Importance of platinum-free interval in second-line chemotherapy for advanced or recurrent endometrial cancer.

PURPOSE: To investigate the effectiveness of platinum-based combination chemotherapy as second-line chemotherapy for patients with advanced or recurrent endometrial cancer treated initially by platinum-based combination chemotherapy. MATERIALS AND METHODS: Subjects were patients who had received platinum-based combination chemotherapy as second-line chemotherapy: 56 patients with recurrent disease who had previously received postoperative adjuvant platinum-based combination chemotherapy (Category 1) and 21 patients who had received first-line chemotherapy but not adjuvant chemotherapy for advanced or recurrent disease (Category 2). Patients' records were searched for the response to second-line chemotherapy and survival, particularly in relation to the platinum-free interval (PFI). RESULTS: APFI over 12 months was a predictor of response (64.7%) and overall survival time (23 months) in Category 1 patients. A PFI of less than three months was a negative predictor of response (0%) and overall survival (nine months) in Category 2 patients. CONCLUSION: Platinum-based combination chemotherapy appears to be effective as second-line chemotherapy for endometrial cancer if the PFI is sufficiently long.

Immortalization of human esophageal keratinocytes by E6 and E7 of human papillomavirus type 16.

Transduction of human papillomavirus type 16 (HPV16) E6/E7 into primary culture of human esophageal keratinocytes using a recombinant adenovirus prolonged the life-span, while untreated cells senesced within 14-16 population doublings (PDLs). Up-regulation of telomerase activity and acquisition of serum-resistant growth were observed in the esophageal keratinocytes with extended life-span between 50 and 100 PDLs, and drastically increased after 100 PDLs. A keratinocyte sample with a polymorphism of Pro/Pro at codon 72 of p53 showed resistance to HPV16 E6/E7-induced life-span-extension and immortalization, in contrast to others with p53 polymorphisms of Arg/Arg or Arg/Pro, which did not. The high efficiency of E6/E7-induction by adenovirus vector also revealed the M1 and M2 stages of keratinocyte immortalization first described in this report.

Molecular properties of apelin: tissue distribution and receptor binding.

We analyzed the tissue distribution of apelin mRNA in rats by a quantitative reverse transcription-polymerase chain reaction and that of immunoreactive apelin (ir-apelin) by an enzyme immunoassay (EIA) using a monoclonal antibody. The expression levels of apelin mRNA and ir-apelin seemed to be consistent among tissues: they were highly expressed in the lung and mammary gland. By the combination of gel filtration and EIA, we found that the molecular forms of apelin differ among respective tissues: apelin molecules with sizes close to apelin-36 (long forms) were major components in the lung, testis, and uterus, but both long and short (whose sizes were close to [

Detection of human papillomaviruses in cervical neoplasias using multiple sets of generic polymerase chain reaction primers.

OBJECTIVE: The aim of this study was to evaluate precisely the differences in the spectra of human papillomavirus (HPV) types detected by different generic primer pairs commonly used for detection of this extraordinarily heterogeneous virus. METHODS: Three sets of polymerase chain reaction (PCR) primers for the L1 open reading frame (ORF) and two sets for E6/E7 ORFs were used to detect HPVs in DNAs from 107 cervical tissues, including 77 cervical neoplasias. HPV types were determined by analysis of restriction fragment length polymorphisms (RFLPs) and nucleotide sequencing. RESULTS: A high overall detection rate of HPV in cervical neoplasias (76/77, 98.7%) was achieved by polymerase chain reaction (PCR) amplification with multiple sets of generic primers, while the detection rate for each individual primer pair varied from 48/77 (62%) to 70/77 (91%). Only in 34 of 77 cases (44%) were HPV DNAs positive for all sets of primer pairs. Further determination of HPV types by RFLPs and nucleotide sequencing showed inconsistencies between the PCR primer pairs used. CONCLUSION: Our study revealed that the HPV detection rate is critically affected by the choice of PCR primers, and that appropriate use of combinations of generic PCR primer sets followed by RFLP analyses is both necessary and sufficient for typing most HPVs in cervical lesions. More precise methods such as sequencing would be necessary in only a few cases.

Analyses for susceptibility of rat anterior pituitary cells to prolactin-releasing peptide.

We validated the effect of prolactin-releasing peptide (PrRP) on prolactin (PRL) secretion from rat anterior pituitary cells in in vitro culture. We found that culture conditions considerably influenced the response of the anterior pituitary cells to PrRP. Longer culture term (4 d) was required to obtain better responses of the anterior pituitary cells to PrRP in comparison to thyrotropin-releasing hormone (TRH). Under the culture conditions employed here, PrRP was comparable to TRH in the potency promoting PRL secretion, and the action of PrRP was very specific for PRL secretion. The susceptibility of the anterior pituitary cells to PrRP varied in female rats depending on the process of reproduction: the cells prepared from lactating rats were the most sensitive to PrRP compared with those from random-cycle and pregnant rats. Because the expression levels of PrRP receptor mRNA in the pituitary varied during the reproductive process, we speculated that the susceptibility of the anterior pituitary cells would reflect cellular changes including the expression level of PrRP receptors. In addition, treatment with estrogen in vivo enhanced the susceptibility of the cultured anterior pituitary cells in male rats. Our results indicate that the susceptibility of the rat anterior pituitary cells to PrRP is regulated by physiological mechanisms.

Human papillomavirus-positive well-differentiated villoglandular adenocarcinoma of the uterine cervix: A case report and review of the literature.

OBJECTIVE: A case of well-differentiated villoglandular adenocarcinoma of the uterine cervix, which was positive for human papillomavirus type 18, was reported. METHODS: The patient was a 52-year-old multipara who was referred to our department because of an abnormal Papanicolaou smear. A 4.0-cm exophytic lesion involving the cervix was detected. She was staged as FIGO IIa and radical hysterectomy combined with bilateral pelvic lymphadenectomy was performed. In addition to histopathological examination of the resected tumor, immunohistochemical studies of estrogen and progesterone receptors were performed using monoclonal antibodies. Detection of human papillomavirus DNA was attempted by polymerase chain reaction using consensus primers. RESULTS: The tumor was a typical well-differentiated villoglandular adenocarcinoma involving the vaginal wall. Both estrogen and progesterone receptors were negative. Human papillomavirus type 18 DNA was detected in the resected tumor. CONCLUSION: 'This is the first report of a case of typical well-differentiated villoglandular adenocarcinoma which was positive for human papillomavirus.

Apelin, the natural ligand of the orphan receptor APJ, is abundantly secreted in the colostrum.

By using a strategy that we have developed to search for the ligands of orphan seven-transmembrane-domain receptors [S. Hinuma et al., Nature 393 (1998) 272-276], we have recently identified a natural ligand, apelin, for the orphan 7TMR, APJ [K. Tatemoto et al., Biochem. Biophys. Res. Commun. 251 (1998) 471-476]. In this paper, we isolated rat and mouse apelin cDNAs, and analyzed the tissue distribution of apelin mRNA in rats. Although apelin mRNA was widely detected in a variety of tissues, the highest expression of apelin mRNA was detected in the mammary gland of pregnant rats. In the mammary gland, biologically active apelin and its mRNA considerably increased during pregnancy and lactation, and reached a maximal level around parturition. Moreover, a large amount of apelin (14-93 pmol/ml) was found to be secreted in the bovine colostrum, and it was still detectable even in commercial bovine milk. Since apelin partially suppressed cytokine production by mouse spleen cells in response to T cell receptor/CD3 cross-linking, the oral intake of apelin in the colostrum and milk might modulate immune responses in neonates.

Pure yolk sac tumor of the ovary with mosaic 45X/46X + mar Turner's syndrome with a Y-chromosomal fragment.

A pure yolk sac tumor (endodermal sinus tumor) of the dysgenetic gonad developed in a 23-year-old woman whose karyotype was mosaic 45X/46X + mar Turner's syndrome is reported. Molecular biological studies showed that the patient's DNA contained a fragment of Y chromosome. This case seems to be extremely rare case of developing a pure yolk sac tumor in a patient with mosaic Turner syndrome with a Y-chromosomal fragment.

A prolactin-releasing peptide in the brain.

Hypothalamic peptide hormones regulate the secretion of most of the anterior pituitary hormones, that is, growth hormone, follicle-stimulating hormone, luteinizing hormone, thyroid-stimulating hormone and adrenocorticotropin. These peptides do not regulate the secretion of prolactin, at least in a specific manner, however. The peptides act through specific receptors, which are referred to as seven-transmembrane-domain receptors or G-protein-coupled receptors. Although prolactin is important in pregnancy and lactation in mammals, and is involved in the development of the mammary glands and the promotion of milk synthesis, a specific prolactin-releasing hormone has remained unknown. Here we identify a potent candidate for such a hormone. We first proposed that there may still be unknown peptide hormone factors that control pituitary function through seven-transmembrane-domain receptors. We isolated the complementary DNA encoding an 'orphan' receptor (that is, one for which the ligand is unknown). This receptor, hGR3, is specifically expressed in the human pituitary. We then searched for the hGR3 ligand in the hypothalamus and identified a new peptide, which shares no sequence similarity with known peptides and proteins, as an endogenous ligand. We show that this ligand is a potent prolactin-releasing factor for rat anterior pituitary cells; we have therefore named this peptide prolactin-releasing peptide.

[Usefulness of serum pancreatic phospholipase A2 determination in patients with various pancreatic diseases].

A radioimmunoassay kit (SHIONORIA P-PLA2) to measure human serum pancreatic phospholipase A2 (P-PLA2) concentrations was evaluated for their basic properties and clinical usefulness. The performance of the kit was found to be quite satisfactory. To test its clinical usefulness, specimens mainly from patients with pancreatic diseases were obtained and examined for serum P-PLA2 levels. All serum specimens from patients with acute pancreatitis (n = 7) were found to have elevated levels of serum P-PLA2. In patients with chronic pancreatitis (n = 93) and pancreatic cancer (n = 37), serum P-PLA2 levels showed a wide range of distribution, from abnormally elevated values to abnormally low values. We compared these data with those of other pancreatic markers such as: amylase, elastase 1, trypsin, and PSTI. Among these, P-PLA2 was highly specific to pancreatic disease and best represented the state of pancreatic disorders. Abnormally elevated levels of serum P-PLA2 concentrations seem to reflect the inflammation of pancreas, while abnormally low levels indicate the hypofunction of pancreatic exocrine glands. These results suggest that the measurement of serum P-PLA2 concentrations is a useful diagnostic test for pancreatic disorders.