A novel 5x multiplex immunohistochemical staining reveals PSMA as a helpful marker in prostate cancer with low p504s expression.

The ability to combine multiple immunohistochemical (IHC) markers within a single tissue section facilitates the evaluation and detection of co-expressions, while saving tissue. A newly developed 5x multiplex (MPX) IHC staining of five different IHC markers (Basal cell cocktail (34βE12 + p63), p504s (SP116), ERG (EPR3864), Ki-67 (30-9), PSMA (EP192)) was applied on whole sections of n = 37 radical prostatectomies (RPE) including normal and cancerous tissue. Four different colors including brown, magenta, yellow and teal coded for different stainings, whereas magenta was used twice for nuclear Ki-67 and cytosolic / membranous PSMA.

Performance comparison of anti-p504s (SP116) Rabbit Monoclonal Primary Antibody vs. Monoclonal Rabbit Anti-Human AMACR clone 13H4 when duplexed with VENTANA Basal Cell Cocktail (34βE12+p63) as a diagnostic aid for prostatic adenocarcinoma using immunohistochemistry.

Alpha-methylacyl-coenzyme A-racemase (AMACR), also known as p504s, is overexpressed in prostatic adenocarcinoma and is frequently used in combination with basal cell markers to aid in diagnosing difficult prostate adenocarcinoma cases. In this retrospective method comparison study, we examined the sensitivity and specificity of the ready-to-use anti-p504s (SP116) Rabbit Monoclonal Primary Antibody compared to the monoclonal rabbit anti-human AMACR clone 13H4 in prostatic adenocarcinoma samples. De-identified prostatic adenocarcinoma tissue samples were stained with either the SP116 or 13H4 antibody clone in combination with the VENTANA Basal Cell Cocktail (34βE12+p63) and scored as positive or negative for prostatic adenocarcinoma.

Protein activation mapping of human sun-protected epidermis after an acute dose of erythemic solar simulated light.

Ultraviolet radiation is an important etiologic factor in skin cancer and a better understanding of how solar stimulated light (SSL) affects signal transduction pathways in human skin which is needed in further understanding activated networks that could be targeted for skin cancer prevention. We utilized Reverse Phase Protein Microarray Analysis (RPPA), a powerful technology that allows for broad-scale and quantitative measurement of the activation/phosphorylation state of hundreds of key signaling proteins and protein pathways in sun-protected skin after an acute dose of two minimal erythema dose (MED) of SSL. RPPA analysis was used to map the altered cell signaling networks resulting from acute doses of solar simulated radiation (SSL).

A pilot study exploring the molecular architecture of the tumor microenvironment in human prostate cancer using laser capture microdissection and reverse phase protein microarray.

The cross-talk between tumor epithelium and surrounding stromal/immune microenvironment is essential to sustain tumor growth and progression and provides new opportunities for the development of targeted treatments focused on disrupting the tumor ecology. Identification of novel approaches to study these interactions is of primary importance. Using laser capture microdissection (LCM) coupled with reverse phase protein microarray (RPPA) based protein signaling activation mapping we explored the molecular interconnection between tumor epithelium and surrounding stromal microenvironment in 18 prostate cancer (PCa) specimens.

Inhibition of Akt Enhances the Chemopreventive Effects of Topical Rapamycin in Mouse Skin.

The PI3Kinase/Akt/mTOR pathway has important roles in cancer development for multiple tumor types, including UV-induced nonmelanoma skin cancer. Immunosuppressed populations are at increased risk of aggressive cutaneous squamous cell carcinoma (SCC). Individuals who are treated with rapamycin (sirolimus, a classical mTOR inhibitor) have significantly decreased rates of developing new cutaneous SCCs compared with those that receive traditional immunosuppression.

Phase IIB Randomized Study of Topical Difluoromethylornithine and Topical Diclofenac on Sun-Damaged Skin of the Forearm.

Prevention of nonmelanoma skin cancers remains a health priority due to high costs associated with this disease. Diclofenac and difluoromethylornithine (DFMO) have demonstrated chemopreventive efficacy for cutaneous squamous cell carcinomas. We designed a randomized study of the combination of DFMO and diclofenac in the treatment of sun-damaged skin.

Genetic ablation of caspase-7 promotes solar-simulated light-induced mouse skin carcinogenesis: the involvement of keratin-17.

Solar ultraviolet irradiation is an environmental carcinogen that causes skin cancer. Caspase-7 is reportedly expressed at reduced levels in many cancers. The present study was designed to examine the role of caspase-7 in solar-simulated light (SSL)-induced skin cancer and to elucidate its underlying molecular mechanisms.

Activation of the PI3K/Akt/mTOR and MAPK Signaling Pathways in Response to Acute Solar-Simulated Light Exposure of Human Skin.

The incidence of skin cancer is higher than all other cancers and continues to increase, with an average annual cost over $8 billion in the United States. As a result, identifying molecular pathway alterations that occur with UV exposure to strategize more effective preventive and therapeutic approaches is essential. To that end, we evaluated phosphorylation of proteins within the PI3K/Akt and MAPK pathways by immunohistochemistry in sun-protected skin after acute doses of physiologically relevant solar-simulated ultraviolet light (SSL) in 24 volunteers.

Chronic use of NSAIDs and/or statins does not affect PSA or PSA velocity in men at high risk for prostate cancer.

Background: PSA and PSA velocity (PSAV, rate of PSA change over time) are biomarkers for diagnosis and prognosis of prostate cancer. Men who are at high risk for prostate cancer also have associated comorbidities for which they are taking NSAIDs and statins for long periods; therefore, it is important to understand the effect of these medications on markers used to assess prostate cancer risk.

Methods: Using a population of 699 men, multiple linear regressions were used to investigate the associations between PSA and concomitant medications, and mixed-effects models were used to investigate these associations with PSAV.

Malondialdehyde-derived epitopes in human skin result from acute exposure to solar UV and occur in nonmelanoma skin cancer tissue.

Cutaneous exposure to solar ultraviolet radiation (UVR) is a causative factor in photoaging and photocarcinogenesis. In human skin, oxidative stress is widely considered a key mechanism underlying the detrimental effects of acute and chronic UVR exposure. The lipid peroxidation product malondialdehyde (MDA) accumulates in tissue under conditions of increased oxidative stress, and the occurrence of MDA-derived protein epitopes, including dihydropyridine-lysine (DHP), has recently been substantiated in human skin.

Selenium supplementation has no effect on serum glucose levels in men at high risk of prostate cancer.

Background: Current literature regarding the effect of selenium supplementation on the risk of diabetes is inconclusive. Hence, a longitudinal study was conducted to investigate the effect of selenium supplementation on serum glucose levels in elderly men.

Methods: Data were obtained from 699 men participating in a randomized double-blind placebo-controlled Phase 3 clinical trial investigating the effects of two doses of selenium (200 and 400 μg/day) compared with placebo on the incidence of prostate cancer.

Phase 3 clinical trial investigating the effect of selenium supplementation in men at high-risk for prostate cancer.

Purpose: This study was conducted to investigate the effect of Se supplementation on prostate cancer incidence in men at high risk for prostate cancer.

Methods: A Phase 3 randomized, double-blind, placebo-controlled clinical trial was conducted in 699 men at high risk for prostate cancer (prostate specific antigen (PSA) >4 ng/ml and/or suspicious digital rectal examination and/or PSA velocity >0.75 ng/ml/year), but with a negative prostate biopsy.

Functional protein pathway activation mapping of the progression of normal skin to squamous cell carcinoma.

Reverse phase protein microarray analysis was used to identify cell signaling derangements in squamous cell carcinoma (SCC) compared with actinic keratosis (AK) and upper inner arm (UIA). We analyzed two independent tissue sets with isolation and enrichment of epithelial cells by laser capture microdissection. Set 1 served as a pilot and a means to identify protein pathway activation alterations that could be further validated in a second independent set.

Association of obesity and smoking with PSA and PSA velocity in men with prostate cancer.

Significant number of prostate tumors are slow growing and could probably be left untreated. However, many are aggressive and can spread rapidly causing patient suffering and/or death. Current technology does not allow physicians to differentiate between slow growing and aggressive tumors at diagnosis.

No effect of selenium supplementation on serum glucose levels in men with prostate cancer.

Background: Literature indicates a relationship between selenium supplementation and risk of diabetes. However, because these data are inconclusive, we investigated the effect of selenium supplementation on serum glucose levels in men with prostate cancer enrolled in a clinical trial testing of the effect of selenium on prostate cancer progression.

Methods: Subjects were randomized to receive placebo (n=46), selenium 200 microg/day (n=47), and selenium 800 microg/day (n=47).

Oral selenium supplementation has no effect on prostate-specific antigen velocity in men undergoing active surveillance for localized prostate cancer.

The Nutritional Prevention of Cancer trial showed a 52% lower incidence of prostate cancer in men supplemented with selenium. As a result, our study was designed to assess whether selenium supplementation attenuates the progression of prostate cancer. A phase 2 randomized, double-blind, placebo-controlled clinical trial was conducted in men with localized nonmetastatic prostate cancer who had elected to forgo active treatment and be followed by active surveillance.

Effect of aspirin, other NSAIDs, and statins on PSA and PSA velocity.

Background: Aspirin, other non-steroidal anti-inflammatory drugs (NSAIDs), and statins have been associated with lower risk of prostate cancer and its progression, though results have been inconsistent.

Methods: Data from 140 men with prostate cancer enrolled in a Phase 2 clinical trial of selenium to prevent prostate cancer progression were analyzed to determine association between aspirin, other NSAIDs, or statin use with baseline serum prostate-specific antigen (PSA) levels and PSA velocity (rate of PSA change over time) using repeated measures over an average follow-up time of 3.2 years.

A phase 2a study of topical perillyl alcohol cream for chemoprevention of skin cancer.

The chemopreventive and antitumor properties of perillyl alcohol (POH) that were studied preclinically indicate that topical POH inhibits both UVB-induced murine skin carcinogenesis (squamous cell tumor models) and 7,12-dimethylbenz(a)anthracene-induced murine melanoma (transgenic models involving tyrosinase-driven Ras). A previous phase 1 clinical trial in participants with normal-appearing skin showed that topical POH cream was well tolerated at a dose of 0.76% (w/w).

Preformulation, formulation, and in vivo efficacy of topically applied apomine.

Apomine is a novel compound that inhibits the mevalonate/isoprenoid pathway of cholesterol synthesis and may prove effective as a skin cancer chemoprevention therapy. This research was focused on the development of a new delivery approach for chemoprevention of melanoma using topically delivered apomine. This included evaluating the effect of several factors on the stability of apomine in solution, utilizing these to develop a topical formulation, and conducting efficacy studies with the developed topical formulation in the TPras mouse model.

Phase 1 study of topical perillyl alcohol cream for chemoprevention of skin cancer.

Perillyl alcohol (POH) is a natural product derived from plants such as cherry and lavendin. Previous studies have indicated that topical POH inhibits ultraviolet (UV) B-induced skin carcinogenesis in vivo, and it may be an effective chemopreventive agent for skin cancer. We performed a 1-mo, first-in-man, Phase 1 trial of topically administered POH cream in human subjects.

Gemcitabine plus celecoxib in patients with advanced or metastatic pancreatic adenocarcinoma: results of a phase II trial.

Objectives: Cycloxygenase-2 (COX-2) is overexpressed in pancreatic tumors where it may be involved in inflammation, carcinogenesis, and the regulation of neoangiogenesis. The purpose of this trial was to evaluate the combination of intravenous gemcitabine with selective COX-2 inhibitor, celecoxib for effect on survival, disease progression, and tolerability in patients with advanced pancreatic cancer. In addition, limited pharmacokinetic and pharmacodynamic analyses were preformed.

Cross-validation of murine UV signal transduction pathways in human skin.

Acute UVB irradiation of mouse skin results in activation of phospatidyinositol-3 (PI-3) kinase and mitogen-activated protein kinase (MAPK) pathways leading to altered protein phosphorylation and downstream transcription of genes. We determined whether activation of these pathways also occurs in human skin exposed to 4x minimal erythemic dose of UVB in 23 volunteers. Biopsies were taken prior to, at 30 min, 1 and 24 h post-UVB.

Workshop on imaging science development for cancer prevention and preemption.

The concept of intraepithelial neoplasm (IEN) as a near-obligate precursor of cancers has generated opportunities to examine drug or device intervention strategies that may reverse or retard the sometimes lengthy process of carcinogenesis. Chemopreventive agents with high therapeutic indices, well-monitored for efficacy and safety, are greatly needed, as is development of less invasive or minimally disruptive visualization and assessment methods to safely screen nominally healthy but at-risk patients, often for extended periods of time and at repeated intervals. Imaging devices, alone or in combination with anticancer drugs, may also provide novel interventions to treat or prevent precancer.

A Phase I pharmacokinetic and pharmacodynamic study of PX-12, a novel inhibitor of thioredoxin-1, in patients with advanced solid tumors.

Purpose: Thioredoxin-1 (Trx-1) is a cellular redox protein that promotes tumor growth, inhibits apoptosis, and up-regulates hypoxia-inducible factor-1alpha and vascular endothelial growth factor. Objectives of this study were to determine safety, tolerability, pharmacodynamics, and pharmacokinetics of PX-12, a small-molecule inhibitor of Trx-1.

Experimental Design: Thirty-eight patients with advanced solid tumors received PX-12 at doses of 9 to 300 mg/m(2), as a 1- or 3-h i.

Cytotoxic activity of Apomine is due to a novel membrane-mediated cytolytic mechanism independent of apoptosis in the A375 human melanoma cell line.

Apomine, a novel bisphosphonate ester, has demonstrated anticancer activity in a variety of cancer cell lines; however, its mechanism of cytotoxicity is not well understood. Previous work has demonstrated that Apomine induces cell death by activation of caspase-3 in several cancer cell types. However, we have demonstrated that Apomine induces cell death in the A375 human melanoma cell line through a novel membrane-mediated mechanism that is independent of caspase-3 activation.