Efficacy against Lung Cancer Is Augmented by Combining Aberrantly N-Glycosylated T Cells with a Chimeric Antigen Receptor Targeting Fragile X Mental Retardation 1 Neighbor.

The adaptive transfer of T cells redirected to cancer cells via chimeric Ag receptors (CARs) has produced clinical benefits for the treatment of hematologic diseases. To extend this approach to solid cancer, we screened CARs targeting surface Ags on human lung cancer cells using (to our knowledge) novel expression cloning based on the Ag receptor-induced transcriptional activation of IL-2. Isolated CARs were directed against fragile X mental retardation 1 neighbor (FMR1NB), a cancer-testis Ag that is expressed by malignant cells and adult testicular germ cells. Anti-FMR1NB CAR human T cells demonstrated target-specific cytotoxicity and successfully controlled tumor growth in mouse xenograft models of lung cancer. Furthermore, to protect CAR T cells from immune-inhibitory molecules, which are present in the tumor microenvironment, we introduced anti-FMR1NB CARs into 2-deoxy-glucose (2DG)-treated human T cells. These cells exhibited reduced binding affinity to immune-inhibitory molecules, and the suppressive effects of these molecules were resisted through blockade of the N-glycosylation of their receptors. Anti-FMR1NB CARs in 2DG-treated human T cells augmented target-specific cytotoxicity in vitro and in vivo. Thus, our findings demonstrated the feasibility of eradicating lung cancer cells using 2DG-treated human T cells, which are able to direct tumor-specific FMR1NB via CARs and survive in the suppressive tumor microenvironment.

Physical function decline predictors in nursing home residents using new national quality indicators.

AIM: To determine the predictors of physical function (PF) decline among nursing home residents using items from the Long-term care Information system For Evidence (LIFE), a system launched in 2021 to ensure the quality of long-term care. METHODS: The LIFE data of 1648 residents from 45 nursing homes in Japan were retrospectively collected in July 2021 (T0) and January 2022 (T1), including demographics, PF assessed by the Barthel index (BI), nutrition and oral health, and cognitive function. The Dementia Behavior Disturbance scale was used to assess the frequency of certain behaviors, such as "waking at midnight." The predictors of PF decline, defined as a decrease ≥5 in the BI score at T1 compared with that at T0, were determined using mixed-effects logistic regression analyses. PF at T0 was classified into high (>60 BI) and low (≤60 BI) groups. RESULTS: The participants' mean age was 87.2 ± 7.1 years, and 45.3% experienced PF decline. The significant predictors of PF decline were age ≥ 90 years, body mass index <18.5 kg/m2 , dementia diagnosis, moderate and severe cognitive impairments, not vocalizing reciprocal exchanges at will, always "waking at midnight," and high PF at T0. CONCLUSIONS: The LIFE items predicted PF decline among nursing home residents, suggesting that LIFE data can be used to ensure the quality of long-term care. Geriatr Gerontol Int 2024; 24: 123-132.

Unplanned Hospital Visits and Poor Oral Health With Undernutrition in Nursing Home Residents.

OBJECTIVES: In 2021, the Japanese government began operating a long-term care (LTC) database called the Long-Term Care Information System for Evidence (LIFE). However, its utility has not been verified. Regarding unplanned hospital visits of nursing home residents, one of the challenges in LTC is that poor oral health with undernutrition could indicate high-risk residents. Therefore, this study examined the association between poor oral health with undernutrition assessed using the LIFE data and unplanned hospital visits of nursing home residents. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: The participants were 237 residents aged ≥65 years in 4 nursing homes in Japan. The analyses included 1041 LIFE data entries repeatedly measured for the participants every month and unplanned hospital visit data during the observation period. METHODS: The participants' LIFE and unplanned hospital visit data were obtained from the nursing home providers. Poor oral health was defined using oral items included in the LIFE data and body mass index. Using the LIFE data, the association between poor oral health and unplanned hospital visits within 1 month after LIFE assessment entries was analyzed. The odds ratios (ORs) and 95% CIs were calculated using a generalized linear mixed model. RESULTS: In total, 59 of 1041 LIFE data (5.7%) entries were unplanned hospital visits within 1 month after LIFE assessment. Among patient characteristics, significant differences were noted in dementia diagnosis [OR (95% CI): 2.66 (1.26-5.63)], although no significant differences were observed in other characteristics. Multivariate analysis using participant identification as a random effect confirmed that poor oral health was associated with unplanned hospital visits within 1 month [adjusted OR (95% CI): 2.63 (1.05-6.61)]. CONCLUSIONS AND IMPLICATIONS: Poor oral health assessed using the LIFE data could be used as an indicator to identify nursing home residents at high risk for unplanned hospital visits.

Psychological and educational support for cancer patients who return to work: A scoping review.

BACKGROUND: Many patients with cancer experience challenges when they return to work (RTW) following cancer diagnosis and treatment. Psycho-educational support is important to facilitate the RTW process. OBJECTIVE: This scoping review examined published reports on psycho-educational support for patients with cancer who RTW. METHODS: We followed the preferred reported items for systematic reviews and meta-analyses statement and the framework of Arksey and O'Malley. We searched the Cochrane Central Register of Controlled Trials database, PubMed, CINAHL (EBSCO), and ICHUSHI and performed manual searches. RESULTS: We retrieved 1,586 articles and retained 48 for analysis (published January 2000 to December 2020). Physicians, occupational physicians, nurses, social workers, and psychologists provide considerable support in hospitals. Delivery modes included individual, face-to-face, and workbook. Psychological support included emotional, stress coping, counseling, and knowledge. Educational support included information or advice provision, communication skills, problem discussion, and work planning. Employment status was typically the primary outcome. We included 50 measurement scales across quality of life, cognitive functioning and illness, self-efficacy, psychological distress, and fatigue. CONCLUSION: This review elucidated psycho-educational support for patients with cancer who RTW, and measurement tools for related effects. Based on the characteristics of the psycho-educational support revealed in this study, future studies should examine the development, intervention, and implementation of support programs for patients' RTW.

Factors related to a sense of security with medical and long-term care services among community-dwelling middle-aged and older adults in Japan.

AIM: The aim of this study was to identify factors related to a sense of security with regard to medical and long-term care services among middle-aged and older adults. These are for consideration of strategies for the establishment of a community-based integrated care system. METHODS: A cross-sectional survey was conducted in 2400 men and women aged ≥40 years in two cities. Survey items included a scale for sense of security for medical and long-term care, experience of medical and long-term care services, and social and demographic factors. Data were analyzed using univariate and multiple regression analyses. RESULTS: In total, 945 respondents were included in the analysis. In multiple regression analysis, sense of security was significantly higher with ability to consult with medical professionals on medical and long-term care, availability of emotional and instrumental support, norm of reciprocity in the community, community attachment, economic comfort, higher age and male gender, and significantly lower with experience of bereavement at a hospital and depression. CONCLUSIONS: These findings stress the importance of facilitating consultation with medical professionals, support for caregivers of terminally ill patients, and mutual support in the community in a community-based integrated care system. Geriatr Gerontol Int 2022; 22: 568-574.

Factors Related to End-of-Life Care Discussions Among Community-Dwelling People in Japan.

CONTEXT: End-of-life discussions regarding healthcare preferences are important to ensure a dignified end of life. OBJECTIVES: This study clarifies the factors associated with such discussions among community-dwelling people in Japan. METHODS: We conducted a cross-sectional survey of 2400 randomly selected community-dwelling adults over the age of 40 in one urban and rural area each, in Japan. The survey investigated whether the respondents had engaged in discussions about their end-of-life care preferences. Logistic regression analyses were conducted to examine the physical, psychological, social, and demographic factors influencing end-of-life care discussions. RESULTS: Of the final sample comprising 1172 respondents, 41.0% had engaged in end-of-life discussions. Of these, 95.2% had engaged in these discussions with family members, 11.0% with friends and acquaintances, and 4.4% with medical or long-term care personnel. Factors associated with end-of-life discussion engagement included requiring outpatient visits, long-term care requirements, availability of emotional support services, experience of the death of a relative within the past five years, living with a spouse, and being unemployed. CONCLUSION: The results showed that roughly 41% of the surveyed community-dwelling respondents had engaged in end-of-life discussions. The findings suggest that providing emotional support to relieve anxiety regarding one's health and the awareness of death, and having the opportunity to interact with others to discuss end-of-life issues, promote the engagement in such discussions in Japan. This study suggests that it is necessary to create an environment that provides social support and engenders awareness of the importance of end-of-life discussions while the community-dwelling people are still healthy.

Measuring well-being in older adults: Identifying an appropriate single-item questionnaire.

AIM: As the older adult population increases globally, it is important for local governments to measure their health and well-being consistently to effectively support this group. Because definitions of subjective well-being - such as happiness, life satisfaction and subjective health - overlap, it is worth considering which single-item indicator local governments can rely on to measure individual well-being. This study, therefore, explored the correlation between three single-item questionnaires on happiness, life satisfaction and subjective health used in government surveys, and established psychometric scales of happiness, life satisfaction and quality of life, and analyzed which of the three single-item indicators most effectively captured the target well-being. METHODS: Randomly selected people aged ≥65 years in urban and rural areas (n = 1440) answered the questions on the Happiness Scale, the Satisfaction with Life Scale and the Quality of Life scale, and the three single-item questionnaires (happiness, life satisfaction and subjective health). We analyzed the data using correlation and multiple regression analyses. RESULTS: The results showed a high positive correlation between the scales and the single-item questionnaires. The single-item life satisfaction and subjective health questionnaires were significantly correlated with all the three scales. Although there was not much difference in the adjusted R2 values between putting three items jointly and separately, the value of single-item life satisfaction was the best and the subjective health was the second best. CONCLUSION: The results showed that the single-item life satisfaction and subjective health effectively captured the target well-being; these could be the appropriate indicators for a potential optimal index. Geriatr Gerontol Int 2021; 21: 1131-1137.

Predictors of home being the preferred place of death among Japanese older people: JAGES cross-sectional study.

AIM: There is a large discrepancy between people's preferred and actual place of death in Japan. To manage this discrepancy, this study aimed to identify the variability in preferred places of death and their associated factors among Japanese older people. METHODS: Cross-sectional survey data were collected in 2016 as part of the Japan Gerontological Evaluation Study, in which 20 204 participants were asked about their preferred place of death. Logistic regression analyses were conducted to examine the final determinants for home as the preferred place of death. RESULTS: Based on survey data, 35.8% of respondents preferred home as the place of death, 42.7% preferred some sort of facility and 21.5% were unsure. Those who preferred to be at home when receiving end-of-life care were more likely to be older in age, live with others, be employed, be homeowners, have lived in their current residence for a longer period, not be vaccinated for influenza in the past year, engage in physical work or intense sports, not have participated in end-of-life discussions regarding preferred place of death, have experienced relatives dying at home, practice norms of reciprocity, have a sense of attachment to their neighborhood, receive instrumental social support, interact with neighbors and live in a rural area. CONCLUSIONS: Factors related to community attachment were associated with choosing home as the preferred place of death. To fulfill the preferences of Japanese older people, a broad range of demographic, health, behavioral, social, cultural and environmental factors should be considered. Geriatr Gerontol Int 2021; 21: 345-352.

LRRK2 regulates endoplasmic reticulum-mitochondrial tethering through the PERK-mediated ubiquitination pathway.

Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common cause of familial Parkinson's disease (PD). Impaired mitochondrial function is suspected to play a major role in PD. Nonetheless, the underlying mechanism by which impaired LRRK2 activity contributes to PD pathology remains unclear. Here, we identified the role of LRRK2 in endoplasmic reticulum (ER)-mitochondrial tethering, which is essential for mitochondrial bioenergetics. LRRK2 regulated the activities of E3 ubiquitin ligases MARCH5, MULAN, and Parkin via kinase-dependent protein-protein interactions. Kinase-active LRRK2(G2019S) dissociated from these ligases, leading to their PERK-mediated phosphorylation and activation, thereby increasing ubiquitin-mediated degradation of ER-mitochondrial tethering proteins. By contrast, kinase-dead LRRK2(D1994A)-bound ligases blocked PERK-mediated phosphorylation and activation of E3 ligases, thereby increasing the levels of ER-mitochondrial tethering proteins. Thus, the role of LRRK2 in the ER-mitochondrial interaction represents an important control point for cell fate and pathogenesis in PD.

Advance care planning and home death in patients with advanced cancer: a structured interview analysis.

BACKGROUND:: Discrepancy between preferred and actual place of death is common in patients with advanced cancer. AIM:: To investigate the association between advance care planning (ACP) and home death in patients with advanced cancer. METHODS:: Using structured interviews, 44 primary nurses from 19 home-visit nursing agencies in Japan were asked about status changes for 123 advanced cancer patients receiving home care. The main outcome was the place of death. RESULTS:: Of the 123 patients, 16 were alive, 54 died at home and 53 died at hospital. Multivariate analyses revealed that home death was more likely if: i) physicians or nurses practised ACP during the whole home-visit period (odds ratio (OR) 41.76; confidence interval (CI) 5.87-297.07); ii) patients had adequate insight concerning their prognosis just before death or at hospitalisation (OR 7.85; CI 1.18-52.24); and iii) the baseline preference of families was a home death (OR 0.09; 95% CI 0.01-0.73). CONCLUSION:: ACP practiced by physicians or nurses for advanced cancer patients may contribute to achieving home death.

Efficacy of Juzentaihoto for Tumor Immunotherapy in B16 Melanoma Metastasis Model.

Introduction. Medical care for Japanese cancer patients includes Western and Kampo medicines, and treatments with juzentaihoto (JTT) reportedly prevent cancer metastasis and recurrence. In this study, we examined the effects of JTT on natural killer (NK) cell activity and metastasis in combined treatments with anti-PD-1 antibody in a mouse model of melanoma metastasis. Methods. C57BL/6 male mice were intravenously injected with B16 melanoma cells (B16 cell) and were given chow containing 3% JTT. In subsequent in vivo experiments, we assessed serum cytokine levels and tumor colony formation in the lungs. Additionally, we assessed NK cell activity in ex vivo experiments. Results. JTT significantly suppressed B16 cell metastasis, whereas injection of anti-asialo-GM1 antibody into mice abrogated the inhibitory actions of JTT. JTT significantly increased interleukin- (IL-) 12 and interferon- (IFN-) γ levels in serum and induced NK cell activity. It increased the inhibitory actions of the anti-PD-1 antibody on B16 cell metastasis. Discussion. These data suggest that JTT inhibits B16 cell metastasis by inducing NK cell activity. Additionally, combination therapy with JTT and anti-PD-1 antibody increased treatment response rates for B16 melanoma.

Do Symptoms among Home Palliative Care Patients with Advanced Cancer Decide the Place of Death? Focusing on the Presence or Absence of Symptoms during Home Care.

OBJECTIVE: Our goal was to investigate the association between actual place of death among Japanese home end-of-life care patients with advanced cancer and individual, illness, and environmental factors, including the presence or absence of symptoms. METHODS: Using structured interviews, we asked 44 nurses from 19 home-visit nursing agencies about changes in status of all 123 of their home end-of-life care patients with advanced cancer between April and September 2013. The main outcome variable was actual place of death (Home/Hospital/Still surviving) and independent variables were the patient's symptoms as a time-dependent variable. Competing risk analysis was conducted with adjustment for patient individual factors (demographics, medical factors, caregiver support, and patient's and caregiver's preference for place of death) and environmental factors (availability of physician-visit and policy at discharge). RESULTS: Among all patients, 53 died in the hospital, 52 at home, and 16 still survived. Multivariate analyses revealed the following: 1) patients were more likely to die in the hospital when pain and dyspnea were present (adjusted sub hazard ratio [SHR]: 1.50 [95% confidence interval (CI): 1.23-1.83] and 1.71 [95% CI: 1.36-2.15], respectively); 2) patients were less likely to die in the hospital when delirium was present (adjusted SHR: 0.64 [95%CI: 0.43-0.96]); and 3) other factors associated with hospital death were patient's gender, primary cancer site, caregiver support, health care service, policy at discharge, and congruence between the patient's and family's preference for place of death. CONCLUSION: To alleviate pain and dyspnea among home end-of-life care patients, development of both a rapid admission system to a hospital/hospice/care facility in the community and specialist-level palliative care at home is needed.

Survey on the use of health consultation services provided in a Japanese urban public housing area with a high elderly population.

OBJECTIVE: The aim of the present study was to determine how the elderly in an urban public housing area intends to utilize health consultation services. METHODS: In December 2011, a cross-sectional posting survey was carried out on 2000 randomly selected elderly residents in an urban public housing area in Japan. The survey included information on the intention of use of health consultation services provided in the community, demographic background, living situation, medical and social care situation, and the concerns and desires about the services. RESULTS: We received 553 responses from the survey. Of the 534 responders who had never used the service, 150 (28.1%) intended to use, 313 (58.6%) were undecided and 71 (13.3%) expressed having no intention to use. Binominal logistic regression analysis showed that individuals who intended to use it tended to have the following features: aged ≥70 years (OR 2.35, 95% CI 1.41-3.93), resident of the complex for <10 years (OR 1.94, 95% CI 1.15-3.27), low sense of well-being (OR 3.69, 95% CI 1.03-13.26), family-related stress (OR 1.72, 95% CI 1.01-2.93), outpatient of internal medicine (OR 1.74, 95% CI 1.10-2.75), outpatient of cancer treatment (OR 2.58, 95% CI 1.15-5.77), history of unpleasant medical experience (OR 1.68, 95% CI 1.03-2.73), desire for a free health consultation (OR 1.80, 95% CI 1.07-3.04), desiring to consult about diseases (OR 2.01, 95% CI 1.27-3.18) and desiring to consult about caregiving (OR 1.64, 95% CI 1.05-2.56). CONCLUSION: Approximately 30% of residents had the intention of using the health consultation services provided in the community. The people who were more likely to use the services tended to have more intensive consultation support.

[Age differences in decision-making factors on end-of-life care location for Musashino-city residents].

OBJECTIVES: Japan is predicted to continue its fast-aging trend, especially in urban areas. Therefore, promoting end-of-life services in urban areas is an urgent policy issue. In addition, the recognition of end-of-life care greatly varies by age. The aim of this study was thus to clarify the association by age between preferences regarding care location among people in urban communities and their experiences, knowledge, and perceptions related to end-of-life care. METHODS: A total of 1,500 people aged 40 and older in Musashino-city participated in a cross-sectional nationwide survey. We asked about preferences regarding care location, demographic data, experiences, knowledge, and perceptions related to end-of-life care. We used logistic regression analyses. RESULTS: A total of 769 (51.6%) responded. Of those over 65, 40.9% preferred homes and 59.1% preferred places other than homes as end-of-life care locations. For those aged 40-64, 54.1% preferred homes and 45.9% preferred places other than homes (P<0.001). Logistic regression analyses revealed that the following factors affect people's preferences regarding location of care for those over 65: not recognizing that medication use can lead to addiction (odds ratio: 1.90; 95% confidence interval: 1.17-3.08); taking precautions before taking medicine (1.97; 1.21-3.22); volunteering (2.38; 1.34-4.21) ; recognizing that home cost is cheaper than hospital cost (1.82; 1.10-3.03); recognizing that they have health care workers to consult (1.90; 1.06-3.41); and recognizing that end-of-life care at home provides enough treatment (2.30; 1.37-3.87). Factors for the 40-64 year old group were as follows: not wanting informal caregivers to care (2.80; 1.62-4.83); recognizing that they can respond to sudden changes at home (2.97; 1.15-7.66); and want to be free at the end of the life (4.57; 2.43-8.59). CONCLUSION: These results suggest that changing people's thinking about the socialization of care is required to increase preferences of people over 65 for home death. For the 40-64 year old group, developing an awareness of death is required. For all generations, providing appropriate information and educating the people is required.

[The need for health consultation services and related factors among non-users of health consultation services residing in urban public apartment complexes].

OBJECTIVES: The aim of this study was to identify the factors associated with the need for health consultation services among non-users of such services within residents of urban public apartment complexes. METHODS: In December 2011, a cross-sectional mail survey was conducted with the inclusion of 2,000 elderly residents, randomly selected from a total of 6,000 residents. We asked about the need for health consultation services, demographic data, daily living situation, medical and care-giving experiences, and health concerns and desires. Data were analyzed using ordinal logistic regression analyses. RESULTS: A total of 534 questionnaires were analyzed from the 553 respondents (response rate 27.7%). Respondents expressed need for health consultation services: very important 21.5%; important 38.2%; unknown 19.1%; not so much important 14.0%; unimportant 6.9%. The analyses revealed that people with greater need tended to have the following features compared to those with less need: lack of independence in daily activities (P=.03), experiencing stress in family relationships (P=.003), having nurses to consult about health concerns (P=.04), do not necessarily need doctor's consultation regarding their health problems (P<.001), feel it difficult to consult doctors when they have health-related questions (P=.007), know about locally-available health consultation services (P=.02). They also wanted to use services they can visit accompanied by acquaintances (P=.002), with one-on-one health consultation regarding their problems (P=.003), where service is free (P=.008), where they receive advice about their illnesses (P<.001) and about their medical and caregiving cost (P=.008), and maintain contact with others using the services (P<.001). CONCLUSION: Although the response rate was low, most of residents expressed a need for a health consultation service. Based on the results of this study, a health consultation service provided by nurses may be an effective solution. They also desire the services to be accessible in the company of their acquaintances, provided one-on-one, free of charge, and to provide opportunities not only for consultation concerning their illnesses but also for interaction with others.

Changes of blood fluidity in the early hepatopathy in rats.

The present study was designed to examine the influence of the early stage hepatopathy on blood fluidity by using a rat experimental system. F344 male rats, 4 weeks of age, were fed chow containing 3'-methyl-4-dimethylaminoazobenzene (DAB) at 0.06%. These rats were autopsied 8, 12, 16 and 20 weeks after starting DAB feeding. Blood samples were collected from the inferior vena cava under pentobarbital anesthesia and blood fluidity and platelet aggregation activity were examined by a Micro Channel Array Flow Analyzer and a platelet aggregometer, respectively. We also examined histological changes in the liver after staining with hematoxylin-eosin. Histological observation of the liver revealed early-stage hepathopathy when the organs were obtained from rats that fed DAB for more than 16 weeks. Although DAB-feeding of rats for 8 and 12 weeks barely affected blood fluidity, long-term intake (>16 weeks) caused decrease in fluidity. On the other hand, platelet aggregation activity was increased when rats were fed DAB for more than 16 weeks. The present results suggest that assaying for blood fluidity may be useful for the assessment of the degree of hepatopathy.

Endosomal sorting by Semaphorin 4A in retinal pigment epithelium supports photoreceptor survival.

Photoreceptor cell death is the hallmark of a group of human inherited retinal degeneration. Although the causative genetic mutations are often known, the mechanisms leading to photoreceptor degeneration remain poorly defined. Here, we show that Semaphorin 4A (Sema4A), a member of axonal guidance molecule semaphorin, plays a role in Rab11/FIP2-mediated endosomal sorting in retinal pigment epithelial cells to support photoreceptor function. In response to oxidative stress, Sema4A switches the endosomal sorting of the lysosomal precursor protein prosaposin from the lysosome to the exosomal release, which prevents light-induced photoreceptor apoptosis. In the absence of oxidative stress, Sema4A sorts retinoid-binding proteins with retinoids between the cell surface and endoplasmic reticulum, by which 11-cis-retinal, a chromophore for phototransduction, is regenerated and transported back to photoreceptors. Owing to defects in these processes, Sema4A-deficient mice exhibit marked photoreceptor degeneration. Our findings therefore indicate that Sema4A regulates two distinct endosomal-sorting pathways that are critical for photoreceptor survival and phototransduction during the transition between daylight and darkness.

Suppressive effect of juzentaihoto on vascularization induced by b16 melanoma cells in vitro and in vivo.

Juzentaihoto (JTT) is well known to be one of Japanese herbal medicines, and used for the supplemental therapy of cancer patients with remarkable success. The present study, therefore, was undertaken to examine the possible therapeutic mechanisms of JTT on cancer using B16 melanoma cell (B16 cell)/experimental mouse system. JTT was well mixed with rodent chow at 3.0% concentrations, and was administered orally ad libitum. Administration of JTT was started one week before tumor cell injection and continued throughout the experiment. Administration of JTT into mice significantly inhibited tumor metastasis in lungs after intravenous injection of 2 × 10(5) B16 cells in a volume of 50 µL. JTT also significantly suppressed enlargement of tumor size in hind footpad after the subcutaneous injection of 2 × 10(5) (50 µL) B16 cells. In the second part of experiments, the chamber that containing B16 cells was buried in the murine back. In JTT administrated group, vascular endothelial growth factor (VEGF) of chamber internal fluid significantly decreased, and vascularization of chamber circumference was also inhibited. These results strongly suggest that oral administration of JTT caused decrease in the generation of VEGF, which is responsible for vascularization, and results in inhibition of B16 cell metastasis.