The EPR effect: Unique features of tumor blood vessels for drug delivery, factors involved, and limitations and augmentation of the effect.

Human exposure to bisphenol A (BPA).

One of the main engines that drives cellular transformation is the loss of proper control of the mammalian cell cycle. The cyclin-dependent kinase inhibitor p21 (also known as p21WAF1/Cip1) promotes cell cycle arrest in response to many stimuli. It is well positioned to function as both a sensor and an effector of multiple anti-proliferative signals. This Review focuses on recent advances in our understanding of the regulation of p21 and its biological functions with emphasis on its p53-independent tumour suppressor activities and paradoxical tumour-promoting activities, and their implications in cancer.

p21 in cancer: intricate networks and multiple activities

https://dspace.library.uu.nl/bitstream/handle/1874/1590/PMPP-van+Loon-1999.pdf?sequence=1

The families of pathogenesis-related proteins, their activities, and comparative analysis of PR-1 type proteins

We provide here a list of 221 P450 genes and 12 putative pseudogenes that have been characterized as of December 14, 1992. These genes have been described in 31 eukaryotes (including 11 mammalian and 3 plant species) and 11 prokaryotes. Of 36 gene families so far described, 12 families exist in all mammals examined to date. These 12 families comprise 22 mammalian subfamilies, of which 17 and 15 have been mapped in the human and mouse genome, respectively. To date, each subfamily appears to represent a cluster of tightly linked genes. This revision supersedes the previous updates [Nebert et al., DNA 6, 1–11, 1987; Nebert et al., DNA 8, 1–13, 1989; Nebert et al., DNA Cell Biol. 10, 1–14 (1991)] in which a nomenclature system, based on divergent evolution of the superfamily, has been described. For the gene and cDNA, we recommend that the italicized root symbol "CYP" for human ("Cyp" for mouse), representing "cytochrome P450," be followed by an Arabic number denoting the family, a letter designating...

https://www.liebertpub.com/doi/pdf/10.1089/dna.1993.12.1

The P450 superfamily: update on new sequences, gene mapping, accession numbers, early trivial names of enzymes, and nomenclature.

Treatment of interstitial ectopic pregnancy with methotrexate: report of a successful case

To determine the influence of FSH receptor variants Thr307-Asn680 (TN) and Ala307-Ser680 (AS) on ovarian function, we investigated the frequency of these gene polymorphisms by using restriction fragment length polymorphism analysis and observed their effects on clinical manifestations. In a population of 522 Japanese women, the overall frequency of TN/TN (NN), TN/AS (NS), and AS/AS (SS) was 41.0, 46.9 and 12.1% respectively. In polycystic ovary patients, the NS population was significantly larger when compared with the spontaneously ovulating group (66.7 versus 43.5%, P < 0.05). In the SS group, a significantly higher (46%) basal level of serum FSH was observed as compared with that in the NS group (P < 0.05). A higher dose of the exogenous gonadotrophin was required to achieve ovulation induction in the SS group as compared with the NS group (P < 0.05). At the time of hCG administration, estradiol levels per oocyte retrieved for IVF in the SS group were significantly lower as compared with the levels in the NS and NN groups (P < 0.05). There were no significant differences in FSH-stimulated cAMP production and PI turnover as well as ligand-binding affinity between the two receptor isoforms when overexpressed in transfected 293T cells. These results suggest that although FSH receptor polymorphisms have no discernible effect on FSH receptor function in vitro, there are associations between the genotype and some aspects of patient status.

/pdf/genetic-and-functional-analyses-of-polymorphisms-in-the-3vdrz5omts.pdf

Genetic and functional analyses of polymorphisms in the human FSH receptor gene

Maternal serum and amniotic fluid bisphenol A concentrations in the early second trimester.

Acta Obstet Gynecol Scand 2002; 81: 1144-1151. © Acta Obstet Gynecol Scand 2002 Background. The aim of this study was to identify the independent histopathologic prognostic factors for patients with cervical carcinoma treated with radical hysterectomy including paraaortic lymphadenectomy. Methods. A total of 187 patients with stage IB to IIB cervical carcinomas treated with radical hysterectomy and systematic retroperitoneal lymphadenectomy were retrospectively analyzed. The median follow-up period was 83 months. Cox regression analysis was used to select independent prognostic factors. Results. Using multivariate Cox regression analysis, lymph node (LN) status (negative vs. metastasis to pelvic nodes except for common iliac nodes vs. common iliac/paraaortic node metastasis), histopathologic parametrial invasion, lymph-vascular space invasion (LVSI), and histology of pure adenocarcinoma were found to be independently related to patients' poor survival. For patients who had a tumor histologically confined ...

https://obgyn.onlinelibrary.wiley.com/doi/pdf/10.1034/j.1600-0412.2002.811208.x

Multivariate analysis of histopathologic prognostic factors for invasive cervical cancer treated with radical hysterectomy and systematic retroperitoneal lymphadenectomy

The expressions of two isoforms of human progesterone receptor (PR) are under the control of the two different promoters. Recent studies revealed differences between these isoforms, PRA and PRB, in their expression and function in endometrial cells. Aberrant methylation of normally unmethylated CpG islands has been associated with inactivation of several genes in human cancers. In this study, we investigated the methylation status and the expression of the two different PR isoforms, PRA and PRB, in uterine endometrial carcinoma (UEC) using methylation-specific PCR (MSP), reverse transcription-PCR (RT-PCR), the 5' rapid amplification of cDNA ends method (5'RACE), and immunohistochemical staining. The results of RT-PCR and 5'RACE suggest that only PRB is inactivated, although PRA is activated in all UEC cell lines. Treatment with a demethylating agent, 5-aza-2'-deoxycytidine, restored PRB expression in all cell lines, suggesting that inactivation of this gene is through methylation. By MSP and direct DNA sequencing, PRB was methylated, whereas PRA was unmethylated in all of the cell lines. To determine the methylation status of PRB in UEC patients, we investigated 83 cancerous and 33 normal samples. Sixty-two of 83 cancer samples had only methylated alleles of PRB, although all cancer samples had only unmethylated PRA alleles. Seventy-one of 83 cancer samples were negative for PRB expression. All 62 cancer samples that had only methylated PRB alleles were negative for PRB expression. No significant changes were observed in PRA methylation status or immunohistochemistry positivity in normal and cancer samples. To determine whether de novo methylation of PRB occurred in UEC patients, we studied 32 pairs of cancer and normal samples from the same patient. Twenty of 32 cancer samples had only methylated PRB alleles, although all 32 normal samples had only unmethylated PRB alleles. The loss of unmethylated alleles was well correlated with negativity in immunohistochemical staining for PRB. This is the first report of the selective methylation and the subsequent silencing of PRB in uterine endometrial cancer.

https://cancerres.aacrjournals.org/content/canres/61/1/97.full.pdf

Seiichiro Fujimoto

Papers

Treatment of interstitial ectopic pregnancy with methotrexate: report of a successful case

Genetic and functional analyses of polymorphisms in the human FSH receptor gene

Maternal serum and amniotic fluid bisphenol A concentrations in the early second trimester.

Multivariate analysis of histopathologic prognostic factors for invasive cervical cancer treated with radical hysterectomy and systematic retroperitoneal lymphadenectomy

Progesterone receptor B gene inactivation and CpG hypermethylation in human uterine endometrial cancer.