Scirrhous gastric cancer, which has the worst prognosis among the various types of gastric cancer, is highly invasive and associated with abundant stromal fibroblasts. Although cancer-associated ...fibroblasts (CAFs) have been proposed to generate a tumor-supportive extracellular matrix that promotes the expansion of this type of cancer, the molecular mechanisms by which CAFs assist cancer cells are not yet fully understood. Here, we show for the first time that Asporin, a small leucine-rich proteoglycan (SLRP), is predominantly expressed in CAFs, and has essential roles in promoting co-invasion of CAFs and cancer cells. CAFs of scirrhous gastric cancer possess high potential for invasion, and invasion by CAFs frequently proceeded invasion by cancer cells, both in vitro and in vivo. Expression of Asporin was induced in fibroblasts by exposure to gastric cancer cells. Asporin secreted from CAFs activates Rac1 via an interaction with CD44 and promotes invasion by CAFs themselves. Moreover, Asporin promoted invasion by neighboring cancer cells, via paracrine effects mediated by activation of the CD44-Rac1 pathway. These results suggest that Asporin is a unique SLRP that promotes progression of scirrhous gastric cancer and is required for coordinated invasion by CAFs and cancer cells. Therefore, Asporin may represent a new therapeutic target molecule for the development of drugs aimed at manipulating the cancer microenvironment.
Lipoma preferred partner (LPP) is a LIM domain protein, which has multiple functions as an actin-binding protein and a transcriptional coactivator, and it has been suggested that LPP has some roles ...in cell migration or invasion, however, its role in cancer cells remains to be elucidated. Here, we showed that LPP degraded N-cadherin in lung cancer, PC14PE6 cells via regulating the expression of matrix metalloproteinase 15 (MMP-15), and loss-of-LPP increases collective cell migration (CCM) and dissemination consequently. Knockdown of LPP and its functional partner, Etv5, markedly restores the full-length N-cadherin and increases cell-cell adhesion. We investigated the common target of LPP and Etv5, and found that MMP-15 is transcribed as their direct transcriptional target. Furthermore, MMP-15 could directly digest the N-cadherin extracellular domain. LPP knockdown in PC14PE6 cells increases N-cadherin-dependent CCM in the three-dimensional collagen gel invasion assays, and promoted the dissemination of cancer cells when they were orthotopically implanted in nude mice. Immunohistochemistry of lung adenocarcinoma specimens revealed the heterogeneity of LPP intensity and complementary expression of LPP and N-cadherin in the primary tumors. These findings suggest that loss-of-LPP, Etv5 or MMP-15 can be a prognostic marker of increasing malignancy.
In a prospective study of 23 995 Japanese women, short sleep duration was associated with higher risk of breast cancer (143 cases), compared with women who slept 7 h per day, the multivariate hazard ...ratio of those who slept </=6 h per day was 1.62 (95% confidence interval: 1.05-2.50; P for trend=0.03).
Helicobacter pylori eradication rates by triple therapy with a proton pump inhibitor, amoxicillin, and clarithromycin at standard doses depend on bacterial susceptibility to clarithromycin and ...patient CYP2C19 genotypes. We examined the usefulness of a personalized therapy for H. pylori infection based on these factors as determined by genetic testing. First, optimal lansoprazole dosing schedules that would achieve sufficient acid inhibition to allow H. pylori eradication therapy in each of different CYP2C19 genotype groups were determined by a 24‐h intragastric pH monitoring. Next, 300 H. pylori‐positive patients were randomly assigned to the standard regimen group (lansoprazole 30 mg twice daily (b.i.d.)), clarithromycin 400 mg b.i.d., and amoxicillin 750 mg b.i.d. for 1 week) or the tailored regimen group based on CYP2C19 status and bacterial susceptibility to clarithromycin assessed by genetic testing. Patients with failure of eradication underwent the second‐line regimen. The per‐patient cost required for successful eradication was calculated for each of the groups. In the first‐line therapy, the intention‐to‐treat eradication rate in the tailored regimen group was 96.0% (95% CI=91.5–98.2%, 144/150), significantly higher than that in the standard regimen group (70.0%: 95% CI=62.2–77.2%, 105/150) (P<0.001). Final costs per successful eradication in the tailored and standard regimen groups were $669 and $657, respectively. In conclusion, the pharmacogenomics‐based tailored treatment for H. pylori infection allowed a higher eradication rate by the initial treatment without an increase of the final per‐patient cost for successful eradication. However, the precise cost‐effectiveness of this strategy remains to be determined.
Clinical Pharmacology & Therapeutics (2007) 81, 521–528. doi:10.1038/sj.clpt.6100043; published online 10 January 2007
Unicompartmental knee arthroplasty (UKA) is one surgical option for treating symptomatic medial osteoarthritis. Clinical studies have shown the functional benefits of UKA; however, the optimal ...alignment of the tibial component is still debated. The purpose of this study was to evaluate the effects of tibial coronal and sagittal plane alignment in UKA on knee kinematics and cruciate ligament tension, using a musculoskeletal computer simulation.
The tibial component was first aligned perpendicular to the mechanical axis of the tibia, with a 7° posterior slope (basic model). Subsequently, coronal and sagittal plane alignments were changed in a simulation programme. Kinematics and cruciate ligament tensions were simulated during weight-bearing deep knee bend and gait motions. Translation was defined as the distance between the most medial and the most lateral femoral positions throughout the cycle.
The femur was positioned more medially relative to the tibia, with increasing varus alignment of the tibial component. Medial/lateral (ML) translation was smallest in the 2° varus model. A greater posterior slope posteriorized the medial condyle and increased anterior cruciate ligament (ACL) tension. ML translation was increased in the > 7° posterior slope model and the 0° model.
The current study suggests that the preferred tibial component alignment is between neutral and 2° varus in the coronal plane, and between 3° and 7° posterior slope in the sagittal plane. Varus > 4° or valgus alignment and excessive posterior slope caused excessive ML translation, which could be related to feelings of instability and could potentially have negative effects on clinical outcomes and implant durability.
: K. Sekiguchi, S. Nakamura, S. Kuriyama, K. Nishitani, H. Ito, Y. Tanaka, M. Watanabe, S. Matsuda.
2019;8:126-135. DOI: 10.1302/2046-3758.83.BJR-2018-0208.R2.
Objective: The aim of this study is to evaluate the validity and the utility of the Japanese version of the WHO-Five Well-Being Index (WHO-5-J) in the context of detecting suicidal ideation in ...elderly community residents. Methods: A sample of 696 subjects aged 70 years or over who completed a set of questionnaires was examined. Results: Cronbach's α was 0.87 and Loevinger's coefficient was 0.64. The total score was significantly correlated with the number of cohabitants, the number of physical illnesses, physical functioning, instrumental activities of daily living, and depressive symptoms. Subjects with suicidal ideation had significantly lower scores on the WHO-5-J. The receiver-operating characteristic curve analysis indicated that the scale significantly discriminated the subjects with suicidal ideation. When combined with the assessment of a lack of perceived social support (PSS), a standard cut-off criterion of “a total score ≤ 12 or answering 0 or 1 to any of the five items” more appropriately identified elderly subjects with suicidal ideation: sensitivity = 87%, specificity = 75%, negative predictive value = 99%, and positive predictive value = 10%. Conclusions: In combination with PSS, the scale has predictive utility to detect suicidal ideation in elderly community residents.
Summary
Background
Although thiopurines have a proven role in maintenance therapy for Crohn's disease, an alternative therapy is needed for patients intolerant or resistant to thiopurines.
Aim
To ...evaluate the effectiveness of home enteral nutrition as a maintenance therapy regimen in which half of the daily calorie requirement is provided by an elemental diet and the remaining half by a free diet. We refer to this home enteral nutrition therapy as ‘half elemental diet’.
Methods
Between 2002 and 2005, 51 patients in remission from two hospitals were randomly assigned to a half elemental diet group (n = 26) or a free diet group (n = 25). The primary outcome measure of this study was the occurrence of relapse over the 2‐year period.
Results
The relapse rate in the half elemental diet group was significantly lower 34.6% vs. 64.0%; multivariate hazard ratio 0.40 (95% CI: 0.16–0.98) than that in the free diet group after a mean follow‐up of 11.9 months. Compliance was similar in the two groups. No adverse event occurred in any of the patients throughout the study.
Conclusion
This randomized‐controlled trial shows the effectiveness of an half elemental diet, which is a promising maintenance therapy for Crohn's disease patients.
Previous studies have reported the relationship between housing environment and health, although due to cost and effort, it was difficult to conduct housing condition surveys on a large scale. The ...CASBEE Housing Health Checklist (the Checklist) made it possible to easily evaluate the housing condition from the resident's perspective. This study examined the relationship between housing coldness/warmth evaluation using the Checklist and psychological distress in a large-scale general Japanese population.
A cross-sectional study.
We analysed data from 29,380 people aged ≥20 years who lived in Miyagi Prefecture, Japan. As an assessment of housing coldness/warmth, we used the Checklist. We classified participants' total scores on the Checklist related to coldness/warmth into quartiles. The Kessler 6 scale was used as an indicator of psychological distress. Multivariable logistic regression models were used to estimate the adjusted odds ratio (OR) and 95% confidence intervals (CIs). Adjusted OR and P-values for linear trends were calculated using the quartiles of the Checklists' score.
Among participants in Q1 (i.e., poorer subjective house condition), the percentage of people with psychological distress was high. Compared to the highest quartile, Q1 showed poorer evaluation of housing coldness/warmth, and higher OR for psychological distress. The OR (95% CI) of psychological distress for Q3, Q2, and Q1 compared with Q4 were 1.93 (1.74–2.14), 2.82 (2.55–3.12), and 5.78 (5.25–6.35), respectively.
Housing coldness/warmth evaluation was significantly related to psychological distress. This finding suggests that maintaining a comfortable thermal environment at home could be important for residents’ mental health.
Background Although ecological observations suggest that the Japanese diet may reduce the risk of cardiovascular disease (CVD), the impact of a Japanese dietary pattern upon mortality due to CVD is ...unclear. Methods We prospectively assessed the association between dietary patterns among the Japanese and CVD mortality. Dietary information was collected from 40 547 Japanese men and women aged 40–79 years without a history of diabetes, stroke, myocardial infarction or cancer at the baseline in 1994. Results During 7 years of follow-up, 801 participants died of CVD. Factor analysis (principal component) based on a validated food frequency questionnaire identified three dietary patterns: (i) a Japanese dietary pattern highly correlated with soybean products, fish, seaweeds, vegetables, fruits and green tea, (ii) an ‘animal food’ dietary pattern and (iii) a high-dairy, high-fruit-and-vegetable, low-alcohol (DFA) dietary pattern. The Japanese dietary pattern was related to high sodium intake and high prevalence of hypertension. After adjustment for potential confounders, the Japanese dietary pattern score was associated with a lower risk of CVD mortality (hazard ratio of the highest quartile vs the lowest, 0.73; 95% confidence interval: 0.59–0.90; P for trend = 0.003). The ‘animal food’ dietary pattern was associated with an increased risk of CVD, but the DFA dietary pattern was not. Conclusion The Japanese dietary pattern was associated with a decreased risk of CVD mortality, despite its relation to sodium intake and hypertension.
The role of adult weight change in breast cancer (BC) risk is unclear in Japanese women.
A total of 10,106 postmenopausal women aged 40-64 years (the Miyagi Cohort) were followed from 1990 to 2003, ...and 108 BC cases were identified. Hazard ratios (HRs) were estimated according to body mass index (BMI) at the current age and at the of age 20 years, and weight change since age 20 years.
Higher current BMI was associated with an increased risk of BC (P for trend=0.02), whereas higher BMI at the age 20 years was inversely associated with this risk (P for trend=0.002). There was a significant association between weight change since age 20 years and BC risk (P for trend=0.0086). Compared with stable weight, HR was 0.35 for weight loss of 5 kg or more (P for weight loss trend=0.04) and 1.55 for weight gain of 12 kg or more (P for weight gain trend=0.05).
Adiposity at younger and current age has differential effects on BC risk among postmenopausal women; weight gain in adulthood being associated with an increased, and weight loss with a decreased risk.
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