Gastric fundic gland polyposis and cancer development after eradication of Helicobacter pylori in patient with gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS).

A 44-year-old woman with gastric cancer (GC) and fundic gland polyposis (FGPs) was referred to our hospital for further diagnosis and treatment. She successfully underwent eradication therapy for Helicobacter pylori (HP) 6 years ago, but did not exhibit FGPs at that time. When she underwent an esophagogastroduodenoscopy 2, 4, and 5 years after the eradication of HP, her imaging results revealed the existence of FGPs which gradually increased in her gastric fundus and body. Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) was suspected and a mutational analysis was performed, revealing an APC promoter 1B variant c.-191T > C. A robotic total gastrectomy with lymphadenectomy was performed. Histopathological analysis of the surgical specimens revealed GC with no lymph node metastasis. GAPPS is characterized by GC and FGPs. However, our case shows different gastric phenotypes that are dependent on the status of HP infection.

Association of metabolic dysfunction-associated fatty liver disease with gallstone development: A longitudinal study.

BACKGROUND AND AIM: The influence of metabolic dysfunction-associated fatty liver disease on gallstone development remains unclear. We aimed to investigate the longitudinal association between metabolic dysfunction-associated fatty liver disease and gallstone development in both men and women. METHODS: This observational cohort study included 5398 patients without gallstones who underwent > 2 health check-ups between April 1, 2014, and March 31, 2020. A generalized estimation equation model was used to analyze the association between metabolic dysfunction-associated fatty liver disease and gallstone development according to repeated measures at baseline and most recent stage. RESULTS: After adjustment, the odds ratios of metabolic dysfunction-associated fatty liver disease for gallstone development in men and women were 3.019 (95% confidence interval [CI]: 1.901-4.794) and 2.201 (95% CI: 1.321-3.667), respectively. Among patients aged ≥ 50 years, the odds ratio for gallstone development was significantly enhanced with increasing metabolic dysfunction-associated fatty liver disease component numbers in both sexes; however, no significance was observed in those aged < 50 years. Other significant risk factors for gallstone development were age (odds ratio: 1.093, 95% CI: 1.060-1.126) and waist circumference (odds ratio: 1.048, 95% CI: 1.018-1.079) in men and age (odds ratio: 1.035, 95% CI: 1.003-1.067) and current smoking (odd ratio: 5.465, 95% CI: 1.881-15.88) in women. CONCLUSION: Although the risk factors for gallstone development differed between sexes, metabolic dysfunction-associated fatty liver disease was common. Paying attention to an increase in the number of metabolic dysfunction-associated fatty liver disease components in patients aged ≥ 50 years is important for gallstone prevention.

Association of metabolic dysfunction-associated steatotic liver disease with erosive esophagitis development: a longitudinal observational study.

BACKGROUND AND AIM: Although erosive esophagitis (EE) is associated with fatty liver and metabolic dysregulation, the association between EE and metabolic dysfunction-associated steatotic liver disease (MASLD) remains unclear. Thus, this study aimed to investigate the longitudinal association between MASLD and EE. METHODS: We included 1578 patients without EE at baseline who underwent more than two health checkups over 2 years. Generalized estimation equations were used to analyze associations between MASLD and EE according to repeated measures at baseline and most recent stages. RESULTS: EE development rates in men and women were 14.5% and 7.2%, respectively. After adjusting for lifestyle habits, the odds ratios of MASLD for EE development in men and women were 1.907 (95% confidence interval [CI]: 1.289-2.832, P < 0.005) and 1.483 (95% CI: 0.783-2.811, P = 0.227), respectively. In the subgroup analysis, after adjusting for lifestyle habits, among men and women aged ≥50 years with more than three MASLD components, the odds ratios for EE development were 2.408 (95% CI: 1.505-3.855, P < 0.001) and 2.148 (95% CI: 1.093-4.221, P < 0.05), respectively. After adjusting for various factors, the significant risk factors for EE development were different between men and women. CONCLUSION: The influence of MASLD and other factors on EE development differed by sex and age. Particularly, patients aged ≥50 years with MASLD and with an increased number of MASLD components should be considered at increased risk for EE.

Cancer-associated adipocytes promote pancreatic cancer progression through SAA1 expression.

Although pancreatic cancer often invades peripancreatic adipose tissue, little information is known about cancer-adipocyte interaction. We first investigated the ability of adipocytes to de-differentiate to cancer-associated adipocytes (CAAs) by co-culturing with pancreatic cancer cells. We then examined the effects of CAA-conditioned medium (CAA-CM) on the malignant characteristics of cancer cells, the mechanism underlying those effects, and their clinical relevance in pancreatic cancer. When 3T3-L1 adipocytes were co-cultured with pancreatic cancer cells (PANC-1) using the Transwell system, adipocytes lost their lipid droplets and changed morphologically to fibroblast-like cells (CAA). Adipocyte-specific marker mRNA levels significantly decreased but those of fibroblast-specific markers appeared, characteristic findings of CAA, as revealed by real-time PCR. When PANC-1 cells were cultured with CAA-CM, significantly higher migration/invasion capability, chemoresistance, and epithelial-mesenchymal transition (EMT) properties were observed compared with control cells. To investigate the mechanism underlying these effects, we performed microarray analysis of PANC-1 cells cultured with CAA-CM and found a 78.5-fold higher expression of SAA1 compared with control cells. When the SAA1 gene in PANC-1 cells was knocked down with SAA1 siRNA, migration/invasion capability, chemoresistance, and EMT properties were significantly attenuated compared with control cells. Immunohistochemical analysis on human pancreatic cancer tissues revealed positive SAA1 expression in 46/61 (75.4%). Overall survival in the SAA1-positive group was significantly shorter than in the SAA1-negative group (P = .013). In conclusion, we demonstrated that pancreatic cancer cells induced de-differentiation in adipocytes toward CAA, and that CAA promoted malignant characteristics of pancreatic cancer via SAA1 expression, suggesting that SAA1 is a novel therapeutic target in pancreatic cancer.

MicroRNA-296-5p Promotes Cell Invasion and Drug Resistance by Targeting Bcl2-Related Ovarian Killer, Leading to a Poor Prognosis in Pancreatic Cancer.

BACKGROUND/AIMS: Pancreatic ductal adenocarcinoma (PDAC) is characterized by aggressive invasion, early metastasis, and resistance to chemotherapy, leading to a poor prognosis. To clarify the molecular mechanism of these malignant characteristics, we performed a genome-wide microRNA (miRNA) array analysis utilizing micro-cancer tissues from patients with unresectable PDAC (stage IV), obtained by endoscopic ultrasound-fine needle aspiration (EUS-FNA). METHODS: The expression profiles of 2,042 miRNAs were determined using micro-cancer tissues from 13 patients with unresectable PDAC obtained by EUS-FNA. The relationship between individual miRNA levels and overall survival (OS) was analyzed. Possible target genes for miRNAs were bioinformatically analyzed using the online database miRDB. Pancreatic cancer cell lines PANC-1, MIA PaCa-2, and PK-8 were transfected with miRNA mimic or small interfering RNA, and cell invasion, epithelial-mesenchymal transition (EMT), and apoptosis markers were examined. miRNA and mRNA expressions were examined by quantitative polymerase chain reaction. RESULTS: Of 2,042 miRNAs, the 10 that exhibited the lowest correlation coefficient (p ≤ 0.005) between miRNA expression level and OS among the patients were identified. The miRDB and expression analysis in cancer cell lines for the 10 miRNAs identified miR-296-5p and miR-1207-5p as biomarkers predictive of shorter survival (p < 0.0005). Bioinformative target gene analysis and transfection experiments with miRNA mimics showed that Bcl2-related ovarian killer (BOK), a pro-apoptotic gene, is a target for miR296-5p in pancreatic cancer cells; transfection of miR-296-5p mimic into PANC-1, MIA PaCa-2, and PK-8 cells resulted in significant suppression of BOK mRNA and protein expression. These transfectants showed significantly higher invasion capability compared with control cells, and knock down of BOK in pancreatic cancer cells similarly enhanced invasion capability. Transfectants of miR-296-5p mimic also exhibited aberrant expression of EMT markers, including vimentin and N-cadherin. Moreover, these transfectants showed a significantly lower apoptosis rate in response to 5-fluorouracil and gemcitabine with a decrease of BOK expression, suggesting a role of miR-296-5p in drug resistance. CONCLUSION: These results suggest that miR-296-5p is a useful biomarker for a poor prognosis in patients with PDAC, and that the miR-296-5p/BOK signaling axis plays an important role in cell invasion, drug resistance, and EMT in PDACs.

Epidermal growth factor receptor-targeted molecular imaging of colorectal tumors: Detection and treatment evaluation of tumors in animal models.

To overcome the problem of overlooking colorectal tumors, a new and highly sensitive modality of colonoscopy is needed. Moreover, it is also important to establish a new modality to evaluate viable tumor volume in primary lesions of colorectal cancer (CRC) during chemotherapy. Therefore, we carried out molecular imaging of colorectal tumors targeting epidermal growth factor receptor (EGFR), which is highly expressed on tumor cells, for evaluating chemotherapeutic efficacy and for endoscopic detection of colorectal adenomas. We first attempted to image five CRC cell lines with various levels of EGFR expression using an Alexa Fluor-labeled anti-EGFR monoclonal antibody (AF-EGFR-Ab). A strong fluorescence signal was observed in the cells depending on the level of EGFR expression. When nude mice xenografted with LIM1215 CRC cells, which highly express EGFR, were i.v. injected with AF-EGFR-Ab, a strong fluorescence signal appeared in the tumor with a high signal to noise ratio, peaking at 48 hours after injection and then gradually decreasing, as shown using an IVIS Spectrum system. When the xenografted mice were treated with 5-fluorouracil, fluorescence intensity in the tumor decreased in proportion to the viable tumor cell volume. Moreover, when the colorectum of azoxymethane-treated rats was observed using a thin fluorescent endoscope with AF-EGFR-Ab, all 10 small colorectal adenomas (≤3 mm) were detected with a clear fluorescence signal. These preliminary results of animal experiments suggest that EGFR-targeted fluorescent molecular imaging may be useful for quantitatively evaluating cell viability in CRC during chemotherapy, and also for detecting small adenomas using a fluorescent endoscope.

Peripheral blood cell-free DNA is an alternative tumor DNA source reflecting disease status in myelodysplastic syndromes.

Genetic alterations in myelodysplastic syndromes (MDS) are critical for pathogenesis. We previously showed that peripheral blood cell-free DNA (PBcfDNA) may be more sensitive for genetic/epigenetic analyses than whole bone marrow (BM) cells and mononuclear cells in peripheral blood (PB). Here we analyzed the detailed features of PBcfDNA and its utility in genetic analyses in MDS. The plasma-PBcfDNA concentration in MDS and related diseases (N = 33) was significantly higher than that in healthy donors (N = 14; P = 0.041) and in International Prognostic Scoring System higher-risk groups than that in lower-risk groups (P = 0.034). The concentration of plasma-/serum-PBcfDNA was significantly correlated with the serum lactate dehydrogenase level (both P < 0.0001) and the blast cell count in PB (P = 0.034 and 0.025, respectively). One nanogram of PBcfDNA was sufficient for one assay of Sanger sequencing using optimized primer sets to amplify approximately 160-bp PCR products. PBcfDNA (approximately 50 ng) can also be utilized for targeted sequencing. Almost all mutations detected in BM-DNA were also detected using corresponding PBcfDNA. Analyses using serially harvested PBcfDNA from an RAEB-2 patient showed that the somatic mutations and a single nucleotide polymorphism that were detected before allogeneic transplantation were undetectable after transplantation, indicating that PBcfDNA likely comes from MDS clones that reflect the disease status. PBcfDNA may be a safer and easier alternative to obtain tumor DNA in MDS.

Association of variabilities in body mass index and waist circumference with newly achieved remission of metabolic dysfunction-associated fatty liver disease.

AIMS: Although body weight reduction is recommended to ameliorate nonalcoholic fatty liver disease, the effects of body mass index (BMI) and waist circumference (WC) variability on newly achieved remission of metabolic dysfunction-associated fatty liver disease (MAFLD) remain unclear. We aimed to investigate the longitudinal association between BMI and WC variabilities and newly achieved MAFLD remission in both sexes. METHODS: Among 26,952 patients, 1823 with MAFLD diagnosed by ultrasonography and with >2 health checkups over >2 years from April 2014 to March 2021 were included in this observational cohort study. A generalized estimation equation model analyzed the association between BMI and WC and newly achieved MAFLD remission according to repeated measures at baseline and the most recent stage. RESULTS: Rates of MAFLD remission in male and female patients were 7.4 % and 6.0 %, respectively. Regarding decreased BMI variability, newly achieved MAFLD remission prevalence among the subgroups differed significantly between sexes (p < 0.001). In male patients, a decrease in BMI variability of ≥1.5 kg/m2 and WC variability of ≥4.2 cm had adjusted odds ratios (ORs) of 5.215 and 2.820, respectively, for newly achieved MAFLD remission. Among female patients, regular exercise and breakfast consumption were accelerating factors for newly achieved MAFLD remission. Non-invasive liver fibrosis scores significantly differed between MAFLD and newly achieved MAFLD remission, including in the subgroups (p < 0.01 and p < 0.001, respectively). CONCLUSIONS: Reducing BMI and WC variabilities in male patients and improving lifestyle habits in female patients may accelerate MAFLD remission.

Efficacy of immune checkpoint inhibitors in patients with anorectal melanoma in association with immune-related adverse events: a case series.

Anorectal melanoma (AM) is a rare subtype of mucosal melanoma with a poor prognosis. Given its rarity compared to its cutaneous counterpart, the benefits and side effects of immune checkpoint inhibitor (ICI) therapy and the relationship between side effects and prognosis remain unclear. Herein, we describe the clinical presentation of five patients with AM treated with ICI as well as their relationship to the treatment course and the development of immune-related adverse events (irAEs). Three patients received sequential or concurrent administrations of nivolumab and ipilimumab, one received nivolumab alone, and one received ipilimumab alone. The response rate (RR) and disease control rate (DCR) were 40% and 80%, respectively. Pituitary and hepatic dysfunctions were the most common irAEs observed (40% each), followed by thyroid, diarrhea, and renal dysfunctions (20% each). The RR was 67% in patients with irAEs while no response was observed in patients without irAEs. DCR was 100% and 50% in patients with and without irAEs, respectively. Overall survival was 34 months in irAE and 8.75 months in non-irAE cases, with a longer survival trend in irAE cases. ICI therapy was effective and well-tolerated by AM patients, with potentially better outcomes for those who experienced irAEs compared to those who did not.

Urokinase-type plasminogen activator blockade ameliorates experimental colitis in mice.

Although several angiogenesis-related factors are reportedly involved in the pathogenesis of ulcerative colitis (UC), the mechanisms by which they contribute to disease are unclear. We first examined the expression of angiogenesis-related factors in inflamed colorectal tissue of UC patients using antibody array, and identified the 5 factors with highest expression, which included matrix metalloproteinase-8, urokinase-type plasminogen activator (uPA), angiostatin/plasminogen, hepatocyte growth factor and endoglin. Subsequent real-time PCR experiments using additional colorectal tissues revealed that uPA mRNA levels were significantly higher in inflamed tissues than in non-inflamed tissues, and significantly correlated with the severity of UC. Mirror section immunohistochemistry revealed that uPA was expressed in the neutrophils of inflamed colorectal tissues. We administered dextran sulfate sodium (DSS) in drinking water to uPA knockout (uPA-/-) mice, and found that the disease activity index in uPA-/- mice was marginally lower and the histological score in uPA-/- mice was significantly lower than those in wild-type mice, suggesting the importance of uPA in colitis. When an uPA-selective inhibitor, UK122, was administered to DSS-treated C57BL6J mice, the disease activity index and histological score in those mice were significantly lower compared with control mice. Multiple cytokine/chemokine assay using colorectal tissues from uPA-/- and UK122-treated mice revealed significantly lowered level of RANTES. In conclusion, uPA was highly expressed in neutrophils of the inflamed mucosa of UC patients, and the expression level correlated with the severity of UC. Genetic uPA deletion or pharmacological uPA blockade significantly ameliorated colitis in mice, concomitant with downregulation of RANTES.

Treatment Response Predictors of Neoadjuvant Therapy for Locally Advanced Gastric Cancer: Current Status and Future Perspectives.

Neoadjuvant chemotherapy (NAC) for locally advanced gastric cancer (LAGC) has been recognized as an effective therapeutic option because it is expected to improve the curative resection rate by reducing the tumor size and preventing recurrence of micrometastases. However, for patients resistant to NAC, not only will operation timing be delayed, but they will also suffer from side effects. Thus, it is crucial to develop a comprehensive strategy and select patients sensitive to NAC. However, the therapeutic effect of NAC is unpredictable due to tumor heterogeneity and a lack of predictive biomarkers for guiding the choice of optimal preoperative treatment in clinical practice. This article summarizes the related research progress on predictive biomarkers of NAC for gastric cancer. Among the many investigated biomarkers, metabolic enzymes for cytotoxic agents, nucleotide excision repair, and microsatellite instability, have shown promising results and should be assessed in prospective clinical trials. Noninvasive liquid biopsy detection, including miRNA and exosome detection, is also a promising strategy.

Colorectal carcinoma occurring via the adenoma-carcinoma pathway in patients with serrated polyposis syndrome.

BACKGROUND: Although serrated polyposis syndrome (SPS) is associated with an increased colorectal cancer (CRC) risk, the carcinogenic mechanisms remain unknown. We investigated clinicopathological characteristics and genetic abnormalities in colorectal polyps and CRC to elucidate carcinogenic mechanisms in SPS. METHODS: We retrospectively analyzed clinicopathological features of colorectal polyps in 44 SPS patients, and examined mutations of genes including APC, RAS, BRAF, and TP53, and microsatellite instability (MSI) in CRC tissues. RESULTS: Of the 44 patients, 25 (56%) fulfilled WHO criterion 1, 11 (25%) fulfilled criterion 2, and 8 (18%) fulfilled both. A total of 956 polyps were observed; 642 (67%) hyperplastic polyps (HP), 204 (21%) sessile serrated lesions (SSL), 10 (1%) traditional serrated adenoma (TSA), and 100 (11%) adenomas. The median numbers of polyps (/patient) were 10.5 (IQR 2.75-23) HPs, 4.0 (2.0-6.0) SSLs, 0 (0-0) TSA, and 1 (0-3.3) adenoma. SSL and HP located preferentially in the proximal and distal colon, respectively. Twenty-two CRCs were found in 18 patients. Based on the histological coexistence of SSL/TSA, BRAF mutation and MSI, 5 CRCs (26%) were classified as serrated-neoplasia pathway. Conversely, based on the coexistence of adenoma, APC/RAS and TP53 mutations, 11 CRCs (58%) were classified as adenoma-carcinoma pathway. The remaining three were unclassifiable. Most CRCs through adenoma-carcinoma pathway were located in the left-side colorectum and patients bearing those met criterion 2, characterized by many HP and advanced adenomas. Adenoma was a significant risk factor for CRC. CONCLUSIONS: Our results suggest that more than half of the CRCs, particularly those in the left-side colorectum, developed through the adenoma-carcinoma pathway in SPS patients. Adenoma was a risk factor for CRCs, suggesting its importance in colorectal carcinogenesis.

Direct Wiring of Liquid Metal on an Ultrasoft Substrate Using a Polyvinyl Alcohol Lift-off Method.

In recent years, wiring and system construction on ultrasoft materials such as biological tissues and hydrogels have been proposed for advanced wearable devices, implantable devices, and soft robotics. Among the soft conductive materials, Ga-based liquid metals (LMs) are both biocompatible and ultrasoft, making them a good match for electrodes on the ultrasoft substrates. However, gels and tissues are softer and less wettable to the LMs than conventional soft substrates such as Ecoflex and polydimethylsiloxane. In this study, we demonstrated the transfer of LM paste composed of Ga-based LM and Ni nanoparticles onto ultrasoft substrates such as biological tissue and gels using sacrificial polyvinyl alcohol (PVA) films. The LM paste pattern fabricated on the PVA film adhered to the ultrasoft substrate along surface irregularities and was transferred without being destroyed by the PVA film before the PVA's dissolution in water. The minimum line width that could be wired was approximately 165 µm. Three-dimensional wiring, such as the helical structure on the gel fiber surface, is also possible. Application of this transfer method to tissues using LM paste wiring allowed the successful stimulation of the vagus nerve in rats. In addition, we succeeded in transferring a temperature measurement system fabricated on a PVA film onto the gel. The connection between the solid-state electrical element and the LM paste was stable and maintained the functionality of the temperature-sensing system. This fundamental study of wiring fabrication and system integration can contribute to the development of advanced electric devices based on ultrasoft substrates.

Clinicopathological characteristics of colorectal serrated polyposis syndrome (SPS): results of a multicenter study by the SPS Study Group in Japan.

BACKGROUND: Serrated polyposis syndrome (SPS), a type of colorectal polyposis characterized by multiple serrated polyps, is associated with a high risk of colorectal carcinoma (CRC). This study aimed to clarify the clinicopathological characteristics of SPS in Japan. METHODS: We investigated the clinicopathological characteristics of patients with SPS from the "Multicenter Study on Clinicopathological Characteristics of SPS (UMIN 000032138)" by the Colorectal Serrated Polyposis Syndrome (SPS) Study Group. In this study, patients were diagnosed with SPS based on the 2019 World Health Organization (WHO) SPS diagnostic criteria. RESULTS: Ninety-four patients were diagnosed with SPS in 10 institutions between January 2001 and December 2017. The mean number (± standard deviation [SD]) of resected lesions per patient was 11.3 ± 13.8. The mean age at diagnosis of SPS was 63.3 ± 11.6 years, and 58 patients (61.7%) were male. Eighty-seven (92.6%) and 16 (17.0%) patients satisfied WHO diagnostic criteria I and II, respectively. Nine patients (9.6%) satisfied both criteria I and II. Carcinoma (T1-T4) were observed in 21 patients (22.3%) and 24 lesions. Of the 21 patients with CRC, 19 (90.4%) satisfied diagnostic criterion I, 1 (4.8%) satisfied diagnostic criterion II, and 1 (4.8%) satisfied diagnostic criteria I and II. There was no notable difference in the prevalence of CRC among patients who met diagnostic criterion I, II, and both I and II. CONCLUSIONS: Patients with SPS have a high risk of CRC and should undergo regular surveillance colonoscopy. Raising awareness of this syndrome is crucial.

Liquid metal-based nanocomposite materials: fabrication technology and applications.

Research on liquid metals has been steadily garnering more interest in recent times, especially in flexible electronics applications because of their properties like possessing high conductivity and being liquid state at room temperature. The unique properties afforded by such materials at low temperatures can compensate for the limitations of stretchable electronic devices, particularly robustness and their fluidic property, which can enhance the flexibility and deformation of these devices. Therefore, interest in liquid-metal nanoparticles and liquid metals with nanocomposites has enabled research into their fabrication technologies as well as utilisation in fields such as chemistry, polymer engineering, computational modelling, and nanotechnology. In particular, in flexible and stretchable electronic device applications, the research attention is focused on the fabrication methodologies of liquid-metal nanoparticles and liquid metals containing nanocomposites. This review attempts to summarise the available stretchable and flexible electronics applications that use liquid-metal nanoparticles as well as liquid metals with nanomaterial additives.

Transformable Electrocardiograph Using Robust Liquid-Solid Heteroconnector.

In this study, a highly transformable electrocardiograph that can considerably deform the position of stretchable electrodes based on the lead method for diagnosing heart disease was developed; these electrodes exhibited high resistance stability against considerable stretching and multiple stretching. To realize the large deformable functionality of the electrodes of a system, liquid metal electrodes and a heteroconnector composed of a liquid metal paste and carbon-based conductive rubber were employed. The developed device can achieve a 200% strain with only 6% resistance change and a high stability of resistances after the 100-time stretching test. In addition, the study demonstrated electrocardiograms in different lead methods of adult and child using the same device. The proposed combination of large deformable electrodes with high electric stability and a robust heteroconnector is an important technology, and it presents a considerable advancement in the application of stretchable electronic systems.

Neonatal wearable device for colorimetry-based real-time detection of jaundice with simultaneous sensing of vitals.

Neonatal jaundice occurs in >80% of newborns in the first week of life owing to physiological hyperbilirubinemia. Severe hyperbilirubinemia could cause brain damage owing to its neurotoxicity, a state commonly known as kernicterus. Therefore, periodic bilirubin monitoring is essential to identify infants at-risk and to initiate treatment including phototherapy. However, devices for continuous measurements of bilirubin have not been developed yet. Here, we established a wearable transcutaneous bilirubinometer that also has oxygen saturation (SpO2) and heart rate (HR) sensing functionalities. Clinical experiments with neonates demonstrated the possibility of simultaneous detection of bilirubin, SpO2, and HR. Moreover, our device could consistently measure bilirubin during phototherapy. These results demonstrate the potential for development of a combined treatment approach with an automatic link via the wearable bilirubinometer and phototherapy device for optimization of the treatment of neonatal jaundice.

Highly stretchable sensing array for independent detection of pressure and strain exploiting structural and resistive control.

Stretchable physical sensors are crucial for the development of advanced electrical systems, particularly wearable devices and soft robotics. Currently available stretchable sensors that detect both pressure and strain are based on piezoelectric, piezoresistive, or piezocapacitive effects. The range of pressure sensing is 1-800 kPa with large deformations being within the range of deformations of parts of the human body, such as elbows and knees. However, these devices cannot easily allow simultaneous and independent detection of pressure and strain with sensor arrays at large tensions (> 50%) because strain affects the pressure signal. In this study, we propose a monolithic silicone-based array of pressure and strain sensors that can simultaneously and independently detect the in-plane biaxial tensile deformation and pressure. To realize these functionalities, the deformation of the device structure was optimized using a hetero-silicone substrate made of two types of silicone with different hardness characteristics and porous silicone bodies. In addition, the resistances of the sensors were controlled by adjusting a mixture based on carbon nanoparticles to improve the sensitivity and independence between the pressure and strain sensors. These concepts demonstrate the potential of this approach and its compatibility with the current architectures of stretchable physical sensors.

Synergistic anti-tumor activity of miriplatin and radiation through PUMA-mediated apoptosis in hepatocellular carcinoma.

BACKGROUND: The prognosis for patients with unresectable advanced hepatocellular carcinoma (HCC) is poor. Miriplatin is a hydrophobic platinum compound that has a long retention time in lesions after transarterial chemoembolization (TACE). We investigated anti-tumor activity of miriplatin combined with irradiation on HCC cells, and its underlying mechanism of apoptosis. We also analyzed the effectiveness of miriplatin-TACE and radiotherapy for locally advanced HCC. METHODS: Human HCC cell lines HepG2 and HuH-7 were treated with DPC (active form of miriplatin) and radiation, and synergy was evaluated using a combination index (CI). Apoptosis-related proteins and cell cycles were analyzed by western blotting and flowcytometry. We retrospectively analyzed treatment outcomes in 10 unresectable HCC patients with vascular/bile duct invasion treated with miriplatin-TACE and radiotherapy. RESULTS: DPC or X-ray irradiation decreased cell viability dose-dependently. DPC plus irradiation decreased cell viability synergistically in both cell lines (CI < 1, respectively). Cleaved PARP expression was induced much more strongly by DPC plus irradiation than by each treatment alone. Expression of p53 up-regulated modulator of apoptosis (PUMA) was significantly induced by the combination, and knockdown of PUMA with siRNA significantly decreased apoptosis in both cell lines. DPC plus irradiation caused sub-G1, G2/M, and S phase cell arrest in those cells. The combination of miriplatin-TACE and radiotherapy showed a high response rate for patients with locally advanced HCC despite small number of patients. CONCLUSIONS: Miriplatin plus irradiation had synergistic anti-tumor activity on HCC cells through PUMA-mediated apoptosis and cell cycle arrest. This combination may possibly be effective in treating locally advanced HCC.