Immunocytochemistry for MUC4 and MUC16 is a useful adjunct in the diagnosis of pancreatic adenocarcinoma on fine-needle aspiration cytology.

Context: Diagnoses rendered as atypical/suspicious for malignancy on fine-needle aspiration (FNA) of pancreatic mass lesions range from 2% to 29% in various studies. We have identified the expression of 3 genes, MUC4, MUC16, and NGAL that are highly upregulated in pancreatic adenocarcinoma. In this study, we analyzed the expression of these markers in FNA samples to determine whether they could improve sensitivity and specificity.

Targeting the NF-κB and mTOR pathways with a quinoxaline urea analog that inhibits IKKβ for pancreas cancer therapy.

Purpose: The presence of TNF-α in approximately 50% of surgically resected tumors suggests that the canonical NF-κB and the mTOR pathways are activated. Inhibitor of IκB kinase β (IKKβ) acts as the signaling node that regulates transcription via the p-IκBα/NF-κB axis and regulates translation via the mTOR/p-S6K/p-eIF4EBP axis. A kinome screen identified a quinoxaline urea analog 13-197 as an IKKβ inhibitor.

MUC4 overexpression augments cell migration and metastasis through EGFR family proteins in triple negative breast cancer cells.

Introduction: Current studies indicate that triple negative breast cancer (TNBC), an aggressive breast cancer subtype, is associated with poor prognosis and an early pattern of metastasis. Emerging evidence suggests that MUC4 mucin is associated with metastasis of various cancers, including breast cancer. However, the functional role of MUC4 remains unclear in breast cancers, especially in TNBCs.

Intraepithelial T cells and tumor-associated macrophages in ovarian cancer patients.

The aims of this study were to evaluate the prognostic significance of tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs) in patients with familial ovarian cancer. Clinical and pathological information were retrieved from the Gilda Radner Familial Ovarian Cancer Registry (GRFOCR) in Buffalo, NY. Immunohistochemistry was performed on paraffin-embedded tissue specimens of GRFOCR participants using specific antibodies for CD3+, CD8+, CD25+, FOXP3+, CD68+, and CD163+.

Prognostic evaluation of catalytic iron in patients with acute coronary syndromes.

Background: The potential of iron to generate reactive oxygen species has motivated a long-standing interest in whether excess iron is causally linked to atherosclerotic heart disease. Circulating catalytic iron ("free" iron) is that which is not bound to transferrin or ferritin and is available to generate reactive oxygen species that may have deleterious vascular effects.

Hypothesis: We hypothesized that increased levels of catalytic iron would be associated with increased cardiovascular events.

Evaluation of the outcome benefit conferred by intensive surveillance strategies in women with early-stage endometrial cancer.

Introduction: The optimum follow-up regimen after treatment for early-stage endometrial cancer with curative intent is unknown. The National Comprehensive Cancer Network recommends a physical exam and vaginal cytology every three to six months for two years then at six to 12 month intervals with annual chest X-rays (CXR). However, there is debate as to whether intensive follow-up results in an improvement in outcomes for those with recurrent endometrial cancer.

The effects of aircraft on climate and pollution. Part II: 20-year impacts of exhaust from all commercial aircraft worldwide treated individually at the subgrid scale.

This study examines the 20-year impacts of emissions from all commercial aircraft flights worldwide on climate, cloudiness, and atmospheric composition. Aircraft emissions from each individual flight worldwide were modeled to evolve from the subgrid to grid scale with the global model described and evaluated in Part I of this study. Simulations with and without aircraft emissions were run for 20 years.

Interactive case vignettes utilizing simulated pathologist-clinician encounters with whole slide imaging and video tutorials of whole slide scans improves student understanding of disease processes.

Background: One of the drawbacks of studying pathology in the second year of medical school in a classroom setting is the relatively limited exposure to patient encounters/clinical rotations, making it difficult to understand and fully appreciate the significance of the course material, specifically the molecular and tissue aspects of disease. In this study, we determined if case vignettes incorporating pathologist-clinician encounters with whole slide imaging (WSI) and narrated/annotated videos of whole slide (WS) scans in addition to clinical data improved student understanding of pathologic disease processes.

Materials And Methods: Case vignettes were created for several genitourinary disease processes that utilized clinical data including narratives of pathologist-clinician encounters, WSI, and annotated video tutorials of WS scans (designed to simulate "double-heading").

Elevated expression of the serine-arginine protein kinase 1 gene in ovarian cancer and its role in Cisplatin cytotoxicity in vitro.

Alternatively spliced variants of several oncogenes and tumor suppressors have been shown to be important for their tumorigenicity. In the present study we have tested whether serine-arginine protein kinase 1 (SRPK1), a major regulator of splicing factors, is involved in ovarian cancer progression and plays a role in chemo-sensitivity. By Western blot analyses, SRPK1 protein was found to be overexpressed in 4 out of 6 ovarian cancer cell lines as compared with an immortalized ovarian surface epithelial cell line; and in 55% of ovarian tumor samples as compared with non-neoplastic ovarian tissue samples.

Full-gene-sequencing analysis of N-acetyltransferase-2 in an adult Indian population.

Aims: Drug-metabolizing enzymes play a major role in determining the outcome of drug therapy. N-acetyltransferase-2 (NAT2) is one of the main enzymes involved in metabolism of isoniazid used in treatment of tuberculosis (TB). Several variations in the NAT2 gene give rise to multiple haplotypes that phenotypically code for different acetylator status.

Novel mechanism of apoptosis resistance in cancer mediated by extracellular PAR-4.

Tumor suppressor PAR-4 acts in part by modulating sensitivity to apoptosis, but the basis for its activity is not fully understood. In this study, we describe a novel mechanism of antiapoptosis by NF-κB, revealing that it can block PAR-4-mediated apoptosis by downregulating trafficking of the PAR-4 receptor GRP78 from the endoplasmic reticulum to the cell surface. Mechanistic investigations revealed that NF-κB mediated this antiapoptotic mechanism by upregulating expression of UACA, a proinflammatory protein in certain disease settings.

Comparison of outcomes in patients treated with multi-agent regiments of cisplatin, adriamycin, and VP-16 versus carboplatin and paclitaxel for advanced and recurrent endometrial cancer.

Objective: The objective of this study was to compare the efficacy of two multi-agent chemotherapeutic regiments that were previously used at the Institution for treatment of advanced and recurrent endometrial cancer.

Methods: A retrospective review of patients with Stage III, IV, and recurrent endometrial cancer who received adjuvant chemotherapy at Roswell Park Cancer Institute over a period of 21 years. Two patient groups were defined based on treatment received: cisplatin, adriamycin, and VP-16 with or without megace (PAV-M), or carboplatin and paclitaxel (CT).

Transforming growth factor alpha (TGFα) regulates granulosa cell tumor (GCT) cell proliferation and migration through activation of multiple pathways.

Granulosa cell tumors (GCTs) are the most common ovarian estrogen producing tumors, leading to symptoms of excessive estrogen such as endometrial hyperplasia and endometrial adenocarcinoma. These tumors have malignant potential and often recur. The etiology of GCT is unknown.

Ovarian cancer, version 3.2012.

These NCCN Guidelines Insights focus on the major updates for the 2012 NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Ovarian Cancer by describing how and why the new recommendations were made. The 6 update topics were selected based on recent important updates in the guidelines and on debate among panel members about recent clinical trials, and include: 1) screening, 2) diagnostic tests for assessing pelvic masses, 3) primary treatment using neoadjuvant chemotherapy, 4) primary adjuvant treatment using bevacizumab in combination with chemotherapy, 5) therapy for recurrent disease, and 6) management of drug/hypersensitivity reactions. These NCCN Guidelines Insights also discuss why some recommendations were not made (eg, panel members did not feel the new data warranted changing the guideline).

Associations between gene expression variations and ovarian cancer risk alleles identified from genome wide association studies.

Functional genetic variations play important roles in shaping phenotypic differences among individuals through affecting gene expression, and thus, very likely to influence disease susceptibility, such as cancer susceptibility. One critical question in this era of post-genome wide association studies (GWAS) is how to assess the functional significance of the genetic variations identified from GWAS. In the current study, with lymphoblastoid cell lines (LCLs) from 74 non-related women with familial ovarian cancer and 47 unrelated controls matched on gender and race, we explored the associations between seven ovarian cancer risk variants identified from GWAS (rs3814113 on 9p22.

A study on genetic test of lactase persistence in relation to milk consumption in regional groups of India.

Background: Lactase nonpersistence (LNP) is characterized by the decrease in lactase expression in the small intestine. Studies have shown that -13910 C>T and -22018 G>A single-nucleotide polymorphisms (SNPs) located upstream of the lactase gene are associated with an LNP/lactase persistence (LP) trait.

Objective: The current study evaluated the LP allelic frequency in 227 healthy Indian subjects consisting of North Indians, Maharashtrians, Gujaratis, Parsis, and South Indians, and for the first time assessed its relation with milk consumption pattern in Indian subjects.

Overexpression of ecdysoneless in pancreatic cancer and its role in oncogenesis by regulating glycolysis.

Purpose: To study the expression and function of a novel cell-cycle regulatory protein, human ecdysoneless (Ecd), during pancreatic cancer pathogenesis.

Experimental Design: Immunohistochemical expression profiling of Ecd was done in nonneoplastic normal pancreatic tissues and pancreatic ductal adenocarcinoma lesions (from tissue microarray and Rapid Autopsy program) as well as precancerous PanIN lesions and metastatic organs. To analyze the biological significance of Ecd in pancreatic cancer progression, Ecd was stably knocked down in pancreatic cancer cell line followed by in vitro and in vivo functional assays.

The role of hypoxic-inducible factor (HIF1α) and aldolaseC protein in endometrial carcinogenesis: a retrospective study of 279 patients.

Objectives: Hypoxia-inducible factor (HIF1α) plays an integral role in response to hypoxia, controlling dozens of target genes including aldolaseC (ALDC), an important enzyme in the glycolytic pathway. It also induces angiogenesis, allowing survival and proliferation of cancer cells. The aims of our study were to evaluate the expressions of HIF1α and ALDC in patients with endometrial cancer (EC) and define their association with disease outcome and to determine the existence of an association between HIF1α and ALDC proteins.

A nodular growth on maxillary gingiva.

A case of angiosarcoma of maxilla is presented. The occurrence of angiosarcoma in the oral cavity is a rare incidence and maxilla is one of the rarest sites to be involved. The purpose of this article is also to emphasize the fact that sometimes small, innocent-looking masses in the oral cavity might actually turn out to be a highly destructive malignant tumor.

Clinically undiagnosed prostate carcinoma metastatic to renal oncocytoma.

Tumors-to-tumor metastasis is an uncommon occurrence and can be a source of great diagnostic difficulty, especially when the donor tumor is undiagnosed. Here we report a case of a kidney resected for a primary neoplasm (oncocytoma) that harbored metastases from a clinically undiagnosed prostatic adenocarcinoma. The presence of the poorly differentiated metastasis within an otherwise typical oncocytoma in the absence of metastases in the surrounding nonneoplastic renal parenchyma resulted in a diagnostic dilemma.

Pair Box 8 (PAX8) protein expression in high grade, late stage (stages III and IV) ovarian serous carcinoma.

Objectives: Pair-Box 8 (PAX8) is a transcription factor which has been found to be overexpressed in ovarian serous carcinoma (OSC). Silencing PAX8 by using shRNA led to a drop in cell viability in ovarian cancer cell lines, suggesting its use as a targeted therapeutic agent. The prognostic value of PAX8 in OSC is still widely unknown.

Pair-Box (PAX8) protein-positive expression is associated with poor disease outcome in women with endometrial cancer.

Background: The Pax8 transcription factor genes have a role in cell differentiation and cell growth, and silencing of Pax8 in cell cultures results in cell death. The aims of this study were to determine the expression and correlation of Pax8 protein with several clinicopathological variables in patients with endometrial cancer.

Methods: The following clinical parameters from 229 patients were used for correlation with Pax8 expression; age, histological subtype, myometrial depth of invasion, lymphovascular invasion (LVI), the International Federation of Gynecology and Obstetrics grade, lymph nodes status, and disease status.

A bilobed schwannoma in roof of orbit: a rare case report.

In this paper, we report a case of bilobed schwannoma, presented in the roof of orbit arising from supraorbital nerve. A 62-year male presented with a nontender mass in superior part of orbit and eccentric proptosis. Visual acuity and rest of ocular examination were normal.

Concordance between whole-slide imaging and light microscopy for routine surgical pathology.

The use of high-resolution digital images of histopathology slides as a routine diagnostic tool for surgical pathology was investigated. The study purpose was to determine the diagnostic concordance between pathologic interpretations using whole-slide imaging and standard light microscopy. Two hundred fifty-one consecutive surgical pathology cases (312 parts, 1085 slides) from a single pathology service were included in the study after cases had been signed out and reports generated.

Reactive oxygen species induced by p66Shc longevity protein mediate nongenomic androgen action via tyrosine phosphorylation signaling to enhance tumorigenicity of prostate cancer cells.

Steroid hormones exhibit diverse biological activities. Despite intensive studies on steroid function at the genomic level, their nongenomic actions remain an enigma. In this study, we investigated the role of reactive oxygen species (ROS) in androgen-stimulated prostate cancer (PCa) cell proliferation.