New pituitary oncogenes.

2000 ◽  
pp. 3-15 ◽  
Author(s):  
A P Heaney ◽  
S Melmed
Keyword(s):  
Pituitary Tumor ◽  
Molecular Mechanisms ◽  
Cell Clone ◽  
Tumor Therapy ◽  
Pituitary Tumors ◽  
Molecular Probes ◽  
Molecular Events ◽  
Therapeutic Decisions ◽  
Pituitary Cell Clone ◽  
Considerable Morbidity

Pituitary tumors are common monoclonal neoplasms which cause considerable morbidity and mortality. Several molecular events underlying pituitary tumorigenesis have been elucidated in recent years, but no tumor marker has clearly emerged which assists clinical and therapeutic decisions. Activating mutations and loss of inactivating mutations, together with hypothalamic hormones, circulating hormones, growth factors and cytokines cooperatively ensure the inexorable expansion of the initial mutated pituitary cell clone. This review describes new developments in our understanding of the molecular mechanisms involved in the pathogenesis of pituitary tumors. The availability of molecular probes will allow the early prediction of tumor behavior, identify targets for designing subcellular pituitary tumor therapy and provide novel approaches to pituitary tumor management.

scholarly journals Resistance to Dopamine Agonists in Pituitary Tumors: Molecular Mechanisms

2022 ◽  
Vol 12 ◽  
Author(s):  
Claudia Pivonello ◽  
Roberta Patalano ◽  
Mariarosaria Negri ◽  
Rosa Pirchio ◽  
Annamaria Colao ◽  
...  
Keyword(s):  
Dopamine Agonists ◽  
Molecular Mechanisms ◽  
Signal Transduction Pathway ◽  
Pituitary Tumors ◽  
Benign Tumors ◽  
Membrane Expression ◽  
Secondary Resistance ◽  
First Line Therapy ◽  
Molecular Events ◽  
Predominant Type

Pituitary neuroendocrine tumors (PitNET) are commonly benign tumors accounting for 10-25% of intracranial tumors. Prolactin-secreting adenomas represent the most predominant type of all PitNET and for this subtype of tumors, the medical therapy relies on the use of dopamine agonists (DAs). DAs yield an excellent therapeutic response in reducing tumor size and hormonal secretion targeting the dopamine receptor type 2 (D2DR) whose higher expression in prolactin-secreting adenomas compared to other PitNET is now well established. Moreover, although DAs therapy does not represent the first-line therapy for other PitNET, off-label use of DAs is considered in PitNET expressing D2DR. Nevertheless, DAs primary or secondary resistance, occurring in a subset of patients, may involve several molecular mechanisms, presently not fully elucidated. Dopamine receptors (DRs) expression is a prerequisite for a proper DA function in PitNET and several molecular events may negatively modify DR membrane expression, through the DRs down-regulation and intracellular trafficking, and DR signal transduction pathway. The current mini-review will summarise the presently known molecular events that underpin the unsuccessful therapy with DAs.

How I treat primary CNS lymphoma

Blood ◽  
2011 ◽  
Vol 118 (3) ◽  
pp. 510-522 ◽  
Author(s):  
Andrés J. M. Ferreri
Keyword(s):  
Molecular Mechanisms ◽  
Performance Status ◽  
Primary Cns Lymphoma ◽  
Poor Performance ◽  
Cns Lymphoma ◽  
Poor Performance Status ◽  
Level Of Evidence ◽  
Therapeutic Decisions ◽  
New Ideas ◽  
Rare Malignancy

Abstract Primary CNS lymphoma (PCNSL) is a rare malignancy with peculiar clinical and biologic features, aggressive course, and unsatisfactory outcome. It represents a challenge for multidisciplinary clinicians and scientists as therapeutic progress is inhibited by several issues. Molecular and biologic knowledge is incomplete, limiting the identification of new therapeutic targets, and the particular microenvironment of this malignancy, and sanctuary sites where tumor cells grow undisturbed, strongly affects treatment efficacy. Moreover, active treatments are known to be associated with disabling neurotoxicity, posing the dilemma of whether to intensify therapy to improve the cure rate or to de-escalate treatment to avoid sequels. The execution of prospective trials is also difficult because of the rarity of the tumor and the impaired general condition and poor performance status of patients. Thus, level of evidence is low, with consequent uncertainties in therapeutic decisions and lack of consensus on primary endpoints for future trials. Despite this unfavorable background, laboratory and clinical researchers are coordinating efforts to develop new ideas, resulting in the recent publication of studies on PCNSL's biology and molecular mechanisms and of the first international randomized trials. Herein, these important contributions are analyzed to provide recommendations for everyday practice and the rationale for future trials.

Hemorrhagic and nonhemorrhagic Rathke cleft cysts mimicking pituitary apoplexy

2008 ◽  
Vol 108 (1) ◽  
pp. 3-8 ◽  
Author(s):  
Mandy J. Binning ◽  
James K. Liu ◽  
John Gannon ◽  
Anne G. Osborn ◽  
William T. Couldwell
Keyword(s):  
Mr Imaging ◽  
Pituitary Tumor ◽  
Pituitary Apoplexy ◽  
Pituitary Tumors ◽  
Imaging Features ◽  
Mr Images ◽  
Acute Hemorrhage ◽  
Consistent Finding ◽  
Imaging Characteristics ◽  
Intracystic Hemorrhage

Object Rathke cleft cysts (RCCs) are infrequently symptomatic, and apoplexy is one of the most unusual presentations. Only a few cases of apoplexy associated with RCCs have been reported, and their clinical, imaging, surgical, and pathological features are poorly understood. In the cases that have been reported, intracystic hemorrhage has been a consistent finding. The authors report 6 cases of RCCs in which the presenting clinical and imaging features indicated pituitary apoplexy, both with and without intracystic hemorrhage. Methods The authors retrospectively reviewed charts and magnetic resonance (MR) imaging studies obtained in patients who underwent transsphenoidal surgery for RCC. Six patients were identified who presented with symptoms and MR imaging characteristics consistent with pituitary apoplexy but were found intraoperatively to have an RCC. All 6 patients presented with a sudden headache, 2 with visual loss, and 1 with diplopia. Review of the preoperative MR images demonstrated mixed signal intensities in the sellar masses suggestive of a hemorrhagic pituitary tumor. In all patients there was a presumed clinical diagnosis of pituitary tumor apoplexy and an imaging-documented diagnosis of hemorrhagic pituitary tumor. Results All 6 patients underwent transsphenoidal resection to treat the suspected pituitary apoplexy. Intraoperative and histopathological findings were consistent with the diagnosis of an RCC in all cases. Only 2 cases showed evidence of hemorrhage intraoperatively. In all cases, an intracystic nodule was found within the RCC at surgery, and this intracystic nodule was present on the initial MR imaging when retrospectively reviewed. The imaging characteristics of the intracystic nodules were similar to those of acute hemorrhage seen in cases of pituitary apoplexy. Conclusions The clinical and imaging features of RCCs appear similar to those of hemorrhagic pituitary tumors, making them often indistinguishable from pituitary apoplexy.

The therapeutic value and molecular mechanisms of lncRNA FENDRR in human cancer

2021 ◽  
Vol 27 ◽  
Author(s):  
Wen Xu ◽  
Bei Wang ◽  
Yuxuan Cai ◽  
Jinlan Chen ◽  
Enqing Meng ◽  
...  
Keyword(s):  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Malignant Tumors ◽  
Human Cancer ◽  
Tumor Therapy ◽  
Pathophysiological Mechanism ◽  
Regulatory Processes ◽  
Carcinoma Prostate ◽  
Therapeutic Value ◽  
And Migration

Background: Long noncoding RNA (lncRNA) fetal-lethal non-coding developmental regulatory RNA (FENDRR), a newly known lncRNA, has been reported to be abnormally expressed in diverse tumors. This review is focused on clarifying the mechanism of FENDRR to regulate the biological process of tumors, affirming its value as a target for tumor therapy. Methods: The pathophysiological mechanism of FENDRR acting on tumors has been analyzed and summarized by reviewing PubMed. Results: The expression of lncRNA FENDRR is abnormally altered in clinical cancers, promoting the malignant transformation of a variety of tumors, including colon cancer, cervical cancer, hepatocellular carcinoma, prostate cancer, Malignant melanoma, lung cancer, osteosarcoma, breast cancer, etc. Cellular processions, including proliferation, invasion, apoptosis and migration affected by FENDRR, have been revealed. Conclusion: Specific evidences for the involvement of LncRNA FENDRR in cancer regulatory processes suggest that FENDRR has the potential to be a biomarker or clinical therapeutic target for malignant tumors.

scholarly journals Epigenetic Effects Induced by Methamphetamine and Methamphetamine-Dependent Oxidative Stress

2018 ◽  
Vol 2018 ◽  
pp. 1-28 ◽  
Author(s):  
Fiona Limanaqi ◽  
Stefano Gambardella ◽  
Francesca Biagioni ◽  
Carla L. Busceti ◽  
Francesco Fornai
Keyword(s):  
Molecular Mechanisms ◽  
Neuropsychiatric Disorders ◽  
Behavioral Alterations ◽  
Neuronal Phenotype ◽  
Cellular Events ◽  
Epigenetic Effects ◽  
Molecular Events ◽  
Epigenetic Events ◽  
Genetic Modifications ◽  
Altered Gene

Methamphetamine is a widely abused drug, which possesses neurotoxic activity and powerful addictive effects. Understanding methamphetamine toxicity is key beyond the field of drug abuse since it allows getting an insight into the molecular mechanisms which operate in a variety of neuropsychiatric disorders. In fact, key alterations produced by methamphetamine involve dopamine neurotransmission in a way, which is reminiscent of spontaneous neurodegeneration and psychiatric schizophrenia. Thus, understanding the molecular mechanisms operated by methamphetamine represents a wide window to understand both the addicted brain and a variety of neuropsychiatric disorders. This overlapping, which is already present when looking at the molecular and cellular events promoted immediately after methamphetamine intake, becomes impressive when plastic changes induced in the brain of methamphetamine-addicted patients are considered. Thus, the present manuscript is an attempt to encompass all the molecular events starting at the presynaptic dopamine terminals to reach the nucleus of postsynaptic neurons to explain how specific neurotransmitters and signaling cascades produce persistent genetic modifications, which shift neuronal phenotype and induce behavioral alterations. A special emphasis is posed on disclosing those early and delayed molecular events, which translate an altered neurotransmitter function into epigenetic events, which are derived from the translation of postsynaptic noncanonical signaling into altered gene regulation. All epigenetic effects are considered in light of their persistent changes induced in the postsynaptic neurons including sensitization and desensitization, priming, and shift of neuronal phenotype.

scholarly journals Molecular Events Involved in Influenza A Virus-Induced Cell Death

2022 ◽  
Vol 12 ◽  
Author(s):  
Rui Gui ◽  
Quanjiao Chen
Keyword(s):  
Cell Death ◽  
Influenza A Virus ◽  
Influenza A ◽  
Regulatory Networks ◽  
Molecular Mechanisms ◽  
Tissue Destruction ◽  
Inflammatory Reactions ◽  
Molecular Events ◽  
Host Death

Viral infection usually leads to cell death. Moderate cell death is a protective innate immune response. By contrast, excessive, uncontrolled cell death causes tissue destruction, cytokine storm, or even host death. Thus, the struggle between the host and virus determines whether the host survives. Influenza A virus (IAV) infection in humans can lead to unbridled hyper-inflammatory reactions and cause serious illnesses and even death. A full understanding of the molecular mechanisms and regulatory networks through which IAVs induce cell death could facilitate the development of more effective antiviral treatments. In this review, we discuss current progress in research on cell death induced by IAV infection and evaluate the role of cell death in IAV replication and disease prognosis.

scholarly journals Spatiotemporal Dynamics of Molecular Pathology in Amyotrophic Lateral Sclerosis

2018 ◽  
Author(s):  
Silas Maniatis ◽  
Tarmo Äijö ◽  
Sanja Vickovic ◽  
Catherine Braine ◽  
Kristy Kang ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Neuron ◽  
Motor Neurons ◽  
Molecular Mechanisms ◽  
Early Time ◽  
Spatiotemporal Dynamics ◽  
Course Of Disease ◽  
Molecular Events ◽  
Als Patients ◽  
Lateral Sclerosis

AbstractParalysis occurring in amyotrophic lateral sclerosis (ALS) results from denervation of skeletal muscle as a consequence of motor neuron degeneration. Interactions between motor neurons and glia contribute to motor neuron loss, but the spatiotemporal ordering of molecular events that drive these processes in intact spinal tissue remains poorly understood. Here, we use spatial transcriptomics to obtain gene expression measurements of mouse spinal cords over the course of disease, as well as of postmortem tissue from ALS patients, to characterize the underlying molecular mechanisms in ALS. We identify novel pathway dynamics, regional differences between microglia and astrocyte populations at early time-points, and discern perturbations in several transcriptional pathways shared between murine models of ALS and human postmortem spinal cords.One Sentence SummaryAnalysis of the ALS spinal cord using Spatial Transcriptomics reveals spatiotemporal dynamics of disease driven gene regulation.

scholarly journals Human Endometrial Transcriptome and Progesterone Receptor Cistrome Reveal Important Pathways and Epithelial Regulators

2019 ◽  
Author(s):  
Ru-pin Alicia Chi ◽  
Tianyuan Wang ◽  
Nyssa Adams ◽  
San-pin Wu ◽  
Steven L. Young ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Rna Seq ◽  
Uterine Receptivity ◽  
Normal Cycle ◽  
Estrogen Response ◽  
Molecular Events ◽  
History Of ◽  
And Function ◽  
Genomic Regions ◽  
Fertile Women

ABSTRACTContextPoor uterine receptivity is one major factor leading to pregnancy loss and infertility. Understanding the molecular events governing successful implantation is hence critical in combating infertility.ObjectiveTo define PGR-regulated molecular mechanisms and epithelial roles in receptivity.DesignRNA-seq and PGR-ChIP-seq were conducted in parallel to identify PGR-regulated pathways during the WOI in endometrium of fertile women.SettingEndometrial biopsies from the proliferative and mid-secretory phases were analyzed.Patients or Other ParticipantsParticipants were fertile, reproductive aged (18-37) women with normal cycle length; and without any history of dysmenorrhea, infertility, or irregular cycles. In total, 42 endometrial biopsies obtained from 42 women were analyzed in this study.InterventionsThere were no interventions during this study.Main Outcome MeasuresHere we measured the alterations in gene expression and PGR occupancy in the genome during the WOI, based on the hypothesis that PGR binds uterine chromatin cycle-dependently to regulate genes involved in uterine cell differentiation and function.Results653 genes were identified with regulated PGR binding and differential expression during the WOI. These were involved in regulating inflammatory response, xenobiotic metabolism, EMT, cell death, interleukin/STAT signaling, estrogen response, and MTORC1 response. Transcriptome of the epithelium identified 3,052 DEGs, of which 658 were uniquely regulated. Transcription factors IRF8 and MEF2C were found to be regulated in the epithelium during the WOI at the protein level, suggesting potentially important functions that are previously unrecognized.ConclusionPGR binds the genomic regions of genes regulating critical processes in uterine receptivity and function.PrécisUsing a combination of RNA-seq and PGR ChIP-seq, novel signaling pathways and epithelial regulators were identified in the endometrium of fertile women during the window of implantation.

scholarly journals Iron as a Central Player and Promising Target in Cancer Progression

2019 ◽  
Vol 20 (2) ◽  
pp. 273 ◽  
Author(s):  
Michaela Jung ◽  
Christina Mertens ◽  
Elisa Tomat ◽  
Bernhard Brüne
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Cell ◽  
Cancer Progression ◽  
Crucial Role ◽  
Iron Homeostasis ◽  
Molecular Mechanisms ◽  
Tumor Therapy ◽  
Essential Element ◽  
Major Function ◽  
Iron Pool

Iron is an essential element for virtually all organisms. On the one hand, it facilitates cell proliferation and growth. On the other hand, iron may be detrimental due to its redox abilities, thereby contributing to free radical formation, which in turn may provoke oxidative stress and DNA damage. Iron also plays a crucial role in tumor progression and metastasis due to its major function in tumor cell survival and reprogramming of the tumor microenvironment. Therefore, pathways of iron acquisition, export, and storage are often perturbed in cancers, suggesting that targeting iron metabolic pathways might represent opportunities towards innovative approaches in cancer treatment. Recent evidence points to a crucial role of tumor-associated macrophages (TAMs) as a source of iron within the tumor microenvironment, implying that specifically targeting the TAM iron pool might add to the efficacy of tumor therapy. Here, we provide a brief summary of tumor cell iron metabolism and updated molecular mechanisms that regulate cellular and systemic iron homeostasis with regard to the development of cancer. Since iron adds to shaping major hallmarks of cancer, we emphasize innovative therapeutic strategies to address the iron pool of tumor cells or cells of the tumor microenvironment for the treatment of cancer.

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