Adjuvant chemotherapy after surgery improves survival of patients with stage II–III, resectable gastric cancer. However, the overall survival benefit observed after adjuvant chemotherapy is moderate, ...suggesting that not all patients with resectable gastric cancer treated with adjuvant chemotherapy benefit from it. We aimed to develop and validate a predictive test for adjuvant chemotherapy response in patients with resectable, stage II–III gastric cancer.
In this multi-cohort, retrospective study, we developed through a multi-step strategy a predictive test consisting of two rule-based classifier algorithms with predictive value for adjuvant chemotherapy response and prognosis. Exploratory bioinformatics analyses identified biologically relevant candidate genes in gastric cancer transcriptome datasets. In the discovery analysis, a four-gene, real-time RT-PCR assay was developed and analytically validated in formalin-fixed, paraffin-embedded (FFPE) tumour tissues from an internal cohort of 307 patients with stage II–III gastric cancer treated at the Yonsei Cancer Center with D2 gastrectomy plus adjuvant fluorouracil-based chemotherapy (n=193) or surgery alone (n=114). The same internal cohort was used to evaluate the prognostic and chemotherapy response predictive value of the single patient classifier genes using associations with 5-year overall survival. The results were validated with a subset (n=625) of FFPE tumour samples from an independent cohort of patients treated in the CLASSIC trial (NCT00411229), who received D2 gastrectomy plus capecitabine and oxaliplatin chemotherapy (n=323) or surgery alone (n=302). The primary endpoint was 5-year overall survival.
We identified four classifier genes related to relevant gastric cancer features (GZMB, WARS, SFRP4, and CDX1) that formed the single patient classifier assay. In the validation cohort, the prognostic single patient classifier (based on the expression of GZMB, WARS, and SFRP4) identified 79 (13%) of 625 patients as low risk, 296 (47%) as intermediate risk, and 250 (40%) as high risk, and 5-year overall survival for these groups was 83·2% (95% CI 75·2–92·0), 74·8% (69·9–80·1), and 66·0% (60·1–72·4), respectively (p=0·012). The predictive single patient classifier (based on the expression of GZMB, WARS, and CDX1) assigned 281 (45%) of 625 patients in the validation cohort to the chemotherapy-benefit group and 344 (55%) to the no-benefit group. In the predicted chemotherapy-benefit group, 5-year overall survival was significantly improved in those patients who had received adjuvant chemotherapy after surgery compared with those who received surgery only (80% 95% CI 73·5–87·1 vs 64·5% 56·8–73·3; univariate hazard ratio 0·47 95% CI 0·30–0·75, p=0·0015), whereas no such improvement in 5-year overall survival was observed in the no-benefit group (72·9% 66·5–79·9 in patients who received chemotherapy plus surgery vs 72·5% 65·8–79·9 in patients who only had surgery; 0·93 0·62–1·38, p=0·71). The predictive single patient classifier groups (chemotherapy benefit vs no-benefit) could predict adjuvant chemotherapy benefit in terms of 5-year overall survival in the validation cohort (pinteraction=0·036 in univariate analysis). Similar results were obtained in the internal evaluation cohort.
The single patient classifiers validated in this study provide clinically important prognostic information independent of standard risk-stratification methods and predicted chemotherapy response after surgery in two independent cohorts of patients with resectable, stage II–III gastric cancer. The single patient classifiers could complement TNM staging to optimise decision making in patients with resectable gastric cancer who are eligible for adjuvant chemotherapy after surgery. Further validation of these results in prospective studies is warranted.
Ministry of ICT and Future Planning; Ministry of Trade, Industry, and Energy; and Ministry of Health and Welfare.
In this review, we survey several recent developments in printing of nanomaterials for contacts, transistors, sensors of various kinds, light-emitting diodes, solar cells, memory devices, and bone ...and organ implants. The commonly used nanomaterials are classified according to whether they are conductive, semiconducting/insulating or biological in nature. While many printing processes are covered, special attention is paid to inkjet printing and roll-to-roll printing in light of their complexity and popularity. In conclusion, we present our view of the future development of this field.
In this review article, we survey the current state of art of printed nanomaterial systems and their future prospects.
Overcoming the trade-offs among power consumption, fabrication cost, and signal amplification has been a long-standing issue for wearable electronics. We report a high-gain, fully inkjet-printed ...Schottky barrier organic thin-film transistor amplifier circuit. The transistor signal amplification efficiency is 38.2 siemens per ampere, which is near the theoretical thermionic limit, with an ultralow power consumption of <1 nanowatt. The use of a Schottky barrier for the source gave the transistor geometry-independent electrical characteristics and accommodated the large dimensional variation in inkjet-printed features. These transistors exhibited good reliability with negligible threshold-voltage shift. We demonstrated this capability with an ultralow-power high-gain amplifier for the detection of electrophysiological signals and showed a signal-to-noise ratio of >60 decibels and noise voltage of <0.3 microvolt per hertz
at 100 hertz.
A highly stretchable, low-cost strain sensor was successfully prepared using an extremely cost-effective ionic liquid of ethylene glycol/sodium chloride. The hysteresis performance of the ...ionic-liquid-based sensor was able to be improved by introducing a wavy-shaped fluidic channel diminishing the hysteresis by the viscoelastic relaxation of elastomers. From the simulations on visco-hyperelastic behavior of the elastomeric channel, we demonstrated that the wavy structure can offer lower energy dissipation compared to a flat structure under a given deformation. The resistance response of the ionic-liquid-based wavy (ILBW) sensor was fairly deterministic with no hysteresis, and it was well-matched to the theoretically estimated curves. The ILBW sensors exhibited a low degree of hysteresis (0.15% at 250%), low overshoot (1.7% at 150% strain), and outstanding durability (3000 cycles at 300% strain). The ILBW sensor has excellent potential for use in precise and quantitative strain detections in various areas, such as human motion monitoring, healthcare, virtual reality, and smart clothes.
Woody biomass has gained popularity as an environmentally friendly, renewable and sustainable resource for liquid fuel production. Here, we demonstrate biotechnological improvement of the quantity ...and quality of woody biomass by employing developing xylem (DX)‐preferential production of gibberellin (GA), a phytohormone that positively regulates stem growth. First, for the proof of concept experiment, we produced transgenic Arabidopsis plants expressing GA20‐oxidase, a key enzyme in the production of bioactive GAs, from Pinus densiflora (PdGA20ox1) under the control of either a constitutive 35S promoter, designated 35S::PdGA20ox1, or a DX‐specific promoter (originated from poplar), designated DX15::PdGA20ox1. As we hypothesized, both transgenic Arabidopsis plants (35S::PdGA20ox1 and DX15::PdGA20ox1) exhibited an accelerated stem growth that resulted in a large increase of biomass, up to 300% compared to wild‐type control plants, together with increased secondary wall thickening and elongation of fibre cells. Next, we applied our concept to the production of transgenic poplar trees. Both transgenic poplar trees (35S::PdGA20ox1 and DX15::PdGA20ox1) showed dramatic increases in biomass, up to 300%, with accelerated stem growth and xylem differentiation. Cell wall monosaccharide composition analysis revealed that in both Arabidopsis and poplar, glucose and xylose contents were significantly increased. However, undesirable phenotypes of 35S::PdGA20ox1 poplar, including poor root growth and leaf development, were found. Interestingly, DX15::PdGA20ox1 poplar resulted in a reduction of undesirable phenotypes. Our results indicate that the controlled production of GAs through a tissue‐specific promoter can be utilized as an efficient biotechnological tool for producing enhanced plant biomass, minimizing unwanted effects.
Background
The number of gastric cancer survivors has been increasing, and such survivors experience various changes in their lives post-recovery. Adapting to these changes requires appropriate ...interventions that can improve their quality of life (QoL). This study was conducted to investigate the factors affecting the QoL of gastric cancer survivors and provide basic data for effective intervention.
Methods
Data were collected between September 8 and September 29, 2017, from the Gastric Cancer Center at a tertiary hospital. Questionnaire surveys were conducted using the EORTC QLQ-C30/STO22, Self-Efficacy-Scale, Multidimensional Scale of Perceived Social Support, and Quality of Life-Cancer Survivors Questionnaire on gastric cancer survivors who were followed up for 3 years after gastrectomy. Data were analyzed using descriptive statistics,
t
test, ANOVA, Pearson’s correlation coefficient, and multiple regression analysis.
Results
A total of 136 gastric cancer survivors completed the questionnaire survey. There were significant positive correlations of QoL with self-efficacy, functional status, and social support (
r
= .35,
p
< .001;
r
= .53,
p
< .001;
r
= .26,
p
< .001, respectively). There were significant negative correlations of QoL with general symptoms (
r
= − .39,
p
< .001) and gastric cancer-specific symptoms (
r
= − .51,
p
< .001). The regression model explained 48.3% of the QoL, and the affecting factors were gastric cancer-specific symptoms (
β
= − .397,
p
< .001), religious belief (
β
= .299,
p
< .001), functional status (
β
= .251,
p
= .003), and self-efficacy (
β
= .191,
p
= .004).
Conclusion
This study confirmed that gastric cancer-specific symptoms, spiritual well-being, self-efficacy, and functional status affect the QoL of gastric cancer survivors. Hence, these factors should be considered in the interventions to improve the QoL of gastric cancer survivors.
Electrical stimuli play an important role in regulating the delivery of plasmonic nanomaterials with cancer targeting peptides. Here, we developed an electro-responsive hydrogel-based microfluidic ...actuator platform for brain tumor targeting and photothermal therapy (PTT) applications. The electro-responsive hydrogels consisted of highly conductive silver nanowires (AgNWs) and biocompatible collagen I gels. We confirmed that an electrically conductive hydrogel could be used as an effective actuator by applying an electrical signal in the microfluidic platform. Furthermore, we successfully demonstrated PTT efficacy for brain tumor cells using targetable Arg-Gly-Asp (RGD) peptide-conjugated gold nanorods (GNRs). Therefore, our electro-responsive hydrogel-based microfluidic actuator platform could be useful for electro-responsive intelligent nanomaterial delivery and PTT applications.
Electrical stimuli play an important role in regulating the delivery of plasmonic nanomaterials with cancer targeting peptides.
The development of biocompatible and precisely printable bioink addresses the growing demand for three-dimensional (3D) bioprinting applications in the field of tissue engineering. We developed a ...methacrylated photocurable silk fibroin (SF) bioink for digital light processing 3D bioprinting to generate structures with high mechanical stability and biocompatibility for tissue engineering applications. Procedure 1 describes the synthesis of photocurable methacrylated SF bioink, which takes 2 weeks to complete. Digital light processing is used to fabricate 3D hydrogels using the bioink (1.5 h), which are characterized in terms of methacrylation, printability, mechanical and rheological properties, and biocompatibility. The physicochemical properties of the bioink can be modulated by varying photopolymerization conditions such as the degree of methacrylation, light intensity, and concentration of the photoinitiator and bioink. The versatile bioink can be used broadly in a range of applications, including nerve tissue engineering through co-polymerization of the bioink with graphene oxide, and for wound healing as a sealant. Procedure 2 outlines how to apply 3D-printed SF hydrogels embedded with chondrocytes and turbinate-derived mesenchymal stem cells in one specific in vivo application, trachea tissue engineering, which takes 2-9 weeks.
Background
Indocyanine green fluorescent lymphography helps visualize the lymphatic drainage pattern in gastric cancer; however, it is unknown whether fluorescent lymphography visualizes all ...metastatic lymph nodes. This study aimed to evaluate the sensitivity of fluorescent lymphography to detect metastatic lymph node stations and lymph nodes and the risk of false-negative findings.
Methods
Patients with clinical T1–4a gastric cancer were included. Indocyanine green was peritumorally injected the day prior to surgery by endoscopy. Gastrectomy with systematic D1+ or D2 lymphadenectomy was performed. Stations and lymph nodes were retrieved at the back-table using near-infrared imaging and classified as “fluorescent” or “non-fluorescent” and later matched with histopathological findings.
Results
Among 592 patients who underwent minimally invasive gastrectomy from September 2013 until December 2016, lymph node metastases were present in 150. The sensitivity of fluorescent lymphography in detecting all metastatic lymph node stations was 95.3% (143/150 patients), with a false-negative rate of 4.7% (7/150 patients) and the sensitivity in detecting all metastatic lymph nodes was 81.3% (122/150 patients). The negative predictive value was 99.3% for non-fluorescent stations and 99.2% for non-fluorescent LNs. For detecting all metastatic LN stations, subgroup analysis revealed 100% sensitivity for pT1a, 96.8% for pT1b, 100% for pT2, 91.3% for pT3, and 93.6% for pT4a tumors.
Conclusions
Fluorescent lymphography-guided lymphadenectomy can be a useful method for radical lymphadenectomy by facilitating the complete dissection of all potentially positive LN stations. Fluorescent lymphography-guided lymphadenectomy appears to be a reasonable alternative to conventional systematic lymphadenectomy for gastric cancer.
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