Publications by authors named "James Elliot Carter"

8 Publications

  • Page 1 of 1

Clinicopathologic significance and race-specific prognostic association of MYB overexpression in ovarian cancer.

Sci Rep 2021 Jun 18;11(1):12901. Epub 2021 Jun 18.

Department of Pathology, College of Medicine, University of South Alabama, Mobile, AL, 36617, USA.

Late diagnosis, unreliable prognostic assessment, and poorly-guided therapeutic planning result in dismal survival of ovarian cancer (OC) patients. Therefore, identifying novel functional biomarker(s) is highly desired for improved clinical management. MYB is an oncogenic transcription factor with emerging functional significance in OC. Here we examined its clinicopathologic significance by immunohistochemistry and TCGA/GTex data analyses. Aberrant MYB expression was detected in 94% of OC cases (n = 373), but not in the normal ovarian tissues (n = 23). MYB was overexpressed in all major epithelial OC histological subtypes exhibiting the highest incidence (~ 97%) and overall expression in serous and mucinous carcinomas. MYB expression correlated positively with tumor grades and stages. Moreover, MYB exhibited race-specific prognostic association. Moderate-to-high MYB levels were significantly associated with both poor overall- (p = 0.02) and progression-free (p = 0.02) survival in African American (AA), but not in the Caucasian American (CA) patients. Consistent with immunohistochemistry data, we observed significantly higher MYB transcripts in OC cases (n = 426) than normal ovary (n = 88). MYB transcripts were significantly higher in all epithelial OC subtypes, compared to normal, and its greater levels predicted poor survival in AA OC, but not CA OC, patients. Thus, MYB appears to be a useful clinical biomarker for prognostication, especially in AA patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-92352-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213794PMC
June 2021

Co-targeting of CXCR4 and hedgehog pathways disrupts tumor-stromal crosstalk and improves chemotherapeutic efficacy in pancreatic cancer.

J Biol Chem 2020 06 1;295(25):8413-8424. Epub 2020 May 1.

Department of Pathology, College of Medicine, University of South Alabama, Mobile, Alabama

Pancreatic cancer (PC) remains a therapeutic challenge because of its intrinsic and extrinsic chemoresistance mechanisms. Here, we report that C--C motif chemokine receptor 4 (CXCR4) and hedgehog pathways cooperate in PC chemoresistance via bidirectional tumor-stromal crosstalk. We show that when PC cells are co-cultured with pancreatic stellate cells (PSCs) they are significantly more resistant to gemcitabine toxicity than those grown in monoculture. We also demonstrate that this co-culture-induced chemoresistance is abrogated by inhibition of the CXCR4 and hedgehog pathways. Similarly, the co-culture-induced altered expression of genes in PC cells associated with gemcitabine metabolism, antioxidant defense, and cancer stemness is also reversed upon CXCR4 and hedgehog inhibition. We have confirmed the functional impact of these genetic alterations by measuring gemcitabine metabolites, reactive oxygen species production, and sphere formation in vehicle- or gemcitabine-treated monocultures and co-cultured PC cells. Treatment of orthotopic pancreatic tumor-bearing mice with gemcitabine alone or in combination with a CXCR4 antagonist (AMD3100) or hedgehog inhibitor (GDC-0449) displays reduced tumor growth. Notably, we show that the triple combination treatment is the most effective, resulting in nearly complete suppression of tumor growth. Immunohistochemical analysis of Ki67 and cleaved caspase-3 confirm these findings from imaging and tumor measurements. Our findings provide preclinical and mechanistic evidence that a combination of gemcitabine treatment with targeted inhibition of both the CXCR4 and hedgehog pathways improves outcomes in a PC mouse model.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1074/jbc.RA119.011748DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7307206PMC
June 2020

Looking at cancer health disparities without the colored lenses.

Cancer Health Disparities 2019 19;3:e1-e9. Epub 2019 Aug 19.

Department of Oncologic Sciences, Mitchell Cancer Institute, University of South Alabama, Mobile, AL 36604, USA.

Cancer health disparities (CHDs), defined as the adverse differences in cancer incidence and mortality, are prevalent in certain racial and ethnic groups. Underlying causes of CHDs are multi-factorial and debatable. While low socioeconomic status, geographical location, lifestyle and behavioral factors are mostly believed to contribute to CHDs, regardless of ethnic and racial background, significant data now also exist to support a genetic basis of such disparities as well. Clearly, CHDs could best be understood by studying the interplay of multiple (genetic and non-genetic) factors and then translating the resulting knowledge into effective approaches for reducing the existing disparity gaps. This review article highlights these aspects in brief and calls the people of different expertise to work together to make an impact and tackle the challenges associated with CHDs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.9777/chd.2019.1004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6705599PMC
August 2019

Gemcitabine treatment promotes immunosuppressive microenvironment in pancreatic tumors by supporting the infiltration, growth, and polarization of macrophages.

Sci Rep 2018 08 10;8(1):12000. Epub 2018 Aug 10.

Department of Oncologic Sciences, Mitchell Cancer Institute, University of South Alabama, Mobile, AL, 36604, USA.

Chemotherapy-induced immunosuppression poses an additional challenge to its limited efficacy in pancreatic cancer (PC). Here we investigated the effect of gemcitabine on macrophages, which are the first line of immune-defense mechanisms. We observed an increased presence of macrophages in orthotopic human pancreatic tumor xenografts from mice treated with gemcitabine as compared to those from vehicle only-treated mice. Conditioned media from gemcitabine-treated PC cells (Gem-CM) promoted growth, migration and invasion of RAW264.7 macrophage. In addition, Gem-CM also induced upregulation of M2-polarized macrophage markers, arginase-1 and TGF-β1. Cytokine profiling of gemcitabine-treated PC cells identified IL-8 as the most differentially-expressed cytokine. Incubation of Gem-CM with IL-8 neutralizing antibody diminished its ability to induce growth, migration and invasion of RAW264.7 macrophages, but did not abrogate their M2 polarization. Together, our findings identify IL-8 as an important mediator in the gemcitabine-induced infiltration of macrophages within the pancreatic tumor microenvironment and suggest the requirement of additional mechanism(s) for macrophage polarization.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-018-30437-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6086900PMC
August 2018

Glucose Metabolism Reprogrammed by Overexpression of IKKε Promotes Pancreatic Tumor Growth.

Cancer Res 2016 12 20;76(24):7254-7264. Epub 2016 Oct 20.

Department of Oncologic Sciences, Mitchell Cancer Institute, University of South Alabama, Mobile, Alabama.

Aberrant expression of the kinase IKKε in pancreatic ductal adenocarcinoma (PDAC) has been associated with poor prognosis. In this study, we define a pathobiologic function for IKKε in reprogramming glucose metabolism and driving progression in PDAC. Silencing IKKε in PDAC cells, which overexpressed it endogenously, was sufficient to reduce malignant cell growth, clonogenic potential, glucose consumption, lactate secretion, and expression of genes involved in glucose metabolism, without impacting the basal oxygen consumption rate. IKKε silencing also attenuated c-Myc in a manner associated with diminished signaling through an AKT/GSK3β/c-MYC phosphorylation cascade that promoted MYC nuclear accumulation. In an orthotopic mouse model, IKKε-silenced PDAC exhibited a relative reduction in glucose uptake, tumorigenicity, and metastasis. Overall, our findings offer a preclinical mechanistic rationale to target IKKε to improve the therapeutic management of PDAC in patients. Cancer Res; 76(24); 7254-64. ©2016 AACR.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/0008-5472.CAN-16-1666DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5161695PMC
December 2016

Check Sample Abstracts.

Am J Clin Pathol 2009 Feb;131(2):286-299

The following abstracts are compiled from Check Sample exercises published in 2008. These peer-reviewed case studies assist laboratory professionals with continuing medical education and are developed in the areas of clinical chemistry, cytopathology, forensic pathology, hematology, microbiology, surgical pathology, and transfusion medicine. Abstracts for all exercises published in the program will appear annually in AJCP.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1309/AJCPCW0RNBEZVB2GDOI Listing
February 2009

Mammary-type fibroepithelial neoplasms of the vulva: a case report and review of the literature.

J Cutan Pathol 2008 Feb;35(2):246-9

Department of Pathology, University of South Alabama, Mobile, AL 36617, USA.

Mammary-type fibroepithelial neoplasms of the vulva are rare lesions of uncertain histogenesis. Origin from ectopic breast tissue and from anogenital glandular tissue that shares similar histologic homology with breast tissue has been postulated. We report the case of a 45-year-old woman who presented with a vulvar mass of several years duration. Excision of the lesion and subsequent histologic examination showed a mammary-type fibroadenoma with apocrine change. No ectopic breast tissue was identified outside the lesion. The theories of histogenesis of these neoplasms and additional cases of mammary-type lesions of the vulva reported in the medical literature are reviewed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1600-0560.2007.00796.xDOI Listing
February 2008
-->