Comparison of the Effects of OPRM1 A118G Polymorphism Using Different Opioids: A Prospective Study.

CONTEXT: µ-opioid receptor gene (OPRM1) A118G polymorphism (rs1799971) causes loss of N-glycosylation sites at the extracellular domain of µ-opioid receptors. G-allele carriers show a limited response to morphine; however, studies investigating the impact of A118G polymorphism on the efficacy of opioids other than morphine are limited. OBJECTIVE: To compare the impact of A118G polymorphism on the efficacy of various opioids. METHODS: This prospective cohort study enrolled 222 in-patients administered one of the following opioid therapies for cancer pain as part of an opioid introduction or rotation strategy: tapentadol extended-release tablets, methadone tablets, hydromorphone controlled-release tablets, oxycodone controlled-release tablets, or transdermal fentanyl patches. The impact of A118G polymorphism on the difference in the Brief Pain Inventory-Short Form score on days three, seven, and 14 from baseline was compared among the groups. RESULTS: Overall, 81, 74, and 67 patients had the AA, AG, and GG genotypes, respectively, with an OPRM1 A118G G-allele variant frequency of 0.47. The reduction in the Brief Pain Inventory-Short Form score after opioid therapy initiation did not differ significantly among the patients with the three A118G genotypes treated with tapentadol (p = 0.84) or methadone (p = 0.97), whereas it was significantly smaller in G-allele carriers than that in AA homozygous patients treated with hydromorphone (p < 0.001), oxycodone (p = 0.031), or fentanyl (p < 0.001). CONCLUSION: Tapentadol and methadone may be more suitable than hydromorphone, oxycodone, and fentanyl for G-allele carriers due to their dual mechanism of action and low susceptibility to OPRM1 A118G polymorphism.

Differences in the Analgesic Effect of Opioids on Pain in Cancer Patients With Spinal Metastases.

Background: Spinal metastasis pain includes both inflammatory and neuropathic pain, and opioids, which have only a µ-opioid receptor-stimulating effect, are generally less effective in neuropathic pain. However, no previous study has been conducted for the comparisons of the efficacy of opioids in treating spinal metastasis pain. Objective: To compare the efficacy of tapentadol and methadone with other opioids for back pain caused by a metastatic spinal tumor. Design: Retrospective cohort study. Setting/Subjects: A total of 274 patients were enrolled, who started a tapentadol extended-release tablet, methadone tablet, hydromorphone extended-release tablet, oxycodone extended-release tablet, or transdermal fentanyl patch for cancer pain due to spinal metastasis in Japan from January 1, 2013 to October 31, 2021. Measurements: The primary endpoint, the difference in the numerical rating scale (NRS) scores before and seven days after each opioid administration, was compared among the five groups. Results: In patients with numbness, a decrease of the NRS score on day seven compared with before starting each opioid was significantly higher in the tapentadol group than those in the hydromorphone, oxycodone, and fentanyl groups and comparable to that in the methadone group. In patients without numbness, no significant differences were observed in decreases of the NRS scores on day seven among the five groups. Conclusions: Tapentadol and methadone may be more effective than hydromorphone, oxycodone, and fentanyl for cancer pain due to spinal metastasis with numbness.

Identification of Factors Contributing to Methadone-Induced Daytime Sleepiness in Cancer Patients and Proposal of the Conversion Ratio from Other Opioids to Oral Methadone: A Retrospective Cohort Study.

Background: When methadone is used to treat cancer pain, the Japanese health insurance system recommends to determine the starting dose according to the equivalency conversion table based on the morphine-equivalent daily dose (MEDD) of prior opioids proposed by the National Comprehensive Cancer Network. Owing to the wide range in variability of the conversion table, methadone increases the incidence of daytime sleepiness. Objective: To identify the factors associated with daytime sleepiness and propose a conversion ratio from pretreatment MEDD to oral methadone that decreases the risk of daytime sleepiness. Design: Retrospective cohort study. Setting/Subjects: One hundred patients who started oral methadone to relieve cancer pain at Ashiya Municipal Hospital (Hyogo, Japan) from January 1, 2013, to August 31, 2022, were enrolled. Measurements: The primary endpoint, the conversion ratio from pretreatment MEDD to oral methadone without daytime sleepiness, was determined using receiver operator characteristic (ROC) curve analysis. Results: The incidence of daytime sleepiness within seven days of methadone initiation was 40.0%. The factors identified as contributing to daytime sleepiness were pretreatment MEDD (odds ratio [OR]: 0.941, 95% confidence interval [CI]: 0.916-0.966, p <0.001) and methadone dose (OR: 1.395, 95% CI: 1.178-1.652, p <0.001). The conversion ratio from pretreatment MEDD to oral methadone was 0.24, with an area under the ROC curve of 0.909 (p <0.001). Conclusions: Daytime sleepiness developed when methadone dose is high relative to pretreatment MEDD. To the best of our knowledge, this is the first study to suggest the conversion ratio from pretreatment MEDD to oral methadone without causing daytime sleepiness.

Naldemedine-laxative combination: retrospective inpatient study.

OBJECTIVES: The initiation of peripherally acting µ-opioid receptor antagonists (PAMORAs) should be considered 2 weeks after conventional laxatives have failed to achieve an adequate response, and affected patients should be evaluated every 2 weeks thereafter. However, this guidance is difficult to implement in acute care hospitals. This study aimed to examine how naldemedine (PAMORA) should be introduced in combination with other laxatives in the acute care setting. METHODS: This retrospective study evaluated 93 inpatients who received at least four doses of naldemedine. We investigated changes in the average daily defecation counts during the first 7 days after compared with before naldemedine administration and the incidence of diarrhoea. RESULTS: Daily defecation counts during the first 7 days after compared with before naldemedine administration were greater in both the naldemedine, magnesium oxide (MgO) and another laxative group, and in the naldemedine and another laxative other than MgO group than in the naldemedine only group. The incidence rates of diarrhoea were significantly higher in the naldemedine, MgO, and another laxative group, and in the naldemedine and another laxative other than MgO group than in the naldemedine only group. CONCLUSIONS: The introduction of naldemedine alone or in combination with MgO should be considered.

Tapentadol in Cancer Patients with Neuropathic Pain: A Comparison of Methadone, Oxycodone, Fentanyl, and Hydromorphone.

Tapentadol has µ-opioid receptor stimulating and noradrenaline reuptake inhibiting properties, and should be effective for neuropathic pain (NP). However, the efficacy of tapentadol for NP in cancer patients is unclear. Ashiya Municipal Hospital (Hyogo, Japan) enrolled five groups of Japanese cancer patients between January 1, 2013, and December 31, 2019. Patients with NP were administered tapentadol (n = 29), methadone (n = 32), oxycodone (n = 20), fentanyl (n = 26), or hydromorphone (n = 20). The primary endpoint was the difference in the verbal rating scale (VRS) scores between days 0 and 7. The secondary endpoint was the tolerability of each opioid. Before administering opioids among the five groups, there was no significant difference in the VRS score (p = 0.99). The mean reduction in the VRS score on day 7 was significantly greater in the tapentadol group than in the oxycodone group (p = 0.0024) and was larger than that of the methadone, fentanyl, and hydromorphone groups. Regarding safety, the discontinuation rate in the tapentadol group was the lowest of all groups (tapentadol vs. methadone vs. oxycodone vs. fentanyl vs. hydromorphone, 0.0% vs. 6.3% vs. 5.0% vs. 3.8% vs. 10.0%, respectively). This study suggests that tapentadol could be efficacious for cancer patients with NP, and a preferred option in cases that require immediate dose adjustment or for those at high risk for adverse effects. However, the pain intensity was evaluated without pain assessment scales specific to NP. Thus, we think that it is desirable to validate our findings using assessment scales, such as the painDETECT questionnaire in future.

Remote Reminiscence Using Immersive Virtual Reality May Be Efficacious for Reducing Anxiety in Patients with Mild Cognitive Impairment Even in COVID-19 Pandemic: A Case Report.

To prevent cognitive decline, non-pharmacological therapies such as reminiscence for mild cognitive impairment (MCI) are required, however, the use of nursing homes was limited due to coronavirus disease 2019 (COVID-19). Therefore, the demand for remote-care is increasing. We hypothesized that immersive virtual reality (iVR) could be used more effectively than conventional reminiscence for anxiety. We first examined the effectiveness and safety of reminiscence using iVR (iVR reminiscence session) in patients with MCI. After COVID-19 imposed restriction on visiting nursing homes, we conducted online iVR reminiscence session (remote iVR reminiscence session) and compared its effectiveness with that of interpersonal iVR reminiscence session (face-to-face iVR reminiscence session). The results of two elderly with MCI suggested that iVR reminiscence could reduce anxiety and the burden of care without serious side effects. The effects of remote iVR reminiscence might be almost as effective as those of face-to-face one.

A Pilot Study to Develop a New Method of Assisting Children in Taking Their Medication by Using Immersive Virtual Reality.

Taking bitter-tasting drugs can be stressful for children who have underdeveloped swallowing skills and do not understand the meaning of medication. Furthermore, the senses of vision and smell are known to majorly influence taste. This pilot study was aimed at determining the effect of visual stimulation by immersive virtual reality (iVR) on taste and the safety of this approach for developing a new method to assist children with taking medication. Ten subjects participated in this study, and their mean (standard deviation (S.D.)) age was 21.8 (0.8) years. The subjects tasted the bitter aqueous solution (quinine 0.00375%) while viewing two different VR images (strawberry sponge cake and orange juice) alternately and received sensory tests immediately after the tasting and again 30 s later. In addition, nausea was assessed 30 s after tasting for each VR image. The primary endpoint was the difference in sensory test scores immediately after the tasting and 30 s later, between the two images. There were no significant differences in the sensory test scores between the placebo and either strawberry sponge cake or orange juice immediately after tasting. However, 30 s after tasting, the scores changed significantly to a tendency to perceive sweetness from the strawberry sponge cake and orange juice images compared with the placebo. No subject experienced nausea. Therefore, the findings of this study suggest that displaying images of sweet foods by using iVR to stimulate visual perception could safely reduce the sense of bitterness.

The Adequateness of Methadone for Japanese Terminal Cancer Patients Can Be Determined Earlier than 7 Days: A Preliminary Retrospective Study.

INTRODUCTION: The Japanese packaging instructions for methadone prohibit dose escalation within 7 days of administration initiation as this may result in overdose and subsequent adverse events. However, for terminal cancer patients, evaluation of the effects of methadone may be desirable within 7 days because they have limited prognoses. We aimed to determine the possibility of estimating the adequateness of methadone earlier than the 7th day by investigating the onset timing of analgesic effects and adverse events of methadone in Japanese terminal cancer patients. METHODS: Japanese terminal cancer patients who started taking methadone in Ashiya Municipal Hospital were enrolled from January 1, 2013 to February 28, 2019. Verbal rating scale (VRS) scores on pain and adverse events before and after methadone administration (on days 3, 5, and 7) were retrospectively investigated from medical records. RESULTS: We enrolled 25 patients, of which 20 (80.0%) received methadone until day 7. The VRS score (mean ± standard deviation) on pain was significantly reduced to 0.90 ± 0.55 on day 3, compared with 1.65 ± 0.67 before the administration of methadone (p < 0.05). The mean VRS scores did not differ significantly on days 3, 5, and 7. Additionally, of the 23 patients who received methadone until day 3, 20 (87.0%) showed an analgesic effect on day 3 and 17 (85.0%) received methadone without experiencing serious adverse events until day 7. CONCLUSIONS: The adequateness of methadone in Japanese terminal cancer patients could be determined before day 7, considering the high analgesia incidence and few adverse events 3 days after the methadone administration under careful observation by a physician experienced in methadone administration. However, as this is a preliminary study, the relationship between pharmacokinetic parameters and analgesic effects was not evaluated. Further studies involving pharmacokinetics and multicenter prospective studies are required to support these findings.

Immersive Virtual Reality Reminiscence Reduces Anxiety in the Oldest-Old Without Causing Serious Side Effects: A Single-Center, Pilot, and Randomized Crossover Study.

Background: Dementia is one the major problems of aging societies, and, novel and effective non-drug therapies are required as interventions in the oldest-old to prevent cognitive decline. Objective: This study aims to examine the efficacy and safety of reminiscence using immersive virtual reality (iVR reminiscence) focusing on anxiety that often appears with cognitive decline. The secondary objective is to reveal the preference for VR image types for reminiscence: live-action (LA) or computer graphics (CG). Methods: This was a pilot, open-label, and randomized crossover study which was conducted on January 2020 at a single nursing home. The subjects were randomly divided into two groups (A or B) in equal numbers, and they alternately viewed two types of VR images (LA and CG) themed on the mid- to late Showa era (A.D. 1955-1980) in Japan. In group A, the CG images were viewed first, and then the LA images were viewed (CG→ LA). In group B, the images were viewed in the opposite order (LA→ CG). Before VR viewing, subjects responded to Mini-Mental State Examination (MMSE) Japanese version and State-Trait Anxiety Inventory (STAI) Japanese version. After viewing the first and second VR, subjects responded to STAI and the numerical rating scale (NRS) for satisfaction and side effects (nausea, dizziness, headache, and tiredness). Results: Ten subjects participated in this study. The values of analyses are presented in the mean (SD). The age was 87.1 years (4.2), and the MMSE was 28.5 (1.8). The total STAI score before VR viewing was 36.1 (7.2), but it significantly decreased to 26.8 (4.9) after the first VR viewing (P = 0.0010), and further decreased to 23.4 (2.8) after the second VR viewing (P < 0.001). The NRS score for satisfaction tended to be higher after viewing LA in group A (CG→ LA) (CG vs. LA; 7.0 (2.3) vs. 8.6 (1.5), P = 0.0993), while in group B (LA→ CG), the score after CG was slightly lower than that after LA. There were no serious side effects. Conclusions: This study suggests that iVR reminiscence can reduce anxiety in the oldest-old without causing serious side effects. Furthermore, the impacts might be better with LA images.

11ß-hydroxysteroid dehydrogenase type 1 is associated with antiretroviral therapy-induced increase in low-density lipoprotein cholesterol
.

OBJECTIVE: To investigate the association between 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) activity and antiretroviral therapy (ART)-induced increase in low-density lipoprotein cholesterol (LDL). MATERIALS AND METHODS: We enrolled 62 patients and used liquid chromatography-tandem mass spectrometry to measure 11ß-HSD1 activity, which was expressed as a ratio of the sum of urinary tetrahydrocortisol and allo-tetrahydrocortisol concentrations to urinary tetrahydrocortisone concentration. Patient data, including baseline laboratory values, were extracted from medical records for logistic regression analyses of factors associated with LDL increase during ART. The cutoff 11ß-HSD1 activity ratio associated with the LDL increase during ART was determined using receiver operator characteristic (ROC) curve analysis. RESULTS: The LDL level increased significantly from 88.8 mg/dL before ART to 106.7 mg/dL during ART (p = 0.04). Additionally, patients with increased LDL tended to have a higher 11ß-HSD1 activity ratio (1.59 vs. 1.21, p = 0.06) and longer duration of ART (13.9 vs. 10.2 months, p = 0.07) than patients with unchanged or decreased LDL. The cutoff 11ß-HSD1 activity ratio was 1.226. Results of the univariate logistic regression analysis suggested that 11ß-HSD1 activity ratio ≥ 1.226 was associated with LDL increase during ART (p = 0.011), with an odds ratio of 8.000. CONCLUSION: This study revealed the possible association between 11ß-HSD1 activity and ART-induced LDL increase. The findings of this study suggest that 11ß-HSD1 could be a useful drug target for the treatment of ART-induced hyperlipidemia.

A Novel Palliative Care Approach Using Virtual Reality for Improving Various Symptoms of Terminal Cancer Patients: A Preliminary Prospective, Multicenter Study.

Background: Some terminal cancer patients wish to "go to a memorable place" or "return home." However, owing to various symptom burdens and physical dysfunction, these wishes are difficult for them to realize. Objective: The aim of the study is to verify whether simulated travel using virtual reality (VR travel) is efficacious in improving symptoms in terminal cancer patients. Design: This is a prospective, multicenter, single-arm study. Setting/Subjects: Twenty participants with terminal cancer were recruited from two palliative care wards; data were collected from November 2017 to April 2018. Measurements: The VR software Google Earth VR® was used. The primary endpoint was the change in the Edmonton Symptom Assessment System scores for each symptom before and after VR travel. Results: The average age of the participants was 72.3 (standard deviation [SD] = 11.9) years. Significant improvements were observed for pain (2.35, SD = 2.25 vs. 1.15, SD = 2.03, p = 0.005), tiredness (2.90, SD = 2.71 vs. 1.35, SD = 1.90, p = 0.004), drowsiness (2.70, SD = 2.87 vs. 1.35, SD = 2.30, p = 0.012), shortness of breath (1.74, SD = 2.73 vs. 0.35, SD = 0.99, p = 0.022), depression (2.45, SD = 2.63 vs. 0.40, SD = 0.82, p = 0.001), anxiety (2.60, SD = 2.64 vs. 0.80, SD = 1.51, p < 0.001), and well-being (4.50, SD = 2.78 vs. 2.20, SD = 1.99, p < 0.001; pre- vs. post-VR travel score, respectively). No participants complained of serious side effects. Conclusions: This preliminary study suggests that VR travel can be efficacious and safe for terminal cancer patients for improving symptom burden.

Risk Factors for Polypharmacy in Elderly Patients With Cancer Pain.

OBJECTIVE: Polypharmacy (PP) is a burden in elderly patients with cancer pain; however, risk factors for PP remain unclear. The purpose of this study was to investigate the risk factors for PP in this patient population. METHODS: We retrospectively reviewed the medical charts of patients aged ≥65 years with cancer pain who were treated at Osaka University Hospital between February 2014 and June 2016 according to the World Health Organization 3-step ladder for cancer pain relief. We defined PP as ≥5 medications and conducted exploratory research to examine the association between PP and patient characteristics. Performance status (PS) was estimated according to the Eastern Cooperative Oncology Group system and is categorized as good PS (0-1) and poor PS (2-4). RESULTS: We reviewed 206 patients (122 men and 84 women) with a median age of 71 years (range, 65-89 years) and found that 174 patients (84.5%) had PP. In multivariate logistic analysis, PP was significantly associated with an increased number of comorbidities (odds ratio [OR]: 4.93, 95% confidence interval [CI], 2.57-11.42, P < .001), poor PS (OR: 4.50, 95% CI, 1.06-31.68, P = .039), and administration of an anticancer or molecular targeted drug (OR: 2.78, 95% CI, 1.13-7.16, P = .025). CONCLUSIONS: An increased number of comorbidities, poor PS, and administration of an anticancer or molecular targeted drug were considered risk factors for PP in elderly patients with cancer pain. Sharing these risk factors with medical staff will help reduce the occurrence of problems associated with PP.

Validation of a Short-Term, Objective, Prognostic Predictive Method for Terminal Cancer Patients in a Palliative Care Unit Using a Combination of Six Laboratory Test Items.

Background: There is no established method to objectively predict short-term prognosis. Recently, we proposed objective, short-term, prognostic predictive methods that are combinations of laboratory test items: WPCBAL score, derived from six values (white blood cell, platelet, C-reactive protein, blood urea nitrogen, aspartate aminotransferase, and lactate dehydrogenase). However, that study was conducted in an acute-phase hospital to identify the test items useful for prognostic prediction; thus, whether WPCBAL score could be applied to terminal cancer patients in a palliative care unit was unverified. Objective: To verify the usefulness of WPCBAL score for terminal cancer patients. Design: A retrospective study. Setting/Subjects: Patients admitted to the palliative care unit of Ashiya Municipal Hospital (N = 128) in Japan in 2016. Measurements: The sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and area under the receiver operating characteristic curve (AUROC) were compared between WPCBAL score and the Glasgow prognostic score (GPS). Results: For predicting three-week prognosis, WPCBAL score showed higher AUROC compared with GPS (0.7540 and 0.6573, respectively). WPCBAL score predicting two-week prognosis showed greater AUROC than GPS predicting three-week prognosis (0.7491 and 0.6573, respectively). Conclusion: WPCBAL score was verified to objectively predict the two- or three-week prognosis for terminal cancer patients in a palliative care unit. WPCBAL score may be a new option for prognostic prediction for terminal cancer patients.

[The Present Implementation Status and Problems of Vital-signs Measurement by Community Pharmacists in Home Medical Care in Osaka].

　While the community-based integrated care systems are in the process of being structured currently, more and more community pharmacists want to learn physical assessment skills. However, no large-scale survey focusing on present implementation status and problems of physical assessment by community pharmacists has been conducted yet. Osaka has the 2nd highest number of community pharmacies in Japan now, and the population aged ≥65 years will be expected to become the 3rd highest in 2025. Thus, Osaka can become a national leading model case for community pharmacists' activity in future home medical care. Therefore, this study aimed to reveal the present implementation status and problems of physical assessment by community pharmacists in Osaka, especially focusing on vital-signs. The questionnaires were sent to all the 3571 insurance pharmacies belonging to the Osaka Pharmaceutical Association and 871 pharmacies responded. Many pharmacists recognized the necessity for vital-signs measurement by pharmacists in home medical care (81.5% of pharmacies that offered home medical care and 75.4% of pharmacies that did not offer one). However, the proportion of pharmacies that conduct vital-signs measurement in home medical care was 18.7%, therefore, it was suggested that the present problem is "many pharmacists cannot conduct vital-signs measurement, although they think it should be conducted". Moreover, the most common reason for not measuring vital-signs was the lack of instruments, such as stethoscopes and sphygmomanometer (43.2%). This is the latest report with a large-scale sample, thus, it can serve as valuable knowledge in considering what pharmacists do for the future.

A New Approach for Determining Short-Term, Objective Prognostic Predictive Methods for Terminal Cancer Patients Based on the Change Point of Laboratory Test Values.

BACKGROUND: In terminal phase cancer, predicting a prognosis precisely plays an important role for patients and their families to live meaningful lives. However, there are no established short-term, objective prognostic predictive methods. OBJECTIVE: To develop simple, short-term, objective prognostic predictive methods through detecting a change point for laboratory test values. DESIGN: A retrospective chart review. SETTING/SUBJECTS: Subjects were cancer patients aged ≥16 years and discharged dead from Osaka University Hospital in 2008. MEASUREMENTS: Using different laboratory test values, new prognostic predictive methods were determined based on either six laboratory test values (white blood cell [WBC], platelet [PLT], C-reactive protein, blood urea nitrogen [BUN], aspartate aminotransferase [AST], and lactase dehydrogenase [LDH]): the WPCBAL score, or five test values (WBC, PLT, BUN, AST, and LDH): the WPBAL score. Their utility, including sensitivity and specificity, was compared with that of Glasgow prognostic scores (GPSs). RESULTS: In total, 121 cancer patients were enrolled. WPCBAL and WPBAL scores showed higher sensitivity (0.88 and 0.91 vs. 0.68), specificity (0.79 and 0.70 vs. 0.53), negative predictive value (0.98 and 0.97 vs. 0.76), and a much larger relative risk (16.5 and 14.2 vs. 1.78) as prognostic predictors within two weeks of death than GPS as a prognostic predictor within three weeks of death. CONCLUSION: This is the first study that suggests that the objective prognostic predictive methods, through detecting the change point of laboratory test values, are useful for predicting short-term prognosis. The WPCBAL score and WPBAL score could objectively predict the remaining lifetime within two weeks of mortality.

Weight Loss Associated with Platinum-Based Chemotherapy in Patients with Advanced Lung Cancer.

BACKGROUND: We examined whether the weight loss that occurs with platinum-based chemotherapy in lung cancer patients is associated with chemotherapy side effects, treatment completion rates and therapeutic effect. METHODS: We retrospectively reviewed charts of advanced lung cancer patients treated with ≥2 cycles of platinum-based chemotherapy. Patients were divided into 2 groups based on ≥5 or <5% weight loss. Relationships between weight loss and other variables were investigated. RESULTS: Among 114 patients, 18 (15.8%) experienced ≥5% weight loss. Significantly more patients with small-cell lung cancer (SCLC) than with non-SCLC were found to have ≥5% weight loss (30.8 vs. 11.4%, p = 0.023). Patients with ≥5% weight loss experienced higher incidences of grade 3-4 leukopenia (p = 0.008) and neutropenia (p = 0.005), and treatment completion rates were lower in this group (p = 0.035). Weight loss was not significantly associated with therapeutic effect. CONCLUSION: The weight loss in patients with advanced lung cancer receiving platinum-based chemotherapy is associated with SCLC, grade 3-4 leukopenia, neutropenia and a decrease in treatment completion rate.

Induction of endoplasmic reticulum-endosome fusion for antigen cross-presentation induced by poly (γ-glutamic acid) nanoparticles.

We previously reported that poly (γ-glutamic acid)-based nanoparticles (γ-PGA NPs) are excellent vaccine carriers for inducing efficient cross-presentation in dendritic cells, thereby producing strong antitumor immunity in vivo. Analyzing the mechanism of cross-presentation induced by γ-PGA NPs will be useful toward designing novel vaccine carriers. In this study, we show an intracellular mechanism of efficient cross-presentation induced by OVA-loaded γ-PGA NPs. Cross-presentation induced by γ-PGA NPs depended on cytoplasmic proteasomes and TAP, similar to the classical MHC class I presentation pathway for endogenous Ags. Intracellular behavior analyzed by confocal laser scanning microscopy revealed that encapsulated OVA and γ-PGA accumulated in both the endoplasmic reticulum (ER) and endosome compartments within 2 h. At the same time, electron microscopy analysis clearly showed that intracellular γ-PGA NPs and encapsulated Au NPs were enveloped in endosome-like vesicles, not in the ER. These findings strongly suggest that γ-PGA NPs enhance ER-endosome fusion for cross-presentation. Moreover, inhibition of ER translocon sec61 significantly decreased the γ-PGA NP/OVA-mediated cross-presentation efficiency, indicating that sec61 is important for transporting Ags from the fused ER-endosome to the cytoplasm. These findings imply that the ER-endosome complex is key for the efficient cross-presentation of Ags encapsulated in γ-PGA NPs.