Parental rearing style as a predictor of attachment and psychosocial adjustment during young adulthood

Parental rearing-styles are crucial for psychosocial adjustment both during childhood and adulthood. The current study examined whether: (a) parental rearing-styles predicted psychosocial adjustment in young-adulthood, (b) this relationship was mediated by attachment styles , and ( c ) gender differences occur in these relationships. Two hundred and forty (103 male and 132 female) university students completed measures assessing parental rearing-style , current attachment style, romantic relationship satisfaction, friendship quality, self-esteem, and social competence. Multigroup structural equation modelling, conducted separately by gender, revealed that parental rearing-style predicted psychosocial adjustment during young-adulthood. Further, there was also evidence of gender differences and that self-models and other-models of attachment mediated this relationship. Together, these findings reinforce the importance of perceived parental rearing-style for subsequent psychosocial adjustment

Case Study: Lung transplantation for cystic fibrosis – A complex nutritional setting

No Abstrac

Newcastle disease virus degrades HIF-1a through proteasomal pathways independent of VHL and p53

Newcastle disease virus (NDV) is a candidate agent for oncolytic virotherapy. Despite its potential, the exact mechanism of its oncolysis is still not known. Recently, we reported that NDV exhibited an increased oncolytic activity in hypoxic cancer cells. These types of cells negatively affect therapeutic outcome by overexpressing pro-survival genes under the control of the hypoxia-inducible factor (HIF). HIF-1 is a heterodimeric transcriptional factor consisting of a regulated α (HIF-1α) and a constitutive β subunit (HIF-1β). To investigate the effects of NDV infection on HIF-1α in cancer cells, the osteosarcoma (Saos-2), breast carcinoma (MCF-7), colon carcinoma (HCT116) and fibrosarcoma (HT1080) cell lines were used in the present study. Data obtained showed that a velogenic NDV infection diminished hypoxia-induced HIF-1α accumulation, leading to a decreased activation of its downstream target gene, carbonic anhydrase 9. This NDV-induced downregulation of HIF-1α occurred post-translationally and was partially abrogated by proteasomal inhibition. The process appeared to be independent of the tumour suppressor protein p53. These data revealed a correlation between NDV infection and HIF-1α downregulation, which highlights NDV as a promising agent to eliminate hypoxic cancer cells

Bortezomib attenuates HIF-1- but not HIF-2-mediated transcriptional activation

Bortezomib is the first proteasomal inhibitor (PI) to be used therapeutically for treating relapse cases of multiple myeloma and mantle cell lymphoma. A proposed mechanism for its action is that it prevents the proteasomal degradation of proapoptotic proteins, leading to enhanced apoptosis. Although the α subunit of hypoxia‑inducible factor (HIF)‑1 is not degraded with bortezomib treatment, the heterodimeric HIF‑1 fails to transactivate target genes. HIF‑1 and HIF‑2 are related hypoxia‑inducible transcription factors that are important for the survival of hypoxic tumor cells. The majority of reports have focused on the effects of bortezomib on the transcriptional activities of HIF‑1, but not HIF‑2. The present study investigated the effects of bortezomib on HIF‑2 activity in cancer cells with different levels of HIF‑1α and HIF‑2α subunits. HIF‑α subunit levels were detected using specific antibodies, while HIF transcriptional activities were evaluated using immunodetection, reverse transcription‑polymerase chain reaction and luciferase reporter assay. Bortezomib treatment was found to suppress the transcription and expression of CA9, a HIF‑1‑specific target gene; however, it had minimal effects on EPO and GLUT‑1, which are target genes of both HIF‑1 and HIF‑2. These data suggest that bortezomib attenuates the transcriptional activity only of HIF‑1, and not HIF‑2. This novel finding on the lack of an inhibitory effect of bortezomib on HIF‑2 transcriptional activity has implications for the improvement of design and treatment modalities of bortezomib and other PI drugs

Baculoviruses as Vectors for Gene Therapy against Human Prostate Cancer

Current curative strategies for prostate cancer are restricted to the primary tumour, and the effect of treatments to control metastatic disease is not sustained. Therefore, the application of gene therapy to prostate cancer is an attractive alternative. Baculoviruses are highly restricted insect viruses, which can enter, but not replicate in mammalian cells. Baculoviruses can incorporate large amounts of extra genetic material, and will express transgenes in mammalian cells when under the control of a mammalian or strong viral promoter. Successful gene delivery has been achieved both in vitro and in vivo and into both dividing and nondividing cells, which is important since prostate cancers divide relatively slowly. In addition, the envelope protein gp64 is sufficiently mutable to allow targeted transduction of particular cell types. In this review, the advantages of using baculoviruses for prostate cancer gene therapy are explored, and the mechanisms of viral entry and transgene expression are described

Endocervical glandular neoplasia associated with lobular endocervical glandular hyperplasia is HPV-independent and correlates with carbonic anhydrase-IX expression: a Gynaecological Oncology Group Study.

BackgroundLobular endocervical glandular hyperplasia (LEGH) is a rare lesion of the uterine cervix. It has been proposed that LEGH may represent a precursor lesion to a group of mucinous adenocarcinoma with gastric phenotype (GA) that is independent of high-risk human papillomavirus (H-HPV) infection. Carbonic anhydrase-IX (CA-IX) is highly expressed in conventional glandular lesions (CGLs). However, expression of CA-IX in LEGH or GA has not been studied.MethodsIn all, 12 CGLs, 7 LEGHs, 6 LEGHs with coexisting adenocarcinoma in situ (AIS, 3) and GA (3) were identified from Japanese women with a cytological diagnosis of atypical glandular cells of undetermined significance. Immunostaining was used to detect CA-IX and p16(INK)4(a) (hereafter termed p16) protein expression in the tissues and CA-IX protein expression in the Papanicolaou smears (PSs). Polymerase chain reaction was used to detect H-HPV DNA in liquid-based cytology.ResultsOut of 12 (83%) CGLs, 10 were positive with H-HPV and high levels of CA-IX expression were seen in all (100%) cases. P16 protein expression was observed in 11 out of 12 (92%) cases. None of the LEGHs, LEGHs with AIS or GA were positive for H-HPV and only 8 out of 13 (62%) showed focal weak (1+) p16 expression. In contrast, all cases (100%) exhibited strong CA-IX protein expression.ConclusionOur study suggests that there are different molecular mechanisms of carcinogenesis resulting in CGLs vs LEGHs associated with AIS or GA. There is also a possible link between LEGHs and GAs. Furthermore, CA-IX expression may serve as a useful biomarker for the detection of GAs in the absence of H-HPV infection