Expression of cyclo‐oxygenase‐2 in gastrointestinal carcinoid tumors

Mizuno, Shigeaki; Kato, Kimitoshi; Hashimoto, Akemi; Sugitani, Masahiko; Sheikh, Aleemuzzaman; Komuro, Sachiko; Jike, Toyoharu; Iwasaki, Atsushi; Arakawa, Yasuyuki; Nemoto, Norimichi

doi:10.1111/j.1440-1746.2005.04153.x

Cited by 9 publications

(3 citation statements)

References 24 publications

(54 reference statements)

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“…This effect may result from the ability to block cyclooxygenase isoforms, COX-1 and COX-2, activity which in turn is linked with carcinogenesis and tumor growth [36]. Of note, it has been reported that COX-2 is expressed in gastrointestinal NETs [37] and in pancreatic endocrine tumors [38], and that treatment with COX-2 inhibitors reduces the viability of carcinoid cells [38]. The potential of aspirin or other COX-2 inhibitors as chemopreventive or active agents in patients diagnosed with NETs, including SI-NETs, has not been reported before.…”

Section: Discussionmentioning

confidence: 99%

Risk and Protective Factors for Small Intestine Neuroendocrine Tumors: A Prospective Case-Control Study

et al. 2015

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Background: The incidence of small intestine neuroendocrine tumors (SI-NETs) is increasing, but few studies have investigated risk factors for their occurrence, suggesting that family history (FH) of any cancer, smoking and previous cholecystectomy are associated with an increased risk. Such studies investigated small series or examined cancer registries without direct interviews. Aim: We therefore aimed at clarifying risk and protective factors for the occurrence of sporadic SI-NETs. Subjects and Methods: We performed a multicenter case-control study. Patients with a histologic diagnosis of SI-NETs were prospectively evaluated, excluding familial syndromes. Controls with non-neoplastic/non-chronic disorders seen at gastrointestinal outpatients clinics were matched for sex and age (4:1). All subjects were directly interviewed by means of a specific questionnaire on potential risk and protective factors. Cases and controls were compared by Fisher's test or Student's t test for categorical or continuous variables. Explanatory variables were analyzed by simple logistic regression analysis. A multiple logistic regression analysis was performed with an Enter model; p < 0.05 was considered significant. Results: 215 SI-NET patients and 860 controls were enrolled. FH of colorectal cancer (CRC) (8.8 vs. 5.0%) and breast cancer (10.2 vs. 4.8%), heavy smoking (24.7 vs. 14.8%) and drinking >21 alcohol units per week (7.4 vs. 3.8%) were all significantly more frequent in SI-NET patients than in controls. Multivariate analysis showed that FH of CRC (OR 2.23, 95% CI 1.29-3.84, p = 0.003), FH of breast cancer (OR 2.05, 95% CI 1.13-3.69, p = 0.01) and smoking (OR 1.47, 95% CI 1.07-2.03, p = 0.01) and in particular heavy smoking (OR 1.94, 95% CI 1.29-3.84, p = 0.0008) were associated with an increased risk for carcinoid occurrence, while use of aspirin can be considered a protective factor (OR 0.20, 95% CI 0.06-0.65, p = 0.008). Conclusion: FH of colorectal and breast cancer as well as smoking seem to be risk factors for the development of SI-NETs, while use of aspirin might be a protective factor. These factors partially overlap with those associated with CRC, but are different from those previously associated with pancreatic neuroendocrine tumors. These findings may suggest that the mechanisms of carcinogenesis for endocrine cells in different sites can be specific and similar to those of their exocrine counterparts.

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Section: Discussionmentioning

confidence: 99%

Risk and Protective Factors for Small Intestine Neuroendocrine Tumors: A Prospective Case-Control Study

et al. 2015

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“…Indeed, several studies suggested a role of COX-2 in the pathogenesis and progression of NETs. COX-2 is expressed in pheochromocytoma tissue (Salmenkivi et al 2001) and up-regulated in gastrointestinal and bronchopulmonary carcinoids (Mizuno et al 2006). Moreover, COX-2 up-regulates both expression and bioactivity of chromogranin A in a cell line of rat pheochromocytoma (PC12) (Connolly et al 2007).…”

Section: Pasireotide Plus Cyclooxygenase-2 Inhibitorsmentioning

confidence: 99%

Pasireotide in the treatment of neuroendocrine tumors: a review of the literature

Mantovani

Dicitore

Sciammarella

et al. 2018

Endocrine-Related Cancer

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Somatostatin analogs have an important role in the medical therapy of neuroendocrine tumors (NETs). Octreotide and lanreotide, both somatostatin analogs binding with high affinity for the somatostatin receptor (SSTR)2, can control symptoms in functional NETs. In addition, these compounds, because of their antiproliferative effects, can stabilize growth of well-differentiated NETs. Pasireotide is a novel multireceptor-targeted somatostatin analog with high affinity for SSTR1, 2, 3, and 5. This review provides an overview of the state of the art of pasireotide in the treatment of NETs, with the aim of addressing clinical relevance and future perspectives for this molecule in the management of NETs.

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“…Ciclooxigenase-2 (COX-2) is expressed in gastrointestinal carcinoids, especially at the tumours advancing edges and mostly in rectal carcinoids [79], and in some 50% of PETs [80,81]. Cyclooxygenase-2 may therefore play a role in carcinoid progression, and its inhibition through nonsteroidal anti-inflammatory drugs has been shown to inhibit growth of human neuroendocrine tumour cell lines, via G1 cell-cycle arrest [82].…”

Section: Other Possible Therapeutic Targetsmentioning

confidence: 99%

A Critical View of Molecularly Target Therapy for Digestive Endocrine Tumours

Capurso¹,

Festa²,

Panzuto³

et al. 2007

EMI

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Enteropancreatic endocrine tumours (EP ETs) are relatively rare neoplasms constituting a heterogeneous nosological category. Most EP ETs present with metastatic disease, are well-differentiated and have a relatively slow growth-rate, with high percentage of stable disease and relative long survival. In those patients with progressive disease biotherapy and chemotherapy have relatively low response rates. In this context, novel therapies are needed, especially for the treatment of progressive, metastatic disease which represents, in this field, the main therapeutic challenge. EP ETs seem an appropriate model for targeting angiogenesis, with solid data from animal and in vitro models. Effects of angiogenesis inhibitors, such as bevacizumab, sunitinib, thalidomide and endostatin seem promising especially in patients with pancreatic tumours. Targeting other tyrosine kinases such as EGFR (with gefitinib) or c-KIT (imatinib) has also been tested, with various degree of response. The mTOR pathway also looks as an interesting pathway to be targeted, with interesting data in some clinical trials. The main limits of the available data are represented by the high heterogeneity of patients and of inclusion criteria. Moreover, few studies included patients with documented progressive disease before treatment, thus making difficult to understand the real efficacy of treatment on spontaneous tumour growth. Future studies should evaluate combination therapies in more homogeneous populations of patients, and include clear definition of the individual progression rate before and after the study entry. An informative review of novel patents and therapeutic targets of enteropancreatic endocrine tumours are also discussed.

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Expression of cyclo‐oxygenase‐2 in gastrointestinal carcinoid tumors

Abstract: Enhanced COX-2 expression was observed in gastrointestinal as well as bronchopulmonary carcinoids and their metastases, especially at the advancing edges of the tumors. Cyclo-oxygenase-2 may play a role in carcinoid progression.

Cited by 9 publications

References 24 publications

Risk and Protective Factors for Small Intestine Neuroendocrine Tumors: A Prospective Case-Control Study

Risk and Protective Factors for Small Intestine Neuroendocrine Tumors: A Prospective Case-Control Study

Pasireotide in the treatment of neuroendocrine tumors: a review of the literature

A Critical View of Molecularly Target Therapy for Digestive Endocrine Tumours

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