Novel Lewis Acid-Base Interactions in Polymer-Derived Sodium-Doped Amorphous Si-B-N Ceramic: Towards Main-Group-Mediated Hydrogen Activation.

Interest is growing in transition metal-free compounds for small molecule activation and catalysis. We discuss the opportunities arising from synthesizing sodium-doped amorphous silicon-boron-nitride (Na-doped a-SiBN). Na+ cations and 3-fold coordinated BIII moieties were incorporated into an amorphous silicon nitride network via chemical modification of a polysilazane followed by pyrolysis in ammonia at 1000 °C. Emphasis is placed on the mechanisms of hydrogen (H2) activation within Na-doped a-SiBN structure. This material design approach allows the homogeneous distribution of Na+ and BIII moieties surrounded by SiN4 units contributing to the transformation of the BIII moieties into 4-fold coordinated geometry upon encountering H2, potentially serving as frustrated Lewis acid (FLA) sites. Exposure to H2 induced formation of frustrated Lewis base (FLB) N-= sites with Na+ as a charge-compensating cation, resulting in the in situ formation of a frustrated Lewis pair (FLP) motif (≡BFLA···Hδ-···Hδ+···:N-(Na+)=). Reversible H2 adsorption-desorption behavior with high activation energy for H2 desorption (124 kJ mol-1) suggested the H2 chemisorption on Na-doped a-SiBN. These findings highlight a future landscape full of possibilities within our reach, where we anticipate main-group-mediated small molecule activation will have an important impact on the design of more efficient catalytic processes and the discovery of new catalytic transformations.

Pexidartinib and Immune Checkpoint Inhibitors Combine to Activate Tumor Immunity in a Murine Colorectal Cancer Model by Depleting M2 Macrophages Differentiated by Cancer-Associated Fibroblasts.

Tumor-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs) are known to play supportive roles in tumor development and progression, but their interactions in colorectal cancer (CRC) remain unclear. Here, we investigated the effects of colon-cancer-derived CAFs on TAM differentiation, migration, and tumor immunity, both in vitro and in vivo. When co-cultured with monocytes, CAFs attracted monocytes and induced their differentiation into M2 macrophages. Immunohistology of surgically resected human CRC specimens and orthotopically transplanted mouse tumors revealed a correlation between numbers of CAFs and numbers of M2 macrophages. In a mouse model of CRC orthotopic transplantation, treatment with an inhibitor of the colony-stimulating factor-1 receptor (PLX3397) depleted M2 macrophages and increased CD8-positive T cells infiltrating the tumor nest. While this treatment had a minor effect on tumor growth, combining PLX3397 with anti-PD-1 antibody significantly reduced tumor growth. RNA-seq following combination therapy showed activation of tumor immunity. In summary, CAFs are involved in the induction and mobilization of M2 macrophage differentiation in the CRC tumor immune microenvironment, and the combination of cancer immunotherapy and PLX3397 may represent a novel therapeutic option for CRC.

Treatment Effects of Switching to Faricimab in Eyes with Diabetic Macular Edema Refractory to Aflibercept.

Background and Objectives: Faricimab is a vascular endothelial growth factor A and angiopoietin-2 bispecific antibody. It is a novel therapeutic approach distinct from previous anti-vascular endothelial growth factor agents. This study aimed to evaluate the efficacy of switching from aflibercept to faricimab in the treatment of diabetic macular edema (DME) refractory to aflibercept, with a specific focus on the resolution of macular edema. Materials and Methods: The medical records of 29 eyes of 21 patients with DME that were refractory to intravitreal injections of aflibercept (IVAs) and who had completed the clinical follow-up of at least four intravitreal injections of faricimab (IVFs) were reviewed. The central retinal thickness (CRT), best-corrected visual acuity (BCVA), and the mean period (weeks) until the next injection were measured after the second-to-last IVA, first-to-last IVA, last IVA, and first to fourth IVFs following the transition to IVF. Results: The mean time from the first IVF to the assessment of effectiveness was significantly shorter than the time to the last IVA; however, no significant difference was found in the time from the second, third, and fourth IVFs to the assessment. The mean CRTs after the first and second IVFs were not significantly different from the CRT after the last IVA, but the mean CRT after the third and fourth IVFs was significantly thinner than that after the last IVA (p = 0.0025 and p = 0.0076, respectively). The mean BCVAs after the third and fourth IVFs significantly improved compared with that after the last IVA (p = 0.0050 and p = 0.0052, respectively). Conclusions: When switching the treatment to IVF for eyes with IVA-resistant DME, better treatment outcomes are achieved if IVF is performed three or more times.

Cognitive and self-regulation skills for employment among people with brain injury: A comparison of employed and non-employed people using mixed analysis.

BACKGROUND: Employment for people with brain injuries is challenging, and identifying the factors that can be improved by rehabilitation and establishing appropriate intervention methods are imperative. OBJECTIVE: To examine whether differences in cognitive functions and self-regulation skills exist between employed and non-employed people with brain injuries. In addition, we explored the self-regulation skills characteristic of employed people by qualitatively comparing them to those of non-employed people. METHODS: Using a mixed research method, demographic data, neuropsychological tests, self-efficacy, and self-regulation skills were compared between 38 people with brain injuries (16 employed and 22 unemployed) in the community. Subsequently, self-regulation skills were assessed by the Self-Regulation Skills Interview (SRSI), and participants' responses were qualitatively compared. RESULTS: No significant differences were observed in demographic data and neuropsychological tests, but employed people showed significantly better SRSI scores than unemployed people (p <  0.01). The qualitative analysis of the SRSI showed that employed people recognised themselves as having more specific symptoms than unemployed people. For example, they recognised the behaviour 'when having more than one errand, forgetting it', whereas non-employed people only recognised the category 'failure of prospective memory'. Furthermore, employed people reviewed their behaviour and developed ingenious coping strategies, such as 'looking back on appointments that have been made', 'writing down as soon as having a schedule', whereas unemployed people only exhibited categories such as 'writing schedules on the cell phone'. CONCLUSIONS: Self-regulation skills, such as recognising specific symptoms and developing relevant coping strategies, are effective for gaining employment.

Analysis of anti-tumor effect and mechanism of GLS1 inhibitor CB-839 in colorectal cancer using a stroma-abundant tumor model.

BACKGROUND: Glutaminase 1 (GLS1), a key enzyme in glutamine metabolism in cancer cells, acts as a tumor promoter and could be a potential therapeutic target. CB-839, a GLS1-specific inhibitor, was developed recently. Herein, we aimed to elucidate the anti-tumor effects and mechanism of action of CB-839 in colorectal cancer (CRC). METHODS: Using the UCSC Xena public database, we evaluated GLS1 expression in various cancers. Immunostaining for GLS1 was performed on 154 surgically resected human CRC specimens. Subsequently, we examined the GLS1 mRNA expression levels in eight CRC cell lines and evaluated the association between GLS1 expression and CB-839 efficacy. To create a reproducible CRC model with abundant stroma and an allogeneic immune response, we co-transplanted CT26 and stem cells into BALB/c mice and treated them with CB-839. Finally, RNA sequencing of mouse tumors was performed. RESULTS: Database analysis showed higher GLS1 expression in CRC tissues than in normal colon tissues. Clinical samples from 114 of the 154 patients with CRC showed positive GLS1 expression. GLS1 expression in clinical CRC tissues correlated with vascular invasion. CB-839 treatment inhibited cancer cell proliferation depending on GLS1 expression in vitro and inhibited tumor growth and metastasis in the CRC mouse model. RNA sequencing revealed that CB-839 treatment inhibited stromal activation, tumor growth, migration, and angiogenesis. These findings were validated through in vitro and in vivo experiments and clinical specimen analysis. CONCLUSIONS: GLS1 expression in CRC plays important roles in tumor progression. CB-839 has inhibitory effects on cancer proliferation and the tumor microenvironment.

Technical note: A universal worksheet for failure mode and effects analysis-A project of the Japanese College of Medical Physics.

BACKGROUND: Failure mode and effects analysis (FMEA), which is an effective tool for error prevention, has garnered considerable attention in radiotherapy. FMEA can be performed individually, by a group or committee, and online. PURPOSE: To meet the needs of FMEA for various purposes and improve its accessibility, we developed a simple, self-contained, and versatile web-based FMEA risk analysis worksheet. METHODS: We developed an FMEA worksheet using Google products, such as Google Sheets, Google Forms, and Google Apps Script. The main sheet was created in Google Sheets and contained elements necessary for performing FMEA by a single person. Automated tasks were implemented using Apps Script to facilitate multiperson FMEA; these functions were built into buttons located on the main sheet. RESULTS: The usability of the FMEA worksheet was tested in several situations. The worksheet was feasible for individual, multiperson, seminar, meeting, and online purposes. Simultaneous online editing, automated survey form creation, automatic analysis, and the ability to respond to the form from multiple devices, including mobile phones, were particularly useful for online and multiperson FMEA. Automation enabled through Google Apps Script reduced the FMEA workload. CONCLUSIONS: The FMEA worksheet is versatile and has a seamless workflow that promotes collaborative work for safety.

A prospective comparison study utilizing patient-reported outcomes of taxane-related peripheral neuropathy between nab-paclitaxel and standard paclitaxel in patients with breast cancer.

BACKGROUND: Characteristics of taxane-induced peripheral neuropathy (PN) could be different between paclitaxel and nab-paclitaxel. The purpose of this prospective observational multicenter cohort study was to compare tri-weekly nab-paclitaxel to weekly standard paclitaxel regarding the severity, onset and recovery of sensory and motor PN in patients with breast cancer. METHODS: Patients with histologically confirmed breast cancer who were scheduled to receive standard weekly paclitaxel (80 mg/m2) or tri-weekly nab-paclitaxel (260 mg/m2) at institutions in our multicenter group were eligible for this study. Sensory and motor PN were evaluated every 3 weeks until PN improved for up to one year using patient-reported outcome. RESULTS: Between February 2011 and April 2013, 115 patients were enrolled, including 57 and 58 in the paclitaxel and nab-paclitaxel groups, respectively. The incidence of moderate or severe sensory PN was not significantly different between the two groups (p = 0.40). The incidence of moderate or higher motor PN was more frequent in the nab-paclitaxel group than in the paclitaxel group (p = 0.048). The median period for demonstrating PN were shorter in the nab-paclitaxel group than in the paclitaxel group (sensory, p = 0.003; motor, p = 0.001). The recovery of motor PN was slower in the nab-paclitaxel group than in the paclitaxel group (p = 0.035), while the recovery period of sensory PN was not statistically different. CONCLUSION: Nab-paclitaxel induced sensory PN sooner than paclitaxel, and no difference was observed in the severity and recovery duration between the two agents. Motor PN was more severe, started sooner, and improved over a longer period in the nab-paclitaxel-treated patients than in the paclitaxel-treated patients.

Retinal Pigment Epithelial Tears after Ex-PRESS Filtration Surgery in a Glaucoma Patient with a History of Ischemic Optic Neuropathy.

Background: To describe a case of retinal pigment epithelial tears (RPE tears) and serous retinal detachment (SRD) after Ex-PRESS filtration surgery for primary open-angle glaucoma (POAG) combined with ischemic optic neuropathy. Case Presentation. This case report involved a 69-year-old woman who underwent Ex-PRESS filtration surgery for right POAG. She had a history of systemic arteriosclerotic disease and subacute progressive visual field loss due to suspected ischemic optic neuropathy in her right eye. The right preoperative visual acuity was 0.7, and intraocular pressure (IOP) was 19 mmHg with maximum glaucoma eye drops. RPE detachment was not observed in the fundus. On day 9 after surgery, the IOP was 6 mmHg, and mild choroidal detachment was observed. On day 13, although IOP remained almost unchanged at 7 mmHg, bullous SRD was observed in the inferior retina, including the macula, and RPE tears were observed along the superior arcade vessel. While subretinal fluid gradually decreased with increasing IOP, tractional retinal folds persisted along the superior arcade, accompanied by macular degeneration. Conclusion: We experienced a case of RPE tears after Ex-PRESS filtration surgery. In addition to choroidal detachment in the setting of hypotony, a pathologic condition causing structural fragility of the RPE layer may contribute to the development of RPE tears.

Long-term follow-up of a young male who developed acute macular neuroretinopathy following COVID-19 vaccination.

This report presents the clinical findings and prognosis of a healthy male patient who developed acute macular neuroretinopathy after COVID-19 vaccination. Abnormal findings improved about 1 month after the onset and disappeared 3 months later. The subjective symptoms disappeared in 3 months, and no recurrence was observed for 1 year.

A survey of the current status of neonatal disseminated intravascular coagulation in neonatal intensive care units in Kyushu, Japan.

BACKGROUND: Neonatal disseminated intravascular coagulation (DIC) is a rare disease with a poor outcome. However, data on the incidence, treatment, and outcome of neonatal DIC are scarce. Thus, this study investigated the status of neonatal DIC in Japan. METHODS: We sent a retrospective questionnaire-based survey regarding the status of diagnosis and treatment of neonatal DIC from January 1, 2016, to December 31, 2018, to 30 hospitals in Kyushu with a neonatal-perinatal medicine division. The data collected by the questionnaire survey included information about the patients diagnosed with neonatal DIC. RESULTS: Among the 13,582 neonates surveyed, 120 (0.9 %) were diagnosed with DIC. Of them, clinical data were available for 105 cases. There were 11 deaths (mortality rate: 10.4 %), with the most common underlying condition being infection (n = 9), followed by neonatal asphyxia and hematologic disease (both, n = 1). Compared with the survival group, the death group had more infections, as well as a higher rate of bleeding symptoms and organ dysfunction. CONCLUSIONS: Neonatal DIC associated with infectious diseases has a poor outcome. Therefore, it is necessary to formulate diagnostic and treatment guidelines for early intervention in such cases.

Clinicopathological Characteristics and Prognosis of Triple-Negative Apocrine Carcinoma: A Case-Control Study.

Background: With a prevalence of only 1% among all breast cancers in Japan, apocrine carcinoma (AC) is a rare type of breast cancer, and its clinicopathological characteristics remain unclear. The aim of this study was to evaluate the characteristics and prognosis of AC, in relation to the presence or absence of androgen receptor (AR). Methods: We conducted a retrospective multi-center case-control study (Yokohama Clinical Oncology Group (YCOG): YCOG1701 study) in Japan. A total of 53 patients were registered who were diagnosed with AC between 2000 and 2017 in YCOG-affiliated hospitals. Results: The median age of the patients was 67 (43 - 94) years, and the median observation time was 6.1 years. Among the 53 cases, 24 had triple-negative pure AC (TN-PAC; AR-positive), whereas 29 had other types of AC (other-AC; estrogen receptor-positive and/or human epidermal growth factor receptor 2-positive or AR-negative). Tumor size was smaller (1.4 vs. 2.1 cm, P = 0.024) and metastasis occurred in fewer nodes (12.5% vs. 37.9%, P = 0.036) in the TN-PAC group than in the other-AC group. The number of patients who were administered perioperative adjuvant chemotherapy did not significantly differ between the two groups (TN-PAC/other-AC = 50.0%/55.2%, P = 0.525); however, there was no recurrence in the TN-PAC group, compared to five cases with relapse in the other-AC group. Conclusions: AR-positive AC patients showed a favorable prognosis without adjuvant chemotherapy, even with the TN subtype. A clinical trial exploring the possibility of treatment de-escalation is anticipated.

Radial polarity in the first cranial neuromast of selected teleost fishes.

The neuromast is a sensory structure of the lateral line system in aquatic vertebrates, which consists of hair cells and supporting cells. Hair cells are mechanosensory cells, generally arranged with bidirectional polarity. Here, we describe a neuromast with hair cells arranged radially instead of bidirectionally in the first cranial neuromast of four teleost species: red seabream (Pagrus major), spotted halibut (Verasper variegatus), brown sole (Pseudopleuronectes herzensteini), and marbled sole (Pseudopleuronectes yokohamae). In these four species, this polarity was identified only in the first cranial neuromast, where it appeared at the rostral edge of the otic vesicle before hatching. We investigated the initial appearance and fate of this unique neuromast using scanning electron microscopy. We also assessed characteristics of radial neuromast pertaining to morphogenesis, development, and innervation using a vital fluorescent marker and immunohistochemistry in V. variegatus. The kinocilium initially appears at the center of each hair cell, then moves to its outer perimeter to form radial polarity by around 7 days postfertilization. However, hair cells arranged radially disappear about 15 days after hatching. This is followed by the appearance of bidirectionally arranged hair cells, indicating that polarity replacement from radial to bidirectional has occurred. In P. herzensteini, both afferent and efferent synapses between the nerve fibers and hair cells were observed by transmission electron microscopy, suggesting that radial neuromast is functional. Our discovery suggests that neuromasts with radial polarity could enable larval fish to assimilate multiaxial stimuli during this life stage, potentially assisting them in detecting small water vibrations or water pressure changes.

Efficacy and safety of pegfilgrastim biosimilar MD-110 in patients with breast cancer receiving chemotherapy: Single-arm phase III.

INTRODUCTION: Pegfilgrastim is indicated to decrease the incidence of chemotherapy-induced febrile neutropenia. It is the first granulocyte-colony stimulating factor approved for prophylactic use regardless of carcinoma type and is marketed in Japan as G-LASTA (Kyowa Kirin Co., Ltd., Tokyo, Japan). MD-110 is a biosimilar of pegfilgrastim. This phase III, multicenter, open-label, single-arm study investigated the efficacy and safety of MD-110 in early-stage breast cancer patients receiving neoadjuvant or adjuvant myelosuppressive chemotherapy. METHODS: A total of 101 patients received the study drug. Each patient received docetaxel 75 mg/m2 and cyclophosphamide 600 mg/m2 (TC) for four cycles on day 1 of each cycle. MD-110 (3.6 mg) was administered subcutaneously on day 2 of each cycle. The primary efficacy endpoint was the duration of severe neutropenia during cycle 1 (days with absolute neutrophil count < 500/mm3 ). The safety endpoints were adverse events and the presence of antidrug antibodies. RESULTS: The mean (SD) duration of severe neutropenia for MD-110 was 0.2 (0.4) days. The upper limit of the two-sided 95% confidence interval for the mean duration of severe neutropenia was 0.2 days, below the predefined threshold of 3.0 days. The incidence of febrile neutropenia, the secondary efficacy endpoint, was 6.9% (7/101). Adverse events, occurring in more than 50% of patients, were alopecia, constipation, and malaise, which are common side effects of TC chemotherapy. Antidrug antibodies were negative in all patients. CONCLUSION: MD-110 was effective against chemotherapy-induced neutropenia. No additional safety concern, compared with the originator, was observed in patients with breast cancer receiving TC chemotherapy.(JapicCTI-205230).

Initial tumor volume as an important predictor for indication of intra-cavitary brachytherapy, intra-cavitary/interstitial brachytherapy, and multi-catheter sole interstitial brachytherapy in cervical cancer patients treated with chemoradiotherapy.

Purpose: Advances in three-dimensional image-guided brachytherapy technique allow for using intra-cavitary and interstitial brachytherapy (ICIS-BT), and sole interstitial brachytherapy (ISBT) in addition to conventional intra-cavitary brachytherapy (ICBT). However, no consensus has been reached regarding the choice of these techniques. The aim of this study was to propose the size criteria for indication of interstitial techniques. Material and methods: We examined initial gross tumor volume (GTV) at presentation and at each brachytherapy session. Also, dose volume histogram parameters for each modality were compared in 112 patients with cervical cancer treated with brachytherapy (ICBT, 54; ICIS-BT, 11; and ISBT, 47). Results: The average GTV at diagnosis was 80.9 cm3 (range, 4.4-343.2 cm3), which shrank to 20.6 cm3 (25.5% of initial volume, range, 0.0-124.8 cm3) at initial brachytherapy. GTV > 30 cm3 at brachytherapy and high-risk clinical target volume > 40 cm3 were good threshold values for indication of interstitial technique, and tumors with initial GTV > 150 cm3 could be candidates for ISBT. An ISBT dose of 89.10 Gy can be prescribed in equivalent dose in 2 Gy fractions (range, 65.5-107.6 Gy), which was higher than those of ICIS (73.94 Gy, range, 71.44-82.50 Gy) and ICBT (72.83 Gy, range, 62.50-82.27 Gy) (p < 0.0001). Conclusions: Initial tumor volume is an important predictor for indication of ICBT and ICIS-BT. ISBT or at least an interstitial technique is recommended for initial GTV > 150 cm3.

A risk scoring system for early diagnosis of anastomotic leakage after subtotal esophagectomy for esophageal cancer.

BACKGROUND: Anastomotic leakage (AL) is one of the most critical postoperative complications after subtotal esophagectomy in patients with esophageal cancer. This study attempted to develop an optimal scoring system for stratifying the risk for AL. METHODS: The study included 171 patients who underwent subtotal esophagectomy for esophageal cancer followed by esophagogastrostomy in the cervical region from January 2011 to April 2021 at Nagoya University Hospital. AL was defined by radiologic or endoscopic evidence of anastomotic breakdown using some modalities. A risk scoring system for an early diagnosis of AL was established using factors determined in the multivariate analysis. A score was calculated for each patient, and the patients were classified into three categories according to the risk for AL: low-, intermediate- and high-risk. The trend of the risk for AL among the categories was evaluated. RESULTS: Twenty-nine patients (17%) developed AL. Multivariate analysis demonstrated that sinistrous gross features of drain fluid (P < 0.001; odds ratio (OR), 10.2), radiologic air bubble sign (P < 0.001; OR, 15.0) and the level of drain amylase ≥280 U/L on postoperative Day 7 (P < 0.001; OR, 9.0) were significantly associated with AL. According to the matching number of the above three risk factors and categorization into three risk groups, the incidence of AL was 6.1% (8/131) in the low-risk group, 45.5% (15/33) in the intermediate-risk group and 85.7% (6/7) in the high-risk group (area under curve, 0.81; 95% confidence interval, 0.72-0.90). CONCLUSIONS: The present AL-risk scoring system may be useful in postoperative patient care after subtotal esophagectomy.

Early diagnosis of neonatal-onset cyclic vomiting syndrome.

Cyclic vomiting syndrome (CVS) is characterized by recurrent episodes of severe vomiting with a completely asymptomatic interictal interval. Relatively few patients develop CVS in the neonatal period, and an early diagnosis is difficult. We experienced an infant who was diagnosed with neonatal-onset CVS in early infancy. An 8-day-old girl was admitted to our neonatal intensive care unit because of frequent vomiting beginning 12 h after birth and weight loss reaching 84.2% of her birth weight. Despite extensive examinations, no abnormalities to explain the vomiting were found. She continued to vomit, and a cyclical pattern with a vomiting phase lasting for three days followed by a non-vomiting phase lasting for about one to two weeks became obvious. Based on her clinical course, the family history of migraine and the effectiveness of Phenobarbital, she was diagnosed with CVS at three months old. Although CVS is a diagnosis of exclusion, a family history of migraine can aid its early diagnosis. If the illness is suspected in the neonatal period, diagnostic treatment with Phenobarbital may be considered. The case suggests the need to include CVS in the differential diagnosis of neonates with unexplained repetitive vomiting.

Landscape Genetic Analysis for the Japanese Wild Boar in the Early Expanding Stage in the Hokuriku Region of Japan.

As a contribution to improving management of the Japanese wild boar (Sus scrofa leucomystax), which has recently expanded its range and is having some negative effects on the ecosystem, we conducted a landscape genetic study using individual-based genetic analysis and multiple landscape elements to elucidate its dispersal patterns in the early stage of its expansion. Microsatellite DNA analysis of Japanese wild boars in the Hokuriku region of Japan revealed the existence of two ancestral genetic clusters, that they had migrated via different pathways, and that they were inadequately admixed. We also inferred the most suitable habitats for Japanese wild boar using MaxEnt and concluded that lower elevation and snowfall may favor the occurrence of wild boar individuals. Landscape genetic analysis indicated regional differences in Japanese wild boar dispersal patterns, according to the spatial heterogeneity of genetic features and landscape elements. On the western side of the study area, where individuals with a high frequency of one of two ancestral clusters were more abundant, significant effects of isolation by distance and resistance due to the above two landscape factors were detected, suggesting unidirectional dispersion influenced by the alpine landscape. In contrast, on the eastern side, there was indication of resistance to dispersal of individuals predominantly possessing another ancestral cluster, suggesting the influence of irregularly arranged suitable habitats due to the complexity of the mountainous terrain. Based on our findings, we conclude that Japanese wild boar dispersal patterns may be influenced by landscape elements, such as alpine mountains.

The Anti-Tumor Effect of the Newly Developed LAT1 Inhibitor JPH203 in Colorectal Carcinoma, According to a Comprehensive Analysis.

A novel large neutral amino acid transporter 1 (LAT1)-specific inhibitor, JPH203, is expected to cause cancer-specific starvation and possess anti-tumor effects; however, its anti-tumor mechanism for colorectal cancer (CRC) remains unclear. We analyzed LAT family gene expressions in public databases using UCSC Xena and evaluated LAT1 protein expression using immunohistochemistry in 154 cases of surgically resected CRC. We also evaluated mRNA expression using polymerase chain reaction in 10 CRC cell lines. Furthermore, JPH203 treatment experiments were conducted in vitro and in vivo using an allogeneic immune-responsive mouse model with abundant stroma created via the orthotopic transplantation of the mouse-derived CRC cell line CT26 and mesenchymal stem cells. The treatment experiments were followed by comprehensive gene expression analyses with RNA sequencing. Database analyses and immunohistochemistry research on clinical specimens revealed that LAT1 expression was cancer-dominant, and its increase was accompanied by tumor progression. In vitro, JPH203 was effective in an LAT1 expression-dependent manner. In vivo, JPH203 treatment considerably reduced tumor size and metastasis, and RNA sequencing-based pathway analysis showed that not only tumor growth and amino acid metabolism pathways, but also stromal activation-related pathways were suppressed. The results of the RNA sequencing were validated in the clinical specimens, as well as both in vitro and in vivo. LAT1 expression in CRC plays an important role in tumor progression. JPH203 may inhibit the progression of CRC and tumor stromal activity.

Risk Factors for Muscle Loss During Neoadjuvant Therapy for Esophageal Cancer.

BACKGROUND/AIM: In patients with esophageal cancer, muscle loss induced by neoadjuvant therapy before esophagectomy is correlated with poor prognosis. However, little is known about the causes of muscle loss. Thus, the purpose of this retrospective study was to clarify the risk factors for muscle loss during neoadjuvant therapy. PATIENTS AND METHODS: Patients with esophageal cancer who underwent neoadjuvant therapy before esophagectomy between 2009 and 2020 were investigated (n=132). The patients received either cisplatin plus 5-fluorouracil (CF); docetaxel, cisplatin plus 5-fluorouracil (DCF); or CF with radiotherapy as neoadjuvant therapy. The cross-sectional areas of the bilateral psoas muscles were measured at the level of the third lumbar vertebra using CT, before and after neoadjuvant therapy, and psoas muscle loss was calculated. The patients were divided into the high muscle loss group with 5% or more muscle loss or the low muscle loss group with less than 5% loss. Correlations between muscle loss and clinical factors were evaluated. RESULTS: The median value of psoas muscle loss was 5.30%. Psoas muscle loss was significantly correlated with a poor 3-year overall survival rate (p=0.034). Multivariate analysis showed that the independent factors associated with muscle loss were age ≥70 years [odds ratio (OR)=2.43, p=0.022], treatment with DCF (OR=3.47, p=0.034), and a poor response to neoadjuvant therapy (OR=2.68, p=0.028). CONCLUSION: A regimen of DCF was a major trigger of muscle loss during neoadjuvant therapy.

Usefulness of Acetic Acid Spray with Narrow-Band Imaging for Identifying the Margin of Sessile Serrated Lesions.

BACKGROUND: Sessile serrated lesions (SSLs) are precursors of colon cancer, especially in cases of large, right colon. However, they are difficult to not only detect, but only clarify the margin of the lesion, which can lead to the poor endoscopic treatment outcomes. AIMS: This study evaluated the usefulness of acetic acid spray with narrow-band imaging (A-NBI) for the better visualization of the margin of SSLs. METHODS: From January 2013 to March 2022, patients with superficial elevated polyps suspected of being SSLs ≥ 10 mm with an endoscopic diagnosis that had been endoscopically resected at Hiroshima City Hiroshima Citizens Hospital were enrolled. Endoscopic images with white-light imaging (WLI), narrow-band imaging (NBI), indigo-carmine (IC), and A-NBI were recorded in each lesion and were randomly arranged and assessed by 10 endoscopists. We compared the visibility score (1 to 4) and color differences (ΔE) between inside and outside of the lesions among WLI, NBI, IC, and A-NBI. RESULTS: Forty-one lesions in 33 cases were included, and a total of 164 images were evaluated. As for the visibility score, most of the lesions were scored as 1 or 2 on WLI, whereas most were scored 4 on A-NBI. The median ΔE of A-NBI was also significantly higher than that of WLI, NBI, or IC (20.5 vs. 8.3 vs. 8.2 vs. 12.3, P < 0.01). A significant correlation was observed between the color difference and visibility score (r = 0.53, P < 0.01). CONCLUSIONS: A-NBI may be a useful modality for identifying the margin of SSLs.