SPARC-Independent Delivery of Nab-Paclitaxel without Depleting Tumor Stroma in Patient-Derived Pancreatic Cancer Xenografts.

The study goal was to examine the relationship between nab-paclitaxel delivery and SPARC (secreted protein acidic and rich in cysteine) expression in pancreatic tumor xenografts and to determine the antistromal effect of nab-paclitaxel, which may affect tumor vascular perfusion. SPARC-positive and -negative mice bearing Panc02 tumor xenografts (n = 5-6/group) were injected with IRDye 800CW (IR800)-labeled nab-paclitaxel. After 24 hours, tumors were collected and stained with DL650-labeled anti-SPARC antibody, and the correlation between nab-paclitaxel and SPARC distributions was examined.

Targeting the Wnt/β-catenin pathway in primary ovarian cancer with the porcupine inhibitor WNT974.

Preclinical studies in ovarian cancer have demonstrated upregulation of the Wnt/β-catenin pathway promoting tumor proliferation and chemoresistance. Our objective was to evaluate the effect of the Wnt/β-catenin pathway inhibitor, WNT974, in primary ovarian cancer ascites cells. Ascites cells from patients with papillary serous ovarian cancer were isolated and treated with 1 μM WNT974±100 μM carboplatin.

Combination therapy with anti-DR5 antibody and tamoxifen for triple negative breast cancer.

TRA-8, a monoclonal antibody targeting death receptor, has demonstrated high therapeutic effect for triple negative breast cancer (TNBC) in preclinical models. Tamoxifen, the standard of care for ERα-positive breast cancer, induces apoptosis via ERβ, which commonly presents in TNBC cells. The current study investigates the combination effects of TRA-8 and tamoxifen for TNBC.

Early therapy assessment of combined anti-DR5 antibody and carboplatin in triple-negative breast cancer xenografts in mice using diffusion-weighted imaging and (1)H MR spectroscopy.

Purpose: To assess the early response of triple-negative breast-cancer (TNBC) following TRA-8 and carboplatin therapy using DWI and MRS in 2LMP and SUM159 mouse models.

Materials And Methods: Four groups (n = 5/group) of each model were untreated or treated with carboplatin, TRA-8, and combination, respectively. DWI and MRS were applied on 0, 3, and 7 days after therapy initiation, and all tumors were collected thereafter for terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) staining.

Lung resistance-related protein (LRP) expression in malignant ascitic cells as a prognostic marker for advanced ovarian serous carcinoma.

Purpose: Ovarian serous carcinoma is an aggressive cancer that often presents with metastatic disease. Although primary tumor and established metastatic foci in the omentum are generally compared to identify proteins involved in drug resistance, we investigated a potential bridge, the malignant cells from ascites, as facilitator of drug resistance and recurrence.

Methods: We evaluated the expression of drug resistance markers P-glycoprotein (P-gp), canalicular multispecific organic anion transporter (MRP2), and lung resistance-related protein (LRP) in malignant cells from ascites and matched omental metastasis from 25 patients with advanced-stage ovarian serous carcinoma who were chemotherapeutic naïve and undergoing initial cytoreductive surgery.

Development of combination tapered fiber-optic biosensor dip probe for quantitative estimation of interleukin-6 in serum samples.

A combination tapered fiber-optic biosensor (CTFOB) dip probe for rapid and cost-effective quantification of proteins in serum samples has been developed. This device relies on diode laser excitation and a charged-coupled device spectrometer and functions on a technique of sandwich immunoassay. As a proof of principle, this technique was applied in a quantitative estimation of interleukin IL-6.

Polyethylene glycosylated curcumin conjugate inhibits pancreatic cancer cell growth through inactivation of Jab1.

Jab1 (Jun activation domain binding protein 1), integrated into COP9 signalosome complex (CSN), induces protein instability of many tumor suppressors and cell cycle regulators and is therefore a novel target in cancer therapy. Curcumin, an inhibitor of Jab1/CSN-associated kinase(s), has been reported to suppress tumor growth; however, curcumin is highly hydrophobic, and this feature prevents its usage as an antitumor drug. To increase the solubility and targeted delivery, we generated a water-soluble polyethylene glycol (PEG)-conjugated curcumin system, in which curcumin is covalently linked to PEG(35kD).

SELDI-TOF MS whole serum proteomic profiling with IMAC surface does not reliably detect prostate cancer.

Background: The analysis of bodily fluids using SELDI-TOF MS has been reported to identify signatures of spectral peaks that can be used to differentiate patients with a specific disease from normal or control patients. This report is the 2nd of 2 companion articles describing a validation study of a SELDI-TOF MS approach with IMAC surface sample processing to identify prostatic adenocarcinoma.

Methods: We sought to derive a decision algorithm for classification of prostate cancer from SELDI-TOF MS spectral data from a new retrospective sample cohort of 400 specimens.

Phosphorylated LIM kinases colocalize with gamma-tubulin in centrosomes during early stages of mitosis.

LIM kinases (LIMK1 and LIMK2) are LIM domain containing serine/threonine kinases that modulate reorganization of actin cytoskeleton through inactivating phosphorylation of cofilin. The Rho family of small GTPases regulates the catalytic activity of LIMK1 and LIMK2 through activating phosphorylation by ROCK or by p21 kinase. Recent studies have suggested that LIMK1 could play a role in modulation of cellular growth by alteration of the cell cycle in breast and prostate tumor cells; however, the direct mitogenic effects of LIMK1 in these tumor cells is yet to be elucidated.

Analytical validation of serum proteomic profiling for diagnosis of prostate cancer: sources of sample bias.

Background: This report and a companion report describe a validation of the ability of serum proteomic profiling via SELDI-TOF mass spectrometry to detect prostatic cancer. Details of this 3-stage process have been described. This report describes the development of the algorithm and results of the blinded test for stage 1.

Methionine inhibits cellular growth dependent on the p53 status of cells.

Background: Methionine, an essential amino acid, is important for normal growth and development, as it is required for both protein and polyamine synthesis as well as in methylation reactions. It has been reported that high concentrations of methionine inhibit cellular growth and gene expression in the human breast tumor-derived MCF-7 cells. These effects are thought to be mediated by the modulation of p53.

Plasma protein profiles differ between women diagnosed with cervical intraepithelial neoplasia (cin) 1 and 3.

Early detection of precancerous cells in the cervix and their clinical management is the main purpose of cervical cancer prevention and treatment programs. Cytological findings or testing for high risk (HR)-human papillomavirus (HPV) are inadequately sensitive for use in triage of women at high risk for cervical cancer. The current study is an exploratory study to identify candidate surface-enhanced laser desorption/ionization (SELDI) time of flight (TOF) mass spectrometry (MS) protein profiles in plasma that may distinguish cervical intraepithelial neoplasia (CIN 3) from CIN 1 among women infected with HR-HPV.

Control of prostate cell growth: BMP antagonizes androgen mitogenic activity with incorporation of MAPK signals in Smad1.

Alterations in the signaling pathways of bone morphogenetic proteins (BMPs) and activation of the ERK/MAP kinase (MAPK) pathway by growth factors have been implicated in the development and progression of prostate cancer. Smad1 acts as a substrate for MAPKs and also performs a central role in transmitting signals from BMPs. We found that BMPs/Smad1 signaling inhibits the growth of androgen-sensitive prostate cancer cells.

Celecoxib inhibits cellular growth, decreases Ki-67 expression and modifies apoptosis in ovarian cancer cell lines.

Background: There is controversy on the safety of inhibitors of cyclooxygenase administered at high doses; however, these drugs have been reported to be effective in the prevention of a variety of human cancers. To determine if celecoxib influences cellular growth, we evaluated several effects in ovarian carcinoma cell lines.

Methods: CAOV3, OVCAR3 and SKOV3 cell lines were exposed to different concentrations of celecoxib (0-100 microM) for 24-96 h.

Smad4 inhibits tumor growth by inducing apoptosis in estrogen receptor-alpha-positive breast cancer cells.

Estrogen is a mitogen in most estrogen receptor-alpha (ERalpha)-positive breast cancers. We have found that Smad4, a common signal transducer in the transforming growth factor-beta superfamily, acts as an ERalpha transcriptional corepressor. Here, we show that Smad4 induces apoptosis in ERalpha-positive MCF-7 breast cancer cells, but not in ERalpha-negative MDA-MB-231 cells.

the need for review and understanding of SELDI/MALDI mass spectroscopy data prior to analysis.

Multiple studies have reported that surface enhanced laser desorption/ionization time of flight mass spectroscopy (SELDI-TOF-MS) is useful in the early detection of disease based on the analysis of bodily fluids. Use of any multiplex mass spectroscopy based approach as in the analysis of bodily fluids to detect disease must be analyzed with great care due to the susceptibility of multiplex and mass spectroscopy methods to biases introduced via experimental design, patient samples, and/or methodology. Specific biases include those related to experimental design, patients, samples, protein chips, chip reader and spectral analysis.

Novel approaches to smoothing and comparing SELDI TOF spectra.

Background: Most published literature using SELDI-TOF has used traditional techniques in Spectral Analysis such as Fourier transforms and wavelets for denoising. Most of these publications also compare spectra using their most prominent feature, i.e, peaks or local maximums.

The pattern of expression of Mn and Cu-Zn superoxide dismutase varies among squamous cell cancers of the lung, larynx, and oral cavity.

Background: Despite the importance of reactive oxygen species (ROS) in the development of smoking-related cancers, little is known about the pattern of expression of ROS scavengers in these cancers.

Methods: In this present study, we examined the expression of manganese superoxide dismutase (Mn-SOD) and copper/zinc superoxide dismutase (Cu-Zn-SOD), which are essential enzymes that eliminate ROS, in squamous cell cancers (SCCs) of the lung (n = 12), larynx (n = 13), and oral cavity (n = 20).

Results: SCCs of larynx and oral cavity showed significantly enhanced immuhistochemical expression of Mn-SOD compared with the matched uninvolved epithelium.

Effects of nonsteroidal anti-inflammatory agents (NSAIDs) on ovarian carcinoma cell lines: preclinical evaluation of NSAIDs as chemopreventive agents.

Purpose: Nonsteroidal anti-inflammatory agents may inhibit carcinogenesis in specific tissues including the colon, breast, and pancreas, and, hence, may prove to be effective chemopreventive agents. The purpose of this study was to investigate the cellular effects of acetylsalicylic acid (ASA), acetaminophen, and a COX-2 inhibitor (NS-398) on the growth of cell lines of human ovarian cancer in vitro.

Experimental Design: SK-OV-3, Caov-3, and NIH:OVCAR-3 ovarian carcinoma cell lines were treated with ASA (10(-6) M-10(-2) M), acetaminophen (10(-6) M-10(-2) M), and a COX-2 inhibitor (10(-6) M-10(-4) M) for 96 h.