The Complete Loss of p53 Expression Uniquely Predicts Worse Prognosis in Colorectal Cancer

p53 immunohistochemistry is considered an accurate surrogate marker reflecting the underlying TP53 mutation status and has utility in tumor diagnostics. In the present study, 269 primary CRCs were immunohistochemically evaluated for p53 expression to assess its utility in diagnostic pathology and prognostication. p53 expression was wild-type in 59 cases (23%), overexpressed in 143 cases (55%), completely lost in 50 cases (19%), and cytoplasmic in 10 cases (4%). p53 immunoreactivity was associated with tumor size (p = 0.0056), mucus production (p = 0.0015), and mismatch repair (MMR) system status (p < 0.0001). Furthermore, among CRCs with wild-type p53 expression, a significantly higher number of cases had decreased CDX2 than those with p53 overexpression (p = 0.012) or complete p53 loss (p = 0.043). In contrast, among CRCs with p53 overexpression, there were significantly fewer ALCAM-positive cases than p53 wild-type cases (p = 0.0045). However, no significant association was detected between p53 immunoreactivity and the “stem-like” immunophenotype defined by CDX2 downregulation and ALCAM-positivity. Multivariate Cox hazards regression analysis identified tubular-forming histology (hazard ratio [HR] = 0.17, p < 0.0001), younger age (HR = 0.52, p = 0.021), and female sex (HR = 0.55, p = 0.046) as potential favorable factors. The analysis also revealed complete p53 loss (HR = 2.16, p = 0.0087), incomplete resection (HR = 2.65, p = 0.0068), and peritoneal metastasis (HR = 5.32, p < 0.0001) as potential independent risk factors for patients with CRC. The sub-cohort survival analyses classified according to chemotherapy after surgery revealed that CRC patients with wild-type p53 expression tended to have better survival than those with overexpression or complete loss after chemotherapy. Thus, immunohistochemistry for p53 could be used for the prognostication and chemotherapy target selection of patients with CRC.     

Ultrasonographic findings of diseases in peripheral lung fields using transtracheobronchial endoscopic ultrasonography (TUS)

Cystic neoplasms of the pancreas constitute about 9% of all cystic lesions of the pancreas and less than 1% of all pancreatic neoplasms. The case of a 70 years-old woman with microcystic cystadenoma is reported. CT-scan of the abdomen diagnosed a 5 cm multilocular septated cyst, with calcifications in the context, localized in the head-uncinate process of the pancreas. The mass was well separated by a sharp cleavage plane with portal vein and superior mesenteric vessels. An ERCP showed cephalic symmetrical stenosis (diameter 3 mm) of the main pancreatic duct (MPD), mildly dilated in the remaining tract (diameter 6 mm). An intraoperative biopsy of the cystic wall was performed. Therefore, it was decided to proceed with a duodenum-preserving resection of the head of the pancreas (DPPHR), including the stenosis tract of the MPD in the surgical specimen. The reconstructive procedure consisted, by i.v. jejunal loop transposition, in a side-to-side pancreatico-jejunostomy, including in the anastomosis both corpocaudal stump and the resection cavity of the pancreatic head, and an end-to-side Roux-en-Y jejuno-jejunostomy. With respect to long-lasting pain relief and preservation of the endocrine and exocrine functions of the pancreas, DPPHR is a highly effective surgical procedure with a low early and late morbidity and mortality due to limited surgical resection. This technique, introduced into surgical practice by Beger, is indicated in patients with chronic pancreatitis with an inflammatory mass in the head of the pancreas. The authors conclude that this procedure can be performed also in case of pancreatic benign tumors, as microcystic cystadenoma. Advantages of this technique makes DPPHR an attractive alternative to Pylorus-Preserving-Pancreatico-Duodenectomy (PPPD).     

Purification and characterization of ouabain-binding protein in human plasma

Ouabainlike factors are thought to be a kind of important modulators of salt and water metabolism in essential hypertension. We purified the binding-protein of ouabain (OBP) from human plasma. The amino-terminal sequence of OBP from human plasma, (NH2-TLGQPREPQVYTLPPXREEM-), indicated that OBP is the carboxy-terminal fragment (14.4 kDa by SDS-PAGE) from T218 of IgG2 heavy chain and from A221 of the IgG1 heavy chain constant region. Moreover, plasmin-cleaved Fc fragment (pFc) of IgG possessed the ouabain-binding activity by the gel-filtration method of pFc and authentic ouabain mixture, whereas neither intact, aggregate, nor papain-cleaved Fc fragment did. The amino-terminal sequence of pFc was NH2-THTXPPXPAPELLGGPXVFL-, and this sequence corresponded to the T105 to L125 fragment of the IgG1 heavy chain constant region. The growth of cultured THP-1 cells were arrested in the dose-dependent manner by ouabain, which was inhibited by the addition of 20 microg/mL of pFc. These results suggested that plasmin-cleaved Fc of human IgG is one of the binding protein of ouabain/ouabainlike factor(s) in human plasma.     

Rewired Cellular Metabolic Profiles in Response to Metformin under Different Oxygen and Nutrient Conditions

Metformin is a metabolic disruptor, and its efficacy and effects on metabolic profiles under different oxygen and nutrient conditions remain unclear. Therefore, the present study examined the effects of metformin on cell growth, the metabolic activities and consumption of glucose, glutamine, and pyruvate, and the intracellular ratio of nicotinamide adenine dinucleotide (NAD⁺) and reduced nicotinamide adenine dinucleotide (NADH) under normoxic (21% O₂) and hypoxic (1% O₂) conditions. The efficacy of metformin with nutrient removal from culture media was also investigated. The results obtained show that the efficacy of metformin was closely associated with cell types and environmental factors. Acute exposure to metformin had no effect on lactate production from glucose, glutamine, or pyruvate, whereas long-term exposure to metformin increased the consumption of glucose and pyruvate and the production of lactate in the culture media of HeLa and HaCaT cells as well as the metabolic activity of glucose. The NAD⁺/NADH ratio decreased during growth with metformin regardless of its efficacy. Furthermore, the inhibitory effects of metformin were enhanced in all cell lines following the removal of glucose or pyruvate from culture media. Collectively, the present results reveal that metformin efficacy may be regulated by oxygen conditions and nutrient availability, and indicate the potential of the metabolic switch induced by metformin as combinational therapy.     

Oxidation resistant ceramic foam from a silicone preceramic polymer/polyurethane blend

Silicon oxycarbide (SiOC) ceramic foams, produced by the pyrolysis of a foamed blend of a methylsilicone preceramic polymer and polyurethane (PU) in a 1/1 wt.% ratio, exhibit excellent physical and mechanical properties. The proposed process allows to easily modify the density and morphology of the foams, making them suitable for several engineering applications. However, it has been shown that, due to residual carbon present in the oxycarbide phase after pyrolysis, the foams are subjected to an oxidation process that reduces their strength after high temperature exposure to air (12 h 1200°C). A modified process, employing the same silicone resin preceramic polymer but a much lower PU content (silicone resin/PU=5.25/1 wt.% ratio), has been developed and is reported in this paper. Microstructural investigations showed that carbon rich regions deriving from the decomposition of the polyurethane template are still present in the SiOC foam, but have a much smaller dimension than those found in foams with a higher PU content. Thermal gravimetric studies performed in air or oxygen showed that the low-PU containing ceramic foams display an excellent oxidation resistance, because the carbon-rich areas are embedded inside the struts or cell walls and are thus protected by the dense silicon oxycarbide matrix surrounding them. SiOC foams obtained with the novel process are capable to maintain their mechanical strength after oxidation treatments at 800 and 1200°C (12 h), while SiOC foams obtained with a higher amount of PU show about a 30% strength decrease after oxidation at 1200°C (12 h).     

Radiation-induced polymerization of ethylene in a pilot plant. I. Bulk process

Radiation-induced bulk polymerization of ethylene was carried out with use of a pilot plant with a 10 liter reactor at pressures of 225–400 kg/cm², temperatures of 30–95°C, ethylene feed rates of 5–28 kg/hr, and dose rate of 3.8 × 10⁵ rad/hr. Characteristics of the process are mild polymerization conditions and capability of producing medium density polyethylene in powder form. The spacetime yield and molecular weight of polymer were in the range of 3.5 to 13.1 g/liter hr and 2.2 × 10⁴ to 14 × 10⁴, respectively. The space-time yield increased with mean residence time and 2.4 powders of pressure, and decreased with temperature. Molecular weight changed similarly with the reaction conditions. These results were consistent with those of the bench plant experiment and the scale effect was small. Polymer deposit to the reactor wall limited a period of continuous operation of the plant. The amount of deposited polymer was increased with the square of reaction time. The rate of polymer deposit was proportional to polymer concentration and to the cube of pressure. The polymer deposit cannot be solved in the bulk process.     

Poly(4-diphenylaminostyrene) with a well-defined polymer chain structure: Controllable optical and electrical properties

The effect of polymer chain structure on the optical and electrical properties are reported for poly(4-diphenylaminostyrene) (PDAS), which was prepared by the living anionic polymerization of 4-diphenylaminostyrene (DAS) with the benzyllithium (BzLi)/N,N,N′,N′-tetramethylethylenediamine (TMEDA) system. The optical properties of PDAS are strongly affected by the stereoregularity of the PDAS polymer chain; intramolecular excimer-forming fluorescence was observed from PDAS with a syndiotactic-rich configuration. The highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energy levels of PDAS were approximately −5.4 and −2.0 eV, respectively, regardless of the polymer chain structure. The hole and electron drift mobilities for PDAS were in the order of 10⁻⁴ to 10⁻⁵ (cm²/V s) and 10⁻⁵ (cm²/V s), respectively, with negative slopes. The distance of each triphenylamino (TPA) group in the polymer chain was a major factor influencing the drift mobility of PDAS. The current-voltage (I-V) characteristics of PDAS were controllable according to the polymer chain structure of PDAS.     

A New Process to Make a Porous PTFE Structure from Aqueous PTFE Dispersion with the Help of Hydrogel

A novel method to make a porous material having relatively large cell diameter (200–300 m), which consisted of mainly poly(tetrafluoroethylene) (PTFE), was developed from aqueous PTFE dispersion by using the characteristics of hydrogel with the addition of carbon nanofiber (CNF). The porous material was produced as follows: firstly, an aqueous agar gel containing PTFE and CNF was prepared; secondly, the gel was freeze-dried; thirdly, the dried gel was heat-treated at 400°C where the agar was almost decomposed and PTFE became molten. The porous material showed electric conductivity (about 50 ), high porosity (about 96 vol%), and relatively uniform cell structures without shrinkage during freeze drying and heat treatment. While the method without CNF resulted in large shrinkage during heat treatment, meaning that CNF prevented the shrinkage. It was explained by the idea that the existence of rigid CNF, which was dispersed in the cell wall, prohibited the shrinkage of PTFE during heat treatment. It was unexpectedly found by SEM analysis that the porous materials had another macro-porous structure inside the cell wall, suggesting that the developed materials had a double porous structure.