Pathological complete response after neoadjuvant chemotherapy with trastuzumab-containing regimen in gastric cancer: a case report

We report a 49-year-old Chinese male with locally advanced gastric adenocarcinoma achieving pathological complete response after neoadjuvant chemotherapy with trastuzumab-containing regimen. He underwent esophagogastroduodenoscopy in September 2009, which revealed a 2-cm gastric ulcer on the lesser curvature proximal to angularis. Biopsy of gastric ulcer showed moderately differentiated adenocarcinoma with overexpression of human epidermal growth factor receptor 2 (HER2) by immunohistochemistry and fluorescence in situ hybridization. Further workups with endoscopic ultrasound, computed tomography and positron emission tomography staged his cancer as T3N1M0. He received 3 cycles of neoadjuvant chemotherapy consisting of trastuzumab, oxaliplatin, docetaxel and capecitabine without severe toxicities except grade 2 diarrhea near the completion of cycle 3 requiring discontinuation of capecitabine. Afterwards, he received total gastrectomy with extended D2 lymph node dissections showing pathological complete response. He went on to receive 3 more cycles of chemotherapy postoperatively. The role of trastuzumab as a part of perioperative therapy in gastric cancer overexpressing HER2 is worth further investigation

Activation of the Syk tyrosine kinase is insufficient for downstream signal transduction in B lymphocytes

BACKGROUND: Immature B lymphocytes and certain B cell lymphomas undergo apoptotic cell death following activation of the B cell antigen receptor (BCR) signal transduction pathway. Several biochemical changes occur in response to BCR engagement, including activation of the Syk tyrosine kinase. Although Syk activation appears to be necessary for some downstream biochemical and cellular responses, the signaling events that precede Syk activation remain ill defined. In addition, the requirements for complete activation of the Syk-dependent signaling step remain to be elucidated. RESULTS: A mutant form of Syk carrying a combination of a K395A substitution in the kinase domain and substitutions of three phenylalanines (3F) for the three C-terminal tyrosines was expressed in a murine B cell lymphoma cell line, BCL(1).3B3 to interfere with normal Syk regulation as a means to examine the Syk activation step in BCR signaling. Introduction of this kinase-inactive mutant led to the constitutive activation of the endogenous wildtype Syk enzyme in the absence of receptor engagement through a 'dominant-positive' effect. Under these conditions, Syk kinase activation occurred in the absence of phosphorylation on Syk tyrosine residues. Although Syk appears to be required for BCR-induced apoptosis in several systems, no increase in spontaneous cell death was observed in these cells. Surprisingly, although the endogenous Syk kinase was enzymatically active, no enhancement in the phosphorylation of cytoplasmic proteins, including phospholipase Cγ2 (PLCγ2), a direct Syk target, was observed. CONCLUSION: These data indicate that activation of Syk kinase enzymatic activity is insufficient for Syk-dependent signal transduction. This observation suggests that other events are required for efficient signaling. We speculate that localization of the active enzyme to a receptor complex specifically assembled for signal transduction may be the missing event

Normal-state magnetic susceptibility in a bilayer cuprate

The magnetic susceptibility of high-T_c superconductors is investigated in the normal state using a coupled bilayer model. While this model describes in a natural way the normal-state pseudogaps seen in c-axis optical conductivity on underdoped samples, it predicts a weakly increasing susceptibility with decreasing temperature and cannot explain the magnetic pseudogaps exhibited in NMR measurements. Our result, together with some experimental evidence suggest that the mechanism governing the c-axis optical pseudogap is different from that for the $a-b$ plane magnetic pseudogap.Comment: 5 pages, 2 figure

Guidance of sentinel lymph node biopsy decisions in patients with T1-T2 melanoma using gene expression profiling.

AIM: Can gene expression profiling be used to identify patients with T1-T2 melanoma at low risk for sentinel lymph node (SLN) positivity? PATIENTS & METHODS: Bioinformatics modeling determined a population in which a 31-gene expression profile test predicted \u3c5% SLN positivity. Multicenter, prospectively-tested (n = 1421) and retrospective (n = 690) cohorts were used for validation and outcomes, respectively. RESULTS: Patients 55-64 years and ≥65 years with a class 1A (low-risk) profile had SLN positivity rates of 4.9% and 1.6%. Class 2B (high-risk) patients had SLN positivity rates of 30.8% and 11.9%. Melanoma-specific survival was 99.3% for patients ≥55 years with class 1A, T1-T2 tumors and 55.0% for class 2B, SLN-positive, T1-T2 tumors. CONCLUSION: The 31-gene expression profile test identifies patients who could potentially avoid SLN biopsy

The Gas Transfer through Polar Sea Ice Experiment: Insights into the Rates and Pathways that Determine Geochemical Fluxes

Sea ice is a defining feature of the polar marine environment. It is a critical domain for marine biota and it regulates ocean-atmosphere exchange, including the exchange of greenhouse gases such as CO2 and CH4. In this study, we determined the rates and pathways that govern gas transport through a mixed sea ice cover. N2O, SF6, 3He, 4He, and Ne were used as gas tracers of the exchange processes that take place at the ice-water and air-water interfaces in a laboratory sea ice experiment. Observation of the changes in gas concentrations during freezing revealed that He is indeed more soluble in ice than in water; Ne is less soluble in ice, and the larger gases (N2O and SF6) are mostly excluded during the freezing process. Model estimates of gas diffusion through ice were calibrated using measurements of bulk gas content in ice cores, yielding gas transfer velocity through ice (kice) of ∼5 × 10−4 m d−1. In comparison, the effective air-sea gas transfer velocities (keff) ranged up to 0.33 m d−1 providing further evidence that very little mixed-layer ventilation takes place via gas diffusion through columnar sea ice. However, this ventilation is distinct from air-ice gas fluxes driven by sea ice biogeochemistry. The magnitude of keff showed a clear increasing trend with wind speed and current velocity beneath the ice, as well as the combination of the two. This result indicates that gas transfer cannot be uniquely predicted by wind speed alone in the presence of sea ice

Stability of Solid State Reaction Fronts

We analyze the stability of a planar solid-solid interface at which a chemical reaction occurs. Examples include oxidation, nitridation, or silicide formation. Using a continuum model, including a general formula for the stress-dependence of the reaction rate, we show that stress effects can render a planar interface dynamically unstable with respect to perturbations of intermediate wavelength

The pseudogap in high-temperature superconductors: an experimental survey

We present an experimental review of the nature of the pseudogap in the cuprate superconductors. Evidence from various experimental techniques points to a common phenomenology. The pseudogap is seen in all high temperature superconductors and there is general agreement on the temperature and doping range where it exists. It is also becoming clear that the superconducting gap emerges from the normal state pseudogap. The d-wave nature of the order parameter holds for both the superconducting gap and the pseudogap. Although an extensive body of evidence is reviewed, a consensus on the origin of the pseudogap is as lacking as it is for the mechanism underlying high temperature superconductivity.Comment: review article, 54 pages, 50 figure

A cut-off of daily sedentary time and all-cause mortality in adults: a meta-regression analysis involving more than 1 million participants

Background The appropriate limit to the amount of daily sedentary time (ST) required to minimize mortality is uncertain. This meta-analysis aimed to quantify the dose-response association between daily ST and all-cause mortality and to explore the cut-off point above which health is impaired in adults aged 18–64 years old. We also examined whether there are differences between studies using self-report ST and those with device-based ST. Methods Prospective cohort studies providing effect estimates of daily ST (exposure) on all-cause mortality (outcome) were identified via MEDLINE, PubMed, Scopus, Web of Science, and Google Scholar databases until January 2018. Dose-response relationships between daily ST and all-cause mortality were examined using random-effects meta-regression models. Results Based on the pooled data for more than 1 million participants from 19 studies, the results showed a log-linear dose-response association between daily ST and all-cause mortality. Overall, more time spent in sedentary behaviors is associated with increased mortality risks. However, the method of measuring ST moderated the association between daily ST and mortality risk (p < 0.05). The cut-off of daily ST in studies with self-report ST was 7 h/day in comparison with 9 h/day for those with device-based ST. Conclusions Higher amounts of daily ST are log-linearly associated with increased risk of all-cause mortality in adults. On the basis of a limited number of studies using device-based measures, the findings suggest that it may be appropriate to encourage adults to engage in less sedentary behaviors, with fewer than 9 h a day being relevant for all-cause mortality

A Threshold of Objectively-Assessed Daily Sedentary Time for All-Cause Mortality in Older Adults: A Meta-Regression of Prospective Cohort Studies

BACKGROUND: This meta-analysis aimed to estimate the shape of the dose-response association between objectively-assessed daily sedentary time (ST) and all-cause mortality, and to explore whether there is a threshold of ST above which there is an increase in mortality risk in older adults. METHODS: Searches for prospective cohort studies providing effect estimates of daily ST (exposure) on all-cause mortality (outcome) were undertaken in five databases up to 31 March 2019. A random-effects meta-regression model was conducted to quantify the dose-response relationship between daily ST and all-cause mortality. Sensitivity analyses were also performed to test the stability of the results. RESULTS: Our analysis of pooled data from 11 eligible studies did not reveal a consistent shape of association between ST and mortality. After excluding three studies with potential confounding bias, there was a log-linear dose-response relationship between daily ST and all-cause mortality. Overall, higher amounts of time spent in sedentary behaviors were associated with elevated mortality risks in older adults. Visual assessments of dose-response relationships based on meta-regression analyses indicated that increased mortality risks became significant when total ST exceeded approximately 9 h/day. CONCLUSIONS: Based on a limited number of studies, this meta-analysis provides a starting point for considering a cut-off of daily sedentary time, suggesting older adults spend less time in daily sitting

Red wine polyphenols prevent metabolic and cardiovascular alterations associated with obesity in Zucker fatty rats (Fa/Fa)

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