Kallikrein family proteases KLK6 and KLK7 are potential early detection and diagnostic biomarkers for serous and papillary serous ovarian cancer subtypes.

BACKGROUND: Early detection of ovarian cancer remains a challenge due to widespread metastases and a lack of biomarkers for early-stage disease. This study was conducted to identify relevant biomarkers for both laparoscopic and serum diagnostics in ovarian cancer. METHODS: Bioinformatics analysis and expression screening in ovarian cancer cell lines were employed. Selected biomarkers were further validated in bio-specimens of diverse cancer types and ovarian cancer subtypes. For non-invasive detection, biomarker proteins were evaluated in serum samples from ovarian cancer patients. RESULTS: Two kallikrein (KLK) serine protease family members (KLK6 and KLK7) were found to be significantly overexpressed relative to normal controls in most of the ovarian cancer cell lines examined. Overexpression of KLK6 and KLK7 mRNA was specific to ovarian cancer, in particular to serous and papillary serous subtypes. In situ hybridization and histopathology further confirmed significantly elevated levels of KLK6 and KLK7 mRNA and proteins in tissue epithelium and a lack of expression in neighboring stroma. Lastly, KLK6 and KLK7 protein levels were significantly elevated in serum samples from serous and papillary serous subtypes in the early stages of ovarian cancer, and therefore could potentially decrease the high false negative rates found in the same patients with the common ovarian cancer biomarkers human epididymis protein 4 (HE4) and cancer antigen 125 (CA-125). CONCLUSION: KLK6 and KLK7 mRNA and protein overexpression is directly associated with early-stage ovarian tumors and can be measured in patient tissue and serum samples. Assays based on KLK6 and KLK7 expression may provide specific and sensitive information for early detection of ovarian cancer

Expression and Function of Androgen Receptor Coactivator p44/Mep50/WDR77 in Ovarian Cancer

Hormones, including estrogen and progesterone, and their receptors play an important role in the development and progression of ovarian carcinoma. Androgen, its receptor and coactivators have also been implicated in these processes. p44/Mep50/WDR77 was identified as a subunit of the methylosome complex and lately characterized as a steroid receptor coactivator that enhances androgen receptor as well as estrogen receptor-mediated transcriptional activity in a ligand-dependent manner. We previously described distinct expression and function of p44 in prostate, testis, and breast cancers. In this report, we examined the expression and function of p44 in ovarian cancer. In contrast to findings in prostate and testicular cancer and similar to breast cancer, p44 shows strong cytoplasmic localization in morphologically normal ovarian surface and fallopian tube epithelia, while nuclear p44 is observed in invasive ovarian carcinoma. We observed that p44 can serve as a coactivator of both androgen receptor (AR) and estrogen receptor (ER) in ovarian cells. Further, overexpression of nuclear-localized p44 stimulates proliferation and invasion in ovarian cancer cells in the presence of estrogen or androgen. These findings strongly suggest that p44 plays a role in mediating the effects of hormones during ovarian tumorigenesis

Lung Cancer and Angiogenesis

Lung cancer usually forms from cells that line the airways and nearby glands since these cells come into contact with the air we breathe which may contain carcinogens (such as tobacco smoke, asbestos, and benzene). Specifically lung cancer can be divided into two major groups: Small Cell Lung Cancer (SCLC) and Non Small Cell Lung Cancer (NSCLC). The purpose of this literature review project is to discuss how angiogenic activators such as vascular endothelial growth factor (VEGF) and platelet derived endothelial cell growth factor (PD-ECGF) have a prognostic significance in the development of lung cancer. Lung cancer occurs over a period of time where normal cells grow into cancerous cells eventually forming a tumor. A tumor cannot grow larger than the head of a pin without a blood supply. For the tumor to get a blood supply it must secrete activators such as: VEGF, platelet derived endothelial growth factor, or basic fibroblast growth factor (bFGF), signaling the surrounding normal host tissue to make new blood vessels, bringing oxygen and nutrients to the tumor and taking the waste products out. The process of forming new blood vessels is known as angiogenesis. The concept of angiogenesis was first popularized by Dr. Judah Folkman in 1971. Before the 1960s, cancer researchers thought that the blood supply reached the tumor through the dilation of the pre-existing blood vessels. Presently researchers are trying to find various inhibitors that can stop angiogenesis from taking place and cure lung cancer and many other types of cancers

The Effects of Zinc on Gene Expression in Saccharomyces cerevisiae using Polymerase Chain Reaction (PCR) for Six Candidate Genes

In this experiment the effects of various concentrations of zinc on Saccharomyces cerevisiae will be investigated using Polymerase Chain Reaction (PCR). Zinc (Zn) is one of the most naturally occurring elements. It is an important integral cofactor for many cellular activities. Zinc participates in all major biochemical reactions such as transcription of DNA and translation of RNA. More than three hundred enzymes require zinc for their catalytic function. Saccharomyces cerevisiae strain S288C is a species of budding yeast. It is the most intensively studied eukaryotic model in molecular and cell biology. The mRNA from these yeast cells grown in different concentrations of zinc (0μM, 1μM, 50μM, 1mM) will be reviewed to determine the expression of patterns specific genes. In particular, the expression of six genes ZRT1, ZRT2, ZRT3, ZRC1, ZAP1, and VEL1 will be examined. The yeast will be grown in CSD media with the appropriate concentration of zinc. Zinc will be added as zinc chloride. A control sample will be grown without the addition of zinc chloride. The 1mM zinc is considered to be an excess amount, while 1μM is considered to be less than the minimum required Zn concentration. RNA will be isolated from yeast exposed to each environmental condition. The mRNA from the total RNA extracted will then be converted to cDNA, and the presence of the various genes will be tested using specially selected primers and polymerase chain reaction (PCR)

Bacteriophage transcytosis provides a mechanism to cross epithelial cell layers

Bacterial viruses are among the most numerous biological entities within the human body. These viruses are found within regions of the body that have conventionally been considered sterile, including the blood, lymph, and organs. However, the primary mechanism that bacterial viruses use to bypass epithelial cell layers and access the body remains unknown. Here, we used in vitro studies to demonstrate the rapid and directional transcytosis of diverse bacteriophages across confluent cell layers originating from the gut, lung, liver, kidney, and brain. Bacteriophage transcytosis across cell layers had a significant preferential directionality for apical-to-basolateral transport, with approximately 0.1% of total bacteriophages applied being transcytosed over a 2-h period. Bacteriophages were capable of crossing the epithelial cell layer within 10 min with transport not significantly affected by the presence of bacterial endotoxins. Microscopy and cellular assays revealed that bacteriophages accessed both the vesicular and cytosolic compartments of the eukaryotic cell, with phage transcytosis suggested to traffic through the Golgi apparatus via the endomembrane system. Extrapolating from these results, we estimated that 31 billion bacteriophage particles are transcytosed across the epithelial cell layers of the gut into the average human body each day. The transcytosis of bacteriophages is a natural and ubiquitous process that provides a mechanistic explanation for the occurrence of phages within the body