Clinically Conserved Genomic Subtypes of Gastric Adenocarcinoma

Gastric adenocarcinoma (GAC) is a lethal disease characterized by genomic and clinical heterogeneity. By integrating 8 previously established genomic signatures for GAC subtypes, we identified 6 clinically and molecularly distinct genomic consensus subtypes (CGSs). CGS1 have the poorest prognosis, very high stem cell characteristics, and high IGF1 expression, but low genomic alterations. CGS2 is enriched with canonical epithelial gene expression. CGS3 and CGS4 have high copy number alterations and low immune reactivity. However, CGS3 and CGS4 differ in that CGS3 has high HER2 activation, while CGS4 has high SALL4 and KRAS activation. CGS5 has the high mutation burden and moderately high immune reactivity that are characteristic of microsatellite instable tumors. Most CGS6 tumors are positive for Epstein Barr virus and show extremely high levels of methylation and high immune reactivity. In a systematic analysis of genomic and proteomic data, we estimated the potential response rate of each consensus subtype to standard and experimental treatments such as radiation therapy, targeted therapy, and immunotherapy. Interestingly, CGS3 was significantly associated with a benefit from chemoradiation therapy owing to its high basal level of ferroptosis. In addition, we also identified potential therapeutic targets for each consensus subtype. Thus, the consensus subtypes produced a robust classification and provide for additional characterizations for subtype-based customized interventions

Comparison of first-line treatment with CHOP versus ICED in patients with peripheral T-cell lymphoma eligible for upfront autologous stem cell transplantation

IntroductionUpfront autologous stem cell transplantation (ASCT) has been recommended for patients who are newly diagnosed with peripheral T-cell lymphoma (PTCL), and CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone), an anthracycline-based chemotherapy has been the frontline chemotherapy for PTCL. However, it is not clear whether anthracycline-based chemotherapies such as CHOP could be standard induction therapy for PTCL.MethodsWe conducted a randomized phase II study to compare CHOP with fractionated ifosfamide, carboplatin, etoposide, and dexamethasone (ICED) for patients eligible for ASCT. The primary endpoint was progression-free survival (PFS) and secondary endpoints included objective response rate, overall survival (OS), and safety profiles.ResultsPatients were randomized into either CHOP (n = 69) or ICED (n = 66), and the characteristics of both arms were not different. PTCL-not otherwise specified (NOS, n = 60) and angioimmunoblastic T-cell lymphoma (AITL, n = 53) were dominant. The objective response rate was not different between CHOP (59.4%) and ICED (56.1%), and the 3-year PFS was not different between CHOP (36.7%) and ICED (33.1%). In AITL patients, CHOP was favored over ICED whereas ICED was associated with more cytopenia and reduced dose intensity. Patients who received upfront ASCT after achieving complete response to CHOP or ICED showed 80% of 3-year OS.DiscussionIn summary, our study showed no therapeutic difference between CHOP and ICED in terms of response and PFS. Thus, CHOP might remain the reference regimen especially for AITL based on its better outcome in AITL, and upfront ASCT could be recommended as a consolidation of complete response in patients with PTCL

Magnetically vectored nanocapsules for tumor penetration and remotely switchable on-demand drug release

Hollow-sphere nanocapsules containing intentionally trapped magnetic nanoparticles and defined anticancer drugs provide a powerful magnetic vector under moderate gradient magnetic fields, and enable the nanocapsules to penetrate into the midst of tumors and allow a controlled on-off switchable release of the anticancer drug cargo by remotely applied Radio Frequency (RF) magnetic field. This imageable smart drug delivery system is compact because the drug molecules and magnetic nanoparticles can all be self-contained within 801̃50 nm capsules. In vitro as well as in vivo results indicate that the nanocapsules are effective in reducing tumor cell growth. In Chapter 1, the concept of Drug Delivery Systems (DDSs) and the impact of nanotechnology on Drug Delivery Systems were introduced. Triggered drug release using magnetothermally-responsive nanomaterials, magnetic nanoparticles for nanomedicine, and ordered mesoporous materials in the context of Drug Delivery System were discussed. In Chapter 2, creation of remotely controllable, On-Off switchable drug release methodology was described. In this thesis work, triggerable nanocapsules which contain magnetic nanoparticles responsive to external radio frequency (RF) magnetic field have been successfully created. This is in contrast to the regular hollow nanospheres for slow passive release of drugs. The new nanocapsule material consists of bio-inert, bio-compatible or bio-degradable material that we can be selected from a variety of materials depending on specific medical applications. In Chapter 3, study and utilization of magnetic vector for guided tumor penetration was discussed. In the presence of a moderate gradient magnetic field, a powerful magnetic vector is created that allows these nanocapsules to cross cell membranes or blood-tissue barriers and penetrate into the midst of tumors, thus overcoming the well-known problem of limited access of anti-cancer drugs to cancer cells in the interior of a tumor tissue. In Chapter 4, potential applications to Blood-Brain-Barrier (BBB) crossing and other therapeutics was described. In Chapter 5, the study was summarized and conclude

The Efficacy and Safety of Jaungo, a Traditional Medicinal Ointment, in Preventing Radiation Dermatitis in Patients with Breast Cancer: A Prospective, Single-Blinded, Randomized Pilot Study

Purpose. This study was performed to evaluate the efficacy and safety of Jaungo in preventing radiation dermatitis in patients with breast cancer. Methods. Thirty patients were prospectively enrolled and randomly assigned to receive Jaungo or general supportive skin care. Radiation dermatitis and pain were examined at daily intervals from the start of radiotherapy until 4 weeks after its completion. The primary endpoint of this study was the incidence of radiation dermatitis. The secondary endpoints were time to onset of radiation dermatitis, duration of radiation dermatitis, and maximum pain score. Results. Jaungo reduced the incidence of grade ≥2 (46.7% versus 78.6%) and grade 3 radiation dermatitis (20.0% versus 50.0%) in comparison with general supportive skin care. Jaungo also delayed the onset of grade 2 dermatitis (35 days versus 30 days). In terms of time to onset of grade 3 dermatitis, duration of dermatitis, and maximum pain score, Jaungo showed results comparable to those achieved with general supportive skin care. No patients experienced adverse effects caused by Jaungo administration. Conclusions. Jaungo minimized radiation dermatitis in patients with breast cancer without causing adverse effects. Further randomized studies with a larger sample size are required to assess clinical use of Jaungo

Magnetically Guided Nano–Micro Shaping and Slicing of Silicon

Silicon is one of the most important materials for modern electronics, telecom, and photovoltaic (PV) solar cells. With the rapidly expanding use of Si in the global economy, it would be highly desirable to reduce the overall use of Si material, especially to make the PVs more affordable and widely used as a renewable energy source. Here we report the first successful direction-guided, nano/microshaping of silicon, the intended direction of which is dictated by an applied magnetic field. Micrometer thin, massively parallel silicon sheets, very tall Si microneedles, zigzag bent Si nanowires, and tunnel drilling into Si substrates have all been demonstrated. The technique, utilizing narrow array of Au/Fe/Au trilayer etch lines, is particularly effective in producing only micrometer-thick Si sheets by rapid and inexpensive means with only 5 μm level slicing loss of Si material, thus practically eliminating the waste (and also the use) of Si material compared to the ∼200 μm kerf loss per slicing and ∼200 μm thick wafer in the typical saw-cut Si solar cell preparation. We expect that such nano/microshaping will enable a whole new family of novel Si geometries and exciting applications, including flexible Si circuits and highly antireflective zigzag nanowire coatings

Miniaturized Portable Total Phosphorus Analysis Device Based on Photocatalytic Reaction for the Prevention of Eutrophication

Phosphorus (P) is one of the most important elements in the aquatic ecosystem, but its overuse causes eutrophication, which is a serious issue worldwide. In this study, we developed a miniaturized portable total phosphorus (TP) analysis device by integrating a TP sensor with a photocatalyst to pretreat analyte and optical components (LED and photodetector) to measure the absorbance of the blue-colored analyte for real-time TP monitoring and prevention of eutrophication. The size of the miniaturized portable TP analysis device is about 10.5 cm × 9.5 cm × 8 cm. Analyte-containing phosphorus was pretreated and colored blue by colorizing agent as a function of the phosphorus concentration. Absorbance of the blue-colored analyte was estimated by the LED and the photodetector such that the phosphorus concentration was quantitatively measured. This device can obtain a wide linear response range from 0.5 mg/L to 2.0 mg/L (R2 = 0.97381), and its performance can be improved by increasing the intensity of the UV light emitted from the LED array. Consequently, the performance of this miniaturized portable TP analysis device was found to be similar to that of a conventional TP analysis system; thus, it can be used in automated in situ TP analysis

A Study on TiO2 Surface Texturing Effect for the Enhancement of Photocatalytic Reaction in a Total Phosphorous Concentration Measurement System

Powerful sunlight, a high water temperature, and stagnation in the water flow induce eutrophication in rivers and lakes, which destroys the aquatic ecosystem and threatens the downstream water supply systems. Accordingly, it is very important to perform real-time measurements of nutrients that induce algal growth, especially total phosphorus, to preserve and manage the aquatic ecosystem. To conduct quantitative analysis of the total phosphorus in the aquatic ecosystem, it is essential to perform a pretreatment process and quickly separate the phosphorus, combined with organic and inorganic materials, into a phosphate. In this study, the sandblasting process was used for the physical etching of the wafer, and photocatalytic materials were deposited on the surface with various roughness in order to improve the photocatalytic reaction surface and efficiency. The photocatalytic reaction was applied to combine the pretreated sample with the coloring agent for color development, and the absorbance of the colored sample was analyzed quantitatively to compare and evaluate the characteristics, followed by the surface increase in the photocatalytic materials. In addition, the pretreatment and measurement parts were materialized in a single chip to produce a small and light total phosphorus analysis sensor