A novel PET scanner with semiconductor detectors may improve diagnostic accuracy in the metastatic survey of head and neck cancer patients

Objectives

Our research group developed new PET scanner with semiconductor detectors for high spatial resolution with low scatter noise. On head and neck cancer (HNC) surgery, FDG-PET may often provide false-positive findings in cervical node involvements. Accordingly, we assessed diagnostic accuracy using this new scanner in the HNC patients as compared with the conventional lutetium oxyorthosilicate (LSO) PET.

Methods

We prospectively studied FDG imaging in 35 HNC patients by both semiconductor PET and LSO-PET. At 60 min after ¹⁸F-FDG injection, two PET scans were obtained using both scanners consecutively and in random order. Two nuclear medicine specialists scored FDG abnormalities using 5 point scale system for receiver operating characteristic (ROC) curve analysis.

Results

63 suspected of metastatic or recurrent lesions were evaluated and correlated by the final confirmation by pathological findings or clinical courses (malignant 26/benign 37). Semiconductor PET showed sensitivity of 92.3 % (24/26), specificity of 51.4 % (19/37), and accuracy of 68.2 % (43/63), while LSO-PET showed sensitivity of 84.6 % (22/26), specificity of 16.2 %(6/37), and accuracy of 44.4 % (28/63), respectively. Especially, semiconductor PET accurately diagnosed as true negative in the 13 of 14 lesions only detected by LSO-PET. ROC analyses revealed the diagnostic superiority of semiconductor PET from location of- and area under curve particularly in the study of small (≤10 mm) lesions.

Conclusion

A new novel semiconductor PET scanner can increase diagnostic accuracy with reduction in false positive findings in the HNC patients mainly due to higher spatial resolution and lower noise than the LSO-PET. This new technology can lead to more accurate diagnosis and the more optimal therapeutic tactics in head and neck surgery.     

Promotion of Hair Growth by Rosmarinus officinalis Leaf Extract

Topical administration of Rosmarinus officinalis leaf extract (RO‐ext, 2 mg/day/mouse) improved hair regrowth in C57BL/6NCrSlc mice that experienced hair regrowth interruption induced by testosterone treatment. In addition, RO‐ext promoted hair growth in C3H/He mice that had their dorsal areas shaved. To investigate the antiandrogenic activity mechanism of RO‐ext, we focused on inhibition of testosterone 5α‐reductase, which is well recognized as one of the most effective strategies for the treatment of androgenic alopecia. RO‐ext showed inhibitory activity of 82.4% and 94.6% at 200 and 500 µg/mL, respectively. As an active constituent of 5α‐reductase inhibition, 12‐methoxycarnosic acid was identified with activity‐guided fractionation. In addition, the extract of R. officinalis and 12‐methoxycarnosic acid inhibited androgen‐dependent proliferation of LNCaP cells as 64.5% and 66.7% at 5 µg/mL and 5 μM, respectively. These results suggest that they inhibit the binding of dihydrotestosterone to androgen receptors. Consequently, RO‐ext is a promising crude drug for hair growth. Copyright © 2012 John Wiley & Sons, Ltd.     

Serum leptin and total dietary energy intake: the INTERLIPID Study

Purpose

It has been hypothesized that leptin-induced appetite suppression is impaired in obese individuals, but little human evidence is available documenting this. We investigated relations between serum leptin and total energy intake using INTERLIPID/INTERMAP data on Japanese–Americans in Hawaii and Japanese in Japan.

Methods

Serum leptin and nutrient intakes were examined by standardized methods in men and women aged 40–59 years from two population samples, one Japanese–American in Hawaii (88 men, 94 women), the other Japanese in central Japan (123 men, 111 women). Multiple linear regression analyses stratified by BMI category (<25 kg/m², 25–29.9 kg/m², and ≥30 kg/m²) with adjustment for possible confounders were used to examine the relation between log-leptin and total dietary energy intake.

Results

In multivariate regression analyses, in those with BMI < 25 kg/m² and in those with BMI between 25 and 29.9 kg/m², log-leptin was not significantly related to total dietary energy intake; in those with BMI ≥ 30 kg/m², it was significantly inversely related to total dietary energy intake (P = 0.029), independent of body weight and physical activity. Physical activity score was significantly positively related to total dietary energy intake only in participants with BMI < 25 kg/m² (P < 0.001).

Conclusion

Leptin was significantly inversely associated with dietary energy intake in obese persons, but not in overweight and normal-weight persons.     

Methylation of breast cancer susceptibility gene 1 (BRCA1) predicts recurrence in patients with curatively resected stage I non–small cell lung cancer

BACKGROUND:

Even after early detection and curative resection of early stage non–small cell lung cancer (NSCLC), a significant fraction of patients develop recurrent disease. Molecular biomarkers that can predict the risk of recurrence thus need to be identified to improve clinical outcomes.

METHODS:

Using the methylation‐specific polymerase chain reaction assay, promoter methylation of the breast cancer susceptibility gene 1 (BRCA1) was assessed in cancer tissues from 70 patients with curatively resected stage I NSCLC. The clinical relevance of BRCA1 methylation status was evaluated in terms of outcome of the disease.

RESULTS:

Methylation of the BRCA1 promoter was detected in 13 of 70 patients (18.6%). Multiple logistic regression analysis revealed that BRCA1 methylation was an independent risk factor for recurrence (P = .0197) and that patients with BRCA1 methylation demonstrated significantly poorer recurrence‐free survival compared to those without (P = .0139). Cox's proportional hazard regression analysis revealed that BRCA1 methylation was an independent risk factor for recurrence‐free survival (P = .0155).

CONCLUSIONS:

Methylated BRCA1 can be a potential biomarker that predicts the prognosis after curative resection of stage I NSCLC. Considering that BRCA1 plays a role in chemotherapy‐induced apoptosis, it is plausible that identification of methylated BRCA1 could provide information that is clinically relevant to tailored adjuvant therapy. Cancer 2013. © 2013 American Cancer Society.     

Estrogen receptor‐β gene polymorphism and colorectal cancer risk: Effect modified by body mass index and isoflavone intake

Estrogen receptor (ER)‐β signaling has generally been implicated in protection against colorectal cancer. The ER‐β gene cytosine‐adenine (ESR2 CA) repeat polymorphism was reported to be associated with colorectal cancer, although showing contradicting results probably caused by ethnicity or age distribution of the subjects. We investigated the association between this polymorphism and the colorectal cancer risk in a community‐based case‐control study in Japan (685 cases/778 controls), including only subjects younger than 75. The effect modifications of the body mass index (BMI) and isoflavone intake were also examined. ESR2 CA repeat polymorphism was determined by polymerase chain reaction using fluorescein‐labeled primers. CA repeat alleles were classified into short (S) allele (<22 repeats) and long (L) allele (≥22 repeats). Subjects were divided into three genotype groups (SS/SL/LL). The risk of colon cancer, but not of rectal cancer, was increased with an increasing number of L alleles among postmenopausal women; age‐adjusted odds ratio (OR) for SL and LL genotypes compared with the SS genotype were 1.78 and 2.91, respectively (trend p = 0.002). Increased risks of colon cancer associated with the L allele were more evident among postmenopausal women with low BMI (<25 kg m^?2) or with high isoflavone intake. Such associations were not observed among men or premenopausal women. Having longer ESR2 CA repeat increases colon cancer risk among postmenopausal women younger than 75, possibly with modification of BMI and isoflavone intake. Aging and estrogenic condition may be important in the colon cancer pathogenesis associated with ESR2 CA repeat polymorphism.     

Metabolomic profiling reveals novel biomarkers of alcohol intake and alcohol-induced liver injury in community-dwelling men

ObjectiveMetabolomics is a promising approach to the identification of biomarkers in plasma. Here, we performed a population-based, cross-sectional study to identify potential biomarkers of alcohol intake and alcohol-induced liver injury by metabolomic profiling using capillary electrophoresis-mass spectrometry (CE-MS).MethodsFasting plasma samples were collected from 896 Japanese men who participated in the baseline survey of the Tsuruoka Metabolomics Cohort Study, and 115 polar metabolites were identified and absolutely quantified by CE-MS. Information on daily ethanol intake was collected through a standardized, self-administered questionnaire. The associations between ethanol intake and plasma concentration of metabolites were examined. Relationships between metabolite concentrations or their ratios and serum liver enzyme levels in the highest ethanol intake group (>46.0 g/day) were then examined by linear regression analysis. Replication analysis was conducted in 193 samples collected from independent population of this cohort.ResultsNineteen metabolites were identified to have an association with daily alcohol consumption both in the original and replication population. Three of these metabolites (threonine, glutamine, and guanidinosuccinate) were found to associate well with elevated levels of serum liver enzymes in the highest ethanol intake group, but not in the non-drinker group. We also found that the glutamate/glutamine ratio had a much stronger relation to serum γ-glutamyltransferase, aspartate transaminase, and alanine transaminase than glutamate or glutamine alone (standardized beta = 0.678, 0.558, 0.498, respectively).ConclusionsWe found 19 metabolites associated with alcohol intake, and three biomarker candidates (threonine, guanidinosuccinate and glutamine) of alcohol-induced liver injury. Glutamate/glutamine ratio might also be good biomarker.

Electronic supplementary material

The online version of this article (doi:10.1007/s12199-015-0494-y) contains supplementary material, which is available to authorized users.     

Effect of bruxism-like activity on the salivary Chromogranin A as a stress marker

Summary  The aim of this study was to determine whether measuring salivary chromogranin A (CgA) is useful in assessing individual stress levels and whether bruxism-like activity influences the salivary CgA level. From 44 adult healthy volunteers, we collected saliva samples with and without a stress condition (loud unpleasant sound). We assayed salivary samples with an ELISA to determine the content of CgA. We investigated also the effect of bruxism-like activity on salivary CgA production during stress. There were three patterns (group A, B, C) of response to the stressor on salivary CgA. They showed different responses and different effects of bruxism-like activity. This study shows the possibility of evaluating stress levels of individuals by measuring salivary CgA. Salivary CgA responds to psychosomatic stress. Bruxism-like activity prevented a stress-induced increase of salivary CgA in group A and B (75% of subjects), suggested that the reaction of the sympathetic-adrenomedullary system is regulated by the bruxism-like activity of the masticatory organ. The effect of bruxism-like activity in group C (high baseline of salivary CgA) was different from the effect in group A and B. Correspondence: S. Sato, Dept. of Craniofacial Growth Development Dentistry, Division Orthodontics, Kanagawa Dental College, 82 Inaoka-cho, Yokosuka, 238-8580 Japan     

The involvement of bradykinin in adrenaline-induced pulmonary edema in rats

We investigated the effect of endogenous bradykinin on adrenaline-induced pulmonary edema (PE) by blocking bradykinin receptors. In preliminary experiments, a bolus injection of adrenaline (ADR; 10 microg/kg) solution (10 microg/ml) was determined to be an edematogenic dose for inducing PE. The lung body weight index (LBI) and incidence of PE (IPE) were determined. The IPE and LBI of the group pretreated with Des-Arg9-[Leu8]-Bradykinin (DA-BK, 50 microg/kg, 50 microg/ml) increased significantly compared with those of the control group (p<0.05). On the other hand, there were no remarkable changes in IPE and LBI in the groups pretreated with Hoe140 (D-Arginyl-[Hyp3, Thi5, D-Tic7, Oic8]-Bradykinin (100 microg/kg, 100 microg/ml), captopril (20 mg/kg, 20 mg/ml) or L-NAME (1 mg/kg, 1 mg/ml). Moreover, the IPE and LBI of the group co-treated with L-NAME and DA-BK decreased compared with the DA-BK group (p<0.05). Thus, bradykinin aggravates adrenaline-induced PE through activation of the B2 receptor by the kallikreins as a result of the ADR administration, although the precise mechanism is not known.