Interplay of DNA damage and cell cycle signaling at the level of human replication protein A.

Replication protein A (RPA) is the main human single-stranded DNA (ssDNA)-binding protein. It is essential for cellular DNA metabolism and has important functions in human cell cycle and DNA damage signaling. RPA is indispensable for accurate homologous recombination (HR)-based DNA double-strand break (DSB) repair and its activity is regulated by phosphorylation and other post-translational modifications.

RPA inhibition increases replication stress and suppresses tumor growth.

The ATR/Chk1 pathway is a critical surveillance network that maintains genomic integrity during DNA replication by stabilizing the replication forks during normal replication to avoid replication stress. One of the many differences between normal cells and cancer cells is the amount of replication stress that occurs during replication. Cancer cells with activated oncogenes generate increased levels of replication stress.

Deficient DNA damage signaling leads to chemoresistance to cisplatin in oral cancer.

Activation of the cellular DNA damage response (DDR) is an important determinant of cell sensitivity to cisplatin and other chemotherapeutic drugs that eliminate tumor cells through induction of DNA damage. It is therefore important to investigate whether alterations of the DNA damage-signaling pathway confer chemoresistance in cancer cells and whether pharmacologic manipulation of the DDR pathway can resensitize these cells to cancer therapy. In a panel of oral/laryngeal squamous cell carcinoma (SCC) cell lines, we observed deficiencies in DNA damage signaling in correlation with cisplatin resistance, but not with DNA repair.

The male phenotype in osteopathia striata congenita with cranial sclerosis.

Osteopathia striata with cranial sclerosis (OSCS) is an X-linked disease caused by truncating mutations in WTX. Females exhibit sclerotic striations on the long bones, cranial sclerosis, and craniofacial dysmorphism. Males with OSCS have significant skeletal sclerosis, do not have striations but do display a more severe phenotype commonly associated with gross structural malformations, patterning defects, and significant pre- and postnatal lethality.

Does vaginal bleeding influence first-trimester markers for Down syndrome?

Objectives: To examine the effect of early vaginal bleeding on first-trimester screening markers for Down syndrome.

Methods: A retrospective study was conducted on 1755 normal singleton fetuses that underwent first-trimester combined screening for Down syndrome on the basis of ultrasound and maternal serum markers. Fetal delta-nuchal translucency (NT), maternal serum pregnancy-associated plasma protein A (PAPP-A) and free beta-hCG were compared between pregnancies with (n = 252) and without (n = 1503) an episode of vaginal bleeding.

[Leiomyosarcoma of the uterus in young identical twins].

The authors describe the occurrence of a confirmed leiomyosarcoma and a tumor suspected of being a leiomyosarcoma in 23-year-old twin sisters. In one of them the tumor had caused clinical symptoms; in the second it was detected at the presymptomatic stage as a result of increased attention after detection of the first tumor. In the first case treatment consisted in an extended abdominal hysterectomy, sparing one ovary, with bilateral interiliac lymph node extirpation; in the second case, in an extended abdominal hysterectomy with both adnexae and bilateral interiliac lymph node extirpation.

[Endometrial carcino-sarcoma in a young woman with Turner syndrome (author's transl)].

Endometrial carcino-sarcoma is a rare rapidly growing mixed muellerian tumor. The pathogenesis of this tumor is not definitely known. However, the current explanation favors the theory of the growth of this tumor from pluripotential sub-epithelial cells.