Search Results

You are looking at 71 - 80 of 548 items for :

  • neuroendocrine cancer x
  • All content x
Clear All
Free access

C Péqueux, B P Keegan, M-T Hagelstein, V Geenen, J-J Legros, and W G North

Introduction As a basic component of oncogenesis, neuroendocrine tumour cells usually develop very potent autocrine/paracrine signalling pathways that play a crucial part in the dysregulation of cellular growth ( Hanahan & Weinberg

Free access

J K Ramage, A H Davies, and EORTC Quality of Life Group

Quality of life is multi-dimensional, including issues relating to symptoms from the disease but also social, emotional, functional and financial domains. Debate remains on the true definition of quality of life and its measurement. Quality of life measurements are best done by patients themselves, although, in some situations a proxy such as carer or relative can be substituted. Healthcare workers can over- or underestimate overall quality of life. Currently used devices for measuring quality of life in cancer include the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30, which is a generic tool for all cancers and which requires the use of add-on modules for specific cancers. We are developing a separate module for carcinoid/neuroendocrine tumours, in accordance with the EORTC guidelines on module development, which will be translated into five languages and will be available for use throughout Europe.

Restricted access

U Meyer-Pannwitt, K Kummerfeldt, G Froeschle, V A Dorss, and R Klapdor

Restricted access

Mark P Labrecque, Joshi J Alumkal, Ilsa M Coleman, Peter S Nelson, and Colm Morrissey

The use of androgen deprivation therapy and second line anti-androgens in prostate cancer has led to the emergence of tumors employing multiple androgen receptor (AR)-dependent and AR-independent mechanisms to resist AR targeted therapies in castration-resistant prostate cancer (CRPC). While the AR signaling axis remains the cornerstone for therapeutic development in CRPC, a clearer understanding of the heterogeneous biology of CRPC tumors is needed for inno-vative treatment strategies. In this review, we discuss the characteristics of CRPC tumors that lack AR activity and the temporal and spatial considerations for the conversion of an AR-dependent to an AR-independent tumor type. We describe the more prevalent treatment-emergent phenotypes aris-ing in the CRPC disease continuum, including amphicrine, AR-low, double-negative, neuroendo-crine and small cell phenotypes. We discuss the association between the loss of AR activity and tumor plasticity with a focus on the roles of transcription factors like SOX2, DNA methylation, alterna-tive splicing, and the activity of epigenetic modifiers like EZH2, BRD4, LSD1, and the nBAF complex in conversion to a neuroendocrine or small cell phenotype in CRPC. We hypothesize that only a subset of CRPC tumors have the propensity for tumor plasticity and conversion to the neuroendo-crine phenotype and outline how we might target these plastic and emergent phenotypes in CRPC. In conclusion, we assess the current and future avenues for treatment and determine that the heter-ogeneity of CRPCs lacking AR activity will require diverse treatment approaches.

Free access

S K Kang, K-C Choi, H-S Yang, and P C K Leung

Gonadotrophin-releasing hormone (GnRH) functions as a key neuroendocrine regulator of the hypothalamic-pituitary-gonadal axis. In addition to the hypothalamus and pituitary gland, GnRH and its receptor have been detected in other reproductive tissues including the gonads, placenta and tumours arising from these tissues. Recently, a second form of GnRH (GnRH-II) and type II GnRH receptor have been found in normal ovarian surface epithelium and neoplastic counterparts. The two types of GnRH may play an important role as an autocrine/paracrine regulator of reproductive functions and ovarian tumour growth. In this review, the distribution and potential roles of GnRH-I/-II and their GnRH receptors in the ovarian cells and ovarian cancer will be discussed.

Restricted access

F W F Hanna, C F Johnston, J E S Ardill, and K D Buchanan

Abstract

Background: Salmon calcitonin (sCT) injection into rats has been reported to induce pituitary tumours. We have demonstrated the co-existence, in the rat-derived α-TSH cell line, of an sCT-like peptide, as well as a receptor for sCT.

Aim: This was to investigate the possible existence of sCT-like immunoreactivity (sCT-LI) in human neuroendocrine tumours.

Methods: A collection of human neuroendocrine tumours was tested, using a highly specific antibody for sCT. Immunostaining was abolished by preabsorption with sCT at concentrations higher than 1 μg/ml. However, as immunofluorescence was still obvious at the highest concentration (100 pg/ml) of hCT employed, any significant cross-reactivity was excluded.

Results: Of the human pituitary null cell tumours studied, positive staining was obtained in 2 out of 12, suggesting a similarity between the rat and human pituitary glands. None of the other pituitary tumours tested showed sCT-LI (these included 8 corticotroph tumours, 6 prolactinomas and 2 somatotroph tumours).

This work was extended to medullary thyroid carcinomas (MTCs) and a further group of neuroendocrine tumours, looking for the specificity of this sCT-LI among the various APUDomas.

All the tested MTCs (n=14) expressed sCT-LI, while none of the examined phaeochromocytomas (n=23), intestinal carcinoids (n=14), lung carcinoids (n=16), stomach carcinoids (n=2), rectal carcinoids (n=2), gastrinomas (n=4), insulinomas (n=12), oat cell carcinomas (n=7), carotid body tumours (n=9), VIPomas (n=3), or a glucagonoma (n=1) expressed sCT-LI. This indicates that this sCT-LI might be unique to MTC (and possibly the pituitary).

Conclusion: The possible existence of the most potent form of CT may provide an explanation for the vasomotor disturbances in MTC and may be a potential new tumour marker for MTC. Phylogenetically, the presence of a lower form of CT in mammalian tissues would give an insight into the conservation of the CT peptide family in evolution.

Endocrine-Related Cancer (1997) 4 191-195

Restricted access

Salma Ben-Salem, Varadha Balaji Venkadakrishnan, and Hannelore V Heemers

Prostate cancer (CaP) remains the second leading cause of cancer deaths in western men. These deaths occur because metastatic CaP acquires resistance to available treatments. The novel and functionally diverse treatment options that have been introduced in the clinic over the past decade each eventually induce resistance for which the molecular basis is diverse. Both initiation and progression of CaP have been associated with enhanced cell proliferation and cell cycle dysregulation. A better understanding of the specific pro-proliferative molecular shifts that control cell division and proliferation during CaP progression may ultimately overcome treatment resistance. Here, we examine literature for support of this possibility. We start by reviewing recently renewed insights in prostate cell types and their proliferative and oncogenic potential. We then provide an overview of the basic knowledge on the molecular machinery in charge of cell cycle progression and its regulation by well-recognized drivers of CaP progression such as androgen receptor and retinoblastoma protein. In this respect, we pay particular attention to interactions and reciprocal interplay between cell cycle regulators and androgen receptor. Somatic alterations that impact the cell cycle-associated and -regulated genes encoding p53, PTEN and MYC during progression from treatment-naïve, to castration-recurrent, and in some cases, neuroendocrine CaP are discussed. We considered also non-genomic events that impact cell cycle determinants, including transcriptional, epigenetic and micro-environmental switches that occur during CaP progression. Finally, we evaluate the therapeutic potential of cell cycle regulators, and address challenges and limitations approaches modulating their action, for CaP treatment.

Free access

J T Arnold and J T Isaacs

The acquisition of an androgen-independent phenotype by prostate cancer cells is presently a death sentence for patients. In order to have a realistic chance of changing this outcome, an understanding of what drives the progression to androgen independence is critical. We review here a working hypothesis based on the position that the development of androgen-independent epithelial cells is the result of a series of cellular and molecular events within the whole tissue that culminates in the loss of normal tissue-maintained growth control. This tissue includes the epithelial and stromal cells, the supporting extracellular matrix and circulating hormones. This review discusses the characteristics of these malignant cells, the role of stromal cells involved in growth and the differentiation of epithelial cells, and the role of the extracellular matrix as a mediator of the phenotypes of stromal and epithelial cells. In addition, environmental, neuroendocrine and immune factors that may contribute to disturbance of the fine balance of the epithelial-stromal-extracellular matrix connection are considered. While the goal of many therapeutic approaches to prostate cancer has been androgen ablation or targeting the androgen receptor (AR) of epithelial cells, these therapies become ineffective as the cells progress beyond dependence on androgen for growth control. Twenty years ago Sir David Smithers debated that cancer is the result of loss of tolerance within tissues and the organizational failure of normal growth-control mechanisms. This is precipitated by prolonged or abnormal demands for regeneration or repair, rather than of any inherent disorder peculiar to each of the individual components involved. He wrote "It is not the cell itself that is disorderly, but its relationship with the rest of the tissue". We have gained significantly large amounts of precise data on the effects of androgenic ablation on cancerous prostate cells and on the role of the AR in prostate cancer. The need has come to compile this information towards a perspective of dysregulation of tissue as a whole, and to develop experimental systems to address this broader perspective to find and develop therapies for treatment and prevention.

Free access

P D Leotlela, A Jauch, H Holtgreve-Grez, and R V Thakker

Neuroendocrine tumours (NETs) originate in tissues that contain cells derived from the embryonic neural crest, neuroectoderm and endoderm. Thus, NETs occur at many sites in the body, although the majority occur within the gastro-entero-pancreatic axis and can be subdivided into those of foregut, midgut and hindgut origin. Amongst these, only those of midgut origin are generally argentaffin positive and secrete serotonin, and hence only these should be referred to as carcinoid tumours. NETs may occur as part of complex familial endocrine cancer syndromes, such as multiple endocrine neoplasia type 1 (MEN1), although the majority occur as non-familial (i.e. sporadic) isolated tumours. Molecular genetic studies have revealed that the development of NETs may involve different genes, each of which may be associated with several different abnormalities that include point mutations, gene deletions, DNA methylation, chromosomal losses and chromosomal gains. Indeed, the foregut, midgut and hindgut NETs develop via different molecular pathways. For example, foregut NETs have frequent deletions and mutations of the MEN1 gene, whereas midgut NETs have losses of chromosome 18, 11q and 16q and hindgut NETs express transforming growth factor-alpha and the epidermal growth factor receptor. Furthermore, in lung NETs, a loss of chromosome 3p is the most frequent change and p53 mutations and chromosomal loss of 5q21 are associated with more aggressive tumours and poor survival. In addition, methylation frequencies of retinoic acid receptor-beta, E-cadherin and RAS-associated domain family genes increase with the severity of lung NETs. Thus the development and progression of NETs is associated with specific genetic abnormalities that indicate the likely involvement of different molecular pathways.

Free access

Vanessa D'Antongiovanni, Serena Martinelli, Susan Richter, Letizia Canu, Daniele Guasti, Tommaso Mello, Paolo Romagnoli, Karel Pacak, Graeme Eisenhofer, Massimo Mannelli, and Elena Rapizzi

that tumor microenvironment plays a pivotal role in modulating cell metabolism, tumor growth and progression ( Rapizzi et al. 2015 ). Solid tumors are very complex tissues, comprising of not only cancer cells but also non-malignant stromal cells