Laura A Kresty

University of Michigan | U-M · Section of Thoracic Surgery

The primary pre-neoplastic lesion of the lower esophagus in the vicinity of the gastroesophageal junction (GEJ) is any Barrett’s esophageal lesions (BE), and esophageal neoplasia has increased in the US population with predispositions (Caucasian males, truncal obesity, age, and GERD). The responses to BE are endoscopic and screening cytologic progr...

Background Esophageal adenocarcinoma (EAC) represents a growing health problem characterized by rising incidence and poor prognosis due to late-stage diagnosis coupled with therapeutic resistance. Moreover, EAC is a cancer with a high mutational burden but lacks highly prevalent oncogenic drivers that can be successfully targeted. Herein, we invest...

INTRODUCTION Early neoplastic progression of Barrett’s esophagus (BE) is often treated with endoscopic therapy. While effective, some patients are refractory to therapy or recur after apparent eradication of the BE. The goal of this study was to determine whether genomic alterations within the treated BE may be associated with persistent or recurre...

Esophageal adenocarcinoma (EAC) represents a growing health problem characterized by rising incidence and poor prognosis. Although it is a cancer with a high mutational burden, it lacks highly prevalent oncogenic drivers that can be therapeutically targeted. Recently, our group characterized isoform switching events, defined by the changing of domi...

The gut and local esophageal microbiome progressively shift from healthy commensal bacteria to inflammatory-linked pathogenic bacteria in patients with gastroesophageal reflux disease, Barrett's esophagus and esophageal adenocarcinoma (EAC). However, mechanisms by which microbial communities and metabolites contribute to reflux-driven EAC remain in...

We recently reported that cranberry proanthocyanidins (C-PACs) inhibit esophageal adenocarcinoma (EAC) by 83% through reversing reflux-induced bacterial, inflammatory and immune-implicated proteins and genes as well as reducing esophageal bile acids, which drive EAC progression. This study investigated whether C-PACs’ mitigation of bile reflux-indu...

Background Esophageal adenocarcinoma (EAC) represents a growing health problem characterized by rising incidence and poor prognosis due to late-stage diagnosis coupled with treatment resistance. Although EAC is a cancer with a high mutational burden, it lacks highly prevalent oncogenic drivers that can be therapeutically targeted. Herein, we invest...

The gut and local esophageal microbiome progressively shift from healthy commensal bacteria to inflammatory-linked pathogenic bacteria in patients with gastroesophageal reflux disease, Barrett's esophagus and esophageal adenocarcinoma (EAC). However, mechanisms by which microbial communities and metabolites contribute to reflux-driven EAC remain in...

Lung cancer remains the leading cause of cancer mortality. Efficacious targeted therapy options are urgently needed for lung cancer prevention and treatment. Epidermal growth factor receptor (EGFR) mutant lung cancer represents about 15% of lung cancer cases generally occurring in patients with minimal to no smoking history and with higher prevalen...

Lung cancer remains the most frequently diagnosed cancer and leading cause of cancer mortality in the United States and worldwide. Efficacious targeted options are urgently needed for lung cancer prevention and treatment. Approximately 30% of non-small cell lung cancer cases have KRAS mutations, yet pharmacological targeting has eluded the scientif...

Background: Esophageal cancer (EC) originates in the setting of chronic inflammation. Although previous studies have sought to understand the role of inflammatory signaling in EC, the effect of these immunologic changes on patient outcomes remains understudied. This study's objective was to identify relationships between cytokine levels and progno...

Isoform switching events with predicted functional consequences are common in many cancers, but characterization of switching events in esophageal adenocarcinoma (EAC) is lacking. Next-generation sequencing was utilized to detect levels of RNA transcripts and identify specific isoforms in treatment naïve esophageal tissues ranging from premalignant...

Esophageal adenocarcinoma (EAC), the major subtype of esophageal cancer in the US, is characterized by increasing incidence rates and high mortality due to ineffective screening, late-stage diagnosis, and poor treatment efficacy. The only known precursor to EAC is Barrett’s Esophagus (BE), but the precise mechanisms and molecular events leading to...

Esophageal adenocarcinoma (EAC) is a cancer characterized by rapidly rising incidence and poor survival, resulting in the need for new prevention and treatment options. We utilized two cranberry polyphenol extracts, one pro-anthocyanidin enriched (C-PAC) and a combination of anthocyanins, flavonoids, and glycosides (AFG) to assess inhibitory mechan...

Persistent and symptomatic reflux of gastric and duodenal contents, known as gastroesophageal reflux disease (GERD), is the strongest risk factor for esophageal adenocarcinoma (EAC). Despite similar rates of GERD and other risk factors across racial groups, EAC progression disproportionately impacts Caucasians. We recently reported that elevated ti...

Persistent and symptomatic reflux of gastric and duodenal contents, known as gastroesophageal reflux disease (GERD), is the strongest risk factor for EAC development. GERD and esophagitis occur at similar rates among Blacks and Caucasians; yet, progression to EAC is significantly elevated among Caucasians. Unique protective factors in the epitheliu...

Esophageal adenocarcinoma (EAC) is a devastating cancer characterized by rising incidence and poor prognosis. The five-year survival rate is 20% due to late stage diagnosis and ineffective treatment. It is estimated that only 15% of EAC patients have a complete histopathological response to standard chemotherapy. Thus, new strategies are urgently n...

Esophageal Adenocarcinoma (EAC) develops from Barrett's Esophagus (BE), a chronic inflammatory state that can progress through a series of transformative dysplastic states before tumor development. While molecular and genetic changes of EAC tumors have been studied, immune microenvironment changes during Barrett's progression to EAC remain poorly u...

Introduction: Melanoma is an aggressive form of skin cancer for which there are no effective drugs for prolonged treatment. The existing kinase inhibitor antiglycolytic drugs (B-Raf serine/threonine kinase or BRAF inhibitors) are effective for a short time followed by a rapid onset of drug resistance. Presentation of case: Here, we show that a m...

Blacks experience disproportionate head and neck cancer (HNC) recurrence and mortality compared to Whites. Overall, vitamin D status is inversely associated to HNC pointing to a potential protective linkage. Although hypovitaminosis D in Blacks is well documented it has not been investigated in Black HNC patients. Thus, we conducted a prospective p...

p>Our laboratory studies chemoprevention of esophageal adenocarcinoma (EAC) through utilization of the rat esophagogastroduodenal anastomosis (EGDA) surgical model of reflux-induced EAC. Specifically, we evaluated mechanisms by which cranberry proanthocyanidins (C-PAC) inhibit reflux-induced EAC by utilizing multi-omics integrative approaches emplo...

Esophageal adenocarcinoma (EAC) is characterized by rising incidence rates and high mortality due to late stage diagnosis and a lack of efficacious options for prevention and treatment. While reasons for the rapid increase in EAC are being unraveled, persistent, symptomatic reflux of gastric and duodenal contents, known as gastroesophageal reflux d...

p>Esophageal adenocarcinoma (EAC) is characterized by rising incidence rates and high mortality due to late stage diagnosis and a lack of efficacious options for prevention and treatment. While reasons for the rapid increase in EAC are being unraveled, persistent, symptomatic reflux of gastric and duodenal contents, known as gastroesophageal reflux...

Lung cancer often has a poor prognosis, with brain metastases a major reason for mortality. We modified lonidamine (LND), an antiglycolytic drug with limited efficacy, to mitochondria-targeted mito-lonidamine (Mito-LND) which is 100-fold more potent. Mito-LND, a tumor-selective inhibitor of oxidative phosphorylation, inhibits mitochondrial bioenerg...

Background & aims: African American and European American individuals have a similar prevalence of gastroesophageal reflux disease (GERD), yet esophageal adenocarcinoma (EAC) disproportionately affects European American individuals. We investigated whether the esophageal squamous mucosa of African American individuals has features that protect aga...

Esophageal adenocarcinoma (EAC) incidence rates have increased sharply (>500%) throughout the Westernized world since the 1980s, despite the widespread use of endoscopy and anti-reflux medications. Reasons for the rapid increase in EAC are still being unraveled; however, persistent, symptomatic reflux of gastric and duodenal contents, known as gast...

Human exposure to environmental contaminants such as persistent chlorinated organics, heavy metals, pesticides, phthalates, flame retardants, electronic waste and airborne pollutants around the world, and especially in Southeast Asian regions, are significant and require urgent attention. Given this widespread contamination and abundance of such to...

Our laboratory has been investigating the cancer inhibitory potential of cranberry proanthocyanidins (C-PAC) against esophageal adenocarcinoma (EAC), a cancer characterized by rapidly rising incident rates and poor survival (18% 5-year survival rate for all stages combined). Utilizing a panel of validated human esophageal cancer cell lines and OE19...

Esophageal adenocarcinoma (EAC) is characterized by rapidly increasing incidence and mortality rates and poor survival. Efficacious preventive and treatment options are urgently needed. An increasing number of pharmacologic agents targeting cancer cell death via autophagy mechanisms are being evaluated in hopes of circumventing apoptotic and therap...

Cranberries are rich in bioactive constituents reported to influence a variety of health benefits, ranging from improved immune function and decreased infections to reduced cardiovascular disease and more recently cancer inhibition. A review of cranberry research targeting cancer revealed positive effects of cranberries or cranberry derived constit...

Black raspberries inhibit a broad range of cancers in preclinical models which has led to clinical evaluations targeting premalignant lesions of the colon, oral cavity and esophagus. A phase I pilot study was conducted in twenty Barrett's esophagus (BE) patients to investigate the effect of lyophilized black raspberries (LBR) on urinary metabolites...

Background: Black raspberries (BRB) inhibit a broad range of cancers in preclinical models, including in vivo models of oral, esophageal, colon, breast and skin cancer. Promising preclinical results have led to clinical evaluations in cancer patients or patients at increased risk for cancer development. Objective: To summarize clinical investiga...

Angle-resolved low coherence interferometry (a/LCI) is an optical technique used to measure nuclear morphology in situ. However, a/LCI is not an imaging modality and can produce ambiguous results when the measurements are not properly oriented to the tissue architecture. Here we present a 2D a/LCI system which incorporates optical coherence tomogra...

Background: We recently reported that a cranberry proanthocyanidin rich extract (C-PAC) induces autophagic cell death in apoptotic resistant esophageal adenocarcinoma (EAC) cells and necrosis in autophagy resistant cells. EAC is characterized by high morbidity and mortality rates supporting development of improved preventive interventions. Object...

Here we present the analysis of two dimensional angle-resolved low coherence interferometry (2D a/LCI) measurements co-registered with optical coherence tomography (OCT) imaging to guide the a/LCI measurements on an esophageal cancer rat model.

Cranberries are rich in bioactive constituents known to improve urinary tract health and more recent evidence supports cranberries possess cancer inhibitory properties. However, mechanisms of cancer inhibition by cranberries remain to be elucidated, particularly in vivo. Properties of a purified cranberry-derived proanthocyanidin extract (C-PAC) we...

Cranberries are rich in bioactive constituents known to improve urinary tract health and more recent evidence supports cranberries possess cancer inhibitory properties. However, mechanisms of cancer inhibition by cranberries remain to be elucidated, particularly in vivo. Properties of a purified cranberry-derived proanthocyanidin extract (C-PAC) we...

Rates of esophageal adenocarcinoma and the only known precursor lesion, Barrett's esophagus (BE), have markedly increased over the last three decades throughout the Westernized world. In the US 18,170 new incident cases and 15,450 deaths are estimated in 2014. These statistics reflect the poor 5-year survival rates (20%) and support the need for im...

Our laboratory has f cancer prevention using freeze-dried berries, mainly black raspberries, for more than two decades. Berries contain many known agents with chemopreventive potential including certain vitamins, minerals, simple and complex polyphenols, phytosterols, and various fiber constituents. Because berries are approximately 80-90 % water,...

The following, from the 12th OESO World Conference: Cancers of the Esophagus, includes commentaries on macronutrients, dietary patterns, and risk of adenocarcinoma in Barrett's esophagus; micronutrients, trace elements, and risk of Barrett's esophagus and esophageal adenocarcinoma; the role of mate consumption in the development of squamous cell ca...

The following, from the 12th OESO World Conference: Cancers of the Esophagus, includes commentaries on laryngopharyngeal reflux as a risk factor for laryngeal cancer; the role of pepsin in laryngopharyngeal neoplasia; natural fruit and vegetable compounds for the prevention and treatment of pharyngeal and esophageal cancers; and evaluation of cranb...

Worldwide head and neck cancer (HNC) is the sixth most frequently diagnosed cancer in men and is associated with significant morbidity, mortality and economic loss. African Americans (AA) experience significantly more HNC compared to Caucasian Americans (CA) and they have markedly reduced 5-year survival rates, 40% compared to 61% among CA. AA bear...

Aberrant expression of small noncoding endogenous RNA molecules known as microRNAs (miRNAs) is documented to occur in multiple cancer types including esophageal adencarcinoma (EAC) and its only known precursor, Barrett's esophagus (BE). Recent studies have linked dysregulation of specific miRNAs to histological grade, neoplastic progression and met...

Cranberries are rich in bioactive constituents purported to enhance immune function, improve urinary tract health, reduce cardiovascular disease and more recently, inhibit cancer in preclinical models. However, identification of the cranberry constituents with the strongest cancer inhibitory potential and the mechanism associated with cancer inhibi...

Worldwide esophageal cancer is the eighth most commonly diagnosed cancer, with squamous cell carcinoma and adenocarcinoma representing the two major histological types. In the United States, rates of esophageal adenocarcinoma (EAC) have increased over 500% in the last 30 years resulting in EAC being identified as the fastest increasing of all cance...

Little is known about the potential involvement of the oncoprotein gankyrin in human oral cancer progression. In this study, the levels of gankyrin mRNA and protein expression were assessed in human oral epithelial cell lines, at-risk normal oral tissues, premalignant oral lesions, and primary oral squamous cell carcinomas (OSCCs). Biopsies include...

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL Rates of esophageal adenocarcinoma (EAC) have dramatically increased (500%) over the last three decades in the US resulting in EAC being identified as the fastest increasing of all cancer types. Persistent, symptomatic, reflux of gastric and duodenal contents, known as gastro...

Defective DNA repair may contribute to early age and late stage at time of diagnosis and mutations in critical tumor suppressor genes, such as TP53 in breast cancer. Using DNA samples from 436 breast cancer cases (374 Caucasians and 62 African-Americans), we tested these associations with 18 non-synonymous single-nucleotide polymorphisms (nsSNPs) i...

This study investigated the cancer inhibitory potential of a proanthocyanidin rich cranberry extract utilizing a panel of authenticated human esophageal adenocarcinoma cell lines (EAC), a nude mouse xenograft model, and the rat esophagogastrodoudenal anastomosis (EGDA) model of EAC. PACs effects on cell morphology, global gene expression, phase of...

Plant foods and associated nutrients may impact prostate cancer (PC) risk and survival. Therefore, we compared dietary intake, mainly plant food groups among 382 controls and 478 PC cases (373 incident and 105 prevalent cases). Caucasian controls had significantly higher daily servings of vegetables (3.4 vs. 2.5, P= 0.002) and fruits and/or fruit j...

Proliferative verrucous leukoplakia (PVL) represents a rare but highly aggressive form of oral leukoplakia with > 70% progressing to malignancy. Yet, PVL remains biologically and genetically poorly understood. This study evaluated the cell cycle regulatory genes, p16INK4a and p14ARF, for homozygous deletion, loss of heterozygosity, and mutation eve...

The aim of this study was to assess the effects of topical application of a 10% (w/w) freeze-dried black raspberry (FBR) gel on oral intraepithelial neoplasia (IEN) variables that included histologic diagnoses and loss of heterozygosity (LOH) indices. Microsatellite instability and/or LOH at tumor suppressor gene-associated chromosomal loci have be...

The occurrence of esophageal adenocarcinoma and its only recognized precursor lesion, Barrett's esophagus, has rapidly increased during the past three decades. The precise reason for the rise remains to be elucidated, but increasing rates have been linked to multiple nutritional factors. Plant-based diets have generally been associated with a reduc...

Sustained inflammation up-regulates the reactive species (RS) generating enzymes inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). While clinical data show that levels of iNOS and COX-2 are increased in epithelium during the transformation of dysplasia to overt head and neck squamous cell carcinoma (HNSCC), the mechanisms by whic...

There is little information on early molecular events in the development of N-nitrosomethylbenzylamine (NMBA)-induced rat esophageal tumorigenesis and of the effects of chemopreventive agents on these events. In this study, we identified genes in rat esophagus that were differentially expressed in response to short-term NMBA treatment and modulated...

Optical spectroscopy was used to evaluate the transformation of nuclear morphology associated with intraepithelial neoplasia in an animal model of carcinogenesis. In this pilot study, we have assessed the capability of angle-resolved low-coherence interferometry (a/LCI) to monitor in situ the neoplastic progression of hamster trachea epithelial tis...

There is increased cyclooxygenase-2 (COX-2) expression in malignant thyroid nodules compared with nonneoplastic and benign thyroid tissue. The objective of the study was to evaluate the efficacy of celecoxib, a selective COX-2 inhibitor, in treating patients with progressive metastatic differentiated thyroid cancer (DTC) and to explore the relation...

As part of ongoing studies aimed at identifying the molecular events involved in head and neck squamous cell carcinoma progression, we recently isolated a novel serine protease, DESC1. This study was conducted to further characterize DESC1. Specimens of normal, dysplastic, and carcinomatous oropharyngeal mucosa (n = 31) were evaluated for DESC1 imm...

For several years, our laboratory has been evaluating the ability of lyophilized (freeze-dried) black raspberries (Rubus occidentalis, BRBs), blackberries (R. fructicosus, BBs), and strawberries (Fragaria ananasia, STRWs) to inhibit carcinogen-induced cancer in the rodent esophagus. To assure "standardized" berry preparations for study, each berry...

Increased fruit and vegetable consumption is associated with decreased risk of a number of cancers of epithelial origin, including esophageal cancer. Dietary administration of lyophilized black raspberries (LBRs) has significantly inhibited chemically induced oral, esophageal, and colon carcinogenesis in animal models. Likewise, berry extracts adde...

The inducible nitric oxide synthase (iNOS) generates a high concentration of nitric oxide (NO) in tissues. Increased NO production is associated with many disorders including esophageal cancer. Previous studies in our laboratory demonstrated an association between increased iNOS expression and the development of N-nitrosomethylbenzylamine (NMBA)-in...

Oral cavity cancers represent 2.5% of the cancers that occur in the United States and are ranked sixth worldwide. Since current therapeutic protocols are relatively ineffective, alternative strategies for prevention need to be developed and tested in appropriate animal models. In the study reported herein, the hamster cheek pouch (HCP) was used to...

Oral cavity cancers represent 2.5% of the cancers that occur in the United States and are ranked sixth worldwide. Since current therapeutic protocols are relatively ineffective, alternative strategies for prevention need to be developed and tested in appropriate animal models. In the study reported herein, the hamster cheek pouch (HCP) was used to...

A number of genetic aberrations have been reported in end-stage squamous cell carcinoma of the head and neck, including p16(INK4a) and p14(ARF) (INK4a/ARF) inactivation rates of 70-85%. Still, the cell cycle-regulatory genes p16(INK4a) and p14(ARF) remain poorly understood in oral cavity premalignant lesions. This study evaluated INK4a/ARF locus al...

N-nitrosomethylbenzylamine (NMBA)-induced rat esophageal tumorigenesis is an important model for squamous cell carcinoma of the human esophagus. In this model, previous studies have shown that the GGA-->GAA Ha-ras codon 12 mutation is present in the majority of papillomas. No other Ha-ras mutation has been identified. Studies using other models of...

Fruit and vegetable consumption has consistently been associated with decreased risk of a number of aerodigestive tract cancers, including esophageal cancer. We have taken a "food-based" chemopreventive approach to evaluate the inhibitory potential of lyophilized black raspberries (LBRs) against N-nitrosomethylbenzylamine (NMBA)-induced esophageal...

N-nitrosomethylbenzylamine (NMBA)–induced rat esophageal tumorigenesis is an important model for squamous cell carcinoma of the human esophagus. In this model, previous studies have shown that the GGA→GAA Ha-ras codon 12 mutation is present in the majority of papillomas. No other Ha-ras mutation has been identified. Studies using other models of ch...