Substantially increased risk of cancer in patients with diabetes mellitus: A systematic review and meta-analysis of epidemiologic evidence in Japan

AimsSeveral meta-analyses have shown that diabetes mellitus affects the risk of certain site-specific cancers. However, a meta-analysis on the overall risk of cancer has not yet been performed.MethodsWe performed a search of MEDLINE and the Cochrane Library for pertinent articles (including their references) that had been published as of June 10, 2010. English-language, original observational cohort studies and case-control studies conducted in Japan were included for a qualitative review and a meta-analysis.ResultsA total of 22,485 cancer cases were reported in four cohort studies and one case-control study (with a total of 250,479 subjects). With these five reports, a meta-analysis of the all-cancer risk in both men and women showed an increased risk in subjects with diabetes, compared with nondiabetic subjects (OR 1.70, 95% CI 1.38–2.10). The increase in the risk ratio adjusted for possible confounders was significant in men and borderline in women (adjusted RR 1.25, 95% CI 1.06–1.46 in men; adjusted RR 1.23, 95% CI 0.97–1.56 in women). An analysis of site-specific cancers revealed increased risks for incident hepatocellular cancer (OR 3.64, 95% CI 2.61–5.07) and endometrial cancer (OR 3.43, 95% CI 1.53–7.72).ConclusionsAs is the case in Western countries, Asian people with diabetes have a higher risk of incident cancer than those without diabetes. Cancer prevention and early detection should be important components of diabetes management in light of the exponentially increasing prevalence of diabetes, which has substantial implications in public health and clinical practices.     

Case of cerebral salt wasting syndrome with difficulty in controling excessive urine volume

Symptoms of hyponatremia and diuresis due to cerebral salt wasting syndrome (CSWS) are often observed after aneurysmal subarachnoid hemorrhage (SAH). Inadequately treated CSWS is known to work as a trigger of symptomatic vasospasm in SAH patients. Therefore, it is indispensable to detect and treat CSWS as early as possible in ICU. A 36-year-old man with SAH was admitted to our ICU. His urine volume increased excessively 3 days after ICU admission, and it reached a peak (39,250 ml x day(-1)) on the 6th day in ICU. Since infusion volume was controlled with regard to daily urinary output, hyponatremia was not noticeable and excessive urine volume stood out conspicuously. Though vasopressin and desmopressin were administered, the symptoms of natriuresis and hyponatremia were aggravated, associated with hyper secretion of natriuretic peptides (ANP 160 pg x dl(-1), BNP 172 pg x dl(-1)). Recent studies revealed that hyponatremia and hypovolemia following SAH might be caused by exaggerated secretion of natriuretic peptides. Experimental studies showed that the administration of vasopressin and desmopressin cause excessive secretion of natriuretic peptides under the circumstance of volume expansion in rats. We infer that the administration of vasopressin and desmopressin to our patient deterionated natriuresis in CSWS as in the previous experimental findings.     

Establishment of a murine model of bone invasion by oral squamous cell carcinoma

This study examines the establishment an animal model of bone invasion by oral squamous cell carcinoma to clarify the mechanisms of osteoclast-mediated bone invasion. C(3)H/HeN mice were inoculated with SCCVII cells into the masseter region. At the end of week 3, all surviving mice were sacrificed and analyzed by three-dimensional imaging using micro-computed tomography, histopathological observation using Hematoxylin-Eosin staining and Tartrate-Resistant Acid Phosphatase staining, and confirmation of mRNA expression of the osteoclast-related cytokines IL-6, TNF-alpha, and PTHrP. SCCVII cells rapidly multiplied in the masseter muscle of the mice. Bone invasion was evident only in the SCCVII transplanted group on micro-computed tomography. The histopathologic findings obtained with H-E and TRAP staining indicated that the tumor cells in the mandible of all animals of the SCCVII transplanted group exhibited funicular invasion and presented a serrated pattern of bone resorption. The mRNA expression of IL-6, PTHrP, and TNF-alpha increased as the control decreased. SCCVII cells were highly invasive into mandibular bone in C(3)H/HeN mice. This model was similar to the invasion of human oral cancer into maxillary and mandibular bone. Our mandibular invasion model may provide a powerful new modality for the diagnosis and treatment of oral cancer with bone invasion.     

Novel corneal morphological alterations in Vogt-Koyanagi-Harada disease

Japanese Journal of Ophthalmology - To determine whether visual function, especially when dependent on the anterior segment of ocular tissue, is altered during high-dose steroid treatment for...     

Plasma vitamin D and risk of colorectal cancer: the Japan Public Health Center-Based Prospective Study

We investigated the association between plasma 25(OH)D and the subsequent colorectal cancer incidence risk by a nested case-control study in The Japan Public Health Center-based Prospective Study, covering 375 newly diagnosed cases of colorectal cancer from 38 373 study subjects during a 11.5-year follow-up after blood collection. Two controls were matched per case on sex, age, study area, date of blood draw, and fasting time. In a conditional logistic regression model with matched pairs adjusted for smoking, alcohol consumption, body mass index, physical exercise, vitamin supplement use, and family history of colorectal cancer, plasma 25(OH)D was not significantly associated with colorectal cancer in men or in women. However, the lowest category of plasma 25(OH)D was associated with an elevated risk of rectal cancer in both men (odds ratio (OR), 4.6; 95% confidence interval (CI), 1.0-20) and women (OR, 2.7, 95% CI, 0.94-7.6), compared with the combined category of the other quartiles. Our results suggest that a low level of plasma 25(OH)D may increase the risk of rectal cancer.     

Pulmonary Arterial Impedance Analysis by the Use of the Oscillated Assist Flow

Abstract: Pulmonary arterial impedance is an important and interesting characteristic that can be used to evaluate the physiological properties of the pulmonary vessel. However, power spectrum analysis of the pulmonary artery pressure and flow pattern have suggested that peak power in the relatively high frequency range (>10 Hz) is significantly low; thus, we cannot analyze the vessel properties in the high frequency range. In this study, we used the newly developed vibrating flow pump (VFP), which can generate oscillated blood flow with a relatively high frequency (10–50 Hz) for right heart bypass, to evaluate the pulmonary arterial impedance pattern in the high frequency range. Acute animal experiments of the right heart bypass from the right atrium to the pulmonary artery using 6 healthy adult goats were performed. The flow pattern and pressure of the pulmonary artery, electrocardiograms (ECGs), and arterial and right atrial pressures were continuously monitored during the experiments. Spectral analysis of the he-modynamic parameters using the fast Fourier transform (FFT) method was performed to evaluate the spectral properties. The coherence function, transfer function, and phase patterns were calculated to analyze the impedance pattern in the relatively high frequency area. Previously, various investigators had tried to analyze the impedance patterns of the pulmonary artery: however, they could not analyze the impedance patterns over 10 Hz because the spectral patterns of the pulmonary flow do not have high power at high frequencies. These physiological analyses may be useful in designing the optimal pulmonary circulation.     

HLA-DPβ and susceptibility to multiple sclerosis: An analysis of caucasoid and Japanese patient populations

Nonradioactive sequence-specific oligonucleotide (SSO) probes specific for the HLA-DPβ locus have been used in a simple dot-blot assay to DPβ-type samples amplified by the polymerase chain reaction (pcr) from Caucasoid (n = 24) and Japanese (n = 23) patients with multiple sclerosis (ms) as well as ethnically matched controls. In contrast to previous reports, no DPβ allele was found to be increased in either patient population. However, the results do show a dramatic difference in the allele frequencies between the two control populations, further emphasizing the need for ethnically matched controls in studies of HLA and disease.     

T helper type 2 differentiation and intracellular trafficking of the interleukin 4 receptor-alpha subunit controlled by the Rac activator Dock2

The lineage commitment of CD4+ T cells is coordinately regulated by signals through the T cell receptor and cytokine receptors, yet how these signals are integrated remains elusive. Here we find that mice lacking Dock2, a Rac activator in lymphocytes, developed allergic disease through a mechanism dependent on CD4+ T cells and the interleukin 4 receptor (IL-4R). Dock2-deficient CD4+ T cells showed impaired antigen-driven downregulation of IL-4Ralpha surface expression, resulting in sustained IL-4R signaling and excessive T helper type 2 responses. Dock2 was required for T cell receptor-mediated phosphorylation of the microtubule-destabilizing protein stathmin and for lysosomal trafficking and the degradation of IL-4Ralpha. Thus, Dock2 links T cell receptor signals to downregulation of IL-4Ralpha to control the lineage commitment of CD4+ T cells.     

Roles for hENT1 and dCK in gemcitabine sensitivity and malignancy of meningioma

BackgroundHigh-grade meningiomas are aggressive tumors with high morbidity and mortality rates that frequently recur even after surgery and adjuvant radiotherapy. However, limited information is currently available on the biology of these tumors, and no alternative adjuvant treatment options exist. Although we previously demonstrated that high-grade meningioma cells were highly sensitive to gemcitabine in vitro and in vivo, the underlying molecular mechanisms remain unknown.MethodsWe examined the roles of hENT1 (human equilibrative nucleoside transporter 1) and dCK (deoxycytidine kinase) in the gemcitabine sensitivity and growth of meningioma cells in vitro. Tissue samples from meningiomas (26 WHO grade I and 21 WHO grade II/III meningiomas) were immunohistochemically analyzed for hENT1 and dCK as well as for Ki-67 as a marker of proliferative activity.ResultshENT1 and dCK, which play critical roles in the intracellular transport and activation of gemcitabine, respectively, were responsible for the high gemcitabine sensitivity of high-grade meningioma cells and were strongly expressed in high-grade meningiomas. hENT1 expression was required for the proliferation and survival of high-grade meningioma cells and dCK expression. Furthermore, high hENT1 and dCK expression levels correlated with stronger tumor cell proliferative activity and shorter survival in meningioma patients.ConclusionsThe present results suggest that hENT1 is a key molecular factor influencing the growth capacity and gemcitabine sensitivity of meningioma cells and also that hENT1, together with dCK, may be a viable prognostic marker for meningioma patients as well as a predictive marker of their responses to gemcitabine.     

Vitamin K<Subscript>2</Subscript> selectively induced apoptosis in ovarian TYK-nu and pancreatic MIA PaCa-2 cells out of eight solid tumor cell lines through a mechanism different from geranylgeraniol

PURPOSE: In this study, we examined the effects of vitamin K(2) (menaquinone 4), which has a geranylgeranyl side chain, on various lines of cells derived from human solid tumors and compared them with the effects of geranylgeraniol (GGO). METHODS: Cell proliferation was determined with 3'-[1-[(phenylamino)carbonyl]-3,4-tetrazolium- bis (4-methoxy-6-nitro) benzene-sulfonic acid hydrate (XTT), and the induction of apoptosis was analyzed by TUNEL staining and flow cytometry as well as by measurement of DNA fragmentation, released nucleosomes and caspase-3 activity. Levels of Bcl-2, Bax and cytochrome c were determined by immunoblotting. RESULTS: GGO inhibited the growth of all eight cell lines derived from solid tumors, while vitamin K(2) selectively inhibited the proliferation of ovarian TYK-nu and pancreatic MIA PaCa-2 cancer cells, inducing apoptosis in both cell lines. Far more time was required for the induction of apoptosis in these two cell lines by vitamin K(2) than by GGO. Apoptotic signals induced in TYK-nu cells during the first 2 days that followed the addition of vitamin K(2) to the culture medium were reversible, but these signals became irreversible after 3 days of treatment with vitamin K(2). The induction of apoptosis in TYK-nu cells by vitamin K(2) was inhibited by cycloheximide and also by starvation at a low concentration of serum. Neither cycloheximide nor starvation had any effect on the induction of apoptosis by GGO. Cytochrome c was released simultaneously with the initiation of apoptosis on treatment of TYK-nu cells with vitamin K(2) or GGO. However, GGO induced the release of cytochrome c from isolated mitochondria, while vitamin K(2) did not. The amount of Bcl-2 in TYK-nu cells was reduced by vitamin K(2), but not by GGO. CONCLUSIONS: In contrast to GGO, vitamin K(2) induced apoptosis selectively in pancreatic MIA-PaCa 2 and ovarian TYK-nu cancer cells. It is suggested that de novo protein synthesis might be necessary for induction of apoptosis by vitamin K(2) but not by GGO, and thus, that vitamin K(2) and GGO might induce apoptosis by different mechanisms.