Modified FOLFOXIRI plus cetuximab versus bevacizumab in RAS wild-type metastatic colorectal cancer: a randomized phase II DEEPER trial.

The clinical significance of FOLFOXIRI (5-FU, leucovorin, oxaliplatin, and irinotecan) plus anti-EGFR monoclonal antibody using cetuximab for metastatic colorectal cancer (mCRC) remains controversial. We report results from a randomized phase 2 DEEPER trial (UMIN000018217, jRCTs061180022) to test the superiority of modified (m)-FOLFOXIRI plus weekly cetuximab over bevacizumab in patients with RAS wild-type (wt) mCRC. Primary endpoint was depth of response (DpR).

Highly circularly polarized monochromatic high harmonic pulses via a reflective phase retarder at 27.9 eV.

A circularly polarized (CP) single-order high harmonic pulse light source, operating at a photon energy of 27.9 eV, is developed. The production of CP harmonic pulses with a degree of polarization exceeding 99% is achieved by utilizing a high-throughput phase retarder composed of SiC mirrors.

Synchrotron speciation of umbilical cord mercury and selenium after environmental exposure in Niigata.

The insidious and deadly nature of mercury's organometallic compounds is informed by two large scale poisonings due to industrial mercury pollution that occurred decades ago in Minamata and Niigata, Japan. The present study examined chemical speciation for both mercury and selenium in a historic umbilical cord sample from a child born to a mother who lived near the Agano River in Niigata. The mother had experienced mercury exposure leading to more than 50 ppm mercury measured in her hair and was symptomatic 9 years prior to the birth.

Real-time observation of the Woodward-Hoffmann rule for 1,3-cyclohexadiene by femtosecond soft X-ray transient absorption.

The stereochemistry of pericyclic reactions is explained by orbital symmetry conservation, referred to as the Woodward-Hoffmann (WH) rule. Although this rule has been verified using the structures of reactants and products, the temporal evolution of the orbital symmetry during the reaction has not been clarified. Herein, we used femtosecond soft X-ray transient absorption spectroscopy to elucidate the thermal pericyclic reaction of 1,3-cyclohexadiene (CHD) molecules, , their isomerization to 1,3,5-hexatriene.

Effects of diet containing astaxanthin on visual function in healthy individuals: a randomized, double-blind, placebo-controlled, parallel study.

Visual display terminal work has increased rapidly in recent years. Loss of visual acuity is an unfortunate associated effect. Here, we performed a randomized, placebo-controlled study in 60 healthy adults.

Sichuan dark tea improves lipid metabolism and prevents aortic lipid deposition in diet-induced atherosclerosis model rats.

Background And Aims: Sichuan dark tea (ST), Zangcha, is a traditional fermented Chinese tea found in Sichuan and Tibet and claimed for beneficial effects against lifestyle-related metabolic disorders. We examined the effects of ST on lipid metabolism and atherosclerosis.

Methods And Results: Sichuan dark tea was given to fat-rich diet-induced atherosclerosis model rats in comparison with dark-fermented Chinese Pu-erh tea (PT) and Japanese green tea (GT).

Dynamic changes in RAS gene status in circulating tumour DNA: a phase II trial of first-line FOLFOXIRI plus bevacizumab for RAS-mutant metastatic colorectal cancer (JACCRO CC-11).

Background: Few prospective studies have used liquid biopsy testing in RAS-mutant metastatic colorectal cancer (mCRC), and its clinical significance remains unknown. Therefore, this study aimed to carry out a biomarker analysis by liquid biopsy using updated data of the phase II trial of FOLFOXIRI plus bevacizumab as first-line chemotherapy for RAS-mutant mCRC.

Materials And Methods: A total of 64 patients who received modified FOLFOXIRI regimen (irinotecan 150 mg/m, oxaliplatin 85 mg/m, levofolinate 200 mg/m, and fluorouracil 2400 mg/m) plus bevacizumab biweekly were enrolled.

F-FDG-PET/CT as an imaging biomarker for regorafenib efficacy in metastatic colorectal cancer (JACCRO CC-12).

Introduction: Regorafenib is a multikinase inhibitor approved for the treatment of metastatic colorectal cancer (mCRC). Despite providing a statistically significant survival benefit, a substantial number of patients fail to respond to or continue with treatment, which has resulted in an unmet clinical need for a biomarker of regorafenib efficacy.

Methods: The JACCRO CC-12 study was a prospective, multicenter, single-arm phase II trial designed to evaluate the usefulness of [F]fluorodeoxyglucose positron emission tomography (FDG-PET) as an imaging biomarker of regorafenib in patients with mCRC that progressed after standard chemotherapies.

Effects of anthocyanin, astaxanthin, and lutein on eye functions: a randomized, double-blind, placebo-controlled study.

We examined the effects of a test food containing anthocyanin, astaxanthin, and lutein on the eye function in healthy Japanese adults with eye fatigue after operating visual display terminals. Forty-four subjects were randomly but equally assigned to the active or placebo group. Two active or placebo capsules were taken once daily for 6 weeks.

Real-Time Probing of an Atmospheric Photochemical Reaction by Ultrashort Extreme Ultraviolet Pulses: Nitrous Acid Release from -Nitrophenol.

Photolysis of -nitrophenol, contained in brown carbon, is considered to be a major process for the generation of nitrous acid (HONO) in the atmosphere. In this Letter, we used time-resolved photoelectron spectroscopy with 29.5 eV probe pulses and ab initio calculations to disentangle all reaction steps from the excitation to the dissociation of HONO.

Cognitive function improvement with astaxanthin and tocotrienol intake: a randomized, double-blind, placebo-controlled study.

We examined the effects of the mixed ingestion of astaxanthin derived from and tocotrienols on the cognitive function of healthy Japanese adults who feel a memory decline. Forty-four subjects were randomly but equally assigned to the astaxanthin-tocotrienols or placebo group. An astaxanthin-tocotrienols or placebo capsule was taken once daily before or after breakfast for a 12-week intervention period.

Design and Synthesis of DDR1 Inhibitors with a Desired Pharmacophore Using Deep Generative Models.

Discoidin domain receptor 1 (DDR1) inhibitors with a desired pharmacophore were designed using deep generative models (DGMs). DDR1 is a receptor tyrosine kinase activated by matrix collagens and implicated in diseases such as cancer, fibrosis and hypoxia. Herein we describe the synthesis and inhibitory activity of compounds generated from DGMs.

Prenatal and postnatal methyl mercury exposure in Niigata, Japan: adult outcomes.

Methyl mercury (MeHg) poisoning or Minamata disease (MD) from fish consumption is a public health concern throughout the world because all fish contain small amounts. The lowest exposure level needed to impair children's development is controversial. Actual poisoning with MeHg from fish consumption has been reliably reported only two times.

1/f spectra of decoherence noise on As nuclear spins in bulk GaAs.

To identify the decoherence origin, frequency spectra using multiple π-pulses have been extensively studied. However, little has been discussed on how to define the spectral intensities from multiple-echo decays and how to incorporate the Hahn-echo T in the noise spectra. Here, we show that experiments based on two theories solve these issues.

Polarimetry of a single-order circularly polarized high harmonic separated by a time-delay compensated monochromator.

Monochromatic elliptically polarized (CP) ultrashort extreme ultraviolet (EUV) light source with higher ellipticity than 0.80 is developed for the investigation of molecular chirality and electromagnetic phenomena. Elliptically polarized 47-nm high harmonic (HH) is monochromatized from the comb spectrum of HHs by a time-delay compensated monochromator (TDCM) consisting of a pair of Pt-coated toroidal gratings.

Time-resolved high-harmonic spectroscopy of ultrafast photoisomerization dynamics.

We report the first time-resolved high-harmonic spectroscopy (TR-HHS) study of a chemical bond rearrangement. We investigate the transient change of the high-harmonic signal from 1,3-cyclohexadiene (CHD), which undergoes ring-opening and isomerizes to 1,3,5-hexatriene (HT) upon photoexcitation. We associated the harmonic yield variation with the changes in the molecule's electronic state and vibrational frequencies, which are caused by isomerization.

Correction: A phase II trial of 1st-line modified-FOLFOXIRI plus bevacizumab treatment for metastatic colorectal cancer harboring RAS mutation: JACCRO CC-11.

[This corrects the article DOI: 10.18632/oncotarget.24702.

Cost-minimization analysis of adjuvant chemotherapy regimens given to patients with colorectal cancer in Japan.

Background: Consideration of medical costs as well as effectiveness and adverse events is rapidly been becoming an important factor in the selection of chemotherapy regimens. However, practical data on the costs of chemotherapy are scarce. We clinically estimated the medical costs of 6 adjuvant chemotherapy regimens for colorectal cancer on the basis of clinical and cost-related data and compared their cost-effectiveness by cost-minimization analyses.

[The risk of adverse events of CPT- 11].

Irinotecan is a camptothecin analog used worldwide for a broad range of solid tumors, including colorectal cancer. It can cause severe adverse drug reactions, such as neutropenia or diarrhea. Recent pharmacogenetic studies on irinotecan have revealed the impact of UGT1A1 polymorphisms on severe adverse effects.

Structural dynamics of photochemical reactions probed by time-resolved photoelectron spectroscopy using high harmonic pulses.

Femtosecond ring-opening dynamics of 1,3-cyclohexadiene (CHD) in gas phase upon two-photon excitation at 400 nm (=3.1 eV) was investigated by time-resolved photoelectron spectroscopy using 42 nm (=29.5 eV) high harmonic photons probing the dynamics of the lower-lying occupied molecular orbitals (MOs), which are the fingerprints of the molecular structure.

Early tumor shrinkage as a predictor of favorable outcomes in patients with advanced pancreatic cancer treated with FOLFIRINOX.

There are several reports on the correlation between early tumor shrinkage (ETS) or depth of response (DpR) and survival in chemotherapies for colorectal cancer; however, few studies have investigated it in pancreatic cancer. We therefore investigated whether the ETS will predict outcomes in 59 patients with advanced pancreatic cancer treated with FOLFIRINOX therapy. The association of ETS with progression-free survival (PFS) and overall survival (OS) was evaluated but also we addressed to the correlation between outcomes and DpR.