Targeting genomic receptors in voided urine for confirmation of benign prostatic hyperplasia.

Objectives: The objective of this study is to validate a hypothesis that a non-invasive optical imaging assay targeting genomic VPAC receptors on malignant cells shed in voided urine will represent either benign prostatic hyperplasia (BPH) or prostatic cancer (PCa). Risk for BPH in men 50-70 years old is 50-70% and PCa is 17%. BPH and PCa can coexist in 20% of men with BPH.

CD8+ and FoxP3+ T-Cell Cellular Density and Spatial Distribution After Programmed Death-Ligand 1 Check Point Inhibition.

Objectives: To analyze CD8+ and FoxP3+ T-cell cellular density (CD) and intercellular distances (ID) in head and neck squamous cell carcinoma (HNSCC) samples from a neoadjuvant trial of durvalumab +/- metformin.

Methods: Paired pre- and post-treatment primary HNSCC tumor samples were stained for CD8+ and FoxP3+. Digital image analysis was used to determine estimated mean CD8+ and FoxP3+ CDs and CD8+-FoxP3+ IDs in the leading tumor edge (LTE) and tumor adjacent stroma (TAS) stratified by treatment arm, human papillomavirus (HPV) status, and pathologic treatment response.

Human abdominal aortic aneurysm (AAA): Evidence for an autoimmune antigen-driven disease.

Abdominal aortic aneurism (AAA) is a complex immunological disease with a strong genetic component, and one of the ten leading causes of death of individuals 55-74 years old worldwide. Strong evidence has been accumulated suggesting that AAA is an autoimmune specific antigen-driven disease. Mononuclear cells infiltrating AAA lesions comprised of T and B lymphocytes and other cells expressing early-, intermediate- and late-activation antigens, and the presence of antigen-presenting cells have been documented, demonstrating an ongoing immune response.

A Single Dose of the Deactivated Rabies-Virus Vectored COVID-19 Vaccine, CORAVAX, Is Highly Efficacious and Alleviates Lung Inflammation in the Hamster Model.

Without sufficient herd immunity through either vaccination or natural infection, the coronavirus disease 2019 pandemic is unlikely to be controlled. Waning immunity with the currently approved vaccines suggests the need to evaluate vaccines causing the induction of long-term responses. Here, we report the immunogenicity and efficacy of our adjuvanted single-dose Rabies-vectored SARS-CoV-2 S1 vaccine, CORAVAX, in hamsters.

Detection of lung carcinoma arising from ground glass opacities (GGO) after 5 years - A retrospective review.

Pure ground glass opacities (GGO) may indicate pre-invasive subtypes of lung carcinoma. These neoplasms typically demonstrate indolent patterns of growth; Fleischner Society guidelines recommend up to five years of serial imaging. Our aim was to determine the frequency of diagnosed carcinoma arising from GGO detected beyond 5 years of surveillance.

Intraoperative Cytologic Sampling for Resected Pancreatic and Periampullary Adenocarcinoma with Implications for Locoregional Recurrence-Free Survival.

Background: We hypothesized that pancreatic and periampullary adenocarcinoma recurrence after surgical resection may be affected by the shedding of malignant epithelial cells during surgical dissection and that this may have implications for disease recurrence and survival.

Study Design: In this ongoing, investigator-initiated prospective randomized controlled trial, patients with pancreatic and periampullary adenocarcinoma were randomized intraoperatively, postresection into 3 study arms: peritoneal lavage using 10 L normal saline or distilled water, or control group with no lavage. Peritoneal fluid was sampled for cytologic analysis (cytospin, cellblock, immunohistochemistry-Ber-EP4 antibody) at 4 stages: (1) abdominal entry pre-dissection, (2) resection bed after tumor extirpation, (3) ex vivo resected specimen, and (4) resection bed postlavage.

Accuracy of cytopathology evaluation for resected benign and malignant pancreatic disease.

Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is the preferred method for diagnosing pancreatic masses. While the diagnostic success of EUS-FNA is widely accepted, the actual performance of EUS-FNA is not known. This study sought to define the EUS-FNA accuracy compared with the gold standard, surgically resected specimens.

Resected WHO grade I meningioma and predictors of local control.

Introduction: Despite optimal surgical resection, meningiomas may recur, with increasing grade and the degree of resection being predictive of risk. We hypothesize that an increasing Ki67 correlates with a higher risk of recurrence of resected WHO grade I meningiomas.

Methods: The study population consisted of patients with resected WHO grade 1 meningiomas in locations outside of the base of skull.

Cytological interpretation of p16 immunohistochemistry in head and neck carcinomas: does the choice of fixative matter?

Introduction: Fine-needle aspiration (FNA) of nodal metastases plays a key role in the diagnosis of oropharyngeal squamous cell carcinoma (OPSCC). Because of significant clinical implications of human papillomavirus (HPV)-related OPSCC, immunohistochemistry for p16 as a surrogate marker for high-risk HPV is an important ancillary test. After our laboratory switched from CytoLyt to formalin fixative for FNA needle rinses generating cell block (CB) material, we investigated the impact of this protocol change on the accuracy of p16 results.

Molecular profiling of key driver genes improves staging accuracy in multifocal non-small cell lung cancer.

Objective: Multifocal non-small cell lung cancer has historically been separated into synchronous primary lung cancers or intrapulmonary metastases with the use of histopathology. We hypothesize that using targeted next-generation sequencing of key driver mutations in multifocal non-small cell lung cancer will improve our ability to differentiate intrapulmonary metastases from synchronous primary lung cancers.

Methods: We identified patients who underwent surgery for non-small cell lung cancer between 2013 and 2018 with multifocal tumors.

Cytohistologic correlation of basaloid salivary gland neoplasms: Can cytomorphologic classification be used to diagnose and grade these tumors?

Background: Basaloid salivary gland neoplasms (BSNs), which include benign primary tumors and primary or metastatic malignancies, show overlapping morphology in fine-needle aspiration (FNA). The Milan system recommends assigning a grade (low or high) to malignant salivary neoplasms because of the impact on surgical planning. This study investigated cytomorphologic features of BSNs on FNA that would help to favor a high-grade malignancy over a low-grade malignancy or a benign tumor.

Metformin Effects on FOXP3 and CD8 T Cell Infiltrates of Head and Neck Squamous Cell Carcinoma.

Objectives: Alterations of cellular metabolism have been implicated in immune dysfunction in the tumor microenvironment (TME) of head and neck squamous cell carcinoma (HNSCC). Metformin has recently emerged as a candidate of interest for combination with immunotherapy in HNSCC. This study investigated the effect of metformin on immune cell infiltrates of HNSCC.

Clonally expanded alpha-chain T-cell receptor (TCR) transcripts are present in aneurysmal lesions of patients with Abdominal Aortic Aneurysm (AAA).

Abdominal aortic aneurysm (AAA) is a life-threatening immunological disease responsible for 1 to 2% of all deaths in 65 year old or older individuals. Although mononuclear cell infiltrates have been demonstrated in AAA lesions and autoimmunity may be responsible for the initiation and account for the propagation of the disease, the information available about the pathogenesis of AAA is limited. To examine whether AAA lesions from patients with AAA contain clonally expanded α-chain TCR transcripts, we amplified by the non-palindromic adaptor-PCR (NPA-PCR)/Vα-specific PCR and/or the Vα-specific PCR these α-chain TCR transcripts.

Vasodilator-Stimulated Phosphoprotein Biomarkers Are Associated with Invasion and Metastasis in Colorectal Cancer.

Background And Aims: The benefit of adjuvant chemotherapy for stage II colorectal cancer (CRC) patients remains unclear, emphasizing the need for improved prognostic biomarkers to identify patients at risk of metastatic recurrence. To address this unmet clinical need, we examined the expression and phosphorylation status of the vasodilator-stimulated phosphoprotein (VASP) in CRC tumor progression. VASP, a processive actin polymerase, promotes the formation of invasive membrane structures leading to extracellular matrix remodeling and tumor invasion.

Performance of Molecular Lymphosonography for Detection and Quantification of Metastatic Involvement in Sentinel Lymph Nodes.

Objectives: To assess the performance of molecular lymphosonography with dual-targeted microbubbles in detecting and quantifying the metastatic involvement in sentinel lymph nodes (SLNs) using a swine melanoma model.

Methods: Targeted microbubbles were labeled with P-selectin and α β -integrin antibodies. Control microbubbles were labeled with immunoglobulin G antibodies.

Contiguous verrucous proliferations in syringocystadenoma papilliferum: A retrospective analysis with additional evaluation via mutation-specific BRAFV600E immunohistochemistry.

Background: Syringocystadenoma papilliferum (SCAP) is an uncommon cutaneous adnexal proliferation. There have been several reports describing collision lesions of SCAP and verruca, although little is known about the frequency of this association. Molecular testing has revealed the BRAFV600E mutation in a large proportion of SCAP cases, although its expression pattern has not been previously evaluated.

Sentinel Lymph Node Characterization with a Dual-Targeted Molecular Ultrasound Contrast Agent.

Purpose: The purpose of this study was to assess the performance of molecular ultrasound with dual-targeted microbubbles to detect metastatic disease in the sentinel lymph nodes (SLNs) in swine model of naturally occurring melanoma. The SLN is the first lymph node in the lymphatic chain draining primary tumor, and early detection of metastatic SLN involvement is critical in the appropriate management of melanoma.

Procedure: Nine Sinclair swine (weight 3-7 kg; Sinclair BioResources, Columbia, MO, USA) with naturally occurring melanoma were examined.

Intratumoral heterogeneity analysis reveals hidden associations between protein expression losses and patient survival in clear cell renal cell carcinoma.

Intratumoral heterogeneity (ITH) is a prominent feature of kidney cancer. It is not known whether it has utility in finding associations between protein expression and clinical parameters. We used ITH that is detected by immunohistochemistry (IHC) to aid the association analysis between the loss of SWI/SNF components and clinical parameters.

IGFBP3 Modulates Lung Tumorigenesis and Cell Growth through IGF1 Signaling.

Insulin-like growth factor binding protein 3 (IGFBP3) modulates cell growth through IGF-dependent and -independent mechanisms. Reports suggest that the serum levels of IGFBP3 are associated with various cancers and that IGFBP3 expression is significantly decreased in cisplatin (CDDP)-resistant lung cancer cells. Based on these findings, we investigated whether deficiency accelerates mouse lung tumorigenesis and if expression of IGFBP3 enhances CDDP response by focusing on the IGF1 signaling cascade.

The role of Nrf2 and ATF2 in resistance to platinum-based chemotherapy.

Purpose: Nrf2 and its role in controlling levels of the AKR family of aldo-keto reductases which have been implicated in resistance to platinum-based chemotherapy was studied in ovarian, cervical and lung cell lines.

Methods: Nrf2 shRNA knockdowns of cells from different tumor origins were prepared to determine the role of this factor in producing resistance to platinum chemotherapy.

Results: Nrf2 knockdowns resulted in marked decreases in AKR1C1, AKR1C2 and to a lesser extent AKR1C3.

Development of a voided urine assay for detecting prostate cancer non-invasively: a pilot study.

Objective: To validate a hypothesis that prostate cancer can be detected non-invasively by a simple and reliable assay by targeting genomic VPAC receptors expressed on malignant prostate cancer cells shed in voided urine.

Patients/subjects And Methods: VPAC receptors were targeted with a specific biomolecule, TP4303, developed in our laboratory. With an Institutional Review Board exempt approval of use of de-identified discarded samples, an aliquot of urine collected as a standard of care, from patients presenting to the urology clinic (207 patients, 176 men and 31 women, aged ≥21 years) was cytospun.

Neutrophil to lymphocyte ratio associated with prognosis of lung cancer.

Purpose: Many studies recently focus on complicated and expensive genomic tests, but the prognostic values of biochemical markers which are easily obtained in clinics are largely overlooked and without further exploration. This study assesses the association of neutrophil-lymphocyte-ratio (NLR) with prognosis of lung cancer patients.

Methods: In 1032 patients with histologically confirmed lung cancer, the association of pretreatment NLR values with overall survival (OS) was evaluated using a Cox proportional hazards model and the temporal relationship of longitudinal NLR was assessed using a mixed effects model.

Immunohistochemistry Successfully Uncovers Intratumoral Heterogeneity and Widespread Co-Losses of Chromatin Regulators in Clear Cell Renal Cell Carcinoma.

Recent studies have shown that intratumoral heterogeneity (ITH) is prevalent in clear cell renal cell carcinoma (ccRCC), based on DNA sequencing and chromosome aberration analysis of multiple regions from the same tumor. VHL mutations were found to be universal throughout individual tumors when it occurred (ubiquitous), while the mutations in other tumor suppressor genes tended to be detected only in parts of the tumors (subclonal). ITH has been studied mostly by DNA sequencing in limited numbers of samples, either by whole genome sequencing or by targeted sequencing.