Oncoprotective Effects of Short-Chain Fatty Acids on Uterine Cervical Neoplasia.

Short-chain fatty acids (SCFAs) produced by fermentation from prebiotics not only provide energy but also activate cell membrane receptors, thereby contributing to the maintenance of homeostasis in the human body. Recently, free fatty acid receptor 2 (FFAR2), which uses SCFAs as ligands, was found to exert oncoprotective effects on several types of neoplasia. This study examined whether SCFAs have oncoprotective effects on uterine cervical neoplasia. Immunohistochemical analysis revealed that FFAR2 was expressed in atypical cells and cancer cells of cervical neoplasia. Moreover, reverse transcription polymerase chain reaction showed that FFAR2 was expressed in a human cervical cancer cell line, HeLa. We also found that SCFAs inhibited the proliferation of HeLa cells, and a FFAR2 antagonist, GLPG0974, used to suppress the binding of SCFAs significantly restored the cell viability of HeLa cells blocked by acetic acid treatment. These results suggest that ingestion of prebiotics and the resulting production of SCFAs may play an oncoprotective role against uterine cervical neoplasia via FFAR2 expression.

Comparison between placental gene expression of 11ß-hydroxysteroid dehydrogenases and infantile growth at 10 months of age.

AIM: The local expression of two isoenzymes of 11ß-hydroxysteroid dehydrogenase, type 1 (11ßHSD-1) and type 2 (11ßHSD-2), regulates the access of glucocorticoid hormones to their target cells. Reports on the association between the placental expression of 11ßHSD and infantile growth are limited. The aim of the present study was to investigate if the placental gene expression of 11ßHSD affects infantile growth at 10 months of age. METHODS: Placentas and umbilical venous cord blood were obtained from 42 singleton cases of cesarean deliveries between 31 and 40 weeks of gestation at Hamamatsu University Hospital between March 2009 and June 2010. The gene expression of both 11ßHSD-1 and 11ßHSD-2 was measured by quantitative reverse transcription polymerase chain reaction. Adiponectin and leptin levels in umbilical cord blood were measured using enzyme-linked immunoassay. RESULTS: 11ßHSD-1 and 11ßHSD-2 gene expression in human placentas did not correlate with bodyweight or the ponderal index (PI) at 10 months of age, whereas the gene expression of 11ßHSD-1, but not 11ßHSD-2, correlated with birthweight as well as PI at birth. Adiponectin levels in umbilical cord blood significantly correlated with the placental gene expression of 11ßHSD-1 as well as bodyweight and PI at 10 months of age, although no direct correlation was observed between them. CONCLUSION: No direct correlation was observed between the placental gene expression of 11ßHSD and infantile growth at 10 months of age. However, the placental gene expression of 11ßHSD-1 may be indirectly connected with infantile growth via adiponectin-associated metabolic regulation represented by adiponectin levels in umbilical cord blood.

Zinc coproporphyrin I derived from meconium has an antitumor effect associated with singlet oxygen generation.

INTRODUCTION: Zinc coproporphyrin I (ZnCP-I) is a photosensitive molecule and a major component of meconium. Here, we examined the effects of ZnCP-I as a potential photosensitizer in photodynamic therapy for tumors. MATERIALS AND METHODS: (1) Aqueous ZnCP-I was irradiated with a pulsed YAG-SHG laser (wavelength: 532 nm)/YAG-SHG dye laser (wavelength: 566 nm). (2) HeLa cells were incubated in 200 mM ZnCP-I, and accumulation of ZnCP-I in HeLa cells was evaluated with ZnCP-I-specific fluorescence over 500 nm. (3) Aqueous ZnCP-I was administered intravenously to HeLa tumor-bearing mice at a dose of 10.2 mg/kg body weight. The tumors were irradiated with a filtered halogen lamp (wavelength: 580 nm) at 100 J/cm(2) 20 min after administration. RESULTS: (1) An intense near-infrared emission spectrum was observed at around 1,270 nm after irradiation. The emission intensity was proportional to the laser power between 10 and 80 mW and was completely inhibited by addition of NaN3, a singlet oxygen scavenger. (2) ZnCP-I-specific fluorescence was detected in the HeLa cell cytoplasm. (3) Irradiated tumors treated with ZnCP-I were mostly necrotized. CONCLUSION: ZnCP-I accumulated in tumor cells, produced singlet oxygen upon irradiation, and necrotized the tumor cells. These results suggest that ZnCP-I may be an effective photosensitizer.

Pulmonary Tumor Thrombotic Microangiopathy Caused by Metastatic Ovarian Cancer: An Antemortem Diagnosis with Pulmonary Aspiration Cytopathology.

A 48-year-old woman with advanced ovarian cancer was diagnosed with pulmonary tumor thrombotic microangiopathy (PTTM) by antemortem pulmonary wedge aspiration cytopathology. Despite the initiation of anti-cancer treatment, she unfortunately died due to progressive respiratory failure. Histopathology of the autopsied lung revealed multiple tumor embolization with fibrin-rich clot and fibro-cellular intimal proliferation at the pulmonary arteriole. The embolized tumor showed strong immune-positivity for pro-thrombotic and fibrotic factors (tissue factor and vascular endothelial growth factor), suggesting the underlying mechanisms of PTTM development. This case suggests that a quick antemortem diagnosis and the early induction of specific treatments might ensure a better prognosis of PTTM.

Partial silencing of fucosyltransferase 8 gene expression inhibits proliferation of Ishikawa cells, a cell line of endometrial cancer.

Endometrial cancer is the most common gynecologic malignancy and is associated with increased morbidity each year, including young people. However, its mechanisms of proliferation and progression are not fully elucidated. It is well known that abnormal glycosylation is involved in oncogenesis, and fucosylation is one of the most important types of glycosylation. In particular, fucosyltransferase 8 (FUT8) is the only FUT responsible for α1, 6-linked fucosylation (core fucosylation), and it is involved in various physiological as well as pathophysiological processes, including cancer biology. Therefore, we aimed to identify the expression of FUT8 in endometrial endometrioid carcinoma and investigate the effect of the partial silencing of the FUT8 gene on the cell proliferation of Ishikawa cells, an epithelial-like endometrial cancer cell line. Quantitative real-time PCR analysis showed that FUT8 gene expression was significantly elevated in the endometrial endometrioid carcinoma, compared to the normal endometrium. The immunostaining of FUT8 and Ulex europaeus Agglutinin 1 (UEA-1), a kind of lectin family specifically binding to fucose, was detected endometrial endometrioid carcinoma. The proliferation assay showed FUT8 partial knockdown by transfection of siRNA significantly suppressed the proliferation of Ishikawa cells, concomitant with the upregulation in the gene expressions associated with the interesting pathways associated with de-ubiquitination, aspirin trigger, mesenchymal-epithelial transition (MET) et al. It was suggested that the core fucosylation brought about by FUT8 might be involved in the proliferation of endometrial endometrioid carcinoma cells.

Antitumor effect of photodynamic therapy in mice using direct application of Photofrin dissolved in lidocaine jelly.

BACKGROUND/PURPOSE: Photodynamic therapy (PDT) is a non-invasive cancer therapy that has a strong antitumor effect with intravenous administration of Photofrin. However, Photofrin causes light hypersensitivity that impairs the quality of life (QOL) of patients, and thus an improved method of administration is needed. Here, we report the antitumor effect of local administration of Photofrin in combination with a vasodilator, lidocaine hydrochloride. METHOD: The antitumor effect was investigated in nude mice transplanted with HeLa cells. An incision was made near the tumor and Photofrin dissolved in lidocaine jelly was applied directly to the tumor. The tumor was irradiated at 100 J/cm(2) with a yttrium aluminum garnet (YAG)-dye laser (630 nm) at 2 h after the direct application and the tumor volume was measured for 30 days after PDT to investigate the antitumor effect. In some mice, the tumor was excised 24 h after PDT and the depth of necrosis was measured in the excised specimen. RESULT: The tumor was mostly necrotized by PDT following direct application of 10 mg/ml Photofrin dissolved in lidocaine jelly and the effect was greater than with direct application of Photofrin alone. The increase in tumor volume observed in control mice was significantly inhibited in mice that received PDT after direct application of Photofrin in lidocaine jelly. CONCLUSION: PDT using direct application of Photofrin in lidocaine jelly has a strong antitumor effect in mice and this approach may avoid the adverse effects of systemic Photofrin administration.

[A recurrent ovarian cancer patient who achieved a complete response following irinotecan plus CDDP therapy].

A 78-year-old patient had abdominal bloating since October 2002, and visited a GP, who noticed ascites, and referred the patient to our hospital. An exploratory laparotomy was performed and stage IIIc ovarian cancer was diagnosed. Six courses of docetaxel-carboplatin (DJ) chemotherapy were administered; however, the lesion was assessed as progressive disease (PD), and 24 courses of weekly paclitaxel were then administered. During the follow-up as an outpatient, a tumor marker increased again. Weekly paclitaxel was not effective this time, and the lesion was assessed as PD. The patient therefore received treatment with irinotecan and cisplatin (CPT-11+CDDP). These drugs have different mechanisms of action. The CA 125 level returned to normal following four courses of CPT-11+CDDP. The patient received a total of six courses, and thus far, no obvious recurrent lesion has been observed. These results suggest that CPT-11+CDDP may be effective against recurrent ovarian cancer, which is difficult to treat due to its resistance to platinum drugs and taxane drugs.