Regulation of Seed Dormancy Genes in Triticeae Species.

Wild progenitors of Triticeae crops generally have long dormancy periods. Domesticated crops inherited these longer dormancy alleles from their wild progenitors, which have since been modified and selected during cultivation and utilization by humans. Thus, allelic combinations at different seed dormancy loci are currently represented in Triticeae germplasm preserved in seed repositories and gene banks as accessions and materials of breeding programs. Methods to evaluate seed dormancy are key to explore, analyze, and exploit optimal alleles in dormancy genes. Recent developments in genomics have accelerated the identification and analysis of seed dormancy loci in Triticeae species. Transgenic experiments have been conducted to validate if candidate genes affect seed dormancy and more recently have yielded an array of mutations derived from genome editing for practical applications. The information gathered on these seed dormancy loci provides a deeper knowledge of germplasm diversity and offers strategies to control seed dormancy in breeding programs in Triticeae crops.

Map-Based Cloning of the Causal Gene for a Seed Dormancy Quantitative Trait Locus in Barley.

Seed dormancy is an important agronomic trait in cereal crops. Throughout the domestication of cereals, seed dormancy has been reduced to obtain uniform germination. However, grain crops must retain moderate levels of seed dormancy to prevent problems such as preharvest sprouting in wheat (Triticum aestivum) and barley (Hordeum vulgare). To produce modern cultivars with the appropriate seed dormancy levels, it is important to identify the genes responsible for seed dormancy. With recent advances in sequencing technology, several causal genes for seed dormancy quantitative trait loci (QTLs) have been identified in barley and wheat. Here, we present a method to identify causal genes for seed dormancy QTLs in barley, a method that is also applicable to other cereals.

Targeted Modification of Grain Dormancy Genes in Barley.

Transgenesis technologies, such as overexpression or RNA interference-mediated suppression, have often been used to alter the activity of target genes. More recently developed targeted genome modification methods using customizable endonucleases allow for the regulation or knockout mutation of target genes without the necessity of integrating recombinant DNA. Such approaches make it possible to create novel alleles of target genes, thereby significantly contributing to crop improvement. Among these technologies, the Cas9 endonuclease-based method is widely applied to several crops, including barley (Hordeum vulgare). In this chapter, we describe an Agrobacterium-based approach to the targeted modification of grain dormancy genes in barley using RNA-guided Cas9 nuclease.

Genome Editing to Produce Knockout Mutations of Seed Dormancy Genes in Wheat.

Knockout mutants provide definitive information about the functions of genes related to agronomic traits, including seed dormancy. However, it takes many years to produce knockout mutants using conventional techniques in polyploid plants such as hexaploid wheat. Genome editing with sequence-specific nucleases is a promising approach for obtaining knockout mutations in all targeted homoeologs of wheat simultaneously. Here, we describe a procedure to produce a triple recessive mutant in wheat via genome editing. This protocol covers the evaluation of gRNA and Agrobacterium-mediated transformation to obtain edited wheat seedlings.

Case report of QT interval prolongation induced by anamorelin in an obese patient with non-small cell lung cancer.

BACKGROUND: Anamorelin, a drug to treat cancer cachexia, binds to ghrelin receptors and improves body weight and appetite. In clinical trials in Japan, patients experienced a 10.7% frequency of stimulant conduction system depression as a severe side effect. Although rare, anamorelin sometimes causes fatal arrhythmias. Because patients with cancer cachexia are often underweight, data on the safety of anamorelin in obese patients are lacking. We report a case of QT interval prolongation after anamorelin administration to an obese patient with non-small cell lung cancer. CASE PRESENTATION: A female patient with a body mass index of 30 kg/m2 underwent immunotherapy for lung adenocarcinoma. She presented with severe weight loss, anorexia, and fatigue. She had no history of heart disease. On day 12, after administration of anamorelin 100 mg once daily, the patient developed nausea, diarrhea, and anorexia, which were considered cancer immunotherapy-induced immune-related adverse events, and she was admitted to the hospital. An electrocardiogram (ECG) on admission showed a QTc interval of 502 ms. On admission, her hepatic function was Child-Pugh class B, and anamorelin was discontinued the next day. On day 3 after anamorelin discontinuation, the QTc interval was prolonged by up to 557 ms, then decreased to 490 ms on day 6, and improved to 450 ms on day 16. Re-administration of anamorelin was avoided. CONCLUSIONS: When administering anamorelin to obese patients, we should be aware of the potential for stimulatory conduction system depression, as in underweight patients. Therefore, we should monitor patients by ECG from the early stages of anamorelin administration. Anamorelin is lipophilic, and its volume of distribution is increased in obese patients. Consequently, obese patients may continue to have QT interval prolongation after discontinuation of anamorelin, requiring long-term side-effect monitoring.

Validating computer applications for calculating spatial resolution and noise property in CT using simulated images with known properties.

The purpose of this study was to evaluate, using simulated images with known property values, how accurately some computer applications for calculating modulation transfer function (MTF), task transfer function (TTF), or noise power spectrum (NPS) in computed tomography (CT) based on widely known techniques produce their results. Specifically, they were three applications applicable to the wire method for MTF calculation, two applications corresponding to the circular edge (CE) and linear edge (LE) methods for TTF, and one application using a two-dimensional Fourier transform for NPS, which are collectively integrated with the software 'CTmeasure' provided by the Japanese Society of CT Technology. Images for the calculation with radial symmetry were generated based on a roll-off type filter function. The accuracy of each application was evaluated by comparing the calculated property with the true one. The calculated MTFs for the wire method accurately matched the true ones with percentage errors of smaller than 1.0%. In contrast, the CE and LE methods presented relatively large errors of up to 50% at high frequencies, whereas the NPS's errors were up to 30%. A closer investigation revealed, however, that these errors were attributable not to the applications but to the insufficiencies in the measurement techniques commonly employed. By improving the measurement conditions to minimize the effects of the insufficiencies, the errors notably decreased, whichvalidated the calculation techniques in the applications we used.

Barley MLA3 recognizes the host-specificity effector Pwl2 from Magnaporthe oryzae.

Plant nucleotide-binding leucine-rich repeat (NLRs) immune receptors directly or indirectly recognize pathogen-secreted effector molecules to initiate plant defense. Recognition of multiple pathogens by a single NLR is rare and usually occurs via monitoring for changes to host proteins; few characterized NLRs have been shown to recognize multiple effectors. The barley (Hordeum vulgare) NLR gene Mildew locus a (Mla) has undergone functional diversification, and the proteins encoded by different Mla alleles recognize host-adapted isolates of barley powdery mildew (Blumeria graminis f. sp. hordei [Bgh]). Here, we show that Mla3 also confers resistance to the rice blast fungus Magnaporthe oryzae in a dosage-dependent manner. Using a forward genetic screen, we discovered that the recognized effector from M. oryzae is Pathogenicity toward Weeping Lovegrass 2 (Pwl2), a host range determinant factor that prevents M. oryzae from infecting weeping lovegrass (Eragrostis curvula). Mla3 has therefore convergently evolved the capacity to recognize effectors from diverse pathogens.

Phase III study of bilayer sustained-release tramadol tablets in patients with cancer pain: a double-blind parallel-group, non-inferiority study with immediate-release tramadol capsules as an active comparator.

PURPOSE: We investigated whether twice-daily administration of a bilayer tablet formulation of tramadol (35% immediate-release [IR] and 65% sustained-release) is as effective as four-times-daily IR tramadol capsules for managing cancer pain. METHODS: This randomized, double-blind, double-dummy, active-comparator, non-inferiority study enrolled opioid-naïve patients using non-steroidal anti-inflammatory drugs or acetaminophen (paracetamol) to manage cancer pain and self-reported pain (mean value over 3 days ≥ 25 mm on a 100-mm visual analog scale [VAS]). Patients were randomized to either bilayer tablets or IR capsules for 14 days. The starting dose was 100 mg/day and could be escalated to 300 mg/day. The primary endpoint was the change in VAS (averaged over 3 days) for pain at rest from baseline to end of treatment/discontinuation. RESULTS: Overall, 251 patients were randomized. The baseline mean VAS at rest was 47.67 mm (range: 25.6-82.7 mm). In the full analysis set, the adjusted mean change in VAS was - 22.07 and - 19.08 mm in the bilayer tablet (n = 124) and IR capsule (n = 120) groups, respectively. The adjusted mean difference was - 2.99 mm (95% confidence interval [CI] - 7.96 to 1.99 mm). The upper 95% CI was less than the predefined non-inferiority margin of 7.5 mm. Other efficacy outcomes were similar in both groups. Adverse events were reported for 97/126 (77.0%) and 101/125 (80.8%) patients in the bilayer tablet and IR capsule groups, respectively. CONCLUSION: Twice-daily administration of bilayer tramadol tablets was as effective as four-times-daily administration of IR capsules regarding the improvement in pain VAS, with comparable safety outcomes. CLINICAL TRIAL REGISTRATION: JapicCTI-184143/jRCT2080224082 (October 5, 2018).

Novel method for calculating the effective dose using size-specific dose estimates conversion factors in abdomen-pelvis computed tomography.

We propose a novel method for calculating the effective dose that closely reflects the individual attenuation, utilizing two conversion coefficients. A total of 180 adult patients who underwent abdomen-pelvis computed tomography were categorized into six groups based on sex and body type. The effective dose was calculated by multiplying the dose-length product with the effective dose conversion coefficient and the size-specific dose estimate conversion factor. The effective dose calculated using a simulation-based dose calculator (WAZA-ARI) was employed as the reference value. The following values, obtained through both methods, were compared within each category: distribution of the effective dose, median effective dose, and relative difference in median effective dose across additional body mass index (BMI) categories. For male patients, no significant disparity was observed in the median effective doses calculated using the two methods. The relative differences in median effective doses across additional BMI categories ranged from - 5 to 6%. Conversely, among female patients, the median effective dose calculated using our method slightly undercut that calculated using WAZA-ARI, with relative differences ranging from - 16 to - 9%. Additionally, relative differences in median effective dose across additional BMI categories ranged from - 18 to - 7%. The median effective dose differed slightly depending on the calculation method because of the different reference phantoms applied in dose calculations. Our proposed method is sensitive to individual size and helps compute a size-specific effective dose.

Effects of polymorphisms in pregnane X receptor and ABC transporters on afatinib in Japanese patients with non-small cell lung cancer: pharmacogenomic-pharmacokinetic and exposure-response analysis.

PURPOSE: Because of the large interindividual variability of afatinib pharmacokinetics and adverse events, we evaluated the effects of polymorphisms in pregnane X receptor (NR1I2) and ABC transporters (ABCB1, ABCG2, and ABCC2) on the pharmacokinetics of afatinib. METHODS: The steady-state area under the concentration-time curve (AUC)0-24 of afatinib was analyzed using blood sampling just prior to and at 1, 2, 4, 6, 8, 12, and 24 h on day 15 after administration. RESULTS: The median oral clearance (CL/F) of afatinib in patients with the NR1I2 7635A allele was significantly lower than those in patients with the 7635G/G genotype (42.0 and 60.0 L/h, respectively, P = 0.025). There were no significant differences in afatinib CL/F between genotypes for NR1I2 8055C > T, -25385C > T, ABCB1, ABCG2, and ABCC2 polymorphisms. Based on the area under the receiver-operating characteristic curve, the threshold afatinib AUC0-24 value for prediction of dose reduction or withdrawal was 689 ng·h/mL at the best sensitivity (81.0%) and specificity (72.7%). In multivariate logistic regression analysis, an afatinib AUC0-24 above 689 ng·h/mL was independently associated with increased risk of dose reduction or withdrawal (OR: 11.66, P = 0.012). CONCLUSIONS: The NR1I2 7635A allele was related to a lower afatinib CL/F. Based on the AUC of 689 ng h/mL and CL/F, the optimal doses for patients with the NR1I2 7635G/G genotype and 7635A allele were recommended to be set at 40 and 30 mg/day, respectively, and subsequent adjustment of the maintenance dose based on the plasma concentrations of afatinib may be necessary to avoid afatinib-related adverse events.

Impact of the COVID-19 pandemic on the primary lung cancer screening program in Akita Prefecture, a region with the fastest aging population in Japan.

AIM: Akita Prefecture has the largest proportion of older inhabitants and the highest cancer mortality rate in Japan. Lung cancer is one of the biggest killers, and early detection is critical. Chest X-ray examinations are the main screening method for lung cancer; however, the COVID-19 pandemic has affected the screening system. Here, we evaluate how COVID-19 has affected lung cancer screening in Akita Prefecture. METHODS: Using the Akita General Health Corporation database, the average annual number of chest X-ray screening tests, close examinations and lung cancer diagnoses (stratified by sex and age) was evaluated during 2016-2019, and compared with the 2020 values. Furthermore, data on lung cancer registrations from 2018 to 2020 were obtained from the Collaborative Akita Prefecture Hospital-Based Cancer Registration System and analyzed. RESULTS: The average annual number of screening tests, close examinations and lung cancer diagnoses declined (by >50%) between 2016 to 2019 and 2020, especially among older people (aged ≥65 years). Furthermore, by stage, the number of patients with early-stage lung cancer (stage 0-I) decreased, and the number with advanced-stage cancer (stage IV) increased. CONCLUSIONS: The COVID-19 pandemic reduced lung cancer screening participation, especially among the older adult population in Akita Prefecture, resulting in a decrease in lung cancer diagnoses through screening. This might have reduced the number of early-stage cancer registrations. It is necessary to improve health education among the public regarding the importance of chest X-ray screening. Geriatr Gerontol Int 2023; 23: 622-627.

FLOURY ENDOSPERM 6 mutations enhance the sugary phenotype caused by the loss of ISOAMYLASE1 in barley.

KEY MESSAGE: Barley double mutants in two genes involved in starch granule morphology, HvFLO6 and HvISA1, had impaired starch accumulation and higher grain sugar levels than either single mutant. Starch is a biologically and commercially important glucose polymer synthesized by plants as semicrystalline starch granules (SGs). Because SG morphology affects starch properties, mutants with altered SG morphology may be useful in breeding crops with desirable starch properties, including potentially novel properties. In this study, we employed a simple screen for mutants with altered SG morphology in barley (Hordeum vulgare). We isolated mutants that formed compound SGs together with the normal simple SGs in the endosperm and found that they were allelic mutants of the starch biosynthesis genes ISOAMYLASE1 (HvISA1) and FLOURY ENDOSPERM 6 (HvFLO6), encoding starch debranching enzyme and CARBOHYDRATE-BINDING MODULE 48-containing protein, respectively. We generated the hvflo6 hvisa1 double mutant and showed that it had significantly reduced starch biosynthesis and developed shrunken grains. In contrast to starch, soluble α-glucan, phytoglycogen, and sugars accumulated to higher levels in the double mutant than in the single mutants. In addition, the double mutants showed defects in SG morphology in the endosperm and in the pollen. This novel genetic interaction suggests that hvflo6 acts as an enhancer of the sugary phenotype caused by hvisa1 mutation.

Escherichia coli-derived outer-membrane vesicles induce immune activation and progression of cirrhosis in mice and humans.

BACKGROUND AND AIMS: Decompensated cirrhosis with fibrosis progression causes portal hypertension followed by an oedematous intestinal tract. These conditions weaken the barrier function against bacteria in the intestinal tract, a condition called leaky gut, resulting in invasion by bacteria and bacterial components. Here, we investigated the role of outer-membrane vesicles (OMVs) of Escherichia coli, which is the representative pathogenic gut-derived bacteria in patients with cirrhosis in the pathogenesis of cirrhosis. METHODS: We investigated the involvement of OMVs in humans using human serum and ascites samples and also investigated the involvement of OMVs from E. coli in mice using mouse liver-derived cells and a mouse cirrhosis model. RESULTS: In vitro, OMVs induced inflammatory responses to macrophages and neutrophils, including the upregulation of C-type lectin domain family 4 member E (Clec4e), and induced the suppression of albumin production in hepatocytes but had a relatively little direct effect on hepatic stellate cells. In a mouse cirrhosis model, administration of OMVs led to increased liver inflammation, especially affecting the activation of macrophages, worsening fibrosis and decreasing albumin production. Albumin administration weakened these inflammatory changes. In addition, multiple antibodies against bacterial components were increased with a progressing Child-Pugh grade, and OMVs were detected in ascites of patients with decompensated cirrhosis. CONCLUSIONS: In conclusion, OMVs induce inflammation, fibrosis and suppression of albumin production, affecting the pathogenesis of cirrhosis. We believe that our study paves the way for the future prevention and treatment of cirrhosis.

Genetic diversity and population structure of barley landraces from Southern Ethiopia's Gumer district: Utilization for breeding and conservation.

Barley is the fifth most important food crop in Ethiopia. The genetic relationship and population structure studies of barley are limited to gene bank collections. Therefore, this study fills a gap by investigating the selection, consumption, economic value, genetic diversity, and population structure of farm-collected barley from the Gumer district of the Gurage Zone, which has received little attention. The information on the use of barley in the study area was collected using semi-structured interviews and questionnaires. 124 households of 11 kebeles, the smallest community unit, were interviewed. Barley landraces collected were compared with those collected from Japan, the United States (USA), and other Ethiopian locations. Illumina iSelect (50K genotyping platform) was used to identify single nucleotide polymorphisms (SNP) (20,367). Thirty landraces were found in Gumer. Burdaenadenber had the highest on-farm Shannon index estimate (2.0), followed by Aselecha (1.97) and Enjefo (1.95). Aselecha and Fetazer had the highest (44%) and the lowest (29%) richness values, respectively. High and low Simpson index values were found in Aselecha (84%) and Wulbaragenateretero (79%), respectively. The neighbor-joining tree revealed that Gumer landraces formed a separate subcluster with a common ancestral node; a sister subcluster contained barley landraces from Japan. According to the population structure analysis, barley landraces from Gumer differed from Japan and the United States. The principal component analysis revealed that US barley was the most distant group from Gumer barley. The markers' allele frequencies ranged from 0.10 to 0.50, with an average value of 0.28. The mean values of Nei's gene diversity (0.38) and the polymorphic information content (0.30) indicated the presence of high genetic diversity in the samples. The clustering of accessions was not based on geographic origin. Significant genetic diversity calls for additional research and analysis of local barley diversity because the selection and use of barley in Ethiopia would have been affected by the preference of ethnic groups.

Exome-wide variation in a diverse barley panel reveals genetic associations with ten agronomic traits in Eastern landraces.

Barley (Hordeum vulgare ssp. vulgare) is one of the first crops to be domesticated and is adapted to a wide range of environments. Worldwide barley germplasm collections possess valuable allelic variations that could further improve barley productivity. Although barley genomics has offered a global picture of allelic variation among varieties and its association with various agronomic traits, polymorphisms from East Asian varieties remain scarce. In this study, we analyze exome polymorphisms in a panel of 274 barley varieties collected worldwide, including 137 varieties from East Asian countries and Ethiopia. We reveal the underlying population structure and conduct genome-wide association studies for 10 agronomic traits. Moreover, we examin genome-wide associations for traits related to grain size such as awn length and glume length. Our results demonstrate the value of diverse barley germplasm panels containing Eastern varieties, highlighting their distinct genomic signatures relative to Western subpopulations.

Optimizing genome editing efficiency in wheat: Effects of heat treatments and different promoters for single guide RNA expression.

Genome editing is a promising method for simultaneously mutagenizing homoeologs in the three subgenomes of wheat (Triticum aestivum L.). However, the mutation rate via genome editing must be improved in order to analyze gene function and to quickly modify agronomic traits in wheat. Here, we examined the Cas9-induced mutation rates in wheat plants using two promoters for single guide RNA (sgRNA) expression and applying heat treatment during Agrobacterium tumefaciens-mediated transformation. Using the TaU6 promoter instead of the OsU6 promoter from rice (Oryza sativa L.) to drive sgRNA expression greatly improved the Cas9-induced mutation rate. Moreover, a heat treatment of 30°C for 1 day during tissue culture increased the Cas9-induced mutation rate and the variety of mutations obtained compared to tissue culture at the normal temperature (25°C). The same heat treatment did not affect the regeneration rates of transgenic plants but tended to increase the number of transgene integration sites in each transgenic plant. These results lay the foundation for improving the Cas9-induced mutation rate in wheat to enhance research on gene function and crop improvement.

A Randomized Phase 2 Study of 5-Aminolevulinic Acid Hydrochloride and Sodium Ferrous Citrate for the Prevention of Nephrotoxicity Induced by Cisplatin-Based Chemotherapy of Lung Cancer.

INTRODUCTION: Cisplatin-based chemotherapy was established in the 1980s, and it has been improved by the development of a short hydration protocol in lung cancer therapy. However, cisplatin-based chemotherapy is still associated with renal toxicity. Because 5-aminolevulinic acid (5-ALA) with sodium ferrous citrate (SFC) is known to be a mitochondrial activator and a heme oxygenase-1 (HO-1) inducer, 5-ALA with SFC is speculated to mitigate cisplatin-induced renal inflammation. METHODS: We investigated the effects of oral administration of 5-ALA with SFC for preventing cisplatin-based nephrotoxicity in patients with lung cancer and evaluated its benefits for patients who received cisplatin-based chemotherapy. The primary endpoint was the significance of the difference between the serum creatinine (sCr) levels of the patients administered 5-ALA with SFC and those given placebo after course 1 of chemotherapy. The difference in the estimated glomerular filtration rate (eGFR) between the two groups was also evaluated as the secondary endpoint. RESULTS: The double-blind, randomized two-arm studies were conducted at 15 medical facilities in Japan; 54 male and 20 female patients with lung cancer who received cisplatin-based chemotherapy between the ages of 42 and 75 years were included in the study. The compliance rate was greater than 94% in the primary assessment and subsequent drug administration periods. All enrolled patients completed the four cycles of cisplatin-based chemotherapy with short hydration. The average level of sCr on day 22 of course 1 was 0.707 mg/dL in the group treated with 5-ALA and SFC and 0.735 mg/dL in the placebo group, respectively, and the sCr in the test group was significantly lower than that in the placebo group (p = 0.038). In addition, the eGFR was significantly higher in the SPP-003 group than in the placebo group up to day 1 of course 3 (84.66 and 75.68 mL/min/1.73 m2, respectively, p = 0.02) and kept better even after the last administration of the study drug (82.37 and 73.49 mL/min/1.73 m2, respectively, p = 0.013). CONCLUSIONS: The oral administration of 5-ALA with SFC is beneficial to patients undergoing cisplatin-based chemotherapy for lung cancer with short hydration.

Effects of CYP3A4/5 and ABC transporter polymorphisms on osimertinib plasma concentrations in Japanese patients with non-small cell lung cancer.

The effects of polymorphisms in CYP3A4 (20230G > A), CYP3A5 (6986A > G), ABCB1 (1236C > T, 2677G > T/A, 3435C > T), ABCG2 (421C > A), and ABCC2 (-24C > T) on the area under the concentration-time curve (AUC) of osimertinib in 23 patients with non-small cell lung cancer were investigated. Blood sampling was performed just prior to and at 1, 2, 4, 6, 8, 12, and 24 h after osimertinib administration at the steady-state on day 15 after beginning therapy. The osimertinib AUC0-24 was significantly correlated with age (P = 0.038), serum albumin (P = 0.002), and serum creatinine (P = 0.012). Additionally, there were significant differences in the AUC0-24 of osimertinib among the groups administered vonoprazan, histamine 2-receptor antagonists or esomeprazole, and no acid suppressants (P = 0.021). By contrast, there were no significant differences in the AUC0-24 of osimertinib between genotypes of CYP3A4/5 or ABC transporters. Furthermore, there were no significant differences in the AUC0-24 of osimertinib between patients with diarrhea, skin rash, or hepatotoxicity and those without these conditions. In multivariate analysis, only serum albumin value was an independent factor predicting the AUC0-24 of osimertinib. Analysis of CYP3A4/5 and ABC transporter polymorphisms before osimertinib therapy may not predict the efficacy or side effects of osimertinib. The lower serum albumin values were associated with an increase in the AUC0-24 of osimertinib; however, further studies are needed to assess the factors contributing to the interindividual variability of osimertinib pharmacokinetics.

Phase II study of nanoparticle albumin-bound paclitaxel monotherapy for relapsed non-small cell lung cancer with patient-reported outcomes (NLCTG1302).

Background: This multicenter, open-label, single-arm phase II study [Niigata Lung Cancer Treatment Group (NLCTG) 1302] was conducted to evaluate the efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) monotherapy for previously treated patients with advanced non-small cell lung cancer (NSCLC). We also investigated chemotherapy-induced peripheral neuropathy (CIPN) to evaluate the quality of life (QOL). Methods: Sixty-five patients with advanced NSCLC from 14 participating institutions who had previously undergone one or two cytotoxic chemotherapy regimens were enrolled in this study. The patients received 100 mg/m2 nab-paclitaxel intravenously on days 1, 8, and 15, every 4 weeks. The primary endpoint was overall objective response rate. CIPN symptoms were prospectively assessed using the Patient Neurotoxicity Questionnaire (PNQ) and Common Terminology Criteria for Adverse Events (CTCAE). Results: The overall response rate (ORR) was 18.5% [95% confidence interval (CI): 10.9-29.6%], and the median progression-free survival (PFS) was 3.4 (95% CI: 2.5-4.3) months. Median overall survival (OS) was 8.6 (95% CI: 7.1-10.2) months. The most common non-hematologic grade ≥3 adverse events were infection (7.7%) and hyponatremia (4.6%). Neutropenia was the most common grade 3 or 4 adverse event (30.8%), and febrile neutropenia developed in 6.2% patients. The PNQ and CTCAE scores for motor peripheral neuropathy were low (kappa =0.10). Conclusions: The primary endpoint was achieved. Nab-paclitaxel was well tolerated and showed anti-tumor activity in patients with previously treated NSCLC. This study demonstrates a low degree of concordance in CIPN grading between physicians and patients. Trial Registration: University hospital Medical Information Network Clinical Trial Registry (ID: UMIN000012343).