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Background Neuropathic pain (NeP) is pain provoked by damage or disease in the nervous system and about one in three Japanese patients with spinal disorders are highly likely to have NeP. The humanistic and economic burden of illness (BOI) of spine-related NeP represents unmet medical needs that should be addressed. The purpose of this targeted literature review was to synthesize the available evidence on the BOI of spine-related NeP in Japanese patients. Methods PubMed and ICHUSHI were searched for relevant studies published between January 2010 and December 2020, in English or Japanese. The population included patients with one or more of prespecified spinal disorders and NeP, and outcomes of interest were data related to humanistic or economic burden. Results Out of 32 studies that assessed the BOI of spine-related disorders in Japan, only six specifically assessed spine-related NeP. Among these studies, five different validated questionnaires were used to measure humanistic burden. Spine-related NeP was consistently shown to be related with a poorer health-related quality of life and higher levels of anxiety and depression compared to the general population as well as patients with nociceptive pain. No articles directly evaluating economic burden were identified in this search, so an exploratory analysis was conducted. Reduction in work productivity by people experiencing spine-related NeP in the whole of Japan were estimated to total JPY 172,266,780,480 per year. Conclusions The humanistic burden of spine-related NeP on Japanese patients is considerable, not only physically but also mentally. Exploratory analysis of the economic burden illustrates the possibility of substantial societal costs associated with NeP. In order to better understand the depth of BOI and the unmet medical need caused by spine-related NeP, further studies on real-world outcomes are recommended.

Supplementary Figure 2 from Lin-7C/VELI3/MALS-3: An Essential Component in Metastasis of Human Squamous Cell Carcinoma

Supplementary Figure 1 from Lin-7C/VELI3/MALS-3: An Essential Component in Metastasis of Human Squamous Cell Carcinoma

Using proteomic selection, functional verification, and clinical validation, we identified specific down-regulation of Lin-7C/VELI3/MALS-3 (Lin-7C), which marks oral squamous cell carcinoma (OSCC) metastasis. Despite a rarity of sequence variations in the Lin-7C gene in both primary OSCC and OSCC-derived cells, a high prevalence of hypermethylation was detected in the CpG island region that strongly correlated with its down-regulation. Inducible Lin-7C mRNA by experimental demethylation was found in all OSCC cells tested. Overexpression of the Lin-7C gene in an OSCC cell clone does not contribute to underproliferation but results in a noninvasive phenotype with elevated β-catenin expression. Experimental metastases in multiple organs of immunodeficient mice were inhibited in cells expressing Lin-7C. Finally, the Lin-7C expression status in primary tumors afforded significantly (P < 0.001) high accuracy for predicting lymph node metastasis. These results establish Lin-7C as a novel target of early detection, prevention, and therapy for OSCC metastasis. [Cancer Res 2007;67(20):9643–8]

Supplementary Information from Lin-7C/VELI3/MALS-3: An Essential Component in Metastasis of Human Squamous Cell Carcinoma

Supplementary Table 1 from Lin-7C/VELI3/MALS-3: An Essential Component in Metastasis of Human Squamous Cell Carcinoma

Supplementary Legends 1-2 from Lin-7C/VELI3/MALS-3: An Essential Component in Metastasis of Human Squamous Cell Carcinoma

Glucocorticoid-induced osteoporosis (GIOP) is associated with elevated fracture risk. Practice guidelines have been published to reduce this risk but are insufficiently followed in everyday practice. The objectives of this study were to estimate fracture incidence in patients exposed to oral glucocorticoids and to analyse the impact of glucocorticoid use on fracture incidence.This retrospective cohort study was performed using the Medical Data Vision (MDV) claims database from Japan. All patients aged ≥ 18 years initiating oral glucocorticoids and fulfilling Japanese guideline criteria for starting prophylactic osteoporosis treatment between 2009 and 2019 were identified. These were matched to a cohort of unexposed controls using propensity score matching. Fracture incidence in the two cohorts were compared using a Fine-Gray proportional sub-distribution hazard model.13,090 glucocorticoid-exposed cases were compared to 13,090 unexposed controls. The 1-year fracture rate (all sites) was 9.3 [95% CI 8.8-9.8] in cases and 5.8 [5.4-6.2] in controls. One-year vertebral fracture rates were 4.3 [4.0-4.7] and 2.3 [2.1-2.6] respectively. In the multivariate analysis, the use of glucocorticoids was associated with an increase in the incidence of osteoporotic fractures (hazard ratio: 1.63 [1.51-1.76]). The glucocorticoid-associated risk tended to be higher in subgroups of patients with rheumatoid arthritis, asthma, COPD and in those aged 65 years.Oral glucocorticoid use is associated with an increase in fracture incidence. It is necessary to raise awareness of GIOP and to take public health measures to change the perceptions and behaviour of doctors prescribing glucocorticoids.

The authors of this paper applied a new approach combining text mining and principal component analysis (PCA) to objectively determine the actual state of regional COVID-19 strategy meetings and verified its utility. The authors used text mining to analyze meeting minutes and extracted words with high phase ubiquity by co-occurrence analysis. Then, they selected words symbolizing the meeting contents (“report,” “prevention,” “rules,” and “decision”) and performed PCA using the occurrence rates of these words as variables. Two principal components (PC1, PC2) were set. For PC1, we observed maximum factor loading for “decision” (0.81) and minimum for “report” (-0.72), so we considered this axis to show the “depth of meeting discussions.” For PC2, we observed maximum factor loading for “prevention” (0.81) and minimum for “rule” (-0.76). We considered this axis to show “regional infection status.” When we created a plot of all 44 meetings, Phase 1 occurred in quadrants 3 to 4 (knowledge sharing), phase 2 began in quadrant 1 (preparation for spread), and phase 3 shifted to quadrant 2 (response to spread) with significant differences between these phases. Our findings suggest that the actual state of regional COVID-19 strategy meetings could be objectively determined by using a combination of text mining and PCA.

Objectives This study investigated changes in bone mineral density (BMD) and erosion after denosumab discontinuation in rheumatoid arthritis (RA) patients without osteoporosis who participated in the DESIRABLE study. Methods This multicentre observational study consisted of a prediscontinuation visit (date of final assessment in DESIRABLE) and a postdiscontinuation visit (2.5 years after the last administered dose of denosumab). Percentage change in lumbar spine (LS) BMD from baseline was assessed as the primary endpoint. Results Fifty-nine patients were enrolled. The percentage change in LS BMD decreased to baseline levels at the postdiscontinuation visit. Compared with baseline, C-telopeptide of type I collagen levels increased after denosumab discontinuation but most patients had levels within the reference range. Bone erosion scores were not significantly different between the on-treatment period and after denosumab discontinuation (p = .0666) but there was a numerical increase postdiscontinuation. The progression in bone erosion score was significantly reduced in patients whose disease activity was in remission versus those not in remission (p = .0195). Conclusions In RA patients without osteoporosis, denosumab discontinuation can be explored while considering patient background factors (disease activity and risk of fracture) and accounting for progression of bone erosion and LS BMD decrease after withdrawal.

Aquaporin-4 (AQP4) is a predominant water channel expressed in astrocytes in the mammalian brain. AQP4 is crucial for the regulation of homeostatic water movement across the blood–brain barrier (BBB). Although the molecular mechanisms regulating AQP4 levels in the cerebral cortex under pathological conditions have been intensively investigated, those under normal physiological conditions are not fully understood. Here we demonstrate that AQP4 is selectively expressed in astrocytes in the mouse cerebral cortex during development. BMP signaling was preferentially activated in AQP4-positive astrocytes. Furthermore, activation of BMP signaling by in utero electroporation markedly increased AQP4 levels in the cerebral cortex, and inhibition of BMP signaling strongly suppressed them. These results indicate that BMP signaling alters AQP4 levels in the mouse cerebral cortex during development.

Background/aim Benzimidazoles are considered potential anticancer candidates. We herein studied the anticancer activity of CCL299, 4-(1H-1,3-benzodiazol-1-yl) benzonitrile. Materials and methods In this in vitro study, we used ATP assays, flow cytometry, western blotting, and caspase-3/7 assays to evaluate the effects of CCL299 on cell proliferation, cell-cycle progression and apoptosis. Results ATP assays showed that CCL299 inhibited cell growth in the hepatoblastoma cell line HepG2 and the cervical cancer cell line HEp-2, without exhibiting cytotoxic effects on non-cancer cells and TIG-1-20 fibroblasts. Flow cytometry, western blotting, and caspase-3/7 assays revealed that CCL299 induced G1-phase cell-cycle arrest followed by apoptosis that was associated with up-regulation of p-p53 (Ser15) and p21 expression and the down-regulation of p-CDK2 (Thr160) expression. Conclusion CCL299 exhibits cytotoxic activity via apoptosis in a subset of cancer cells, and should be considered as a promising anticancer candidate agent.

Sunitinib is an antiangiogenic drug for the treatment of metastatic renal cell carcinoma (mRCC) and imatinib-resistant gastrointestinal stromal tumor (GIST). Toxicities derived from sunitinib, such as altered taste, dry mouth, mucosal sensitivity, oral pain, gingival bleeding, and oral mucositis/stomatitis (OM/S) are widely reported. Additionally, in recent years, osteonecrosis of the jaw (ONJ) is reported to be related with sunitinib. We present here a rare case of ONJ involving mRCC receiving sunitinib monotherapy. A-76-year-old man, treated with sunitinib only, complained about oral pain in April 2019. In the lower mandibular, bone exposure and stomatitis were observed. The patient did not receive bisphosphonates or denosumab. Furthermore, he has not undergone tooth extraction or worn a denture in the left mandibular region. Panoramic radiograph and computed tomography (CT) did not show any obvious radiological changes or bone pathology. During the follow up, healing and bone exposure were repeated with sunitinib dosing and withdrawal. Finally, 3 months later (July 2019), a diameter of 3 × 3 mm necrotic bone was exposed and separated from the left lower mandible. Finally, sunitinib-related jaw osteonecrosis diagnosis was made.

The development and evolution of mammalian higher cognition are represented by gyrification of the laminar cerebral cortex and astrocyte development, but their mechanisms and interrelationships remain unknown. Here, we show that localized astrogenesis plays an important role in gyri formation in the gyrencephalic cerebral cor-tex. In functional genetic experiments, we show that reducing astrocyte number prevents gyri formation in the ferret cortex, while increasing astrocyte number in mice, which do not have cortical folds, can induce gyrus-like protrusions. Morphometric analyses demonstrate that the vertical expansion of deep pallial regions achieved by localized astrogenesis is crucial for gyri formation. Furthermore, our findings suggest that localized astrogenesis by a positive feedback loop of FGF signaling is an important mechanism underlying cortical folding in gyren-cephalic mammalian brains. Our findings reveal both the cellular mechanisms and the mechanical principle of gyrification in the mammalian brain. This work was supported by Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology (MEXT); Takeda Science Foundation; the Uehara Memorial Foundation; the Naito Foundation; European Research Council (ERC) Starting Grant 281961 AstroFunc; European Commission Horizon 2020 Action NCBio 951923; European Commission FP7-PEOPLE-2012-IEF 331018 PlasticAstros; Kanazawa University SAKIGAKE Project 2018; and Kanazawa University CHOZEN Project.

Targeting cell‑cycle regulation to hinder cancer cell proliferation is a promising anticancer strategy. The present study investigated the effects of a novel sulfonamide, CCL113, on cell cycle progression in cancer cell lines (HeLa and HepG2), a noncancerous cell line (Vero) and a normal human fibroblast cell line (TIG‑1‑20). The present results showed that treatment with CCL113 significantly decreased the viability of the cancer cells. FACS analyses showed that CCL113 treatment increased the proportion of cancerous and noncancerous cells in the G2/M phase. Analyses of cell cycle regulatory proteins showed that CCL113 treatment inhibited the activity of CDK1 in HeLa cells, possibly due to the decrease in the level of Cdc25B/C proteins and arrest in the M phase. Using time‑lapse imaging‑assisted analyses of HeLa and Vero cells expressing fluorescent ubiquitination‑based cell cycle indicator (FUCCI), it was observed that CCL113 treatment led to a prolonged G2 phase at the G2/M checkpoint and arrest in the M phase in both cell lines. This possibly activated the DNA damage response in noncancerous cells, while inducing mitotic arrest leading to apoptosis in the cancer cells. The results of molecular docking studies suggested that CCL113 might have the potential to bind to the taxol‑binding site on β‑tubulin. In conclusion, CCL113 holds potential as a reliable anticancer drug due to its ability to induce mitotic arrest followed by apoptosis of cancer cells and to activate the DNA damage response in noncancerous cells, thereby facilitating exit from the cell cycle.

The main symptom of Kimura disease (KD), a rare, chronic inflammatory disorder of unknown etiology, is painless granulation preferentially developing in the head and neck region’s soft tissues, especially in the parotid and submandibular glands and neck lymph nodes. KD is characterized clinically by peripheral blood eosinophilia and elevated serum immunoglobulin E (IgE) levels and histopathologically by high capillary vascularization and lymphoid follicle formation with eosinophil infiltration in the connective tissues. Angiolymphoid hyperplasia with eosinophilia (ALHE), a rare benign tumor of unknown etiology, also occurs in the head and neck frequently as single/multiple angiomatous papules/nodules varying from light brown to pink. Histopathologically, accelerated endothelial cell proliferation and high lymphocyte and eosinophil infiltration are observed. Due to KD’s and ALHE’s similar clinical and pathological symptoms, differential diagnosis is challenging. Their manifestations include a painless head/neck subcutaneous swelling. Here, we have described a case involving a 44-year-old man who presented with an upper lip mass that increased in size for 1 year. Laboratory studies revealed leukocytosis and eosinophilia. Computed tomography and magnetic resonance imaging examinations revealed a submucosal lip mass. Suspect minor salivary gland malignancies and lymphomas were surgically excised. Histopathologically, we observed marked lymphoid follicle proliferation with inflammatory cell, including eosinophil infiltration, capillary proliferation, and a developed vessel not normally present in the lip. Because differentiating between KD and ALHE is difficult, clinical differentiation was our focus. The Asian male patient with lymphadenopathy, eosinophilia, and high IgE levels was finally diagnosed with KD that has not recurred in 1 year.

Purpose Oncolytic viral therapy for neuroblastoma (NB) cells with Sindbis virus (SINV) is a promising strategy for treating high-risk NB. Here, we evaluated the possibility of using SINV structural proteins as therapeutic agents for NB since UV-inactivated SINV could induce cytopathogenic effects. Methods The cytotoxicity of UV-inactivated SINV toward human NB cell lines NB69, NGP, GOTO, NLF, SK-N-SH, SH-SY5Y, CHP134, NB-1, IMR32, and RT-BM-1 were analyzed. Apoptosis was confirmed by TUNEL assays. To determine the components of SINV responsible for the cytotoxicity of UV-inactivated SINV, expression vectors encoding the structural proteins, namely capsid, E2, and E1, were transfected in NB cells. Cytotoxicity was evaluated by MTT assays. Results UV-inactivated SINV elicited more significant cytotoxicity in NB69, NGP, and RT-BM-1 than in normal human fibroblasts. Results of the transfection experiments showed that all NB cell lines susceptible to UV-inactivated SINV were highly susceptible to the E1 protein, whereas fibroblasts transfected with vectors harboring capsid, E1, or E2 were not. Conclusions We demonstrated that the cytotoxicity of the UV-inactivated SINV is due to apoptosis induced by the E1 structural protein of SINV, which can be used selectively as a therapeutic agent for NB.

Brain development involves precisely orchestrated genetic, biochemical, and mechanical events. At the cellular level, neuronal proliferation in the innermost zone of the brain followed by migration towards the outermost layer results in a rapid increase in brain surface area, outpacing the volumetric growth of the brain, and forming the highly folded cortex. This work aims to provide mechanistic insights into the process of brain development and cortical folding using a biomechanical model that couples cell division and migration with volumetric growth. Unlike phenomenological growth models, our model tracks the spatio-temporal development of cohorts of neurons born at different times, with each cohort modeled separately as an advection-diffusion process and the total cell density determining the extent of volume growth. We numerically implement our model in Abaqus/Standard (2020) by writing user-defined element (UEL) subroutines. For model calibration, we apply in utero electroporation (IUE) to ferret brains to visualize and track cohorts of neurons born at different stages of embryonic development. Our calibrated simulations of cortical folding align qualitatively with the ferret experiments. We have made our experimental data and finite-element implementation available online to offer other researchers a modeling platform for future study of neurological disorders associated with atypical neurodevelopment and cortical malformations.

GTPases of immunity-associated protein 2 (GIMAP2) is a GTPase family member associated with T cell survival. However, its mechanisms of action in oral squamous cell carcinoma (OSCC) remain largely unknown. Therefore, the present study aimed to elucidate the possible role of GIMAP2 in OSCC development by investigating its expression levels and molecular mechanisms in OSCC. Reverse transcription quantitative PCR, immunoblotting and immunohistochemistry indicated that GIMAP2 expression was significantly upregulated (P

Phototheranostics represents a highly promising paradigm for cancer therapy, although selecting an appropriate optical imager and sensitizer for clinical use remains challenging.Liposomally formulated phospholipid-conjugated indocyanine green, denoted as LP-iDOPE, was developed as phototheranostic nanoparticle and its cancer imaging-mediated photodynamic reaction, defined as the immune response induced by photodynamic and photothermal effects, was evaluated with a near-infrared (NIR)-light emitting diode (LED) light irradiator.Using in vivo NIR fluorescence imaging, we demonstrated that LP-iDOPE was selectively delivered to tumor sites with high accumulation and a long half-life. Following low-intensity NIR-LED light irradiation on the tumor region of LP-iDOPE accumulated, effector CD8Our anti-cancer strategy based on tumor-specific LP-iDOPE accumulation and low-intensity NIR-LED light irradiation to the tumor regions, i.e., photodynamic reaction, represents a promising approach to noninvasive cancer therapy.

During mammalian neocortical development, neural precursor cells generate neurons first and astrocytes later. The cell fate switch from neurons to astrocytes is a key process generating proper numbers of neurons and astrocytes. Although the intracellular mechanisms regulating this cell fate switch have been well characterized, extracellular regulators are still largely unknown. Here, we uncovered that fibroblast growth factor (FGF) regulates the cell fate switch from neurons to astrocytes in the developing cerebral cortex using mice of both sexes. We found that the FGF signaling pathway is activated in radial glial cells of the ventricular zone at time points corresponding to the switch in cell fate. Our loss- and gain-of-function studies using in utero electroporation indicate that activation of FGF signaling is necessary and sufficient to change cell fates from neurons to astrocytes. We further found that the FGF-induced neuron–astrocyte cell fate switch is mediated by the MAPK pathway. These results indicate that FGF is a critical extracellular regulator of the cell fate switch from neurons to astrocytes in the mammalian cerebral cortex. SIGNIFICANCE STATEMENT Although the intracellular mechanisms regulating the neuron–astrocyte cell fate switch in the mammalian cerebral cortex during development have been well studied, their upstream extracellular regulators remain unknown. By using in utero electroporation, our study provides in vivo data showing that activation of FGF signaling is necessary and sufficient for changing cell fates from neurons to astrocytes. Manipulation of FGF signaling activity led to drastic changes in the numbers of neurons and astrocytes. These results indicate that FGF is a key extracellular regulator determining the numbers of neurons and astrocytes in the mammalian cerebral cortex, and is indispensable for the establishment of appropriate neural circuitry.

Acute encephalopathy (AE) is mainly reported in East Asia and, in most cases, results from pediatric viral infections, leading to fever, seizure, and loss of consciousness. Cerebral edema is the most important pathological symptom of AE. At present, AE is classified into four categories based on clinical and pathophysiological features, and cytokine storm-induced AE is the severest among them. The pathogenesis of AE is currently unclear; this can be attributed to the lack of a simple and convenient animal model for research. Here, we hypothesized that the induction of systemic inflammation using lipopolysaccharide (LPS) injection followed by hyperthermia (HT) treatment can be used to develop an animal model of cytokine storm-induced AE. Postnatal eight-day-old mouse pups were intraperitoneally injected with low-dose LPS (50 or 100 µg/kg) followed by HT treatment (41.5°C, 30 min). Histological analysis of their brains was subsequently performed. Fluorescein isothiocyanate assay combined with immunohistochemistry was used to elucidate blood–brain barrier (BBB) disruption. LPS (100 µg/kg) injection followed by HT treatment increased BBB permeability in the cerebral cortex and induced microglial activation. Astrocytic clasmatodendrosis was also evident. The brains of some pups exhibited small ischemic lesions, particularly in the cerebral cortex. Our results indicate that a low-dose LPS injection followed by HT treatment can produce symptoms of cytokine storm-induced AE, which is observed in diseases, such as acute necrotizing encephalopathy and hemorrhagic shock and encephalopathy syndrome. Thus, this mouse model can help to elucidate the pathogenetic mechanisms underlying AE.Impact statementAcute encephalopathy (AE), mainly reported in East Asia, is classified into four categories based on clinical and neuropathological findings. Among them, AE caused by cytokine storm is known as the severest clinical entity that causes cerebral edema with poor prognosis. Because suitable and convenient model animal of AE had not been developed, the treatment of patients with AE is not established. In the present study, we established a simple and convenient protocol to mimic AE due to cytokine storm. Our model animal should be useful to elucidate the pathogenesis of AE.

Changes in the cerebral cortex of mammals during evolution have been of great interest. Ferrets, monkeys, and humans have more developed cerebral cortices compared with mice. Although the features of progenitors in the developing cortices of these animals have been intensively investigated, those of the fiber layers are still largely elusive. By taking the advantage of our in utero electroporation technique for ferrets, here we systematically investigated the cellular origins and projection patterns of axonal fibers in the developing ferret cortex. We found that ferrets have 2 fiber layers in the developing cerebral cortex, as is the case in monkeys and humans. Axonal fibers in the inner fiber layer projected contralaterally and subcortically, whereas those in the outer fiber layer sent axons to neighboring cortical areas. Furthermore, we performed similar experiments using mice and found unexpected similarities between ferrets and mice. Our results shed light on the cellular origins, the projection patterns, the developmental processes, and the evolution of fiber layers in mammalian brains.

Glucocorticoid-induced osteoporosis (GIOP) is associated with a high fracture risk. Practice guidelines by the Japanese Society for Bone and Mineral Research in 2014 recommend bone densitometry and appropriate treatment to reduce this risk. The study objectives were to describe characteristics of GIOP patients in Japan and to evaluate their management in a subgroup of patients without comorbid cancer. This retrospective cohort study was performed using the Medical Data Vision (MDV) database from Japan. Adult patients initiating oral glucocorticoid treatment with a total GIOP risk score ≥ 3, based on the 2014 practice guideline, identified between 2009 and 2019 were eligible. A subgroup of patients without any cancer diagnosis was also identified. Data were extracted on demographics, concurrent medical conditions, use of bone densitometry, and osteoporosis treatment. 25,569 patients were eligible, of whom 12,227 had a confirmed cancer diagnosis. Mean age was 68.5 years and 12,356 patients (48.3%) were women. Concurrent medical conditions of interest were documented in 14,887 patients, most frequently rheumatoid arthritis (n = 4185) and asthma (n = 3085). Yearly bone densitometry was performed in 6.5% (n = 865) of the cancer-free subgroup; 51.8% (n = 6905) were prescribed an osteoporosis treatment, most frequently bisphosphonates (n = 5132; 74.3%). Between 2011 and 2018, rates of densitometry were stable, whereas prescription rates increased from 40.0 to 51.8%. In spite of publication of guidelines for GIOP management, there is an important treatment gap in their application in everyday practice. For this reason, public health measures to increase physician awareness of GIOP are needed.

Uveal melanoma (UM) is the most common cancer of the eye in adults. Up to 50% of UM patients subsequently develop metastases, especially in the liver. It has been reported that the retinoblastoma (RB) pathway is deregulated in more than 90% of UM despite the rarity of mutations in the RB1 gene itself. CDK4/6 inhibition (CDK4/6i) is a rational strategy for treatment of UM. In this report, we investigated the antiproliferative activity of a selective CDK4/6 inhibitor on metastatic UM. A CDK4/6 inhibitor suppressed UM cell lines growth in in vitro and in vivo experiments. Hepatocyte growth factor (HGF) decreased the effect of CDK4/6 inhibitor on metastatic UM cell lines. When CDK4/6i was combined with cMET inhibitor, enhanced growth suppression was observed in metastatic UM tumors grown in human-HGF knock-in xenograft mouse models. HGF is enriched in the liver and the majority of liver metastases from UM express activated forms of cMET, therefore, signaling through cMET could contribute to the resistance mechanisms against CDK4/6i, especially in UM patients with hepatic metastasis. Together, these results provide a rationale for the use of cMET inhibitor in combination with a CDK4/6 inhibitor for the treatment of metastatic UM.

S-1 is an anticancer agent that is comprised of tegafur, gimeracil, and oteracil potassium, and is widely used in various carcinomas including oral squamous cell carcinoma (OSCC). Although an established prediction tool is not available, we aimed to develop prediction models for the sensitivity of primary OSCC cases to the preoperative administration of S-1. We performed DNA microarray analysis of 95 cases with OSCC. Using global gene expression data and the clinical data, we developed two different prediction models, namely, model 1 that comprised the complete response (CR) + the partial response (PR) versus stable disease (SD) + progressive disease (PD), and model 2 that comprised responders versus non-responders. Twelve and 18 genes were designated as feature genes (FGs) in models 1 and 2, respectively, and, of these, six genes were common to both models. The sensitivity was 96.3%, the specificity was 91.2%, and the accuracy was 92.6% for model 1, and the sensitivity was 95.6%, the specificity was 85.2%, and the accuracy was 92.6% for model 2. These models were validated using receiver operating characteristic analysis, and the areas under the curves were 0.967 and 0.949 in models 1 and 2, respectively. The data led to the development of models that can reliably predict the sensitivity of patients with OSCC to the preoperative administration of S-1. The mechanism that regulates S-1 sensitivity remains unclear; however, the prediction models developed provide hope that further functional investigations into the FGs will lead to a greater understanding of drug resistance., Genetics; Clinical Genetics; Surgery; Pharmacology; Oncology; anti-tumor agent; 5-fluorouracil; oral squamous cell carcinoma; OSCC; prediction model; S-1.