Cytotoxicity of 15-Deoxy-��12,14-prostaglandin J2 through PPAR��-independent Pathway and the Involvement of the JNK and Akt Pathway in Renal Cell Carcinoma

Introduction: Agonists of peroxisome proliferator-activated receptor gamma (PPARγ) have been examined as chemopreventive and chemotherapeutic agents. The aim was to investigate the cytotoxicity and action mechanisms of 15-deoxy-Δ^12,14-prostaglandin J₂ (15d-PGJ₂), one of endogenous ligands for PPARγ, in terms of PPARγ-dependency and the mitogen-activated protein kinase (MAPK) and Akt pathway in three human renal cell carcinoma (RCC)-derived cell lines.Methods: 786-O, Caki-2 and ACHN cells were used as human RCC-derived cell lines. Cell viability and caspase-3 activity was detected by fluorescent reagents, and chromatin-condensation was observed with a brightfield fluorescent microscope after staining cells with Hoechst33342. The expression levels of proteins were detected by Western blot analysis.Results: 15d-PGJ₂ showed cytotoxicity in dose-dependent manner. 15d-PGJ₂ induced chromatin-condensation and elevated caspase-3 activity, and the cell viability was restored by co-treatment with a pan-caspase inhibitor, Z-VAD-FMK, indicating the involvement of caspase-dependent apoptosis. The cytotoxicity was not impaired by a PPARγ inhibitor, GW9662, suggesting that 15d-PGJ₂ exerted the cytotoxicity in a PPARγ-independent manner. Some antioxidants rescued cells from cell death induced by 15d-PGJ₂, but some did not, suggesting that reactive oxygen species (ROS) did not contribute to the apoptosis. 15d-PGJ₂ also increased the expression levels of phospho-c-Jun N terminal kinase (JNK) in Caki-2 cells, and decreased those of phospho-Akt in 786-O cells, indicating that the JNK MAPK and the Akt pathways participated in the anticancer effects of 15d-PGJ₂ in some cell lines.Conclusion: 15d-PGJ₂ exerted cytotoxic effects accompanying caspase-dependent apoptosis, and this effect was elicited in a PPARγ-independent manner in three cell lines. In addition, the JNK MAPK and Akt pathway was involved in the cytotoxicity of 15d-PGJ₂ to some extent in some cell line. Therefore, our study showed the 15d-PGJ₂ to potentially be an interesting approach for RCC treatment.     

Fetal facial expressions in small-for-gestational-age and growth-restricted fetuses

Objective: To evaluate the frequencies of fetal facial expressions among appropriate-for-gestational-age (AGA), small-for-gestational-age (SGA), and growth-restricted (FGR) fetuses.

Methods: Four-dimensional (4D) ultrasound was used to examine the facial expressions of 50 AGA, 25 SGA, and six FGR fetuses between 28 and 35 weeks of gestation. The frequencies of seven facial expressions during 15-minute recordings were assessed. Comparison of facial expressions among the three groups was performed.

Results: Mouthing was the commonest facial expression at 28–35 weeks, and the frequency of mouthing was significantly higher than those of the other six facial expressions in AGA fetuses. Mouthing was the most frequent facial expression, but there was no significant difference in the frequency among mouthing, smiling and blinking in SGA fetuses. Moreover, mouthing displayed a significantly higher frequency than the other facial expressions, except for yawning, smiling, and blinking in FGR fetuses. However, there was no significant difference in the frequency of each facial expression among the three groups.

Conclusions: Our results suggest that the frequencies of fetal facial expressions are not decreased in either SGA or FGR pregnancies. The absence of a decrease in the frequency of each fetal expression in FGR fetuses may be due to increased brain blood flow because of the brain-sparing effect. Moreover, accelerated maturation and development of the brain function, especially the central dopamine system, might be suspected in SGA and FGR fetuses.     

Enamel remineralization effect of a dentifrice containing calcium sodium phosphosilicate: an optical coherence tomography observation

Objective: The purpose of this study was to examine the effects of a dentifrice containing 5% calcium sodium phosphosilicate (CSP) on the remineralization of the enamel using optical coherence tomography (OCT).

Materials and methods: Bovine incisors were sliced and shaped in a rectangular form. One group of five specimens was treated with undersaturated 0.1 M lactic acid buffer solution (pH 4.75) for 10?min and then placed in artificial saliva (pH 7.0) (De group). Other specimens were stored in solutions of toothpaste containing CSP for 10?min, followed by 10-min immersion in the lactic acid buffer solution twice a day before storage in artificial saliva (CSP group). An additional group was stored in only artificial saliva (control group). OCT imaging on the selected location of the enamel surface was performed. The peak intensity and width at 1/e² were recorded in each of the six areas on the sample and averaged, and the sample size of each group was six. The integrated value in units (dB?×?μm) was calculated in the area of peak intensity. The data for each group was subjected to one-way repeated-measures ANOVA and Tukey HSD tests (α?=?0.05).

Results: The changes in integrated values of each group were different. A slight but significant increase in the integrated value was observed in the control group, whereas a slight but significant decrease in the value was observed the De group. Integrated values increased in the CSP group.

Conclusions: Remineralization occurred upon immersion in the toothpaste containing CSP.     

The natural history of radiographically occult bronchogenic squamous cell carcinoma: a retrospective study of overdiagnosis bias

OBJECTIVE: An overdiagnosis bias occurs with the diagnosis of a disease that does not produce signs or symptoms before the patient dies from other causes. We sought to determine whether overdiagnosis bias is a factor when screening for squamous cell carcinoma of the lung. DESIGN: Retrospective study of the Miyagi Population-Based Lung Cancer Screening Registry for high-risk patients who were seen between January 1, 1982 (when sputum cytology tests were added for men with long smoking histories), and December 31, 1996. SETTING: Miyagi Prefecture, Japan. PATIENTS: A total of 251 patients (all men) who had sputum cytology test results that were positive for squamous cell carcinoma but had normal radiograph findings, 44 of whom declined cancer treatment (mean age, 70 years) and 207 of whom were treated with resection within 12 weeks of diagnosis (mean age, 65.5 year). END POINTS: Five-year and 10-year survival rates from primary lung cancer in both groups as of August 15, 2001. RESULTS: Among the 44 untreated patients, 15 (34%) remained asymptomatic. The survival rate due to primary lung cancer death in the untreated group was 53.2% at 5 years and 33.5% at 10 years. The survival rate among treated patients was 96.7% at 5 years and 94.9% at 10 years. Of the 125 treated patients who died, 14 (11.2%) died from primary lung cancer. CONCLUSION: Given that the two thirds of the untreated patients with squamous cell carcinoma of the bronchus died from lung cancer within 10 years, overdiagnosis bias does not appear to be a factor in screening for this disease. Thus, we recommend that patients with radiographically occult squamous cell carcinoma of the bronchus undergo tumor treatment after localization.     

Genotypes at chromosome 22q12-13 are associated with HIV-1-exposed but uninfected status in Italians

OBJECTIVE: Despite multiple and repeated exposures to HIV-1, some individuals possess no detectable HIV genome and show T-cell memory responses to the viral antigens. HIV-1-reactive mucosal IgA detected in such uninfected individuals suggests their possible immune resistance against HIV. We tested if the above HIV-1-exposed but uninfected status was associated with genetic markers other than a homozygous deletion of the CCR5 gene. METHODS: Based on our mapping in chromosome 15 of a gene controlling the production of neutralizing antibodies in a mouse retrovirus infection, we genotyped 42 HIV-1-exposed but uninfected Italians at polymorphic loci in the syntenic segment of human chromosome 22, and compared them with 49 HIV-1-infected and 47 uninfected healthy control individuals by a closed testing procedure. RESULTS: A significant association was found between chromosome 22q12-13 genotypes and a putative dominant locus conferring anti-HIV-1 immune responses in the exposed but uninfected individuals. Distributions of linkage disequilibrium across chromosome 22 also differed between the exposed but uninfected and two other phenotypic groups. CONCLUSIONS: The data indicated the presence of a new genetic factor associated with the HIV-1-exposed but uninfected status.     

Prenatal diagnosis of funisitis: two case reports

Acute funisitis is characterized by the infiltration of fetal neutrophils from the umbilical vessels into Wharton’s jelly and presents as fetal inflammation. However, no reports about its prenatal diagnosis using ultrasonography have been published. We encountered one case of oligohydramnios at 26 weeks and another case of threatened premature delivery at 27 weeks of gestation with ultrasonographic findings of non-uniform thickening of Wharton’s jelly, a heterogeneous internal echo, and a high echoic line of the umbilical vessel wall. Acute funisitis was diagnosed, and the postpartum histopathological examination revealed severe funisitis in both cases. To our knowledge, this is the first case report of prenatal diagnosis of funisitis determined using ultrasonography. When we find such ultrasonographic features under the circumstances of intrauterine infection, severe funisitis should be included in the differential diagnosis.     

Hierarchical CdMoO4 nanowire–graphene composite for photocatalytic hydrogen generation under natural sunlight

Herein, a facile in situ solvothermal technique for the synthesis of a CdMoO₄/graphene composite photocatalyst is reported. Graphene oxide (GO) was synthesised by an improved Hummers'' method and was further used for the in situ synthesis of graphene via GO reduction and the formation of a CdMoO₄ nanowire/graphene composite. The structural phase formation of tetragonal CdMoO₄ was confirmed from X-ray diffraction measurements. The small nanoparticle assembled nanowires, prismatic microsphere morphology and crystalline nature of the synthesized material were investigated using field emission scanning electron microscopy (FESEM) and transmission electron microscopy (TEM). Due to its unique morphology and stability, the CdMoO₄/graphene composite was used as a photocatalyst for H₂O splitting. In comparison to pristine CdMoO₄, the CdMoO₄/graphene composite showed the best hydrogen evolution rate, i.e. 3624 μmole h⁻¹ g⁻¹, with an apparent quantum yield of 30.5%. The CdMoO₄/graphene composite has a higher photocatalytic activity due to the inhibition of charge carrier recombination. H₂ production measurements showed that the ternary semiconductor/graphene composite has enhanced photocatalytic activity for H₂ generation.

Herein, a facile in situ solvothermal technique for the synthesis of a CdMoO₄/graphene composite photocatalyst for hydrogen generation under natural solar light.     

Whole-pelvic volumetric-modulated arc therapy for high-risk prostate cancer: treatment planning and acute toxicity

The objectives of this study were to evaluate dosimetric quality and acute toxicity of volumetric-modulated arc therapy (VMAT) and daily image guidance in high-risk prostate cancer patients. A total of 100 consecutive high-risk prostate cancer patients treated with definitive VMAT with prophylactic whole-pelvic radiotherapy (WPRT) were enrolled. All patients were treated with a double-arc VMAT plan delivering 52 Gy to the prostate planning target volume (PTV), while simultaneously delivering 46.8 Gy to the pelvic nodal PTV in 26 fractions, followed by a single-arc VMAT plan delivering 26 Gy to the prostate PTV in 13 fractions. Image-guided RT was performed with daily cone-beam computed tomography. Dose–volume parameters for the PTV and the organs at risk (OARs), total number of monitor units (MUs) and treatment time were evaluated. Acute toxicity was assessed using the Common Terminology Criteria for Adverse Events, version 4.0. All dosimetric parameters met the present plan acceptance criteria. Mean MU and treatment time were 471 and 146 s for double-arc VMAT, respectively, and were 520 and 76 s for single-arc VMAT, respectively. No Grade 3 or higher acute toxicity was reported. Acute Grade 2 proctitis, diarrhea, and genitourinary toxicity occurred in 12 patients (12%), 6 patients (6%) and 13 patients (13%), respectively. The present study demonstrated that VMAT for WPRT in prostate cancer results in favorable PTV coverage and OAR sparing with short treatment time and an acceptable rate of acute toxicity. These findings support the use of VMAT for delivering WPRT to high-risk prostate cancer patients.