Quality and quantity of visceral fat tissue are associated with insulin resistance and survival outcomes after chemotherapy in patients with breast cancer.

PURPOSE: Recent studies suggest that the quality and quantity of visceral adipose tissue (VAT) play significant roles in adipocyte function, and are related to insulin resistance. We tested the hypothesis that high amounts of upper VAT (aVAT) and low-quality VAT worsen treatment outcomes via altered insulin metabolism. METHODS: Cohort 1 included 106 women with breast cancer who were undergoing surgery. Homeostasis model assessment of insulin resistance (HOMA-R), insulin-like growth factor (IGF)-1, and IGF-binding protein 3 (IGFBP3) were measured before the initiation of treatment. aVAT was measured via computed tomography (CT). VAT quality was assessed using CT-determined Hounsfield units (VAT-HU). Associations between the variables investigated and VAT quality and quantity were analyzed. Cohort 2 included 271 patients who underwent chemotherapy. Associations between the variables investigated and survival outcomes after chemotherapy were analyzed via retrospective chart review. RESULTS: In cohort 1, aVAT was significantly correlated with insulin and HOMA-R levels. As body mass index (BMI) class increased, mean IGF-1 increased and mean IGFBP3 decreased, but these trends were not statistically significant. In cohort 2, aVAT was significantly positively correlated with BMI. The patients in the third aVAT tertiles had significantly shorter distant disease-free survival (dDFS) after neoadjuvant chemotherapy setting. In multivariate analysis, aVAT and VAT-HU were significantly associated with shorter dDFS. CONCLUSIONS: High aVAT and low-quality VAT were associated with poor survival outcome, increased insulin levels, and insulin resistance. The present study suggests the importance of evaluating the quality and quantity of VAT when estimating insulin resistance and treatment outcomes.

Identification of specific and common diagnostic antibody markers for gastrointestinal cancers by SEREX screening using testis cDNA phage library.

The present study was planned to identify novel serum antibody markers for digestive organ cancers. We have used screening by phage expression cloning and identified novel fourteen antigens in this experiment. The presence of auto-antibodies against these antigens in serum specimens was confirmed by western blotting. As for auto-antibodies against fourteen antigens, AlphaLISA (amplified luminescence proximity homogeneous assay) assay was performed in the sera of gastrointestinal cancers patients to confirm the results. Serum antibody levels against these fourteen recombinant proteins as antigens between healthy donors (HD) and esophageal squamous cell carcinoma (ESCC) patients, gastric cancer (GC), or colon cancer (CC) were compared. The serum levels of all fourteen auto-antibodies were significantly higher in ESCC and GC than those of HD. Among those auto-antibodies, except ECSA2 and CCNL2, were also detected significantly higher levels in CC than those of HD. Receiver operating curve (ROC) revealed similar results except CCNL2 in CC. AUC values calculated by ROC were higher than 0.7 in auto-antibodies against TPI1, HOOK2, PUF60, PRDX4, HS3ST1, TUBA1B, TACSTD2, AKR1C3, BAMBI, DCAF15 in ESCC, auto-antibodies against TPI1, HOOK2, PUF60, PRDX4, TACSTD2, AKR1C3, BAMBI, DCAF15 in GC, and auto-antibodies against TPI1, HOOK2, PUF60 in CC. AUC of the combination of HOOK2 and anti-p53 antibodies in ESCC was observed to be as high as 0.8228. Higher serum antibody levels against ten antigens could be potential diagnostic tool for ESCC. Higher serum antibody levels against eight antigens could be potential diagnostic tool for GC, and serum antibody levels against three antigens could be potential diagnostic tool for CC.

Paradoxical effects of thyroid function on glomerular filtration rate estimated from serum creatinine or standardized cystatin C in patients with Japanese Graves' disease.

BACKGROUND: Estimated glomerular filtration rate (eGFR) is clinically valuable for evaluating renal function. Recently, serum cystatin C (sCysC) measurement has been standardized and has demonstrated utility as a novel indicator of renal function. Thyroid hormone is known to affect serum creatinine (sCr) and sCysC, however, the clinical significance of post-treatment renal function evaluation is yet to be completely elucidated. This study examined the effects of thyroid hormones on eGFR by sCr (eGFRCr), and standardized sCysC (eGFRCysC) in patients with Japanese Graves' disease (GD). METHODS: Serum samples were obtained from 113 outpatients with GD. Following pharmacotherapy, 41 of the 113 outpatients with GD achieved remission. Renal function was evaluated by eGFRCr and eGFRCysC. Reference method used Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations. RESULTS: eGFRCr levels significantly increased whereas eGFRCysC levels significantly decreased with elevated FT3 and FT4 levels in patients with GD. In the remission group, eGFRCr levels significantly decreased and eGFRCysC levels significantly increased. No significant differences between eGFRCr and eGFRCysC levels were observed. Furthermore, CKD-EPI equations show a similar trend and eGFRCr-CysC levels were no significant differences regardless of before and after treatment. CONCLUSIONS: Renal function evaluation by eGFRCr and eGFRCysC had clinical utility in post-treatment euthyroidism.

Estimated glomerular filtration rate by serum creatinine or standardized cystatin C in Japanese patients with Graves׳ disease.

Glomerular filtration rate (eGFR) by serum creatinine (eGFRCr) or standardized cystatin C (eGFRCysC) were estimated in Japanese patients with Graves׳ disease (GD) of different sex. Clinical samples were collected from patients with GD with normal renal function to accurately validate eGFRCr and eGFRCysC levels and evaluate how hyperthyroidism affects renal function. Levels of eGFRCr and eGFRCysC showed clinical usefulness in successfully treated euthyroid patients with GD regardless of sex. The article includes detailed experimental methods and data used in our analysis. The data relates to the "Paradoxical effect of thyroid function on the estimated glomerular filtration rate by serum creatinine or standardized cystatin C in Japanese Graves' disease patients" (Suzuki et al., 2015) [1].

[Usefulness of the standardized serum cystatin C reagent in evaluation of renal function].

Serum cystatin C (sCysC) is valuable to evaluate the renal functions in various clinically studies. Since the reagents to detect sCysC are different among institutes or hospitals, the accidental error due to the difference of reagents is not negligible. That is why sCysC is sometimes difficult to use or interpret for patient as estimated Glomerular filtration rate (eGFR) that is one of the most popular factors to evaluate renal function. Recently, the international reference standard is gradually accepted as standardization of chemical measurement of sCysC in Japan. Japan Society of Clinical Chemistry has reported the utilities for sCysC measurement standardization in 2010. In this study, we examined the usefulness of the standardization of sCysC reagent in Chiba University Hospital. Our study indicated that the clinical usefulness of eGFR calculated by sCysC. As results, eGFR from serum creatinine (sCr) was relatively high in patients with reduced muscle mass, such as old-age patients with wheelchair and prolonged hospitalization. On the other hand, eGFR from sCysC was high in patients with hypothyroidism. Together, eGFR calculated by sCysC is clinically available for the patients with reduced muscle mass could be underestimated. Further studies are required to evaluate the validity of standardization of sCysC measurement and find the dissociation among eGFR, sCysC and sCr depending in the renal disease or pathogenesis.

Serum cystatin C as a marker for early detection of chronic kidney disease and grade 2 nephropathy in Japanese patients with type 2 diabetes.

BACKGROUND: Diabetic nephropathy (DN) is a significant cause of hemodialysis, and its early detection is extremely important to prevent or delay end-stage renal disease. The significance of the renal function marker serum cystatin C (sCysC) and its relationship with glomerular filtration rate in chronic kidney disease (CKD) and DN in Japanese patients with type 2 diabetes remains uncertain. In this study, we examined the effectiveness of sCysC as a marker of early DN and CKD in Japanese subjects. METHODS: A total of 325 Japanese patients with type 2 diabetes and 88 healthy subjects were studied retrospectively. sCysC concentration (mg/L) was determined by a latex turbidmetric immunoassay using a BioMajesty 8040 analyzer. The renal function of the diabetic patients was evaluated using the albumin-creatinine ratio (ACR) and Kidney Disease Outcome Quality Initiative-Kidney Disease Improving Global Outcomes (K/DOQI-KDIGO) classification. RESULTS: There was a significant increase in sCysC but not in serum creatinine (sCr) or serum ß2-microglobulin (sß2M) in patients with grade 2 DN (ACR 30-300 mg/g) compared to grade 1 patients. Receiver operating characteristic analysis in grade 2 and 3 DN patients showed that sCysC had superior sensitivity and specificity than sCr and sß2M for early detection of DN. In addition, sCysC showed particularly high sensitivity and specificity in DN patients with stage 2 CKD. CONCLUSIONS: sCysC was effective for detection of grade 2 DN and would be especially useful for screening stage 2 CKD patients (K/DOQI-KDIGO).

[Clinical validity of renal function markers including serum cystatin C on chronic kidney disease classification].

In this study, clinical utility of various renal function markers (Cystatin C, Creatinine, beta2-microglobulin, Urea nitrogen) including serum Cystatin C was evaluated by the latex turbidimetric immunoassay based on the Chronic Kidney Disease (CKD) stage classification. Serum creatinine was most correlated with estimated Glomerular Filtration Rate (eGFR), followed by serum Cystatin C. However, the level of serum Cystatin C increased significantly earlier than other renal function markers in the group of mild renal dysfunction based on the CKD stage classification. Cystatin C also had the most distinctive ability of the renal dysfunction by Receiver Operating Characteristic (ROC) and distinction characteristic analysis. Thus, it is useful to measure serum Cystatin C and serum creatinine at the same time to improve diagnostic sensitivity and specificity, eGFR was 6% higher than Ccr on stage III-V, though Ccr was 30% higher than eGFR on stage I-II by CKD stage classifications. Since eGFR and Ccr showed different results in early and severe CKD groups, it was suggested that Ccr and eGFR need to be evaluated as different renal function markers.

Decreases in the serum VLDL-TG/non-VLDL-TG ratio from early stages of chronic hepatitis C: alterations in TG-rich lipoprotein levels.

BACKGROUND: The liver secretes very-low-density lipoproteins (VLDLs) and plays a key role in lipid metabolism. Plasma total triglyceride (TG) level variations have been studied in patients with hepatitis C virus (HCV)-related chronic hepatitis (CH-C). However, the results of these studies are variable. A homogenous assay protocol was recently proposed to directly measure the TG content in VLDL (VLDL-TG) and VLDL remnants. METHODOLOGY/PRINCIPAL FINDINGS: Using the assay protocol, we determined serum VLDL-TG levels in 69 fasting patients with biopsy-proven HCV-related chronic liver disease and 50 healthy subjects. Patients were classified into stages F0-F4 using the 5-point Desmet scale. Serum total TG levels in patients with non-cirrhotic (F1-F3) CH-C did not demonstrate significant differences compared with healthy subjects, but serum VLDL-TG levels did demonstrate significant differences. Mean serum VLDL-TG levels tended to decrease with disease progression from F1 to F4 (cirrhosis). Compared with healthy subjects, serum non-VLDL-TG levels significantly increased in patients with stages F2 and F3 CH-C; however, we observed no significant difference in patients with liver cirrhosis. Furthermore, the serum VLDL-TG/non-VLDL-TG ratio, when taken, demonstrated a significant decrease in patients with CH-C from the mildest stage F1 onward. CONCLUSIONS/SIGNIFICANCE: The decrease in serum VLDL-TG levels was attenuated by increase in non-VLDL-TG levels in patients with non-cirrhotic CH-C, resulting in comparable total TG levels. Results of previous studies though variable, were confirmed to have a logical basis. The decrease in the serum VLDL-TG/non-VLDL-TG ratio as early as stage F1 demonstrated TG metabolic alterations in early stages of CH-C for the first time. The involvement of TG metabolism in CH-C pathogenesis has been established in experimental animals, while conventional TG measurements are generally considered as poor indicators of CH-C progression in clinical practice. The serum VLDL-TG/non-VLDL-TG ratio, which focuses on TG metabolic alterations, may be an early indicator of CH-C.