James S Goydos

James S Goydos
Rutgers New Jersey Medical School | UMDNJ · Cancer Institute of New Jersey

MD

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99
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Publications

Publications (99)
Article
>1.2 million people in the United States have a personal history of melanoma skin cancer and are at increased risk for disease recurrence and second primary melanomas. Many of these individuals do not follow recommendations to conduct regular, thorough skin self-examinations that facilitate early disease detection and do not sufficiently engage in...
Article
Background: Despite their elevated melanoma risk, young-onset melanoma patients and their families exhibit low rates of engagement in skin cancer surveillance and sun protection behaviors. Interventions that improve skin cancer surveillance (total cutaneous exam [TCE] and skin self-exam [SSE]) and prevention (sun protection) practices among young-o...
Article
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Our research group demonstrated that riluzole, an inhibitor of glutamatergic signaling reduced melanoma cell proliferation in vitro and tumor progression in vivo. The underlying mechanisms of riluzole are largely unknown. Microarray analyses on two human melanoma cell lines revealed that riluzole stimulates expression of the cystine-glutamate amino...
Article
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Studies demonstrate that GRM, expressed by >60% of human melanomas, may be a therapeutic target. We performed a phase II trial of 100 mg po bid of riluzole, an inhibitor of GRM1 signaling, in patients with advanced melanoma with the primary endpoint of response rate. Thirteen patients with GRM1-positive tumors were enrolled. No objective responses...
Preprint
BACKGROUND Despite their elevated melanoma risk, young-onset melanoma patients and their families exhibit low rates of engagement in skin cancer surveillance and sun protection behaviors. Interventions that improve skin cancer surveillance (total cutaneous exam [TCE] and skin self-exam [SSE]) and prevention (sun protection) practices among young-on...
Article
Full-text available
Exosomes are naturally occurring membrane-bound nanovesicles generated constitutively and released by various cell types, and often in higher quantities by tumor cells. Exosomes may facilitate communication between the primary tumor and its local microenvironment, supporting cell invasion and other early events in metastasis. A neuronal receptor, m...
Article
Background/objectives: Skin cancer incidence has been increasing in U.S. Hispanics over several decades and the postdiagnosis outcomes are worse for Hispanics than for non-Hispanic whites. Parents are influential in children's health preventive behaviors, but little is known about parental factors associated with children's skin cancer-related beh...
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Full-text available
Receptor tyrosine kinases-based autocrine loops largely contribute to activate the MAPK and PI3K/AKT pathways in melanoma. However, the molecular mechanisms involved in generating these autocrine loops are still largely unknown. In the present study, we examine the role of the transcription factor RUNX2 in the regulation of receptor tyrosine kinase...
Article
PurposeThe Sunbelt Melanoma Trial is a prospective randomized trial evaluating the role of high-dose interferon alfa-2b therapy (HDI) or completion lymph node dissection (CLND) for patients with melanoma staged by sentinel lymph node (SLN) biopsy.Patients and Methods Patients were eligible if they were age 18 to 70 years with primary cutaneous mela...
Article
This survey of adults with a diagnosis of melanoma assessed patient characteristics associated with a willingness to receive Internet-delivered interventions to promote skin self-examination and sun protection behaviors.Patients with melanoma have a 9-fold increased risk for a diagnosis of another melanoma.1 Contrary to recommendations, many indivi...
Article
Many melanoma patients do not regularly perform thorough skin self-examinations. We examined the extent to which melanoma patients conduct thorough skin self-examination, how they perform skin self-examination, and their related knowledge and self-efficacy. A sample of 176 individuals (61.5% response rate) diagnosed with primary pathologic stage 0-...
Article
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Our group has previously reported that the majority of human melanomas (>60%) express the metabotropic glutamate receptor 1 (GRM1) and that the glutamate release inhibitor riluzole, a drug currently used to treat amyotrophic lateral sclerosis, can induce apoptosis in GRM1-expressing melanoma cells. Our group previously reported that in vitro riluzo...
Article
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Approximately 50% of patients having metastatic melanoma develop brain metastases during the course of their illness. Evidence exists that melanoma cells have increased aptitude for the repair of sub-lethal DNA damage caused by ionizing radiation therapy. To address the radio-resistance of melanoma, many groups adopted radiotherapy schedules that d...
Article
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We report the case of an interdigitating dendritic cell sarcoma (IDCS) presenting in the skin. A 41-year old woman had a slowly enlarging mass on her right scapula that was excised multiple times under a presumptive diagnosis of a recurrent sebaceous cyst. However, the lesion was refractory to standard therapies. History and physical exam was unrev...
Patent
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The present invention provides methods of treating cancer using 2-amino-6-trifluoromethoxybenzothiazole (riluzole). In one aspect, the present invention provides methods of reducing cancer cell growth. In another aspect, the present invention provides a method of inducing apoptosis in a cancer cell. In another aspect, the present invention provides...
Data
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Figure S1. Epac1 overexpression (OE) increases migration of primary melanoma cell lines. (A) Western blot of Epac1 OE in WM115 and WM3248 cells 24 h after adenoviral infection. (B) Epac1 OE increased migration of WM115 and WM3248 cells. *P < 0.05 versus control, n = 4. Figure S2. Epac1 regulates CM-induced migration of primary melanoma cells. (A) W...
Article
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Fibroblast growth factor (FGF2) regulates endothelial and melanoma cell migration. The binding of FGF2 to its receptor requires N-sulfated heparan sulfate (HS) glycosamine. We have previously reported that Epac1, an exchange protein activated by cAMP, increases N-sulfation of HS in melanoma. Therefore, we examined whether Epac1 regulates FGF2-media...
Article
Our lab previously described the oncogenic properties of metabotropic glutamate receptor 1 (mGluR1) in melanocytes. mGluR1 transformed immortalized mouse melanocytes in vitro and induced vigorous tumor formation in vivo. Subsequently, we observed the activation of PI3K/AKT in mGluR1-mediated melanocytic tumorigenesis in vivo. In particular, we iden...
Article
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Store-operated Ca(2+) entry (SOCE) is a major mechanism of Ca(2) (+) import from extracellular to intracellular space, involving detection of Ca(2+) store depletion in endoplasmic reticulum (ER) by stromal interaction molecule (STIM) proteins, which then translocate to plasma membrane and activate Orai Ca(2+) channels there. We found that STIM1 and...
Article
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The incidence of skin cancer among U.S. Hispanics increased 1.3 % annually from 1992 to 2008. However, little research has focused on skin cancer prevention among the rapidly growing Hispanic population. In this study, we examined theory-driven, psychosocial correlates of sun protection behaviors in a population-based sample of 787 Hispanic adults...
Article
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Glutamate-triggered signal transduction is thought to contribute widely to cancer pathogenesis. In melanoma, over-expression of the metabotropic glutamate receptor GRM1 occurs frequently and its ectopic expression in melanocytes is sufficient for neoplastic transformation. Clinical evaluation of the GRM1 signaling inhibitor riluzole in patients wit...
Article
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TNBC is an aggressive breast cancer subtype that does not express hormone receptors (estrogen and progesterone receptors, ER and PR) or amplified human epidermal growth factor receptor type 2 (HER2), and there currently exist no targeted therapies effective against it. Consequently, finding new molecular targets in triple negative breast cancer (TN...
Article
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Gain-of-function of the neuronal receptor, metabotropic glutamate receptor 1 (Grm1), was sufficient to induce melanocytic transformation in vitro and spontaneous melanoma development in vivo when ectopically expressed in melanocytes. The human form of this receptor, GRM1, has been shown to be ectopically expressed in a subset of human melanomas but...
Article
Objective: To examine the association between linguistic acculturation (assessed using the Language Use and Linguistic Preference subscales from the Bidimensional Acculturation Scale for Hispanics) and skin cancer-related behaviors among US Hispanic adults to determine whether, compared with Hispanics denoted as Spanish-acculturated, English-accul...
Article
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Background: Little skin cancer prevention research has focused on the US Hispanic population. Objective: This study examined the prevalence and correlates of skin cancer surveillance behaviors among Hispanic adults. Methods: A population-based sample of 788 Hispanic adults residing in 5 southern and western states completed an online survey in...
Article
Full-text available
Background Skin cancer prevention interventions that target the growing number of U.S. Hispanics are lacking. The current study examined the prevalence and correlates of sun protection and exposure behaviors (i.e., sunscreen use, shade seeking, use of sun protective clothing, and sunburns) among U.S. Hispanics with sun sensitive skin, with a focus...
Article
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Riluzole, an inhibitor of glutamate release, has shown the ability to inhibit melanoma cell xenograft growth. A phase 0 clinical trial of riluzole as a single agent in patients with melanoma resulted in involution of tumors associated with inhibition of both the mitogen-activated protein kinase (MAPK) and phophoinositide-3-kinase/AKT (PI3K/AKT) pat...
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Cancer is a leading cause of death of men and women worldwide. Tumor cell motility contributes to metastatic invasion that causes the vast majority of cancer deaths. Extracellular receptors modified by α2,3-sialic acids that promote this motility can serve as ideal chemotherapeutic targets. For example, the extracellular domain of the mucin recepto...
Article
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The inactivation of the p53 tumor suppressor pathway, which often occurs through mutations in TP53 (encoding tumor protein 53) is a common step in human cancer. However, in melanoma-a highly chemotherapy-resistant disease-TP53 mutations are rare, raising the possibility that this cancer uses alternative ways to overcome p53-mediated tumor suppressi...
Article
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EEctopic expression of a neuronal receptor, Metabotropic Glutamate Receptor 1 (Grm1), in melanocytes has been implicated in melanoma development in mouse models. The human relevance of this receptor's involvement in melanoma pathogenesis was demonstrated by detecting GRM1 expression in subsets of human melanomas, an observation lacking in benign ne...
Article
Compared to non-Hispanic whites, Hispanics are more likely to be diagnosed with melanoma at an earlier age, with thicker and more advanced lesions, and are more likely to die from their disease.1 Physician skin examinations (PSE) may reduce the incidence of thick melanomas that have a poor prognosis.2 Few studies have examined the rate of PSE among...
Article
TPS3112 Background: Metabotropic glutamate receptor 1 (GRM1) has been identified as a potential therapeutic target in melanoma. Over 60% of human melanomas express this cell surface glutamate receptor and excitation of GRM1 results in the activation of MAPK and PI3K/AKT pathways. Riluzole, an oral GRM1 blocking agent, results in growth arrest of me...
Article
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Melanoma is a heterogeneous disease where monotherapies are likely to fail due to variations in genomic signatures. B-RAF inhibitors have been clinically inadequate but response might be augmented with combination therapies targeting multiple signaling pathways. We investigate the preclinical efficacy of combining the multikinase inhibitor sorafeni...
Article
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Recently we reported that activation of Epac1, an exchange protein activated by cAMP, increases melanoma cell migration via Ca 2+ release from the endoplasmic reticulum (ER). G-protein βγ subunits (Gβγ) are known to act as an independent signaling molecule upon activation of G-protein coupled receptor. However, the role of Gβγ in cell migration and...
Article
Melanoma cells are resistant to transforming growth factor-β (TGFβ)-induced cell-cycle arrest. In this study, we investigated a mechanism of resistance involving a regulatory domain, called linker region, in Smad2 and Smad3, main downstream effectors of TGFβ. Melanoma cells in culture and tumor samples exhibited constitutive Smad2 and Smad3 linker...
Article
Our previous report suggested the potential role of the exchange protein directly activated by cyclic AMP (Epac) in melanoma metastasis via heparan sulfate (HS)-mediated cell migration. In order to obtain conclusive evidence that Epac1 plays a critical role in modification of HS and melanoma metastasis, we extensively investigated expression and fu...
Article
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Brain metastases are a common preterminal event in patients with metastatic melanoma and require radiation therapy. Our group has previously shown that human GRM1 (hGRM1) expressing melanoma cells release excess extracellular glutamate and are growth inhibited by riluzole, an inhibitor of glutamate release. Riluzole-treated cells accumulate in G(2)...
Article
Sentinel lymph nodes (SLNs) of melanoma patients show evidence of tumor-induced immune dysfunction. Our previous works have shown that IL-10 and IFNγ co-regulate indoleamine-2,3-dioxygenase (IDO)-expressing immunosuppressive dendritic cells (DCs) in melanoma SLNs. The goal of this study is to examine the relationship between melanoma SLN tumor burd...
Data
miR-211 expression in melanocytes, normal skin and nevus. Both melanocytes and nevus sample indicate a higher expression of miR-211. Melanocyte A - HEM-l, Melanocyte B - HEM (neonatal cell line). (0.26 MB TIF)
Data
Description of human clinical samples. (0.72 MB TIF)
Data
miR-211 expression in stable melanoma cell lines compared to melanocytes. Two stable miR-211-expressing WM1552C cell lines, as well as a “Vector Only” (VO) control cell line, as measured by qRT-PCR relative to levels in the melanocyte cell line HEM-l, are plotted as histograms. Error bars are standard errors of mean of three independent measurement...
Data
Mutagenesis of miR-211 target seed sequence in the 3′UTR of KCNMA1. Diagram indicates the four nucleotides altered in the target seed sequence within the 3′UTR of KCNMA1 relative to the wild type. (0.25 MB TIF)
Data
miR-211 expression levels in clinical samples. Note: Two-tailed t-test comparisons for miR-211 by mean relative quantification levels of melanocyte and primary melanoma, as well as regional, distant, and nodal metastatic melanoma were all statistically significant at P<0.000001. (0.84 MB TIF)
Article
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The immediate molecular mechanisms behind invasive melanoma are poorly understood. Recent studies implicate microRNAs (miRNAs) as important agents in melanoma and other cancers. To investigate the role of miRNAs in melanoma, we subjected human melanoma cell lines to miRNA expression profiling, and report a range of variations in several miRNAs. Spe...
Article
Current recommendations by the National Comprehensive Cancer Network and other groups suggest that follow-up of cutaneous melanoma may include chest radiography (CXR) at 6- to 12-month intervals. The aim of this study was to determine the clinical efficacy of routine CXR for recurrence surveillance in melanoma. Post hoc analysis was performed on da...
Article
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The goal of this study was to examine the effects of metabotropic glutamate receptor-1 (GRM1) blockade on melanoma anchorage-independent growth and invasion. We performed colony and invasion assays using GRM1-expressing melanoma lines and the GRM1-negative UACC930 line. Using the glutamate-release inhibitor Riluzole or the non-competitive GRM1 anta...
Article
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Melanoma remains one of the cancers for which a decline in morbidity has not been achieved with current scientific and medical advances. Mono-therapies targeting melanoma have been largely ineffective, increasing the need for identification of new drugable targets. Multiple tumor suppressors and oncogenes that impart genetic predisposition to melan...
Article
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The transforming growth factor-beta (TGF-beta) pathway, which has both tumor suppressor and pro-oncogenic activities, is often constitutively active in melanoma and is a marker of poor prognosis. Recently, we identified GLI2, a mediator of the hedgehog pathway, as a transcriptional target of TGF-beta signaling. We used real-time reverse transcripti...
Article
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Melanoma has a poor prognosis due to its strong metastatic ability. Although Ca(2+) plays a major role in cell migration, little is known about the role of Ca(2+) in melanoma cell migration. We recently found that the exchange protein directly activated by cyclic AMP (Epac) increases melanoma cell migration via a heparan sulfate-related mechanism....
Article
Mutations in N-RAS and B-RAF, which commonly occur in melanomas, result in constitutive activation of the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated protein kinase (ERK) signaling. Active ERK increases expression and activity of the c-Jun transcription factor, linking ERK and Jun N-terminal kinase (JNK) cascades. Here, w...
Article
Some melanoma patients who undergo sentinel lymph node (SLN) biopsy will have false-negative (FN) results. We sought to determine the factors and outcomes associated with FN SLN biopsy. Analysis was performed of a prospective multi-institutional study that included patients with melanoma of thickness > 1.0 mm who underwent SLN biopsy. FN results we...
Article
Full-text available
Mutations in N-Ras and B-Raf, which commonly occur in melanomas, result in constitutive activation of the Mitogen-Activated Protein Kinase (MAPK)/ Extracellular signal-Regulated protein Kinase (ERK) signaling. Active ERK increases expression and activity of the c-Jun transcription factor, linking ERK and Jun N-terminal Kinase (JNK) cascades. Here,...
Article
Full-text available
Mutations in N-RAS and B-RAF, which commonly occur in melanomas, result in constitutive activation of the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated protein kinase (ERK) signaling. Active ERK increases expression and activity of the c-Jun transcription factor, linking ERK and Jun N-terminal kinase (JNK) cascades. Here, w...
Article
We reported earlier on the oncogenic properties of Grm1 by demonstrating that stable Grm1-mouse-melanocytic clones proliferate in the absence of growth supplement and anchorage in vitro. In addition, these clones also exhibit aggressive tumorigenic phenotypes in vivo with short latency in tumor formation in both immunodeficient and syngeneic mice....
Article
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Ectopic expression of GRM1 in murine melanocytes results in transformation into a form of melanoma, and more than 60% of human melanoma samples tested ectopically express GRM1. Stimulation of this receptor in vitro results in up-regulation of activated extracellular signal-regulated kinase (ERK). Furthermore, a xenograft model of melanoma treated w...
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Activation of the mitogen-activated protein kinase (MAPK) pathway and the phosphatidylinositol 3-kinase/AKT pathway seems to be critical for melanoma proliferation. Components of these pathways are client proteins of heat-shock protein 90 (hsp90), suggesting that inhibition of hsp90 could have significant antimelanoma effects. We conducted a phase...
Article
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The ubiquitin ligase Siah2 has been shown to regulate prolyl hydroxylase 3 (PHD3) stability with concomitant effect on HIF-1α availability. Because HIF-1α is implicated in tumorigenesis and metastasis, we used SW1 mouse melanoma cells, which develop primary tumors with a propensity to metastasize, in a syngeneic mouse model to assess a possible rol...
Article
The number of nodal basins draining a primary cutaneous melanoma is not an independent predictor of outcome. Post hoc analysis of patients entered into a randomized, prospective study. Multi-institutional academic and community medical centers. Patients aged 18 to 70 years with melanoma 1.0 mm or greater Breslow thickness. Wide local excision and s...