The prognostic value of programmed death-ligand 1 (PD-L1) expression in resected colorectal cancer without neoadjuvant therapy - differences between antibody clones and cell types.

Background: Programmed death-ligand 1 (PD-L1) expression on tumor cells is associated with poor prognosis in several malignancies, while partly contradictory and inconclusive results have been presented for colorectal cancer (CRC). This study aimed to evaluate PD-L1 as a prognostic biomarker in CRC by comparing three different antibody clones.

Methods: Patients surgically treated for CRC between January 1st, 2007, and December 31st, 2015, in Kalmar County, Sweden, were retrospectively included.

Detailed analysis of metastatic colorectal cancer patients who developed cardiotoxicity on another fluoropyrimidine and switched to S-1 treatment (subgroup analysis of the CardioSwitch-study).

Background And Purpose: The CardioSwitch-study demonstrated that patients with solid tumors who develop cardiotoxicity on capecitabine or 5-fluorouracil (5-FU) treatment can be safely switched to S-1, an alternative fluoropyrimidine (FP). In light of the European Medicines Agency approval of S-1 in metastatic colorectal cancer (mCRC), this analysis provides more detailed safety and efficacy information, and data regarding metastasectomy and/or local ablative therapy (LAT), on the mCRC patients from the original study.

Materials And Methods: This retrospective cohort study was conducted at 12 European centers.

SOULMATE: the Swedish study of liver transplantation for isolated colorectal cancer liver metastases not suitable for operation or ablation, compared to best established treatment-a randomized controlled multicenter trial.

Background: Around one fourth of patients with colorectal cancer present themselves with distant metastases at the time of diagnosis, and one additional one fifth of the patients will develop distant metastases during the disease, most commonly in the liver. Surgical treatment such as liver resection or ablation, often combined with chemotherapy and targeted therapy, is the only treatment option with curative potential, but only about 20% of the patients with liver metastases are candidates for surgical intervention. Standard treatment for unresectable patients is palliative oncological therapy; however, less than 10% of these patients will achieve a 5-year survival.

Continuation of fluoropyrimidine treatment with S-1 after cardiotoxicity on capecitabine- or 5-fluorouracil-based therapy in patients with solid tumours: a multicentre retrospective observational cohort study.

Background: Capecitabine- or 5-fluorouracil (5-FU)-based chemotherapy is widely used in many solid tumours, but is associated with cardiotoxicity. S-1 is a fluoropyrimidine with low rates of cardiotoxicity, but evidence regarding the safety of switching to S-1 after 5-FU- or capecitabine-associated cardiotoxicity is scarce.

Patients And Methods: This retrospective study (NCT04260269) was conducted at 13 centres in 6 countries.

[Liver transplantation optional treatment of liver metastases from colorectal cancer].

Surgical treatment of liver metastases from colorectal cancer (CLM) is the only treatment option with curative potential; however, only about 15% to 20% of the patients seen at major hospitals are candidates for surgical resection. In a prospective study of liver transplantation (Ltx) for non-resectable CLM a 5-year overall survival rate of 60 % has been shown. We now plan to evaluate if the addition of Ltx to conventional treatment of non-resectable, non-ablatable CLM increases overall survival compared to best established treatment.

Cost analysis comparison between peripherally inserted central catheters and implanted chest ports in patients with cancer-A health economic evaluation of the PICCPORT trial.

Background: A reliable central venous access device is a cornerstone in the treatment of cancer. Both peripherally inserted central catheters (PICC) and totally implanted chest ports (PORT) are commonly used for the delivery of chemotherapy. Both types of catheter can cause adverse events such as catheter-related deep venous thrombosis (CR-DVT), infection and mechanical complications.

Clinical impact of peripherally inserted central catheters vs implanted port catheters in patients with cancer: an open-label, randomised, two-centre trial.

Background: Centrally inserted totally implanted vascular access ports (PORTs) and peripherally inserted central catheters (PICCs) are widely used for the administration of chemotherapy. Our aim was to study the incidence of catheter-related deep venous thrombosis in patients with cancer receiving chemotherapy through either a PICC or a PORT.

Methods: Adults with non-haematological cancer (mainly breast and colorectal) from two Swedish oncology centres were included and followed for up to 1 yr.

Protein array profiling of circulating angiogenesis-related factors during bevacizumab containing treatment in metastatic colorectal cancer.

Background: Prolonged angiogenesis inhibition may improve treatment outcome in metastatic colorectal cancer (mCRC) patients. However, due to the complexity of the angiogenic pathways there is a lack of valid predictive biomarkers for anti-angiogenic agents. Here, we describe and optimize a procedure for simultaneous dynamic profiling of multiple angiogenesis related proteins in patient serum to explore associations with the response and acquired resistance to anti-angiogenic therapy.

Vasoactive peptides associate with treatment outcome ofbevacizumab-containing therapy in metastatic colorectal cancer.

Background: Hypertension is a common early adverse event of anti-angiogenic treatment of cancer and may associate with treatment response. However, blood pressure measurement as a surrogate response biomarker has methodological limitations, and predictive biomarkers of angiogenesis inhibitors are lacking. In disease associated with hypertension, vasoactive peptides have been linked to cardiovascular pressure load.

The histone deacetylase inhibiting drug Entinostat induces lipid accumulation in differentiated HepaRG cells.

Dietary overload of toxic, free metabolic intermediates leads to disrupted insulin signalling and fatty liver disease. However, it was recently reported that this pathway might not be universal: depletion of histone deacetylase (HDAC) enhances insulin sensitivity alongside hepatic lipid accumulation in mice, but the mechanistic role of microscopic lipid structure in this effect remains unclear. Here we study the effect of Entinostat, a synthetic HDAC inhibitor undergoing clinical trials, on hepatic lipid metabolism in the paradigmatic HepaRG liver cell line.

A randomized study of KRAS-guided maintenance therapy with bevacizumab, erlotinib or metronomic capecitabine after first-line induction treatment of metastatic colorectal cancer: the Nordic ACT2 trial.

Background: Maintenance treatment (mt) with bevacizumab (bev) ± erlotinib (erlo) has modest effect after induction chemotherapy in metastatic colorectal cancer (mCRC). We hypothesized the efficacy of erlo to be dependent on KRAS mutational status and investigated this by exploring mt strategies with bev ± erlo and low-dose capecitabine (cap).

Patients And Methods: Included patients had mCRC scheduled for first-line therapy, Eastern Cooperative Oncology Group (ECOG) 0-1 and no major comorbidities.

Plasmon-enhanced four-wave mixing by nanoholes in thin gold films.

Nonlinear plasmonics opens up for wavelength conversion, reduced interaction/emission volumes, and nonlinear enhancement effects at the nanoscale with many compelling nanophotonic applications foreseen. We investigate nonlinear plasmonic responses of nanoholes in thin gold films by exciting the holes individually with tightly focused laser beams, employing a degenerated pump/probe and Stokes excitation scheme. Excitation of the holes results in efficient generation of both narrowband four-wave mixing (FWM) and broadband multiphoton excited luminescence, blueshifted relative to the excitation beams.

A randomized phase III trial on maintenance treatment with bevacizumab alone or in combination with erlotinib after chemotherapy and bevacizumab in metastatic colorectal cancer: the Nordic ACT Trial.

Background: The main objective was to study the effect on progression-free survival (PFS) of adding erlotinib to bevacizumab as maintenance treatment following chemotherapy and bevacizumab as first-line treatment of metastatic colorectal cancer (mCRC).

Patients And Methods: Patients with untreated mCRC received doublet chemotherapy + bevacizumab during 18 weeks and those without tumor progression were eligible for randomization to bevacizumab + erlotinib (arm A) or bevacizumab alone (arm B), until progression or unacceptable toxic effect.

Results: Of the 249 patients enrolled, 80 started maintenance treatment in arm A and 79 in arm B.

Experimental measurement of efficiency and transport coherence of a cold-atom Brownian motor in optical lattices.

The rectification of noise into directed movement or useful energy is utilized by many different systems. The peculiar nature of the energy source and conceptual differences between such Brownian motor systems makes a characterization of the performance far from straightforward. In this work, where the Brownian motor consists of atoms interacting with dissipative optical lattices, we adopt existing theory and present experimental measurements for both the efficiency and the transport coherence.

Directed transport with real-time steering and drifts along predesigned paths using a Brownian motor.

We have realized real-time steering of the directed transport in a Brownian motor based on cold atoms in optical lattices and demonstrate drifts along predesigned paths. The transport is induced by spatiotemporal asymmetries in the system, where we can control the spatial part, and we show that the response to changes in asymmetry is very fast. In addition to directional steering, a real-time control of the magnitude of the average drift velocity and an on-off switching of the motor are also demonstrated.

Fluctuation-induced drift in a gravitationally tilted optical lattice.

Experimental and theoretical studies are made of Brownian particles trapped in a periodic potential, which is very slightly tilted due to gravity. In the presence of fluctuations, these will trigger a measurable average drift along the direction of the tilt. The magnitude of the drift varies with the ratio between the bias force and the trapping potential.

Self-image of anorexic and bulimic female adolescents.

The purpose of this study was to assess the self-concept using the Offer Self-Image Questionnaire (OSIQ) in groups of Finnish adolescent girls with anorexia nervosa and bulimia nervosa, and a normal control group without an eating disorder. A total of 135 adolescent girls aged 16-21 (10 with anorexia nervosa, 10 with bulimia nervosa and 115 normal controls) were investigated using the OSIQ. In comparisons, girls with bulimia nervosa differed significantly from both girls with anorexia nervosa and normal controls with regard to severity on almost all of the OSIQ scales.

Hyphal forms in the central nervous system of patients with coccidioidomycosis.

Coccidioides immitis is a dimorphic fungus that grows as a filamentous mold in soil and as a spherule at human body temperature. The hyphal or soil form is found rarely in human tissue. We report 5 cases of coccidioidomycosis in which hyphae were found in brain tissue or spinal fluid.

Vancomycin-resistant enterococci.

Preview New antimicrobial pathogens resistant to vancomycin are wreaking havoc in medical centers throughout the nation. Their tendency to colonize or infect severely ill, hospitalized patients who have undergone invasive procedures and received prolonged courses of antimicrobial therapy is alarming. The most potent weapon in the physician's arsenal against these enemies is familiarity with their key features, with the guidelines for prudent use of drug therapy, and with the precautionary measures necessary to limit contact and spread.

Vancomycin-resistant enterococci. The 'superbug' scourge that's coming your way.

Strains of vancomycin-resistant enterococci (VRE) have emerged and spread widely throughout the United States during the last few years. Multiply-resistant strains of Enterococcus faecium are especially troublesome because they are often resistant to all commercially available antimicrobial agents. At present, VRE infections occur most often in hospitalized patients with severe underlying disease who have undergone invasive procedures and received prolonged courses of broad-spectrum antimicrobial therapy.

Immunological studies with a monoclonal antibody suggest a different conformation of neurophysin in parvicellular neurons of rat hypothalamus.

A monoclonal antibody (mAb L6) to a carcinoma surface antigen has previously been shown to recognize neurophysins (NP), proteins associated with oxytocin and vasopressin. L6-reactivity in rat hypothalamus was confined to magnocellular neuronal systems. No staining was detected in parvicellular suprachiasmatic or paraventricular systems.

Detection of low-molecular-weight polypeptides on nitrocellulose with monoclonal antibodies.

An immunoblotting method to detect low-molecular-weight peptides with monoclonal antibodies that normally fail to demonstrate immunoreactivity using conventional blotting techniques is described. Detection of neurophysin, insulin, calcitonin, vasopressin, and beta-endorphin electroblotted on nitrocellulose membranes was optimized after introducing four modifications into the conventional procedure. These include renaturing the gels after sodium dodecyl sulfate electrophoresis, electroblotting the renatured gels in basic transfer buffer, fixing and/or heating the blots, and using avidin/alkaline phosphatase conjugates for antigen/antibody detection.