Joško Lešin

Second trimester total human chorionic gonadotropin alpha-fetoprotein and unconjugated estriol in predicting pregnancy complications other than fetal aneuploidy.

OBJECTIVE To assess the value of alpha-fetoprotein (AFP), total human chorionic gonadotropin (ThCG) and unconjugated estriol in predicting certain complications of pregnancy other than fetal aneuploidy. STUDY DESIGN Among 2384 women that underwent biochemical screening between 15 and 22 weeks of gestation, pregnancy outcome was evaluated in 677 women under 35 years of age according to serum marker levels by using cut-off points discriminative for Down syndrome or neural tube defect (NTD). RESULTS High alpha-fetoprotein levels (MoM>/=2.0) were found to be significantly more frequent (P<0.05) in cases of fetal growth restriction (odds ratio=2.7), miscarriage (odds ratio=4.4) and intrauterine fetal death (odds ratio=5.8). High chorionic gonadotropin levels (MoM>/=2.02) were associated with intrauterine growth restriction (odds ratio=2.1; P<0.05), miscarriage (odds ratio=4; P<0.01), preterm birth (odds ratio=2.5; P<0.05), and intrauterine fetal death (odds ratio=4.2; P<0.01). Among pregnancies with intrauterine growth restriction and threatening preterm delivery, low unconjugated estriol levels (MoM</=0.74) were significantly more frequent (odds ratio=2.2; P<0.05 and odds ratio=2.6; P<0.01, respectively). CONCLUSION All three markers predictive for fetal trisomy 21 shown to be associated with various pregnancy complications in euploid pregnancies.

Onkogeni aspekti HPV-genitalnih infekcija kod žena

Genital human papillomavirus (HPV) infection is a most common sexually transmitted infection among women (Munoz et al., 2003). The immune system effectively repels most HPV infections, and is associated with strong localized cell mediated immune responses. However, approximately ten percent of individuals develop a persistent infection, with risk of development of high-grade precursor lesions and eventually invasive carcinoma (Stanley, 2006). The causal role of HPV in all cancers of the uterine cervix has been firmly established (zur Hausen, 1999; Walboomers et al., 1999; Bosch et al., 2008). Most cancers of the vulva and vagina are also induced by oncogenic HPV types. In precancerous lesions, most HPV genomes persist in an episomal state whereas, in many high-grade lesions and carcinomas, genomes are found integrated into the host chromosome. Two viral genes, E6 and E7, are invariably expressed in HPV-positive cancer cells. Their gene products are known to inactivate the major tumour suppressors, p53 and retinoblastoma protein (pRB), respectively. In addition, E6 oncoprotein is also capable to up regulate the expression of inhibitors of apoptosis, and E6 and E7 cooperate to effectively immortalise primary epithelial cells. Tumour formation is not an inevitable consequence of viral infection; it rather reflects the multi-step nature of oncogenesis where each step constitutes an independent (reversible or irreversible) genetic change that cumulatively contributes to deregulation of cell cycle, cell growth and survival.Genital human papillomavirus (HPV) infection is a most common sexually transmitted infection among women (Muñoz et al., 2003). The immune system effectively repels most HPV infections, and is associated with strong localized cell mediated immune responses. However, approximately ten percent of individuals develop a persistent infection, with risk of development of high-grade precursor lesions and eventually invasive carcinoma (Stanley, 2006). The causal role of HPV in all cancers of the uterine cervix has been firmly established (zur Hausen, 1999; Walboomers et al., 1999; Bosch et al., 2008). Most cancers of the vulva and vagina are also induced by oncogenic HPV types. In precancerous lesions, most HPV genomes persist in an episomal state whereas, in many high-grade lesions and carcinomas, genomes are found integrated into the host chromosome. Two viral genes, E6 and E7, are invariably expressed in HPV-positive cancer cells. Their gene products are known to inactivate the major tumour suppressors, p53 and retinoblastoma protein (pRB), respectively. In addition, E6 oncoprotein is also capable to up regulate the expression of inhibitors of apoptosis, and E6 and E7 cooperate to effectively immortalise primary epithelial cells. Tumour formation is not an inevitable consequence of viral infection; it rather reflects the multi-step nature of oncogenesis where each step constitutes an independent (reversible or irreversible) genetic change that cumulatively contributes to deregulation of cell cycle, cell growth and survival.