Purpose
Tryptophan metabolites have immunomodulatory functions, suggesting possible roles in cancer immunity.
Methods
Plasma tryptophan metabolites were measured using liquid chromatography/mass ...spectrometry before immune checkpoint inhibitors (ICIs) in patients with non-small cell lung cancer (NSCLC).
Results
The 19 patients with NSCLC had significantly lower levels of tryptophan (
p
= 0.002) and xanthurenic acid (
p
= 0.032), and a significantly higher level of 3-hydroxyanthranilic acid (3-HAA) (
p
= 0.028) compared with the 10 healthy volunteers. The patients achieving objective responses had significantly lower levels of 3-HAA than those who did not (
p
= 0.045). Receiver operating characteristic analyses determined that the cutoff value of 3-HAA for objective response was 35.4 pmol/mL (sensitivity: 87.5% and specificity: 83.3%). The patients with 3-HAA < 35.4 pmol/mL had significantly longer median progression-free survival (7.0 months) than those without (1.6 months,
p
= 0.022).
Conclusions
Tryptophan metabolites may have a potential for predicting the efficacy of ICIs.
Registration number
University Hospital Medical Information Network Clinical Trial Registry 000026140.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Coping strategies may be significantly associated with health outcomes. This is the first study to investigate the association between baseline coping strategies and cardiovascular disease (CVD) ...incidence and mortality in a general population cohort.
The Japan Public Health Center-based prospective Study asked questions on coping in its third follow-up survey (2000-04). Analyses on CVD incidence and mortality included 57 017 subjects aged 50-79 without a history of CVD and who provided complete answers on approach- and avoidance-oriented coping behaviours and strategies. Cox regression models, adjusted for confounders, were used to determine hazard ratios (HRs) according to coping style. Mean follow-up time was 7.9 years for incidence and 8.0 years for mortality.The premorbid use of an approach-oriented coping strategy was inversely associated with incidence of stroke (HR = 0.85; 95% CI, 0.73-1.00) and CVD mortality (HR = 0.74; 95% CI, 0.55-0.99). Stroke subtype analyses revealed an inverse association between the approach-oriented coping strategy and incidence of ischaemic stroke (HR = 0.79; 95% CI, 0.64-0.98) and a positive association between the combined coping strategy and incidence of intra-parenchymal haemorrhage (HR = 2.03; 95% CI, 1.01-4.10). Utilizing an avoidance coping strategy was associated with increased mortality from ischaemic heart disease (IHD) only in hypertensive individuals (HR = 3.46; 95% CI, 1.07-11.18). The coping behaviours fantasizing and positive reappraisal were associated with increased risk of CVD incidence (HR = 1.24; 95% CI, 1.03-1.50) and reduced risk of IHD mortality (HR = 0.63; 95% CI, 0.40-0.99), respectively.
An approach-oriented coping strategy, i.e. proactively dealing with sources of stress, may be associated with significantly reduced stroke incidence and CVD mortality in a Japanese population-based cohort.
DNA adducts are a major cause of DNA mutation and DNA mutation-related diseases, but the simultaneous identification of multiple DNA adducts has been a challenge for a decade. An adductome approach ...using consecutive liquid chromatography and double mass spectrometry after micrococcal nuclease treatment has paved the way to demonstrations of numerous DNA adducts in a single experiment and is expected to contribute to the comprehensive understanding of overall environmental and endogenous exposures to possible mutagens in individuals. In this report, we applied an adductome approach to gastric mucosa samples taken at the time of a gastrectomy for gastric cancer in Lujiang, China, and in Hamamatsu, Japan. Seven lipid peroxidation-related DNA adducts 1,N6-etheno-2'-deoxyadenosine, butanone-etheno-2'-deoxycytidine (BεdC), butanone-etheno-2'-deoxy-5-methylcytidine, butanone-etheno-2'-deoxyadenosine (BεdA), heptanone-etheno-2'-deoxycytidine, heptanone-etheno-2'-deoxyadenosine (HεdA) and heptanone-etheno- 2'-deoxyguanosine were identified in a total of 22 gastric mucosa samples. The levels of these adducts ranged from 0 to 30,000 per 10(9) bases. Although the presence of Helicobacter pylori DNA in the mucosa was not related to these adducts level, the levels of BεdC, BεdA and HεdA were higher in the Japanese gastric mucosa samples. The profiles of these 7 adduct levels among the 21 cases were capable of discriminating between the possible origins (China or Japan) of the gastric mucosa samples. Our report is the first demonstration of lipid peroxidation-related DNA adducts in the human stomach, and these observations warrant further investigation in the context of the significance of DNA adducts in human gastric carcinogenesis.
The study aimed to evaluate the association between green tea and coffee consumption and the risk of kidney cancer using data from a large prospective cohort study in Japan (the Japan Public Health ...Center-based Prospective Study: JPHC Study). A total of 102,463 participants aged 40-69 were followed during 1,916,421 person-years (mean follow-up period, 19 years). A total of 286 cases of kidney cancer (199 in men, 87 in women) were identified. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) while adjusting for potential confounders. No statistically significant association between green tea intake and kidney cancer risk was found in the total population. Among women who consumed more than five cups of green tea per day, a statistically significant decreased risk was shown with a HR of 0.45 (95% CI: 0.23-0.89), compared to women who rarely consumed green tea. For coffee consumption, the association of kidney cancer risk was not statistically significant. This large prospective cohort study indicated green tea intake may be inversely associated with kidney cancer risk in Japanese adults, particularly in Japanese women.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Chromosomal instability (CIN) is recognised as a hallmark of cancer and is caused by a spindle assembly checkpoint disorder or chromosome mis-segregation during mitosis. Although the recent ...identification of human shugoshin (hSgo1), an important player in proper chromosome segregation, has suggested the involvement of hSgo1 in colorectal tumourigenesis, little is known about how it is involved. The aim of this study was to obtain information about the status of hSgo1 in human colorectal cancer.
Among the 46 colorectal cancer cases, hSgo1 mRNA expression was decreased in the tumour tissue in comparison with the corresponding normal tissue (p = 0.032). Human Sgo1-downregulated tumours (tumour to normal mucosa ratio<0.5) had preferential location on the left side large bowel rather than on the right side (p = 0.012), and a higher variation of centromere numbers revealed by fluorescence in situ hybridisation (FISH). To assess the effects of hSgo1 downregulation, hSgo1 knockdown was performed by transfecting the diploid HCT116 cell line with a short hairpin RNA expression vector. hSgo1 knockdown cells proliferated slowly because of both G(2)/M arrest and apoptosis (p<0.001), and markers of CIN in the form of aneuploidy (p<0.001) and micronuclei (p<0.005) were later observed in hSgo1 knockdown cells. Increased centrosome amplification (p<0.05), the presence of binucleated cells and mitotic catastrophes were also noted in hSgo1 knockdown cells.
These findings suggest that hSgo1-downregulated colorectal cancers have a clinicopathological character of CIN, and hSgo1 downregulation leads to CIN in colorectal cancer cells.
Genomic amplification of oncogenes and inactivation of suppressor genes are critical in the pathogenesis of human cancer. To identify chromosomal alterations associated with hepatocarcinogenesis, we ...performed allelic gene dosage analysis on 36 hepatocellular carcinomas (HCCs). Data from high-density single-nucleotide polymorphism arrays were analysed using the Genome Imbalance Map (GIM) algorithm, which simultaneously detects DNA copy number alterations and loss of heterozygosity (LOH) events. Genome Imbalance Map analysis identified allelic imbalance regions, including uniparental disomy, and predicted the coexistence of a heterozygous population of cancer cells. We observed that gains of 1q, 5p, 5q, 6p, 7q, 8q, 17q and 20q, and LOH of 1p, 4q, 6q, 8p, 10q, 13q, 16p, 16q and 17p were significantly associated with HCC. On 6q24-25, which contains imprinting gene clusters, we observed reduced levels of PLAGL1 expression owing to loss of the unmethylated allele. Finally, we integrated the copy number data with gene expression intensity, and found that genome dosage is correlated with alteration in gene expression. These observations indicated that high-resolution GIM analysis can accurately determine the localizations of genomic regions with allelic imbalance, and when integrated with epigenetic information, a mechanistic basis for inactivation of a tumor suppressor gene in HCC was elucidated.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Purpose
The development of prostate cancer may be impacted by environmental factors, including diet. The aim of this study was to evaluate the association between dietary patterns and risk of ...prostate cancer in a large prospective cohort study among Japanese men.
Methods
A total of 43,469 men who participated in the Japan Public Health Center-based Prospective Study were followed from 1995 to 1998 to the end of 2012, during which 1,156 cases of prostate cancer were newly identified. Dietary intake was assessed using a validated food frequency questionnaire in the 5-year follow-up survey.
Results
Three major dietary patterns were derived using exploratory factors analysis: prudent, westernized, and traditional dietary patterns. The westernized dietary pattern was associated with a higher risk of total prostate cancer (HR: 1.22; 95% CI 1.00–1.49;
p
trend = 0.021), localized cancer (HR: 1.24; 95% CI 0.97–1.57;
p
trend = 0.045), and advanced cancer (HR: 1.23; 95% CI 0.82–1.84;
p
trend = 0.233). The prudent dietary pattern was associated with a lower risk of total and localized prostate cancer, with respective multivariable HRs for the highest and lowest quintiles of 0.71 (95% CI 0.50–1.02;
p
trend = 0.037) and 0.63 (95% CI 0.38–1.03;
p
trend = 0.048) among subjects detected by subjective symptoms. No association was found between the traditional dietary pattern and prostate cancer risk among our subjects.
Conclusion
Our results suggest that a western-style diet may lead to a higher risk of prostate cancer in the total population, whereas the prudent diet contributes to a lower risk among subjects detected by subjective symptoms.
Abstract
A double-$\Lambda$ hypernucleus, _{\Lambda\Lambda}\mathrm{Be}$, was observed by the J-PARC E07 Collaboration in nuclear emulsions tagged by the ($K^{-}, K^{+}$) reaction. This event was ...interpreted as the production and decay of $ {}_{\Lambda\Lambda}^{\;10}\mathrm{Be}$, _{\Lambda\Lambda}^{\;11}\mathrm{Be}$, or _{\Lambda\Lambda}^{\;12}\mathrm{Be}^{*}$ via $\Xi^{-}$ capture in ^{16}\mathrm{O}$. By assuming capture in the atomic 3D state, the binding energies of two $\Lambda$ hyperons ($B_{\Lambda\Lambda}$) of these double-$\Lambda$ hypernuclei are obtained to be $15.05 \pm 0.11\,\mathrm{MeV}$, $19.07 \pm 0.11\,\mathrm{MeV}$, and $13.68 \pm 0.11\,\mathrm{MeV}$, respectively. Based on the kinematic fitting, _{\Lambda\Lambda}^{\;11}\mathrm{Be}$ is the most likely explanation for the observed event.
Background: Plaque erosion is a cause of atherothrombosis that preferentially occurs on smooth muscle cell (SMC)‐ and proteoglycan‐rich rather than lipid‐rich plaques. However, its underlying ...mechanisms remain unknown. Objective: To determine whether disturbed blood flow induces erosive injury and thrombus formation on SMC‐rich neointima. Methods: Three weeks after balloon injury, SMC‐rich neointima with increased tissue factor (TF) activity developed in rabbit femoral arteries that were narrowed with a vascular occluder to disturb blood flow after stenosis. Neointimal injury and thrombus formation were assessed at 15, 30, and 180 min after the vascular narrowing. Results: Endothelial detachment, platelet adhesion and neointimal cell apoptosis became evident at the post‐stenotic regions of all femoral arteries (n = 5) within 15 min of narrowing. Mural thrombi composed of platelet and fibrin developed after 30 min, and then occlusive thrombi were generated in three out of five vessels after 180 min. The identical vascular narrowing of normal femoral arteries also induced endothelial detachment with small platelet thrombi at post‐stenotic regions, but fibrin and occlusive thrombi did not develop. Computational simulation analysis indicated that oscillatory shear stress contributes to the development of erosive damage to the neointima. Conclusions: These results suggest that disturbed post‐stenotic blood flow can induce erosive injury in SMC‐rich plaques and promote thrombus formation that results in vascular events.
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FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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