Browsing by Author "Karavitaki, Niki (10242894500)"

C-type natriuretic peptide (CNP/Nppc) is expressed at high levels in the anterior pituitary of rats and mice and activates guanylyl cyclase B receptors (GC-B/ Npr2) to regulate hormone secretion. Mutations in NPR2/Npr2 can cause achondroplasia, GH deficiency, and female infertility, yet the normal expression profile within the anterior pituitary remains to be established in humans. The current study examined the expression profile and transcriptional regulation of NPR2 and GC-B protein in normal human fetal pituitaries, normal adult pituitaries, and human pituitary adenomas using RT-PCR and immunohistochemistry. Transcriptional regulation of human NPR2 promoter constructs was characterized in anterior pituitary cell lines of gonadotroph, somatolactotroph, and corticotroph origin. NPR2 was detected in all human fetal and adult pituitary samples regardless of age or sex, as well as in all adenoma samples examined regardless of tumor origin. GC-B immunoreactivity was variable in normal pituitary, gonadotrophinomas, and somatotrophinomas. Maximal transcriptional regulation of the NPR2 promoter mapped to a region within -214 bp upstream of the start site in all anterior pituitary cell lines examined. Electrophoretic mobility shift assays revealed that this region contains Sp1/Sp3 response elements. These data are the first to show NPR2 expression in normal human fetal and adult pituitaries and adenomatous pituitary tissue and suggest a role for these receptors in both pituitary development and oncogenesis, introducing a new target to manipulate these processes in pituitary adenomas. © 2012 Society for Endocrinology.

C-type natriuretic peptide (CNP/Nppc) is expressed at high levels in the anterior pituitary of rats and mice and activates guanylyl cyclase B receptors (GC-B/ Npr2) to regulate hormone secretion. Mutations in NPR2/Npr2 can cause achondroplasia, GH deficiency, and female infertility, yet the normal expression profile within the anterior pituitary remains to be established in humans. The current study examined the expression profile and transcriptional regulation of NPR2 and GC-B protein in normal human fetal pituitaries, normal adult pituitaries, and human pituitary adenomas using RT-PCR and immunohistochemistry. Transcriptional regulation of human NPR2 promoter constructs was characterized in anterior pituitary cell lines of gonadotroph, somatolactotroph, and corticotroph origin. NPR2 was detected in all human fetal and adult pituitary samples regardless of age or sex, as well as in all adenoma samples examined regardless of tumor origin. GC-B immunoreactivity was variable in normal pituitary, gonadotrophinomas, and somatotrophinomas. Maximal transcriptional regulation of the NPR2 promoter mapped to a region within -214 bp upstream of the start site in all anterior pituitary cell lines examined. Electrophoretic mobility shift assays revealed that this region contains Sp1/Sp3 response elements. These data are the first to show NPR2 expression in normal human fetal and adult pituitaries and adenomatous pituitary tissue and suggest a role for these receptors in both pituitary development and oncogenesis, introducing a new target to manipulate these processes in pituitary adenomas. © 2012 Society for Endocrinology.

The anatomical and histological complexity of the parasellar region as well as the presence of embryonic remnants determine the huge diversity of parasellar neoplasms. Some of them are only located in the parasellar region, whereas others can occur elsewhere, within or outside the central nervous system. Their spectrum ranges from histologically benign and low-grade malignant to high-grade malignant tumours. Although rare, metastases can pose differential diagnostic dilemmas. The severity of the clinical picture, the challenges of surgery and the risk of adverse sequelae related to surgery or radiotherapy make parasellar tumours interesting entities for the clinicians irrespective of their histological malignancy grade. Due to the different cell origins of parasellar tumours, the World Health Organization classification system does not categorise them as a distinct group. Detailed criteria for classification and malignancy grading are presented in the classification systems covering central nervous system tumours, haematological malignancies and tumours of the soft tissue and bone. In the last few years, molecular genetic features have been integrated into the diagnosis of several types of the parasellar tumours enhancing diagnostic accuracy and providing information of the value for targeting therapies. In this review, we will present histopathological and molecular genetic features, updated classification criteria and recent advances in the diagnostics and rationale for novel pharmacological therapies of selected types of parasellar neoplasms. © 2020 S. Karger AG, Basel. All rights reserved.

The anatomical and histological complexity of the parasellar region as well as the presence of embryonic remnants determine the huge diversity of parasellar neoplasms. Some of them are only located in the parasellar region, whereas others can occur elsewhere, within or outside the central nervous system. Their spectrum ranges from histologically benign and low-grade malignant to high-grade malignant tumours. Although rare, metastases can pose differential diagnostic dilemmas. The severity of the clinical picture, the challenges of surgery and the risk of adverse sequelae related to surgery or radiotherapy make parasellar tumours interesting entities for the clinicians irrespective of their histological malignancy grade. Due to the different cell origins of parasellar tumours, the World Health Organization classification system does not categorise them as a distinct group. Detailed criteria for classification and malignancy grading are presented in the classification systems covering central nervous system tumours, haematological malignancies and tumours of the soft tissue and bone. In the last few years, molecular genetic features have been integrated into the diagnosis of several types of the parasellar tumours enhancing diagnostic accuracy and providing information of the value for targeting therapies. In this review, we will present histopathological and molecular genetic features, updated classification criteria and recent advances in the diagnostics and rationale for novel pharmacological therapies of selected types of parasellar neoplasms. © 2020 S. Karger AG, Basel. All rights reserved.

Growth hormone (GH) has been used for over 35 years, and its safety and efficacy has been studied extensively. Experimental studies showing the permissive role of GH/insulin-like growth factor 1 (IGF-I) in carcinogenesis have raised concerns regarding the safety of GH replacement in children and adults who have received treatment for cancer and those with intracranial and pituitary tumours. A consensus statement was produced to guide decision-making on GH replacement in children and adult survivors of cancer, in those treated for intracranial and pituitary tumours and in patients with increased cancer risk. With the support of the European Society of Endocrinology, the Growth Hormone Research Society convened a Workshop, where 55 international key opinion leaders representing 10 professional societies were invited to participate. This consensus statement utilized: (1) a critical review paper produced before the Workshop, (2) five plenary talks, (3) evidence-based comments from four breakout groups, and (4) discussions during report-back sessions. Current evidence reviewed from the proceedings from the Workshop does not support an association between GH replacement and primary tumour or cancer recurrence. The effect of GH replacement on secondary neoplasia risk is minor compared to host- and tumour treatment-related factors. There is no evidence for an association between GH replacement and increased mortality from cancer amongst GH-deficient childhood cancer survivors. Patients with pituitary tumour or craniopharyngioma remnants receiving GH replacement do not need to be treated or monitored differently than those not receiving GH. GH replacement might be considered in GH-deficient adult cancer survivors in remission after careful individual risk/benefit analysis. In children with cancer predisposition syndromes, GH treatment is generally contraindicated but may be considered cautiously in select patients. © 2022 BioScientifica Ltd.. All rights reserved.

Growth hormone (GH) has been used for over 35 years, and its safety and efficacy has been studied extensively. Experimental studies showing the permissive role of GH/insulin-like growth factor 1 (IGF-I) in carcinogenesis have raised concerns regarding the safety of GH replacement in children and adults who have received treatment for cancer and those with intracranial and pituitary tumours. A consensus statement was produced to guide decision-making on GH replacement in children and adult survivors of cancer, in those treated for intracranial and pituitary tumours and in patients with increased cancer risk. With the support of the European Society of Endocrinology, the Growth Hormone Research Society convened a Workshop, where 55 international key opinion leaders representing 10 professional societies were invited to participate. This consensus statement utilized: (1) a critical review paper produced before the Workshop, (2) five plenary talks, (3) evidence-based comments from four breakout groups, and (4) discussions during report-back sessions. Current evidence reviewed from the proceedings from the Workshop does not support an association between GH replacement and primary tumour or cancer recurrence. The effect of GH replacement on secondary neoplasia risk is minor compared to host- and tumour treatment-related factors. There is no evidence for an association between GH replacement and increased mortality from cancer amongst GH-deficient childhood cancer survivors. Patients with pituitary tumour or craniopharyngioma remnants receiving GH replacement do not need to be treated or monitored differently than those not receiving GH. GH replacement might be considered in GH-deficient adult cancer survivors in remission after careful individual risk/benefit analysis. In children with cancer predisposition syndromes, GH treatment is generally contraindicated but may be considered cautiously in select patients. © 2022 BioScientifica Ltd.. All rights reserved.