics and mesenchymal differentiation in cancer stem cells and cancer-associated fibroblasts. Therefore, understanding the regulation and functional roles of Snail1 in the tumor microenvironment will provide us with new therapies for treating metastatic disease.

Metotrexato en condromatosis sinovial: una serendipia / Methotrexate in sinovial chondromatosis: a case of serendipity

La condromatosis sinovial es una metaplasia idiopática benigna de la membrana sinovial que afecta a 1/100.000 habitantes, en una relación hombre/mujer de 3 a 1 entre los 30 y 50 años. Predomina en grandes articulaciones como rodilla (70%), cadera (20%) y hombro (19%), y en menor proporción en codo y tobillo. Puede ser primaria o secundaria. La etiología es desconocida. La resolución es quirúrgica ya sea por artroscopia o por cirugía a cielo abierto, no existiendo otra alternativa terapéutica. Se presenta el caso clínico de un paciente con condromatosis sinovial en hombro derecho, que se comporta como una artropatía erosiva, indicándose metotrexato y resolviendo casi totalmente los nódulos condromatosos.

The synovial chondromatosis is a benign idiopathic metaplasia ofthe synovial membrane which affects one in 100,000 inhabitants. Itis 3 times more common in males, aged between 30 and 50 yearsold. It is commonly found in large joints such as knee (70%), hip(20%) and shoulder (19%) and less frequently in elbow and heel. Itcan be primary or secondary. The etiology is still unknown.The resolution is surgical by means of arthroscopy or open surgery,existing no other therapeutic alternatives.We present a male patient with primary synovial chondromatosis inthe right shoulder, leading to an erosive arthropathy. Treatment withmethotrexate resolved almost entirely the cartilaginous nodules.

Redox Regulation Of Metabolic And Signaling Pathways By Thioredoxin And Glutaredoxin In Nitric Oxide Treated Hepatoblastoma Cells.

BACKGROUND: NO has an antiproliferative action on HepG2 cells and Thioredoxin (Trx) and Glutaredoxin (Grx) have denitrosilase and deglutathionylase activities. AIMS: To ascertain whether Trx and/or Grx systems intermediate the anti-proliferative effect of NO on hepatoblastoma cells by modulating the redox-state of key proteins. METHODS: HepG2 cells overexpressing Nitric Oxide Synthase-3 (NOS-3) were transfected with specific siRNA to silence Trx1 and Grx1. The expression and thiolic redox state of proteins were determined by Western blot and redox mobility shift assay. RESULTS: Overexpression of NOS3 increased the levels and activities of proteins of the redoxin systems, Trx1, Grx1, TrxR1 and TxnIP, and the levels of signaling proteins (Akt1, pAkt1-Ser473, MapK, pMapK, Stat3, Fas). The thiolic redox state of Trx1, Grx1 and Akt1 shifted to more oxidized. Increases were also observed in Pro-apoptotic Caspase-3 fragment levels; caspase 3, 8 and 9 activities; antiapoptotic (Bcl-2); mitochondrial energetic (Aco2) and heme (Urod) metabolism; Glycolysis (Pkm2); and pentose phosphate pathway (Tkt). However, two cytosolic proteins related to iron (Aco1) and one carbon (Mat2) metabolism decreased markedly. Moreover, the redox state of Urod and Aco1 shifted to more oxidized cysteines. Trx1 or Grx1 silencing augmented Tyr nitration and diminished cell proliferation in WT cells, but attenuated the antiproliferative effect on NO, the increase of Fas, Akt1 and pAkt1-Ser473 and the oxidative modification of Akt1 in NOS3 cells. CONCLUSIONS: Trx1 and Grx1 exert contradictory influences on HepG2 cells. They are required for proliferation but they also contribute to antiproliferative effect of NO, associated to Akt1 redox changes.

Biotechnological strategies to improve production of microbial poly-(3-hydroxybutyrate): a review of recent research work.

Poly-(3-hydroxybutyrate) [P(3HB)] is a polyester synthesized as a carbon and energy reserve material by a wide number of bacteria. This polymer is characterized by its thermo-plastic properties similar to plastics derived from petrochemical industry, such as polyethylene and polypropylene. Furthermore, P(3HB) is an inert, biocompatible and biodegradable material which has been proposed for several uses in medical and biomedical areas. Currently, only few bacterial species such as Cupriavidus necator, Azohydromonas lata and recombinant Escherichia coli have been successfully used for P(3HB) production at industrial level. Nevertheless, in recent years, several fermentation strategies using other microbial models such as Azotobacter vinelandii, A. chroococcum, as well as some methane-utilizing species, have been developed in order to improve the P(3HB) production and also its mean molecular weight.

Genetic analysis in APC, KRAS, and TP53 in patients with stomach and colon cancer.

BACKGROUND: Stomach cancer (SC) and colorectal cancer (CRC) present with high rates of incidence and mortality in the worldwide population. These 2 tumors are characterized by great genetic heterogeneity. Up to now, there have been no molecular studies that analyze the mutations in the APC, KRAS, and TP53 genes in the Colombian/Latin American population. OBJECTIVES: To analyze mutations in the APC, KRAS, and TP53 genes through direct sequencing in 59 patients with SC and CRC. PATIENTS AND METHODS: Twenty-nine patients with SC and 30 with CRC were studied. An analysis of the mutations of the 3 genes was carried out using polymerase chain reaction and direct sequencing techniques. RESULTS: A 30.5% total mutation frequency was found. The most frequently mutated gene was APC (15.3%), followed by KRAS (10.1%) and TP53 (5.1%). The CRC samples had a mutation frequency of 46.7% and it was 13.3% in the SC samples (P=.006). No mutations occurred simultaneously in the 3 genes. Mutations in 2 genes were found in only 6 tumor samples (10%). There was also a high frequency of polymorphisms in both types of cancer, the most common of which was the rs41115 polymorphism, located on the APC gene. CONCLUSION: The APC, KRAS, and TP53 gene mutations were more common in CRC than in SC. Our results suggest the existence of different genetic pathways in the carcinogenesis of SC and CRC and they also reveal a particular mutation frequency in the Colombian patients studied; this could be influenced by factors related to the environment, ethnicity, and lifestyle of this population.