Deborah A Altomare's research while affiliated with University of Central Florida and other places

Publications (99)

Article
Existing therapeutics have failed to improve pancreatic ductal adenocarcinoma (PDAC) patient outcomes, in part due to tumor associated immune suppression and upregulation of compensatory mechanisms. KRAS and c-MYC are important oncogenes in PDAC linked to tumor immune suppression. We describe the use of difluoromethylornithine (DFMO) and a c-RAF in...
Article
Despite having excellent prognosis when detected early, colorectal cancer (CRC) remains a leading cause of cancer-related deaths globally. Barriers to screening reduces compliance and negatively impacts patient outcomes, necessitating alternatives. A blood-based approach provides a more convenient and accessible modality, but serum markers are lack...
Article
Pancreatic cancer has a poor five-year survival rate of less than 8% and is projected to be the second leading cause of cancer related deaths in the US by the year 2030. Polyamine metabolism is an underexplored therapeutic target in pancreatic ductal adenocarcinoma (PDAC). The current investigation profiled RNA expression of genes associated with p...
Article
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There is a great interest in developing natural killer (NK) cells as adoptive cancer immunotherapy. For off-the-shelf approaches and to conduct multicenter clinical trials, cryopreserved NK cells are the preferred product. However, recent studies reported that cryopreservation of NK cells results in loss of cell motility and, as a consequence, cyto...
Article
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The portal venous circulation provides a conduit for pancreatic ductal adenocarcinoma (PDAC) tumor cells to the liver parenchyma sinusoids, a frequent site of metastasis. Turbulent flow in the portal circulation promotes retention of PDAC shed circulating tumor cells (CTC) and myeloid-derived immunosuppressor cells (MDSC). Excessive colony stimulat...
Chapter
Chronic inflammation is known to be associated with pancreatic cancer, however a complete picture regarding how these pathologies intersect is still being characterized. In vivo model systems are critical for the study of mechanisms underlying how inflammation accelerates neoplasia. Repeat injection of cerulein, a cholecystokinin (CCK) analog, is w...
Article
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Pancreatic cancer is the fourth leading cause of cancer death. Existing therapies only moderately improve pancreatic ductal adenocarcinoma (PDAC) patient prognosis. The present study investigates the importance of the polyamine metabolism in the pancreatic tumor microenvironment. Relative mRNA expression analysis identified differential expression...
Article
Full-text available
Pancreatic ductal adenocarcinoma (PDAC) has an extremely poor five-year survival rate of less than 10%. Immune suppression along with chemoresistance are obstacles for PDAC therapeutic treatment. Innate immune cells, such as tumor-associated macrophages, are recruited to the inflammatory environment of PDAC and adversely suppress cytotoxic T lympho...
Article
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Transcriptional profiling of pre- and post-malignant colorectal cancer (CRC) lesions enable temporal monitoring of molecular events underlying neoplastic progression. However, the most widely used transcriptomic dataset for CRC, TCGA-COAD, is devoid of adenoma samples, which increases reliance on an assortment of disparate microarray studies and hi...
Conference Paper
p>Introduction: Colorectal cancer (CRC) is the third most common cancer in the United States. While survival rates have increased in part due to enhanced detection and targeted therapeutics, mortality remains high, highlighting a need to further investigate novel targetable pathways along the neoplastic axis. To explore potential molecular networks...
Article
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Introduction: Bile acids (BAs) arising from duodenogastric reflux are known to facilitate gastric cancer (GC) development. Although BAs traditionally contribute to carcinogenesis through direct cellular cytotoxicity, increasing evidence implicates nuclear and membrane BA receptors (BARs) as additional factors influencing cancer risk. Indeed, some...
Article
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Background: While inflammation is associated with pancreatic cancer, the underlying mechanisms leading to cancer initiation are still being delineated. Eosinophils may promote or inhibit tumor growth, although the specific role in pancreatic cancer has yet to be determined. Eosinophil-supporting cytokine interleukin-5 and receptor are likely to ha...
Preprint
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Pancreatic ductal adenocarcinoma is one of the most lethal cancers, with a five-year survival rate of only 9%. Inflammation-mediated tissue damage plays a role in pancreatic cancer, and chronic pancreatitis is a risk factor for cancer development. Unfortunately, exactly how inflammation drives cancer initiation remains unclear. A recent study ident...
Article
Background & Aim Natural Killer (NK) cells are innate cytotoxic lymphocytes with high potential for development of cell-based anti-cancer therapeutics. To be applied clinically, NK cells need to be expanded to achieve sufficient amounts for therapeutically effective dosages. Methods utilizing stimulation with membrane bound IL21 (mbIL21) expressed...
Preprint
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Anti-PD-1/anti-PD-L1 therapies have shown success in cancer treatment but responses are limited to ~15% of patients with lymphocyte infiltrated, PD-L1 positive tumors. Hence, strategies that increase PD-L1 expression and tumor infiltration should make more patients eligible for PD-1/PD-L1 blockade therapy, thus improving overall outcomes. PD-L1 exp...
Article
13 Background: The PD-1/PDL-1 axis is an immuno-oncology target for abrogating immune suppression. Anti-PD1 targeted mAb therapy has had success in several indications by alleviating suppression of cytolytic T cells. In addition to T cells, NK cells hold promise for adoptive applications for oncology. We developed a nanoparticle based stimulation m...
Article
Pancreatic ductal adenocarcinoma (PDAC) is highly chemo-resistant and has an extremely poor patient prognosis, with a survival rate at five years of <8%. There remains an urgent need for innovative treatments. Targeting polyamine biosynthesis through inhibition of ornithine decarboxylase with difluoromethylornithine (DFMO) has had mixed clinical su...
Article
Full-text available
Immuno-oncology (I-O) is a young and growing field on the frontier of cancer therapy. Contrary to cancer therapies that directly target malignant cells, I-O therapies stimulate the body’s immune system to target and attack the tumor, which is otherwise invisible to, or inhibiting the immune response. To this end, several methods have been developed...
Article
127 Background: Ovarian cancer has high recurrence rate and could benefit from immunotherapy with NK cells. A necessity for NK cell therapy is an efficient way to generate high doses of NK cells. The best method currently used in clinical trials is ex vivo NK cell expansion by co-culture with K562 CML cells, modified to express 41-BBL and membrane...
Article
132 Background: NK cells can kill malignant cells to provide innate immunity against tumors. Due to their low abundance in blood, a focus is to expand NK cells ex vivo having enhanced anti-tumor cytotoxicity to be used as a treatment. Our group has pioneered a cell-free method using plasma membrane (PM) particles derived from K562 cells expressing...
Article
Till date, no analytical method published to detect Cisplatin has been validated according to the U.S. Food and Drug Administration (FDA) guidance using liquid chromatography mass spectrometry (LC–MS/MS). We report, a validated LC–MS/MS method for quantitaitve determination of cisplatin in rat plasma and urine according to FDA guidlines. Cisplatin...
Article
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The purpose of this paper was to better understand the role of polyamine transport in pancreatic cancers.This paper identifies potential biomarkers for assessing the relative tumor commitment to polyamine biosynthesis or transport. Cell lines with low polyamine import activity and low ATP13A3 protein levels appear committed to polyamine biosynthesi...
Poster
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A promising strategy for treating metastatic breast cancer is engaging the immune system to destroy disseminated breast cancer cells. However, breast cancer is a challenge for immunotherapy because of its inherent genetic heterogeneity and decreased immunogenicity. There is an unmet need to develop new, targeted therapies for breast cancer that sti...
Article
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Treatment of ovarian cancer, a leading cause of gynecological malignancy, has good initial efficacy with surgery and platinum/taxane-based chemotherapy, but poor long-term survival in patients. Inferior long-term prognosis is attributed to intraperitoneal spreading, relapse and ineffective alternate therapies. Adoptive cell therapy is promising for...
Article
Protein Kinase B/AKT, has three isoforms (AKT1-3) and is renowned for its central role in the regulation of cell growth and proliferation, due to its constitutive activation in various cancers. AKT2, which is highly expressed in insulin responsive tissues, has been identified as a primary regulator of glucose metabolism as Akt2 knockout mice (Akt2-...
Article
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Pancreatic adenocarcinoma is a deadly disease characterized by metastatic progression and resistance to conventional therapeutics. Mutation of KRAS is the most frequent early event in pancreatic tumor progression. AKT isoforms are frequently activated in pancreatic cancer, and reports have implicated hyperactivation of AKT1, as well as AKT2, in pan...
Article
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Mechanistic target of rapamycin (mTOR) dysregulation is present in a variety of human pathologies including neurological disease, cancer, diabetes, and cardiac disease. Hyperactivation leads to increased protein synthesis and cell growth, which are essential for growth, development, and cancer. Inhibition of mTOR results in induction of autophagy,...
Article
Full-text available
NK cell immunotherapy as a cancer treatment shows promise, but expanding NK cells consistently from a small fraction (∼5%) of peripheral blood mononuclear cells (PBMC) to therapeutic amounts remains challenging. Most current ex vivo expansion methods use co-culture with feeder cells (FC) and their use poses challenges for wide clinical application....
Article
NK cell immunotherapy as a cancer treatment shows promise, but methods for consistent expansion of NK cells from a small fraction (~5%) of peripheral blood mononuclear cells (PBMCs) to therapeutically effective amounts are not widely accessible. Strategies that promote in vivo expansion rely on high-dose IL-2 in combination with lymphodepletion and...
Article
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Long-living Ames dwarf (df/df) mice are homozygous for a mutation of the Prop1df gene. As a result, mice are deficient in growth hormone (GH), prolactin (PRL) and thyrotropin (TSH). In spite of the hormonal deficiencies, df/df mice live significantly longer and healthier lives compared to their wild type siblings. We studied the effects of calorie...
Article
The motuporamines isolated from the sea sponge Xestospongia exigua are of biological interest because of their unique antimigration and antiangiogenic properties. Key bioactive features were found to be a saturated 15-membered heterocycle and a norspermidine motif. This paper describes new analogues that modulate the cytotoxicity of this compound c...
Article
Malignant mesothelioma (MM) is a highly aggressive, asbestos-related cancer frequently marked by mutations of both NF2 and CDKN2A. We demonstrate that germline knockout of one allele of each of these genes causes accelerated onset and progression of asbestos-induced MM compared to asbestos-exposed Nf2+/- or wild-type (WT) mice. Ascites from some Nf...
Article
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The AKT family of serine threonine kinases is of critical importance with regard to growth factor signaling, cell proliferation, survival and oncogenesis. Engagement of signaling receptors induces the lipid kinase, phosphatidylinositol 3-kinase (PI3K), which enables the activation of AKT. Responsive to the PI3K/AKT pathway is the mammalian target o...
Article
The CDKN2A/ARF locus encompasses overlapping tumor suppressor genes p16(INK4A) and p14(ARF), which are frequently co-deleted in human malignant mesothelioma (MM). The importance of p16(INK4A) loss in human cancer is well established, but the relative significance of p14(ARF) loss has been debated. The tumor predisposition of mice singly deficient f...
Data
Retention of mutant Arf allele in MMs from Arf (+/−) mice. A, Abnormally large RT-PCR product amplified with Arf-specific primers for exon 1β. Samples are from MM cells of five Arf (+/−) mice (lanes 1–5); lane 6 is from wild-type mouse embryonic fibroblasts. B, Sequencing of PCR products revealed an 84-bp insertion (grey italicized letters) in the...
Article
Full-text available
The CDKN2A/ARF locus encompasses overlapping tumor suppressor genes p16(INK4A) and p14(ARF), which are frequently co-deleted in human malignant mesothelioma (MM). The importance of p16(INK4A) loss in human cancer is well established, but the relative significance of p14(ARF) loss has been debated. The tumor predisposition of mice singly deficient f...
Data
MM Markers for primary cell cultures derived from asbestos-treated mice. (DOC)
Data
Immunohistochemical staining of a MM tumor with anti-mesothelin (MSN) or anti-MSN plus blocking peptide to show specificity of staining. (TIF)
Article
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This study examines the role of vascular endothelial growth factor (VEGF) as a therapeutic target in clear cell carcinoma (CCC) of the ovary, which has been regarded as a chemoresistant histologic subtype. Immunohistochemical analysis using tissue microarrays of 98 primary ovarian cancers revealed that VEGF was strongly expressed both in early-stag...
Article
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The adaptor protein APPL1 (adaptor protein containing pleckstrin homology (PH), phosphotyrosine binding (PTB), and leucine zipper motifs) was first identified as a binding protein of AKT2 by yeast two-hybrid screening. APPL1 was subsequently found to bind to several membrane-bound receptors and was implicated in their signal transduction through AK...
Data
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Supplemental Table 1. Table detailing Onconase regulated gene (ORG) ontologies.
Article
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Onconase represents a new class of RNA-damaging drugs. Mechanistically, Onconase is thought to internalize, where it degrades intracellular RNAs such as tRNA and double-stranded RNA, and thereby suppresses protein synthesis. However, there may be additional or alternative mechanism(s) of action. In this study, microarray analysis was used to compar...
Article
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Akt plays a central role in regulating tumor cell survival and cell cycle progression and is regarded as a promising therapeutic target. We used genetically defined mouse models that develop spontaneous tumors exhibiting activated Akt to determine if Akt inhibition by GSK690693 is effective in the treatment of cancer. The broad long-term objective...
Article
FAS-associated factor 1, FAF1, is an evolutionarily conserved protein that has several protein interaction domains. Although FAF1 was initially identified as a member of the FAS death-inducing signaling complex, subsequent work has revealed that FAF1 functions in diverse biological processes. FAF1 has been shown to play an important role in normal...
Article
The oncogene v-akt was isolated from a retrovirus that induced naturally occurring thymic lymphomas in AKR mice. We hypothesized that constitutive activation of Akt2 could serve as a first hit for the clonal expansion of malignant T-cells by promoting cell survival and genomic instability, leading to chromosome alterations. Furthermore, genes that...
Article
Full-text available
Mammalian target of rapamycin (mTOR) plays a central role in cell proliferation and is regarded as a promising target in cancer therapy, including for ovarian cancer. This study aimed to examine the role of mTOR as a therapeutic target in clear cell carcinoma of the ovary, which is regarded as an aggressive, chemoresistant histologic subtype. Using...
Article
Full-text available
The human CDKN2A locus encodes 2 distinct proteins, p16(INK4A) and p14(ARF) [mouse p19(Arf)], designated INK4A (inhibitor of cyclin dependent kinase 4) and ARF (alternative reading frame) here, that are translated from alternatively spliced mRNAs. Human ARF is implicated as a tumor suppressor gene, mainly in association with the simultaneous deleti...