66. Late effects of CNS prophylactic irradiation in childhood due to LLA using Magnetic Resonance Spectro-skopy. (preliminary report)

PurposeThe aim of this study was to evaluate changes in magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) of the brain in survivars with Acute Lymphoblastic Leukemia to assess neurotixicity follow profilactic brain irradiation.MethodsTen from 100 patients with LLA treated in Department of Pediatric Hematology from 1990 to 1995 and irradiated in Centre of Oncology were icluded in MRI and MRS studies. The study group included 6 male and 4 female. All patients had been irradiated for brain using fraction dose of 1,8 Gy up to total dose of 18 Gy and had recived MTX based chemotherapy in doses depending on level of risk. Two of them were included in low risk and eight in intermediate risk.ResultsMRI of brain was abnormal in 5 cases. There were mild white matter changes.The changes were Been in H- MRS metabolite ratios. In one of these cases we observed a impair of verbal functions.ConclusionsThe MRS could be valuable method to access brain tissue metabolism after radiotherapy. That noninvasive method may be recomended for children with LLA to observe neurotoxicity of profilactic irradiation

Extension of soil thermal conductivity models to frozen meats with low and high fat content

Thermal conductivity models of frozen soils were analyzed and compared with similar models developed for frozen foods. In total, eight thermal conductivity models and 54 model versions were tested against experimental data of 13 meat products in the temperature range from 0 toK40 8C. The model by deVries, with waterCice (wi) as the continuous phase, showed overall the best predictions. The use of wi leads generally to improved predictions in comparison to ice; water as the continuous phase is beneficial only to deVries model, mostly from K1 to K20 8C; fat is advantageous only to meats with high fat content. The results of this work suggest that the more sophisticated way of estimating the thermal conductivity for a disperse phase in the deVries model might be more appropriate than the use of basic multi-phase models (geometric mean, parallel, and series). Overall, relatively small differences in predictions were observed between the best model versions by deVries, Levy, Mascheroni, Maxwell or Gori as applied to frozen meats with low content of fat. These differences could also be generated by uncertainty in meat composition, temperature dependence of thermal conductivity of ice, measurement errors, and limitation of predictive models

Frequency and Diversity of Nitrate Reductase Genes among Nitrate-Dissimilating Pseudomonas in the Rhizosphere of Perennial Grasses Grown in Field Conditions

A total of 1246 Pseudomonas strains were isolated from the rhizosphere of two perennial grasses (Lolium perenne and Molinia coerulea) with different nitrogen requirements. The plants were grown in their native soil under ambient and elevated atmospheric CO2 content (pCO2) at the Swiss FACE (Free Air CO2 Enrichment) facility. Root-, rhizosphere-, and non-rhizospheric soil-associated strains were characterized in terms of their ability to reduce nitrate during an in vitro assay and with respect to the genes encoding the membrane-bound (named NAR) and periplasmic (NAP) nitrate reductases so far described in the genus Pseudomonas. The diversity of corresponding genes was assessed by PCR-RFLP on narG and napA genes, which encode the catalytic subunit of nitrate reductases. The frequency of nitrate-dissimilating strains decreased with root proximity for both plants and was enhanced under elevated pCO2 in the rhizosphere of L. perenne. NAR (54% of strains) as well as NAP (49%) forms were present in nitrate-reducing strains, 15.5% of the 439 strains tested harbouring both genes. The relative proportions of narG and napA detected in Pseudomonas strains were different according to root proximity and for both pCO2 treatments: the NAR form was more abundant close to the root surface and for plants grown under elevated pCO2. Putative denitrifiers harbored mainly the membrane-bound (NAR) form of nitrate reductase. Finally, both narG and napA sequences displayed a high level of diversity. Anyway, this diversity was correlated neither with the root proximity nor with the pCO2 treatmen

Reduced NGF in gastric endothelial cells is one of the main causes of impaired angiogenesis in aging gastric mucosa

This study detected reduced nerve growth factor (NGF) expression within gastric endothelial cells in both elderly patients and aged rats. Reduced NGF correlated with impaired angiogenesis and delayed gastric ulcer healing in aged rats. The defects could be reversed by exogenous NGF via phosphoinositide-3 kinase/serine threonine kinase signaling protein, and mammalian target of rapamycin signaling, and was dependent on serum response factor. These data show that down-regulation of endothelial NGF expression in aging is a significant contributor to impaired gastric mucosal repair

66. Late effects of CNS prophylactic irradiation in childhood due to LLA using Magnetic Resonance Spectro-skopy. (preliminary report)

PurposeThe aim of this study was to evaluate changes in magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) of the brain in survivars with Acute Lymphoblastic Leukemia to assess neurotixicity follow profilactic brain irradiation.MethodsTen from 100 patients with LLA treated in Department of Pediatric Hematology from 1990 to 1995 and irradiated in Centre of Oncology were icluded in MRI and MRS studies. The study group included 6 male and 4 female. All patients had been irradiated for brain using fraction dose of 1,8 Gy up to total dose of 18 Gy and had recived MTX based chemotherapy in doses depending on level of risk. Two of them were included in low risk and eight in intermediate risk.ResultsMRI of brain was abnormal in 5 cases. There were mild white matter changes.The changes were Been in H- MRS metabolite ratios. In one of these cases we observed a impair of verbal functions.ConclusionsThe MRS could be valuable method to access brain tissue metabolism after radiotherapy. That noninvasive method may be recomended for children with LLA to observe neurotoxicity of profilactic irradiation

Phase 3, randomized, open-label study of pembrolizumab plus lenvatinib versus chemotherapy for first-line treatment of advanced or recurrent endometrial cancer: ENGOT-en9/LEAP-001

BACKGROUND: Pembrolizumab plus lenvatinib is a novel combination with promising efficacy in patients with advanced and recurrent endometrial cancer. This combination demonstrated high objective response rates in a single-arm phase 1b/2 trial of lenvatinib plus pembrolizumab in patients with advanced endometrial cancer (KEYNOTE-146/Study 111) after ≤2 previous lines of therapy. In a randomized phase 3 trial of lenvatinib in combination with pembrolizumab versus treatment of physician's choice in patients with advanced endometrial cancer (KEYNOTE-775/Study 309), after 1‒2 previous lines of therapy (including neoadjuvant/adjuvant), this combination improved objective response rates, progression-free survival, and overall survival compared with chemotherapy. PRIMARY OBJECTIVE: To compare the efficacy and safety of first-line pembrolizumab plus lenvatinib versus paclitaxel plus carboplatin in patients with newly diagnosed stage III/IV or recurrent endometrial cancer, with measurable or radiographically apparent disease. STUDY HYPOTHESIS: Pembrolizumab plus lenvatinib is superior to chemotherapy with respect to progression-free survival and overall survival in patients with mismatch repair-proficient tumors and all patients (all-comers). TRIAL DESIGN: Phase 3, randomized (1:1), open-label, active-controlled trial. Patients will receive pembrolizumab intravenously every 3 weeks plus lenvatinib orally daily or paclitaxel plus carboplatin intravenously every 3 weeks, stratified by mismatch repair status (proficient vs deficient). Patients with mismatch repair-proficient tumors will be further stratified by Eastern Cooperative Oncology Group performance status (0/1), measurable disease (yes/no), and prior chemotherapy and/or chemoradiation (yes/no). MAJOR INCLUSION/EXCLUSION CRITERIA: Adults with stage III/IV/recurrent histologically confirmed endometrial cancer that is measurable or radiographically apparent per blinded independent central review. Patients may have received previous chemotherapy only as neoadjuvant/adjuvant therapy and/or concurrently with radiation. Patients with carcinosarcoma (malignant mixed Müllerian tumor), endometrial leiomyosarcoma, or other high grade sarcomas, or endometrial stromal sarcomas were excluded. PRIMARY ENDPOINTS: Progression-free and overall survival (dual primary endpoints). SAMPLE SIZE: About 875 patients. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Enrollment is expected to take approximately 24 months, with presentation of results in 2022. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03884101

Weak up-regulation of serum response factor in gastric ulcers in patients with co-morbidities is associated with increased risk of recurrent bleeding

<p>Abstract</p> <p>Background</p> <p>Serum response factor (SRF) is crucial for gastric ulcer healing process. The study determined if gastric ulcer tissues up-regulate SRF and if such up-regulation correlated with co-morbidities and the risk of recurrent bleeding.</p> <p>Methods</p> <p>Ulcer and non-ulcer tissues were obtained from 142 patients with active gastric ulcers for SRF expression assessed by immunohistochemistry. Based on the degree of SRF expression between these two tissue types, SRF up-regulation was classified as strong, intermediate, and weak patterns. The patients were followed-up to determine if SRF up-regulation correlated to recurrent bleeding.</p> <p>Results</p> <p>Gastric ulcer tissues had higher SRF expression than non-ulcer tissues (<it>p </it>< 0.05). Patients with strong SRF up-regulation had lower rates of stigmata of recent hemorrhage (SRH) on the ulcer base than the others (<it>p </it>< 0.05). Multivariate logistic regression confirmed that co-morbidities and weak SRF up-regulation were two independent factors of recurrent gastric ulcer bleeding (<it>p </it>< 0.05). Combining both factors, there was an 8.29-fold (95% CI, 1.31~52.62; <it>p </it>= 0.03) higher risk of recurrent gastric ulcer bleeding.</p> <p>Conclusions</p> <p>SRF expression is higher in gastric ulcer tissues than in non-ulcer tissues. Weak SRF up-regulation, combined with the presence of co-morbidities, increase the risk of the recurrent gastric ulcer bleeding.</p

Initial characteristics of RbcX proteins from Arabidopsis thaliana

Form I of Rubisco (ribulose-1,5-bisphosphate carboxylase/oxygenase) is composed of eight large (RbcL) and eight small (RbcS) subunits. Assembly of these subunits into a functional holoenzyme requires the assistance of additional assembly factors. One such factor is RbcX, which has been demonstrated to act as a chaperone in the assembly of most cyanobacterial Rubisco complexes expressed in heterologous system established in Escherichia coli cells. Analysis of Arabidopsis thaliana genomic sequence revealed the presence of two genes encoding putative homologues of cyanobacterial RbcX protein: AtRbcX1 (At4G04330) and AtRbcX2 (At5G19855). In general, both RbcX homologues seem to have the same function which is chaperone activity during Rubisco biogenesis. However, detailed analysis revealed slight differences between them. AtRbcX2 is localized in the stromal fraction of chloroplasts whereas AtRbcX1 was found in the insoluble fraction corresponding with thylakoid membranes. Search for putative “partners” using mass spectrometry analysis suggested that apart from binding to RbcL, AtRbcX1 may also interact with β subunit of chloroplast ATP synthase. Quantitative RT-PCR analysis of AtRbcX1 and AtRbcX2 expression under various stress conditions indicated that AtRbcX2 is transcribed at a relatively stable level, while the transcription level of AtRbcX1 varies significantly. In addition, we present the attempts to elucidate the secondary structure of AtRbcX proteins using CD spectroscopy. Presented results are the first known approach to elucidate the role of RbcX proteins in Rubisco assembly in higher plants

Protective effects of a gastrointestinal agent containing Korean red ginseng on gastric ulcer models in mice

<p>Abstract</p> <p>Background</p> <p>Korean red ginseng (KRG) is a ginseng that has been cultivated and aged for 4-6 years or more, and goes through an extensive cleaning, steaming and drying process. KRG contains more than 30 kinds of saponin components and has been reported as having various biological properties, such as anti-fatigue action, immune restoration, and neurovegetative effect. The purpose of this study was to assess the effects of a KRG-containing drug (KRGCD) on gastric ulcer models in mice.</p> <p>Methods</p> <p>Stomach ulcers were induced by oral ingestion of hydrochloride (HCl)/ethanol or indomethacin. Treatment with KRGCD (30, 100, and 300 mg/kg, p.o.) occurred 1 hr before the ulcer induction. Effect of KRGCD on anti-oxidant activity and gastric mucosal blood flow with a laser Doppler flowmeter in mice stomach tissue was evaluated.</p> <p>Results</p> <p>KRGCD (100 and 300 mg/kg, p.o.) significantly decreased ethanol- and indomethacin-induced gastric ulcer compared with the vehicle-treated (control) group. KRGCD (100 and 300 mg/kg) also decreased the level of thiobarbituric acid reactive substance (TBARS) and increased gastric mucosal blood flow compared with the control group.</p> <p>Conclusions</p> <p>These results suggest that the gastroprotective effects of KRGCD on mice ulcer models can be attributed to its ameliorating effect on oxidative damage and improving effect of gastric mucosal blood flow.</p