Modlin IM, Gustafsson BI, Pavel M, Lawrence B, Svejda B, Kidd M

Most information available to determine neuroendocrine tumor behavior reflects univariate assessment of factors or is anecdotal or experience based. There currently exists no objective multivariate analysis of indices that defines SI Neuroendocrine Tumor (NET) prognosis. A key unmet need is the lack of a rigorous...

Lawrence B, Gustafsson BI, Kidd M, Pavel M, Svejda B, Modlin IM

An accurate tumor marker is a critical tool in tumor management because it establishes an uncertain diagnosis, offers a basis for individual prognostication, signals response to therapy, and identifies relapse. In classical terms, a high-quality tumor marker should represent a biologic attribute unique to the tumor cell or its local environment...

Modlin IM, Oberg K, Chung DC, Jensen RT, de Herder WW, Thakker RV, Caplin M, Delle Fave G, Kaltsas GA, Krenning EP, Moss SF, Nilsson O, Rindi G, Salazar R, Ruszniewski P, Sundin A

Gastroenteropancreatic (GEP) neuroendocrine tumors (NETs) are fairly rare neoplasms that present many clinical challenges. They secrete peptides and neuroamines that cause distinct clinical syndromes, including carcinoid syndrome. However, many are clinically silent until late presentation with mass effects...

Modlin IM, Moss SF, Oberg K, Padbury R, Hicks R, Gustafsson BI, Wright NA, Kidd M

The term carcinoid (carcinoma-like) was introduced by Oberndorfer in 1907 to describe a tumor of the gastroin-testinal tract that was less aggressive than adenocarcinoma. The earliest clear description of carcinoid syndrome (flushing, diarrhoea, and bronchospasm) and carcinoid heart disease waspublished in the early...

Pavel M, Kidd M, Modlin IM

Carcinoids" are mostly slow-growing neuroendocrine neoplasms (NENs) with low proliferativeactivity. A wide range of therapeutic options with variable efficacy exist, including locoregional ablative strategies. Thereafter, some patients may not require medical therapy for years depending on the rate of progression or recurrence...

Frilling A, Akerstrom A, Falconi M, Pavel M, J Ramos, Kidd M, Modlin IM

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) represent a heterogenous group of tumors arising from a variety of neuroendocrine cell types. The incidence and prevalence of GEPNENs have markedly increased over the last three decades. Symptoms are often absent in early disease, or vague and nonspecific even...

Modlin IM, Pavel M, Kidd M, Gustafsson BI

Background: The discovery of somatostatin (SST) and the synthesis of a variety of analogues constituted a major therapeutic advance in the treatment of gastroenteropancreatic neuroendocrine (carcinoid) tumours (GEP-NETs). They currently provide the most efficient treatment to achieve symptomatic relief...

Frilling A, Modlin IM, Kidd M, Russell C, Breitenstein S, Salem R, Kwekkeboom D, Lau W-Y, Klersy C, Vilgrain V, Davidson B, Siegler M, Caplin M, Solcia E, Schilsky R, and the Working Group Neuroendocrine Liver Metastases

Many management strategies exist for neuroendocrine liver metastases. These strategies range from surgery to ablation with various interventional radiology procedures, and include both regional and systemic therapy with diverse biological, cytotoxic, or targeted agents. A paucity of biological, molecular, and genomic...

Drozdov I, Kidd M, Nadler B, Camp R, Mane M, Gustafsson BI, Hauso O, Modlin IM

A more accurate taxonomy of small intestinal (SI) neuroendocrine tumors (NETs) is necessary to accurately predict tumor behavior, prognosis and define therapeutic strategy. We identified a panel of such markers implicated in tumorogenicity, metastasis, and hormone production and hypothesized that transcript levels of...

Drozdov I, Kidd M, Gustafsson BI, Mane S, Hauso O, Pfragner R, Modlin IM

Small intestinal (SI) neuroendocrine tumors (NET) are increasing in incidence, however little is known about their biology. High throughput techniques such as inference of gene regulatory networks from microarray experiments can objectively define signaling machinery in this disease. Genome-wide co-expression analysis was used to infer gene...

Siddique Z-L, Drozdov I, Floch J, Gustafsson BI, Stunes K, Pfragner R, Kidd M, Modlin IM

Neuroendocrine tumors (NETs) of the gastrointestinal (GI) system are increasing in incidence with minimal improvement in prognosis. Although the cell of origin has been identified as the enterochromaffin (EC) cell, its secretory and proliferative regulation has not been defined at a mechanistic level. To date, the BON cell line has been the most...

Lawrence B, Kenney B, Svejda B, Schimmack S, Alaimo D, Barbieri A, Jedrych J, Kidd M, Modlin IM

Accurate neuroendocrine neoplasia (NEN) staging is vital for determining prognosis and therapeutic strategy. The great majority of NENs express chromogranin A (CgA) which can be detected at a protein or transcript level. The current standards for lymph node metastasis detection are histological examination after Hematoxylin and Eosin...

Modlin IM, Gustafsson BI, Drozdov I, Kidd M

We sought to investigate whether detection of circulating messenger RNA (mRNA) alone or in combination with circulating NET-related hormones and growth factors could detect gastrointestinal Neuroendocrine Tumor (NET) disease. The small intestinal (SI) Neuroendocrine Tumor (NET) cell line KRJ-I was used to define the sensitivity...

Svejda B, Kidd M, Timberlake A, Lawrence B, Harry K, Alaimo D, Kazberouk A, Schimmack S, Modlin IM

Platelet-derived serotonin (5-HT) is involved in liver regeneration. The liver is also the metastatic site for malignant enterochromaffin (EC) cell “carcinoid” (neuroendocrine) neoplasms, the principal cellular source of 5-HT. We tested whether 5-HT produced by metastatic EC cells played a role in the hepatic...

Svejda B, Kidd M, Kazberouk A, Lawrence B, Pfragner R, Modlin IM

Treatment of small intestinal neuroendocrine tumors (SINETs) with mammalian target of rapamycin (mTOR) inhibitors alone or with somatostatin analogs has been proposed as effective therapy, because both agents have been reported to exhibit antiproliferative activity. Because adenocarcinomas escape mTOR inhibition, we examined whether...