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Background New approaches to ovarian cancer are needed to improve survival. Wilms’ tumour 1 (WT1) is a tumour-associated antigen expressed in many ovarian cancers. P53 is also often altered. The clinical significance of the combined expression of these two transcription factors has not been studied. Methods One hundred ninety-six ovarian tumours were classified histopathologically. Tumours were stained for WT1 and p53 immunohistochemically. Stains were analysed according to tumour type, grade and FIGO stage. Kaplan–Meier analyses on 96 invasive carcinomas determined whether categorical variables were related to survival. Results WT1 and p53 were related to ovarian tumour type, grade, FIGO stage and patient survival. Uniform nuclear p53 expression was associated with invasion and WT1 expression was associated with advanced grade, FIGO stage and poor survival. When WT1 and p53 were both in the age-adjusted Cox model, WT1 was significant while p53 was not. When we combined tumours expressing WT1 and p53, then adjusted for age and tumour subtype, the hazard ratio compared to tumours without WT1 and with normal p53 was 2.70; when adjusted for age and FIGO stage, the hazard ratio was 2.40. Conclusions WT1, an antigen target, is a biomarker for poor prognosis, particularly when combined with altered p53.

Background: Melanoma is a disease that primarily arises in the skin but is a derivative of the neural crest. Eukaryotic translation initiation factor 4E (eIF4E) regulates translation of multiple malignancy-associated mRNAs and is overexpressed in many epithelial tumours. However, expression in human tumours derived from the neural crest is unknown. Here, we determined the association of eIF4E and phospho-eIF4E expression in melanocytic lesions with malignant conversion, metastatic potential and patient survival. Methods: Archived formalin-fixed, paraffin-embedded surgical specimens from 114 patients with melanocytic lesions were stained immunohistochemically for eIF4E and phospho-eIF4E and evaluated semiquantitatively. The relationship between cytoplasmic and nuclear eIF4E and phospho-eIF4E protein expression, melanocytic lesion subtype and tumour progression was determined. Kaplan–Meier survival analyses and Cox proportional hazard regression were performed. Results: Increased eIF4E and phospho-eIF4E expression was highly associated with malignancy (P

A quartz crystal shear mode resonator operating at 5 MHz has been used to study viscoelastic changes which result from adsorption from solution of a layer of the enzyme nitroreductase on a gold electrode. The enzyme is anchored to the gold via thiol end-groups of cysteine residues the number of which, per molecule, has been varied by genetic modification. Using an appropriate model for the acoustic shear wave load on the resonator, the viscoelasticity of the adsorbed enzyme layer have been monitored as the layer develops. A negative viscosity is deduced for all the enzymes and is attributed to amplification of shear waves in the enzyme layer by energy transfer from a compression mode also produced by the crystal. In addition to gradual changes in the viscoelastic parameters as adsorption proceeds, spontaneous changes in viscoelasticity are observed, which indicate a rapid reorganization of the enzyme layer. These various changes, reflecting alterations in the mechanical response of the adsorbed enzyme to shear forces acting at 5 MHz, suggest that the quartz crystal shear wave resonator has considerable potential for studying structural motions in adsorbed proteins at frequencies not readily accessible by other techniques.

Epithelial ovarian cancer is the leading cause of death from gynecologic cancers with 22,280 new cases anticipated in 2016 and 14,240 deaths. Most patients are diagnosed at late stages and have a poor prognosis. Radical surgery and chemotherapy are the primary treatment. When relapse occurs there are few treatment options. The overall survival rate of women with ovarian cancer is unchanged in 50 years. Approximately 70% of epithelial ovarian cancers are serous including low grade serous tumors, some of which may evolve from serous borderline tumors, and high grade serous carcinomas. The latter are thought to originate in the fallopian tube. There are eight other subtypes of invasive ovarian cancer. All invasive ovarian cancers have recently been classified into two subtypes, Type 1 (indolent) and Type 2 (aggressive). The Wilms’ Tumor 1 (WT1) protein is expressed in some normal tissues including the fallopian tube and ovary as well as in tumors such as ovarian and breast cancers and in leukemia. WT1 is a highly immunogenic tumor associated antigen. Mutated p53 is found in many high grade ovarian cancers. Recent reports indicate that WT1 and p53 may interact physically and functionally. Both WT1 and mutated p53 have been suggested as prognostic markers in ovarian cancer. We sought to determine the role of co-expression of mutated p53 and WT1 in overall survival of patients with ovarian cancer. Histologic sections were prepared from archived FFPE surgical specimens donated by St. Elizabeth Healthcare (Northern KY) and fully annotated by hospital records. H&E stained sections were diagnosed and graded by a board certified pathologist (LED) and included histologic sections from 41 borderline tumors and 98 Type 1 and Type 2 cancers. Adjacent sections were stained immunohistochemically using monoclonal antibodies (DAKO) to WT1 and p53. For survival analysis p53 was considered mutated if 75-100% of the tumor nuclei were stained (missense mutations) or if all nuclei were negative (truncated protein) and WT1 was considered either non-expressed (no stain) or expressed (some or all nuclei stained). While either mutated p53 or WT1 were prognostic alone of patient survival with Type 1 and Type 2 tumors, WT1 was a better predictor as seen by log-rank Chi-square. The 20 year survival probability of patients with tumors negative for both mutated p53 and WT1 was 70% and was significantly better than other patients (p < 0.0001). The 20 year survival probability for tumors negative for WT1 but expressing mutated p53 was 41%, and was 9% for tumors expressing WT1 and non-mutated p53. Patients with tumors expressing both WT1 and mutated p53 had a 20 year survival probability of 6%. Given these data and the immunogenicity of the WT1 tumor associated antigen we conclude that IHC detection of mutated p53 and WT1 in invasive ovarian cancers would be useful in stratifying patients eligible for immunologic approaches targeting WT1 for therapy of lethal ovarian cancers. Citation Format: Julia H. Carter, James A. Deddens, Gretchen Mueller, Thomas G. Lewis, Mariah K. Dooley, Jackson O. Pemberton, Larry E. Douglass. Evidence for WT1 as a potential target for immunotherapy of lethal ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2793. doi:10.1158/1538-7445.AM2017-2793

Breast cancer survival rates vary according to stage, tumor grade, and receptor status. While some cancer patients respond well to targeted therapy many patients respond poorly. Critical for advancing new therapies is developing a better understanding of the molecular drivers of breast cancer tumorigenesis and malignant progression. The synthesis of new proteins (translation) is important for cancer cell survival, growth, and proliferation. eIF4E is a rate limiting step in translation. Targeting translation has been suggested as a novel strategy for therapy of malignancies originating in the epithelium since eIF4E regulates the translation of multiple malignancy associated mRNAs. eIF4E is activated by phosphorylation downstream of the Mnk 1 and 2 kinases. We hypothesized that phosphorylation of eIF4E plays a critical role in driving breast cancer and is elevated in advanced cancers and metastases. Using immunochemistry and semi-quantitative cellular pathology approaches we analyzed expression of eIF4E and phospho-eIF4E in 168 FFPE archived surgical specimens of normal breast, benign breast disease and pre-invasive, invasive, and metastatic breast cancer. Immunohistochemical stain in the cytoplasm and nuclei of breast epithelial cells was evaluated microscopically by the area of epithelium stained and the intensity of stain (Histoscore = Area X Intensity). We found that expression of eIF4E in the cytoplasm and nuclei of breast epithelial cells was highly correlated with tumor progression (p < 0.0001 and p = 0.0025, respectively). Similarly phospho-eIF4E expression increased in concert with tumor progression (p < 0.0001) in both the cytoplasm and nuclei of breast epithelial cells. Interestingly, while expression of both eIF4E and phospho-eIF4E was not significantly increased in benign breast disease, expression of both eIF4E and phospho-eIF4E was significantly increased in atypical duct hyperplasia (p = 0.01) and in carcinoma in situ (p < 0.0001) as well as in invasive ductal carcinoma (p < 0.0001) relative to normal duct epithelium. Expression of eIF4E and phospho-eIF4E was also increased in lobular carcinoma in situ relative to expression in normal lobules. Breast cancers of all receptor types (ER+/-, PR +/-, Her2+/-, and triple negative) had increased expression of eIF4E and phospho-eIF4E relative to normal duct epithelium. These data are consistent with the conclusion that eIF4E and phospho-eIF4E are critical factors in breast cancer development and progression and that targeting either eIF4E or phosphorylation of eIF4E may be an effective strategy for therapy of all subtypes of breast cancer. Citation Format: Chad A. Dumstorf, Larry E. Douglass, James A. Deddens, Thomas G. Lewis, Kyle Darpel, Christian Gausvik, Jeremy R. Graff, Julia H. Carter. Phosphorylation of eIF4E is a critical factor in development and progression of breast cancer in women. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3919.

Intralesional bleomycin has been used for the treatment of warts since the 1970s. Currently, there is a limited amount of evidence from randomized placebo-controlled trials comparing intralesional bleomycin with other local treatments for warts. Numerous reports have been published on the use of intralesional bleomycin for the treatment of recalcitrant warts with cure rates ranging from 14% to 99%. The majority of the data suggests that bleomycin is effective in over two-thirds of the reported cases with minimal side effects. In this paper, we review the mechanism of action, pharmacokinetics, safety profile, supply and storage, dosage scheme, techniques for administration, and efficacy of intralesional bleomycin for the treatment of warts.

Pustular and erythrodermic psoriasis can be a debilitating and recalcitrant disease which may result in secondary complications such as sepsis, electrolyte imbalance, renal failure, and heart failure. We report a case of a 46-year-old patient with life-threatening erythrodermic psoriasis who responded rapidly to intravenous infliximab.

Recent investigations into the March 2003 outbreak of SARS in Hong Kong have concluded that environmental factors played an important role in the transmission of the disease. These studies have focused on a particular outbreak event, the rapid spread of SARS throughout Amoy Gardens, a large, private apartment complex. They have demonstrated that, unlike a typical viral outbreak that is spread through person-to-person contact, the SARS virus in this case was spread primarily through the air. High concentrations of viral aerosols in building plumbing were drawn into apartment bathrooms through floor drains. The initial exposures occurred in these bathrooms. The virus-laden air was then transported by prevailing winds to adjacent buildings at Amoy Gardens, where additional exposures occurred. This article reviews the results of the investigations and provides recommendations for maintenance and other measures that building owners can take to help prevent environmental transmission of SARS and other flulike viruses in their buildings.