Biomedical subjects

D Hodzic

Publications and source records attributed to D Hodzic.

7 recordsLinked to original sources

PubMed2000

[The IGF system: summary and recent data].

We are entitled to state that our knowledge about the IGF system has literally exploded in the last years. Having been considered for some time merely as trophic and mitogenic factors, the IGFs now appear as molecules essential for the differentiation of many cell types, and even more so, as powerful protective agents for the nervous and the cardiovascular systems. However, these properties so beneficial in normal physiological conditions, are subverted by the cancerous cells who use them to extend their life span and resist therapy. The IGFs did not live up to expectations in the treatment of diabetes; however, today their capacity to improve the condition of patients suffering from severe neurological, renal or muscle diseases is tested. The IGF system might also be targetted by the anticancer treatments. In the following paper we have briefly summarized our knowledge on the IGF system, and presented in more detail the recent data.

Apoptosis↗

PubMed1999

Cloning of breakpoints in and downstream the IGF2 gene that are associated with overexpression of IGF2 transcripts in colorectal tumours.

The human IGF2 gene belongs to a group of imprinted genes clustered on the short arm of chromosome 11, band p15.5. It contains 9 exons and spans over 30 kb. IGF2 mRNA overexpression has been reported in human tumours and in some inherited growth disorders. It was recently demonstrated that IGF2 mRNA overexpression contributes to tumour progression and that loss of parental imprinting as well as altered transcription factors are contributing to this overexpression. We have reported structural alterations in the 3' region of the IGF2 gene in two colorectal tumours that overexpressed the IGF2 transcript by 200- and 800-fold. We cloned by the vectorette-PCR strategy, genomic DNA fragments containing the breakpoints from these tumours. The sequencing of these fragments positioned the breakpoint 2 kb downstream the IGF2 gene in one tumour, and in exon 9 in the second. Both breakpoints occurred in regions containing repetitive elements: a TGGA repeat we have identified downstream the gene, and the (CA)n repetition in exon 9. We hypothesize that a negative regulatory element, located downstream the IGF2 gene, has been deleted following these structural alterations and leads to IGF2 gene overexpression.

Chromosome Aberrations↗

PubMed1999

A new cis element is involved in the HER2 gene overexpression in human breast cancer cells.

The HER2 proto-oncogene product is overexpressed in 30% of breast cancers, and this correlates with poor prognosis. Increased levels of HER2 mRNA in breast cancer cell lines result from increased gene transcription. We report the identification of a new 17-bp-long cis sequence located between positions -506 and -489 from the transcription start site. This sequence is recognized by a trans-activating factor that we tentatively named HER2 transcription factor (HTF). This factor, involved in the increased transcription of the HER2 gene in the BT-474 mammary tumor cells, has a molecular weight of about Mr 50,000. HTF can also bind, but with a lower affinity, to a related cis sequence present in the epidermal growth factor receptor promoter. Interestingly, the HTF binding activity is high in nuclear extracts from several mammary tumor cells overexpressing the HER2 gene.

Base Sequence↗

PubMed1997

Characterization of the IGF system and analysis of the possible molecular mechanisms leading to IGF-II overexpression in a mesothelioma.

The expression of members of the IGF system in a mesothelioma from a patient suffering from hypoglycemia, in term placenta and HT29 colon adenocarcinoma cells were compared. Very high levels of IGF-II mRNA and protein were detected in the mesothelioma. Moreover, half of the IGF-II protein took the high-molecular-weight form. We also analyzed the parental imprinting status and the promoter usage of the IGF-II gene. Our results showed loss of imprinting (LOI) in the mesothelioma while the imprinting was maintained in HT29 cells, expressing moderate levels of the transcript. Promoter P4 was active in the three tissues we analyzed, whereas IGF-II mRNA transcription from promoter P3 was only detected in the mesothelioma and the placenta, expressing comparably high levels of the transcript. IGF-II gene structure was identical in the analyzed tissues and cells. The type-I receptor mRNA expression was very low in the tumor. IGFBP-2, -4 and -5 mRNAs were detected in the mesothelioma, while IGFBP-2, -3 and -5 transcripts were detected in the placenta. IGFBP-1 and -6 transcripts were not detected.

Aged↗

PubMed1996

Possible influence of expatriation on perinatal outcome.

BACKGROUND: In order to test the hypothesis of possible influence of environmental stress on the length of gestation the data on deliveries in the Maternity Unit, Zagreb University School of Medicine in three six months periods; May-October 1991 (active war in Croatia), May-October 1990 (pre-war period), and the same period in 1992 are analysed. METHODS: Deliveries of 7845 women from free areas of Croatia (non-displaced population) and deliveries from 712 women from occupied areas of Croatia, as well of 593 Croatian refugees from Bosnia and Herzegovina and Serbia (expatriated population) were compared. The duration of pregnancy, fetal weight, immediate neonatal condition, mode of delivery and perinatal outcome in non-displaced and expatriated population were compared using chi-square test in statistical analysis. RESULTS: During 1992 and 1991, there was a slight increase in total number of deliveries in comparison to 1990. The number of deliveries by displaced women more than doubled. The incidence of major pregnancy complications was almost the same for both groups in all three time periods. The two populations were comparable regarding their age, parity and previous obstetric history. Slight increase in preterm delivery rate (7.7% in l990, 8.7% in 1991 and 9.4% in 1992), and a subsequent slight decrease in birth weight was found in all women. There was no significant change in the proportion of growth-retarded newborns. Expatriated women both in 1990 and in 1991 delivered twice as often prematurely in comparison to non-displaced women (17.5% and l4.3% deliveries), respectively. Birth weight of their infants was significantly more often under 2500 grams. Slight increase in overall perinatal mortality was observed. Perinatal mortality in the experiated population was significantly higher than in the non-displaced population. Increase in perinatal mortality could be attributed exclusively to increase in prematurity rate. CONCLUSION: Our results support the concept of possible influence of stress, fear, exile and inadequate antenatal surveillance on the length of gestation.

Analysis of Variance↗

PubMed1994

Antenatal fetal demise in multiple gestation--the outcome of surviving fetus at one to four years of age.

The outcome of 26 multifetal pregnancies with single fetal demise after 12 weeks of pregnancy cared for at the University Medical School of Zagreb from 1986 to 1991 is presented. Growth retardation of dead and surviving infant and pathohistological findings consistent with reduced uterine blood flow to cotyledonary space was the most frequent complication, irrespective of the type of placentation. Perinatal infection was the most frequent neonatal complication. Neonatal asphyxia was observed in only one infant. The outcome at 1-4 years of age was perfect in 14 out of 15 surviving infants for whom data are available. An early diagnosis of multifetal pregnancy, based essentially on ultrasonography and appropriate monitoring of the mother and the survivor, with cesarean delivery carried out at first signs of imminent asphyxia, is the best guarantee for a favorable outcome.

Asphyxia Neonatorum↗

PubMedDate not supplied

IGF-II in primary human colorectal tumors: peptide level, activated promoters, parental imprinting and gene rearrangement.

IGF-II is a polypeptide growth factor with growth and differentiation promoting activities, involved in human development. We have reported previously IGF-II mRNA and peptide overexpression in primary human colon cancers. Here we show that the IGF-II peptide content is increased in six primary colon cancers compared to the corresponding healthy tissues. The IGF-II transcripts in healthy and cancerous colon tissues were identified by Northern blotting and RT-PCR. Promoters P3 and P4 were active in most tissues. Relaxation of parental imprinting was observed in two tumors and one healthy tissue, without any correlation with the IGF-II transcript levels. Rearrangements of the IGF-II gene in two tumors containing very high amounts of IGF-II mRNA are described. Fragments containing the breakpoints were cloned by the vectorette-PCR strategy. In both tumors, the breakpoints occurred in repetitive sequences. In one tumor (T11), the breakpoint was localized 2 kb downstream the end of exon 9. The second tumor (T18) contains two modified alleles. In one rearranged allele the breakpoint is located in exon 9. The exact position of the breakpoint in the second rearranged allele has not been identified. In future experiments, the correlation between the gene rearrangements and IGF-II mRNA overexpression will be studied.

Adenocarcinoma↗