Overall response of both intrahepatic tumor and portal vein tumor thrombosis is a good prognostic factor for hepatocellular carcinoma patients receiving concurrent chemoradiotherapy

This study investigated the prognostic significance of portal vein tumor thrombosis (PVTT) response in hepatocellular carcinoma (HCC) patients treated with localized concurrent chemoradiotherapy (CCRT). We retrospectively analyzed 100 patients treated with CCRT for UICC Stage T2–4N0M0 HCC with PVTT between 2002 and 2011. The radiotherapy (RT) volume included both primary tumor and PVTT, and the median radiation dose was 45 Gy. Treatment response was evaluated for up to 6 months after RT. With respect to PVTT response to treatment, complete response (CR) and partial response (PR) were achieved in 14% and 48% of patients, respectively, yielding an objective response (OR) rate of 62%. PVTT size (≤3cm diameter) was associated with a higher rate of a CR (P = 0.001). The median overall survival (OS) was 11.6 months. Independent prognostic factors for OS were OR of the tumor to RT and a CR of the PVTT. Achieving an OR in both the tumor and the PVTT demonstrated a significant correlation with improved survival (P = 0.002). Progression of intrahepatic metastasis was affected not by CCRT but by the clinical features of the PVTT, particularly the initial PVTT site. PVTT response following CCRT seems prognostically significant. CR of the PVTT was associated with improved survival. Achieving an OR in both the tumor and PVTT was also associated with improved survival.     

The effects of Di-2-ethylhexyl phthalates (DEHP) on the cell cycle of the endometrial cancer cell lines (ECC-1)

In this study, we evaluated the effects of Di-(2-ethyhexyl) phthalates (DEHP) on cell cycle. We cultured human endometiral cancer cell lines (ECC-1) and then incubated them for 48 h with 50 μM of DEHP. We perfomed the microarray, the quantitative real-time polymerase chain reaction (qRT-PCR) and the FACS analysis. On microarray results, genes associated with functional classification of cell cycle, oocyst meiosis and progesterone mediated oocyte maturation showed significant changes. Among those changed genes, CCNB1 and CCNB2 are involved in the progesterone-mediated oocyte maturation, and CDC2 (CDK1) involved in the oocyte meiosis. The apoptosis and necrosis were both increased at a concentration of DEHP of < 50 μM, but the apoptosis was decreased at a concentration of DEHP of >100 μM. In conclusion, our results indicate that endometriosis and endometrial cancer, abnormal ovulation might occur after DEHP exposure.     

Synthesis of [11C]Bexarotene by Cu-Mediated [11C]Carbon Dioxide Fixation and Preliminary PET Imaging

相似文献   

Phospholipase D1 inhibition sensitizes glioblastoma to temozolomide and suppresses its tumorigenicity

Resistance of glioblastoma to the chemotherapeutic compound temozolomide is associated with the presence of glioblastoma stem cells in glioblastoma and is a key obstacle for the poor prognosis of glioblastoma. Here, we show that phospholipase D1 is elevated in CD44^High glioblastoma stem cells and in glioblastoma, especially recurring glioblastoma. Phospholipase D1 elevation positively correlated with the level of CD44 and poor prognosis in glioblastoma patients. Temozolomide significantly upregulated the expression of phospholipase D1 in the low and moderate CD44 populations of glioblastoma stem cells, but not in the CD44^High population in which phospholipase D1 is highly expressed. Phospholipase D1 conferred resistance to temozolomide in CD44^High glioblastoma stem cells and increased their self-renewal capacity and maintenance. Phospholipase D1 expression significantly correlated with levels of temozolomide resistance factors, which were suppressed by microRNA-320a and -4496 induced by phospholipase D1 inhibition. Genetic and pharmacological targeting of phospholipase D1 attenuated glioblastoma stem cell-derived intracranial tumors of glioblastoma using the microRNAs, and improved survival. Treatment solely with temozolomide produced no benefits on the glioblastoma, whereas in combination, phospholipase D1 inhibition sensitized glioblastoma stem cells to temozolomide and reduced glioblastoma tumorigenesis. Together, these findings indicate that phospholipase D1 inhibition might overcome resistance to temozolomide and represents a potential treatment strategy for glioblastoma. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.     

POLD1 variants leading to reduced polymerase activity can cause hearing loss without syndromic features

DNA polymerase δ, whose catalytic subunit is encoded by POLD1, is responsible for synthesizing the lagging strand of DNA. Single heterozygous POLD1 mutations in domains with polymerase and exonuclease activities have been reported to cause syndromic deafness as a part of multisystem metabolic disorder or predisposition to cancer. However, the phenotypes of diverse combinations of POLD1 genotypes have not been elucidated in humans. We found that five members of a multiplex family segregating autosomal recessive nonsyndromic sensorineural hearing loss (NS‐SNHL) have revealed novel compound heterozygous POLD1 variants (p.Gly1100Arg and a presumptive null function variant, p.Ser197Hisfs*54). The recombinant p.Gly1100Arg polymerase δ showed a reduced polymerase activity by 30–40%, but exhibited normal exonuclease activity. The polymerase activity in cell extracts from the affected subject carrying the two POLD1 mutant alleles was about 33% of normal controls. We suggest that significantly decreased polymerase δ activity, but not a complete absence, with normal exonuclease activity could lead to NS‐SNHL.     

Altered mitochondrial metabolism in the insulin‐resistant heart

Obesity‐induced insulin resistance and type 2 diabetes mellitus can ultimately result in various complications, including diabetic cardiomyopathy. In this case, cardiac dysfunction is characterized by metabolic disturbances such as impaired glucose oxidation and an increased reliance on fatty acid (FA) oxidation. Mitochondrial dysfunction has often been associated with the altered metabolic function in the diabetic heart, and may result from FA‐induced lipotoxicity and uncoupling of oxidative phosphorylation. In this review, we address the metabolic changes in the diabetic heart, focusing on the loss of metabolic flexibility and cardiac mitochondrial function. We consider the alterations observed in mitochondrial substrate utilization, bioenergetics and dynamics, and highlight new areas of research which may improve our understanding of the cause and effect of cardiac mitochondrial dysfunction in diabetes. Finally, we explore how lifestyle (nutrition and exercise) and pharmacological interventions can prevent and treat metabolic and mitochondrial dysfunction in diabetes.     

Immunity against selected piscine flagellates

This discussion is on immune response to Amyloodinium ocellatum, Cryptobia salmositica, Trypanoplasma borreli and Trypanosoma carassii. Piscidin and histone-like proteins enhance innate resistance to Amyloodinium. Fish that are naturally resistant to Cryptobia and Trypanoplasma can be bred. Cryptobia resistance in charr is controlled by a dominant Mendelian locus and protection is via the Alternative Pathway of Complement Activation. Studies on Cryptobia-tolerant charr may lead to production of transgenic Cryptobia-tolerant salmon. Innate response to T. borreli is associated with NO in macrophages. Transferrin regulates resistance and carp have been bred for transferrin genotypes. Recovered fish are protected from homologous challenge, and complement fixing antibodies are crucial in protection. Studies on antigens in T. carassii may lead to a vaccine. There are two vaccines against cryptobiosis; a single dose of the attenuated vaccine protects salmonids. On challenge fish inoculated with the metalloprotease-DNA vaccine do not have the disease and they recover faster.