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1.
Front Endocrinol (Lausanne) ; 14: 1187870, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38053729

RESUMO

Targeted radionuclide therapy plays an increasingly important role in managing endocrine-related tumors and significantly advances the therapeutic landscape for patients with these diseases. With increasing FDA-approved therapies and advances in the field, come an increased knowledge of the potential for long-term toxicities associated with these therapies and the field must develop new strategies to increase potency and efficacy while individualizing the selection of patients to those most likely to respond to treatment. Novel agents and modalities of therapy are also being explored. This review will discuss the current landscape and describe the avenues for growth in the field currently being explored.


Assuntos
Neoplasias das Glândulas Endócrinas , Humanos , Neoplasias das Glândulas Endócrinas/radioterapia , Neoplasias das Glândulas Endócrinas/tratamento farmacológico , Radioisótopos/uso terapêutico
2.
Sci Rep ; 12(1): 1972, 2022 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-35121782

RESUMO

G Protein-Coupled Receptors (GPCRs) represent the largest superfamily of cell-surface proteins. However, the expression and function of majority of GPCRs remain unexplored in breast cancer (BC). We interrogated the expression and phosphorylation status of 398 non-sensory GPCRs using the landmark BC proteogenomics and phosphoproteomic dataset from The Cancer Genome Atlas. Neuropeptide Y Receptor Y1 (NPY1R) gene and protein expression were significantly higher in Luminal A tumors versus other BC subtypes. The trend of NPY1R gene, protein, and phosphosite (NPY1R-S368s) expression was decreasing in the order of Luminal A, Luminal B, Basal, and human epidermal growth factor receptor 2 (HER2) subtypes. NPY1R gene expression increased in response to estrogen and reduced with endocrine therapy in estrogen receptor-positive (ER+) BC cells and xenograft models. Conversely, NPY1R expression decreased in ER+ BC cells resistant to endocrine therapies (estrogen deprivation, tamoxifen, and fulvestrant) in vitro and in vivo. NPY treatment reduced estradiol-stimulated cell growth, which was reversed by NPY1R antagonist (BIBP-3226) in ER+ BC cells. Higher NPY1R gene expression predicted better relapse-free survival and overall survival in ER+ BC. Our study demonstrates that NPY1R mediates the inhibitory action of NPY on estradiol-stimulated growth of ER+ BC cells, and its expression serves as a biomarker to predict endocrine sensitivity and survival in ER+ BC patients.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Neoplasias das Glândulas Endócrinas/tratamento farmacológico , Receptor alfa de Estrogênio/genética , Receptores de Neuropeptídeo Y/genética , Animais , Antineoplásicos Hormonais/farmacologia , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Neoplasias das Glândulas Endócrinas/genética , Neoplasias das Glândulas Endócrinas/patologia , Estradiol/farmacologia , Estrogênios/genética , Feminino , Fulvestranto/farmacologia , Regulação Neoplásica da Expressão Gênica , Xenoenxertos , Humanos , Camundongos , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Receptor ErbB-2/genética , Receptores Acoplados a Proteínas G/genética , Tamoxifeno/farmacologia
3.
Front Endocrinol (Lausanne) ; 12: 646210, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33790868

RESUMO

Epithelial-mesenchymal transition (EMT) is a dynamic process by which epithelial cells loss their phenotype and acquire mesenchymal traits, including increased migratory and invasive capacities. EMT is involved in physiological processes, such as embryogenesis and wound healing, and in pathological processes such as cancer, playing a pivotal role in tumor progression and metastasis. Pituitary tumors, although typically benign, can be locally invasive. Different studies have shown the association of EMT with increased tumor size and invasion in pituitary tumors, and in particular with a poor response to Somatostatin Receptor Ligands (SRLs) treatment in GH-producing pituitary tumors, the main cause of acromegaly. This review will summarize the current knowledge regarding EMT and SRLs resistance in acromegaly and, based on this relation, will suggest new biomarkers and possible therapies to SRLs resistant tumors.


Assuntos
Acromegalia/tratamento farmacológico , Acromegalia/patologia , Resistência a Medicamentos , Neoplasias das Glândulas Endócrinas/tratamento farmacológico , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Adenoma Hipofisário Secretor de Hormônio do Crescimento/tratamento farmacológico , Ligantes , Receptores de Somatostatina/química , Acromegalia/etiologia , Biomarcadores/metabolismo , Caderinas/biossíntese , Citoesqueleto/efeitos dos fármacos , Humanos , Fenótipo , Neoplasias Hipofisárias/tratamento farmacológico , Somatostatina/metabolismo
4.
Eur J Endocrinol ; 181(5): R173-R183, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31398712

RESUMO

Octreotide remains 40 years after its development a drug, which is commonly used in the treatment of acromegaly and GEP-NETs. Very little innovation that competes with this drug occurred over this period. This review discusses several aspects of 40 years of clinical use of octreotide, including the application of radiolabeled forms of the peptide.


Assuntos
Octreotida/uso terapêutico , Acromegalia/tratamento farmacológico , Neoplasias das Glândulas Endócrinas/tratamento farmacológico , História do Século XX , Humanos , Octreotida/efeitos adversos , Octreotida/história
5.
J Mol Endocrinol ; 63(2): R17-R35, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31307011

RESUMO

Incidence of endocrine cancers is rising every year. Over the last decade, evidence has accumulated that demonstrates the anti-cancer effects of an anti-diabetic drug, metformin, in endocrine malignancies. We performed a literature review utilizing the PubMed, Medline and clinicaltrials.gov databases using the keyword 'metformin' plus the following terms: 'thyroid cancer', 'thyroid nodules', 'parathyroid', 'hyperparathyroidism', 'adrenal adenoma', 'Cushing syndrome', 'hyperaldosteronism', 'adrenocortical cancer', 'neuroendocrine tumor (NET)', 'pancreatic NET (pNET)', 'carcinoid', 'pituitary adenoma', 'pituitary neuroendocrine tumor (PitNET)', 'prolactinoma', 'pheochromocytoma/paraganglioma'. We found 37 studies describing the preclinical and clinical role of metformin in endocrine tumors. The available epidemiological data show an association between exposure of metformin and lower incidence of thyroid cancer and pNETs in diabetic patients. Metformin treatment has been associated with better response to cancer therapy in thyroid cancer and pNETs. Preclinical evidence suggests that the primary direct mechanisms of metformin action include inhibition of mitochondrial oxidative phosphorylation via inhibition of both mitochondrial complex I and mitochondrial glycerophosphate dehydrogenase, leading to metabolic stress. Decreased ATP production leads to an activation of a cellular energy sensor, AMPK, and subsequent downregulation of mTOR signaling pathway, which is associated with decreased cellular proliferation. We also describe several AMPK-independent mechanisms of metformin action, as well as the indirect mechanisms targeting insulin resistance. Overall, repositioning of metformin has emerged as a promising strategy for adjuvant therapy of endocrine tumors. The mechanisms of synergy between metformin and other anti-cancer agents need to be elucidated further to guide well-designed prospective trials on combination therapies in endocrine malignancies.


Assuntos
Diabetes Mellitus/tratamento farmacológico , Neoplasias das Glândulas Endócrinas/tratamento farmacológico , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Metformina/farmacologia , Metformina/uso terapêutico , Animais , Humanos , Transdução de Sinais/efeitos dos fármacos
6.
BMJ Case Rep ; 20182018 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-29592980

RESUMO

A 45-year-old woman was diagnosed as having multiple endocrine neoplasia type 2A in 2014. She had bilateral pheochromocytoma, medullary thyroid carcinoma and biopsy-proven cutaneous lichen amyloidosis in the interscapular area. She underwent bilateral adrenalectomy; following which, she achieved clinical and biochemical remission. She was planned for total thyroidectomy at a later date; however, she was lost to follow-up. She presented to us again in December 2016 with abdominal pain. Examination revealed hypertension with postural drop. Positron emission tomography scan showed Ga68 and fluorodeoxyglucose (FDG)-avid suprarenal, hepatic, peritoneal and mesenteric masses with abdominal lymph nodes. Twenty-four-hour urinary metanephrines/normetanephrines were elevated. Serum calcitonin was as high as it was 2-1/2 years ago. Ultrasonography-guided fine-needle aspiration cytology (FNAC) from the liver mass revealed neuroendocrine cells that did not stain for calcitonin. Hence, a diagnosis of metastatic pheochromocytoma was made. She underwent total thyroidectomy and was started on cyclophosphamide, vincristine, dacarbazine-based chemotherapy regimen.


Assuntos
Neoplasias das Glândulas Suprarrenais/patologia , Neoplasias do Sistema Digestório/secundário , Neoplasias das Glândulas Endócrinas/secundário , Neoplasia Endócrina Múltipla Tipo 2a/patologia , Feocromocitoma/patologia , Neoplasias das Glândulas Suprarrenais/cirurgia , Glândulas Suprarrenais/diagnóstico por imagem , Glândulas Suprarrenais/cirurgia , Protocolos de Quimioterapia Combinada Antineoplásica , Diagnóstico Diferencial , Neoplasias do Sistema Digestório/diagnóstico por imagem , Neoplasias do Sistema Digestório/tratamento farmacológico , Neoplasias das Glândulas Endócrinas/diagnóstico por imagem , Neoplasias das Glândulas Endócrinas/tratamento farmacológico , Feminino , Humanos , Fígado/diagnóstico por imagem , Pessoa de Meia-Idade , Neoplasia Endócrina Múltipla Tipo 2a/cirurgia , Pâncreas/diagnóstico por imagem , Feocromocitoma/cirurgia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Baço/diagnóstico por imagem , Glândula Tireoide/diagnóstico por imagem , Imagem Corporal Total
7.
Appl Immunohistochem Mol Morphol ; 26(1): 13-19, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27753656

RESUMO

Tumor heterogeneity has been shown for several cancers including breast cancer (BC). Despite the fact that expression of tumor markers may change throughout the metastatic process, rebiopsies at the time of recurrence are still not performed routinely at all institutions. The aims of the study were to evaluate changes in biomarker profiles during the metastatic process and to investigate whether previous anthracycline or endocrine therapy given in the adjuvant setting could affect the biomarker profile in metastatic lesions. We investigated the expression pattern of ER, HER2, TOP2a, TOP1, p53, Bcl-2, and Ki-67 in 110 paired samples of primary BC and corresponding asynchronous metastases. We found discordant expressions in primary tumor and metastasis for all biomarkers, although only significant for Ki-67. Changes in the expression profile of the metastatic lesions would have altered treatment decisions in 14% of patients. We found no effect of previous anthracycline or endocrine therapy on the expression profiles. Our data confirm that discordant expressions of biomarkers are common in BC and often carry therapeutic consequences. This emphasizes the need for biopsies from metastatic lesions, even in cases where the localization of the metastatic process is not easily accessible.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Perfilação da Expressão Gênica , Antraciclinas/farmacologia , Antraciclinas/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/fisiopatologia , Neoplasias das Glândulas Endócrinas/tratamento farmacológico , Neoplasias das Glândulas Endócrinas/genética , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos
8.
Endocr Relat Cancer ; 24(12): T261-T281, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28893836

RESUMO

Immune checkpoint inhibitors are agents that act by inhibiting the mechanisms of immune escape displayed by various cancers. The success of immune checkpoint inhibitors against several tumors has promoted a new treatment strategy in clinical oncology, and this has encouraged physicians to increase the number of patients who receive the immune checkpoint therapy. In the present article, we review the main concepts regarding immune checkpoint mechanisms and how cancer disrupts them to undergo immune escape. In addition, we describe the most essential concepts related to immune checkpoint inhibitors. We critically review the literature on preclinical and clinical studies of the immune checkpoint inhibitors as a treatment option for thyroid cancer, ovarian carcinoma, pancreatic adenocarcinoma, adrenocortical carcinoma and neuroendocrine tumors. We present the challenges and the opportunities of using immune checkpoint inhibitors against these endocrine malignancies, highlighting the breakthroughs and pitfalls that have recently emerged.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Neoplasias das Glândulas Endócrinas/tratamento farmacológico , Imunoterapia/métodos , Anticorpos Monoclonais/farmacologia , Neoplasias das Glândulas Endócrinas/patologia , Humanos
9.
Endocrine ; 57(2): 220-225, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28685225

RESUMO

INTRODUCTION: Pheochromocytomas and paragangliomas (Pheo/PGL) are rare, vascular, sometimes malignant endocrine tumors. Case reports indicate the activity of vascular endothelium growth factor receptor-targeted kinase inhibitors in these cancers. OBJECTIVES: To assess the antitumor activity and tolerability of pazopanib in progressive malignant Pheo/PGL. PATIENTS AND METHODS: This multicenter Phase II trial (MC107C) enrolled individuals ≥18 years old with disease progression ≤ 6 months prior to registration, Eastern Cooperative Oncology Group PS 0-2, and measurable disease (response evaluation criteria in solid tumors 1.0). Pazopanib was administered in 28-day cycles, with the regimen ultimately being as follows: cycle 1: 400 mg daily on days 1-14, cycle 2: 800 mg daily on days 1-14, and then cycle 2 + : 800 mg daily on all days. RESULTS: The study was halted due to poor accrual. Seven patients were enrolled (05/2011-11/2014). One patient withdrew consent prior to treatment, leaving six evaluable patients. Treatment was discontinued, due to the following reasons: disease progression (4); withdrawal (1); and grade 4 (Takotsubo) cardiomyopathy (1). The median number of cycles administered was 4 (range: 2-29, total: 49). Four patients had >1 dose reduction due to the following reasons: fatigue (1), abnormal liver tests (2), hypertension and (Takotsubo) cardiomyopathy (1), and headaches (1). Common severe (Common Terminology Criteria for Adverse Events v3.0 grades 3-5) toxicities were as follows: hypertension (3/6), (Takotsubo) cardiomyopathy (2/6), diarrhea (1/6), fatigue (1/6), headache (1/6), and hematuria (1/6). One confirmed partial response was observed in PGL (17%, duration 2.4 years); median progression-free survival and overall survival were 6.5 and 14.8 months, respectively. CONCLUSION: Pazopanib has activity in Pheo/PGL requiring more study; optimal alpha- and beta-blockade are imperative pre-therapy in patients with secretory tumors, as risk of hypertension and cardiomyopathy are potentially life threatening.


Assuntos
Neoplasias das Glândulas Suprarrenais/tratamento farmacológico , Inibidores da Angiogênese/uso terapêutico , Neoplasias das Glândulas Endócrinas/tratamento farmacológico , Paraganglioma/tratamento farmacológico , Feocromocitoma/tratamento farmacológico , Pirimidinas/uso terapêutico , Sulfonamidas/uso terapêutico , Neoplasias das Glândulas Suprarrenais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/efeitos adversos , Intervalo Livre de Doença , Eletrocardiografia , Neoplasias das Glândulas Endócrinas/patologia , Feminino , Humanos , Indazóis , Masculino , Pessoa de Meia-Idade , Paraganglioma/patologia , Feocromocitoma/patologia , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/efeitos adversos , Receptores de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Sulfonamidas/efeitos adversos , Falha de Tratamento
10.
Endocr Relat Cancer ; 24(9): T65-T82, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28615236

RESUMO

A colossal amount of basic research over the past few decades has provided unprecedented insights into the highly complex process of cell division. There is an ever-expanding catalog of proteins that orchestrate, participate and coordinate in the exquisite processes of spindle formation, chromosome dynamics and the formation and regulation of kinetochore microtubule attachments. Use of classical microtubule poisons has still been widely and often successfully used to combat a variety of cancers, but their non-selective interference in other crucial physiologic processes necessitate the identification of novel druggable components specific to the cell cycle/division pathway. Considering cell cycle deregulation, unscheduled proliferation, genomic instability and chromosomal instability as a hallmark of tumor cells, there lies an enormous untapped terrain that needs to be unearthed before a drug can pave its way from bench to bedside. This review attempts to systematically summarize the advances made in this context so far with an emphasis on endocrine-related cancers and the avenues for future progress to target mitotic mechanisms in an effort to combat these dreadful cancers.


Assuntos
Antimitóticos/uso terapêutico , Neoplasias das Glândulas Endócrinas/tratamento farmacológico , Mitose/efeitos dos fármacos , Animais , Neoplasias das Glândulas Endócrinas/patologia , Humanos , Microtúbulos/metabolismo , Tubulina (Proteína)/metabolismo
11.
Am Soc Clin Oncol Educ Book ; 37: 674-683, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28561717

RESUMO

Cancer survivorship care and research has typically focused on the health care needs of people with cancer following the acute phase of treatment. Work in this area, however, has faced challenges in identifying when treatment is complete for many forms of cancer. Acknowledging this challenge, the scope of survivorship research is often expanded to include patients also receiving maintenance or prophylactic therapy. Inherent in this expanded definition is the recognition that for many individuals, cancer is a chronic disease requiring extended treatment over many years. Three distinct patient populations can be identified for which extended treatment poses important survivorship care needs that, to date, have not been adequately addressed. The first group includes patients receiving extended endocrine therapy, such as women with breast cancer receiving tamoxifen and/or aromatase inhibitors as well as men with prostate cancer receiving androgen deprivation therapy. The second group includes patients receiving extended targeted therapy to control disease, as exemplified by patients with chronic myelogenous leukemia receiving treatment with tyrosine kinase inhibitors. A key issue in both of these patient groups is the need to identify and address factors that contribute to difficulties in maintaining high levels of adherence to the prescribed therapy over extended periods of time. The third group includes patients receiving novel therapies for advanced or metastatic cancer that can extend life for prolonged periods. A key issue for this group is the need to understand and address their unique supportive care needs.


Assuntos
Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias das Glândulas Endócrinas/tratamento farmacológico , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias das Glândulas Endócrinas/patologia , Feminino , Humanos , Masculino , Recidiva Local de Neoplasia , Neoplasias da Próstata/patologia , Sobrevivência , Tamoxifeno/uso terapêutico
14.
Breast Cancer Res Treat ; 149(1): 69-79, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25491778

RESUMO

Activation of the phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR pathway has been implicated in anti-estrogen resistance in breast cancer. We tested the therapeutic potential of the novel PI3K/mTOR dual inhibitor P7170 in a panel of anti-estrogen-sensitive and anti-estrogen-resistant models of ER+ breast cancer. Estrogen receptor-positive (ER+) breast cancer cells were treated ±P7170. Fresh cores from primary ER+/HER2- tumors from two patients were treated ±P7170 ex vivo. Mice bearing breast cancer xenografts were randomized to treatment with vehicle, fulvestrant, P7170, or combinations, and tumor volumes were measured. Tissues and cells were analyzed for markers of pathway activity, cell viability, and apoptosis. In cell lines, P7170 exhibited IC50 values in the range of 0.9-7 nM and induced apoptosis. P7170 potently inhibited mTOR activity (≤ 25 nM) and inhibited PI3K at higher concentrations (≥ 200 nM). P7170 completely inhibited MCF-7 tumor growth, significantly inhibited growth of fulvestrant-resistant T47D tumors, and suppressed tumor cell proliferation but did not induce apoptosis. While P7170 inhibits PI3K and mTOR in ER+/HER2- human breast cancer cells and tumors ex vivo, in vivo data indicate that the primary mechanism of P7170 anti-tumor action is inhibition of mTOR and cell proliferation. P7170 is a novel agent worthy of further investigation for the treatment of ER+ breast cancer.


Assuntos
Neoplasias da Mama/genética , Neoplasias das Glândulas Endócrinas/tratamento farmacológico , Imidazóis/administração & dosagem , Fosfatidilinositol 3-Quinases/genética , Quinolinas/administração & dosagem , Serina-Treonina Quinases TOR/genética , Animais , Apoptose/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Proliferação de Células/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias das Glândulas Endócrinas/genética , Neoplasias das Glândulas Endócrinas/patologia , Estradiol/administração & dosagem , Estradiol/análogos & derivados , Feminino , Fulvestranto , Regulação Neoplásica da Expressão Gênica , Humanos , Células MCF-7 , Camundongos , Inibidores de Fosfoinositídeo-3 Quinase , Inibidores de Proteínas Quinases/administração & dosagem , Receptores de Estrogênio/genética , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/antagonistas & inibidores , Ensaios Antitumorais Modelo de Xenoenxerto
15.
BMC Cancer ; 14: 561, 2014 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-25086465

RESUMO

BACKGROUND: Patients with advanced endocrine cancers, such as adrenocortical carcinoma and medullary thyroid carcinoma, have few well-validated therapeutic options. Pre-clinical studies have suggested potential activity of imatinib in these tumors. We therefore sought to establish a safe, novel treatment regimen combining imatinib with cytotoxic chemotherapy for future study in endocrine cancers. METHODS: A standard 3 + 3 dose-escalation design was used with a 21-day cycle, including imatinib on days 1-21, dacarbazine on days 1-3, and capecitabine on days 1-14. RESULTS: Twenty patients were treated. The most frequent toxicities were edema and fatigue, with dose-limiting fatigue and dyspnea. The recommended phase II regimen is dacarbazine 250 mg/m2 daily on day 1-3, capecitabine 500 mg/m2 twice daily on days 1-14, and imatinib 300 mg daily on days 1-21 of a 21-day cycle. Interestingly, responses were seen in patients with adrenocortical carcinoma, with 1 of 6 patients experiencing a partial response and a second experiencing a minor response, with progression-free survival of 8.8 and 6.4 months, respectively. CONCLUSIONS: The regimen of imatinib, dacarbazine, and capecitabine is well-tolerated. It may have some activity in adrenocortical carcinoma, and further study of this combination or its components may be beneficial for this disease with limited treatment options. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT00354523, registered July 18, 2006.


Assuntos
Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias das Glândulas Endócrinas/tratamento farmacológico , Adulto , Idoso , Antineoplásicos/uso terapêutico , Benzamidas/administração & dosagem , Benzamidas/uso terapêutico , Capecitabina , Dacarbazina/administração & dosagem , Dacarbazina/uso terapêutico , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Intervalo Livre de Doença , Esquema de Medicação , Neoplasias das Glândulas Endócrinas/patologia , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/análogos & derivados , Fluoruracila/uso terapêutico , Humanos , Mesilato de Imatinib , Masculino , Pessoa de Meia-Idade , Piperazinas/administração & dosagem , Piperazinas/uso terapêutico , Pirimidinas/administração & dosagem , Pirimidinas/uso terapêutico , Resultado do Tratamento
16.
Gan To Kagaku Ryoho ; 41(1): 107-12, 2014 Jan.
Artigo em Japonês | MEDLINE | ID: mdl-24423963

RESUMO

A 77-year-old man who complained of melena was admitted to our department. Colonoscopy revealed a type 2 tumor in the hepatic flexure of the ascending colon. Biopsy examination revealed a poorly differentiated adenocarcinoma. Abdominal computed tomography(CT)revealed 3 tumors within the posterior segment of the right hepatic lobe. Initially, a right hemicolectomy was performed. Immunohistochemically, the tumor was diagnosed as an endocrine cell carcinoma. After surgery, a capecitabine, oxaliplatin, and bevacizumab(CapeOX/BEV)regimen was administered. However, after 5 chemotherapy courses, abdominal CT revealed enlargement of the 3 tumors in the posterior segment of the right hepatic lobe. There was no metastasis besides the liver metastasis. The patient underwent a radical hepatectomy of the posterior segment. At 8 months post-surgery, the patient remains alive and well. Endocrine cell carcinoma of the colon and rectum is usually malignant and is associated with a very poor prognosis because of rapid hematogenous or lymphogenous metastasis. Effective multimodal treatment regimens, including surgery and new chemotherapies such as molecular targeted therapies, should be established to improve the prognosis of patients with endocrine cell carcinomas of the colon and rectum.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Colo Ascendente/patologia , Neoplasias do Colo/tratamento farmacológico , Neoplasias das Glândulas Endócrinas/tratamento farmacológico , Neoplasias Hepáticas/cirurgia , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Bevacizumab , Capecitabina , Colo Ascendente/cirurgia , Neoplasias do Colo/patologia , Neoplasias do Colo/cirurgia , Terapia Combinada , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Neoplasias das Glândulas Endócrinas/cirurgia , Fluoruracila/administração & dosagem , Fluoruracila/análogos & derivados , Hepatectomia , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Masculino , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina
17.
Ann Endocrinol (Paris) ; 74 Suppl 1: S13-22, 2013 Oct.
Artigo em Francês | MEDLINE | ID: mdl-24356287

RESUMO

A better understanding of molecular mechanisms responsible for tumorigenesis has allowed the development of targeted drugs designed to improve the outcome of cancer. In endocrine tumors, several molecules have demonstrated efficacy in terms of progression free survival during phase III trials such as vandetanib and cabozantinib in medullary thyroid carcinoma, sorafenib in differentiated thyroid carcinoma and everolimus or sunitinib for pancreatic neuroendocrine tumors. Rare cancer network has allowed ongoing phase III trials in malignant pheochromocytoma and adrenocortical carcinoma. However, to date no specific predictive biomarker has yet been identified for a personalized cancer medicine. We review recent advances in endocrine oncology concerning molecular targets identification, targeted therapies and predictive or prognostic markers.


Assuntos
Neoplasias das Glândulas Endócrinas/tratamento farmacológico , Terapia de Alvo Molecular , Antineoplásicos/uso terapêutico , Carcinoma Neuroendócrino , Ensaios Clínicos Fase III como Assunto , Intervalo Livre de Doença , Everolimo , Humanos , Indóis/uso terapêutico , Tumores Neuroendócrinos/tratamento farmacológico , Niacinamida/análogos & derivados , Niacinamida/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Compostos de Fenilureia/uso terapêutico , Piperidinas/uso terapêutico , Prognóstico , Pirróis/uso terapêutico , Quinazolinas/uso terapêutico , Sirolimo/análogos & derivados , Sirolimo/uso terapêutico , Sorafenibe , Sunitinibe , Neoplasias da Glândula Tireoide/tratamento farmacológico , Resultado do Tratamento
18.
Clin. transl. oncol. (Print) ; 15(9): 725-731, sept. 2013. tab
Artigo em Inglês | IBECS | ID: ibc-127492

RESUMO

AIM: Malignant insulinoma is an infrequent functional endocrine tumor of the pancreas. Adequate therapy is a demanding challenge for oncologists and endocrinologists. OBJECTIVE: To evaluate the results of multidisciplinary management of malignant insulinoma. MATERIALS AND METHODS: Retrospective review of patients with malignant insulinoma treated from 1995 to 2011. RESULTS: Seven patients with malignant insulinoma were included: four males and three females; median age was 61.8 years (range 37-78). Six tumors were sporadic and one was diagnosed in a patient with a type 1 multiple endocrine neoplasia (MEN-1). Surgery was performed in six cases and one patient was considered unresectable. Hypoglycemias persisted in all cases and somatostatin analogs, glucocorticoids and diazoxide were used. Two patients received everolimus. Other techniques were chemoembolization and internal radiation therapy with yttrium-90. Successful liver transplant was done in the patient with MEN-1. CONCLUSION: hypoglycemia management is complex and requires multiple therapies. Further evaluations will be necessary to determine the best treatment (AU)


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias das Glândulas Endócrinas/tratamento farmacológico , Neoplasias das Glândulas Endócrinas/metabolismo , Neoplasias das Glândulas Endócrinas/radioterapia , Neoplasias das Glândulas Endócrinas/terapia , Neoplasias das Glândulas Endócrinas/diagnóstico , Pâncreas/anormalidades , Transplante de Fígado/métodos
20.
Neuroendocrinology ; 97(1): 67-73, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-22441103

RESUMO

The most frequent molecular abnormalities in pancreatic endocrine tumours (PETs) are mutations of the MEN1 gene, deregulation of the PI3K/AKT/mTOR signalling pathway and overactivation of growth factors and their receptors, such as the VEGF. On this basis, everolimus (Afinitor®; Novartis) and sunitinib (Sutent®; Pfizer) have both been approved by the FDA for the treatment of progressive, unresectable, locally advanced or metastatic PETs. However, molecular or surrogate markers able to predict the response of PET patients to treatment with these drugs are not available, and cancer cells treated with targeted therapies might develop escape pathways that evoke pro-survival feedback responses. The existence of cross-talk between different molecular pathways in PETs has been poorly investigated. In the present review, we present data supporting an important role for Src family kinases (SFKs) in PETs, together with the recent observation of a novel role for SFK in modulating the mTOR pathway activity. Of note, while treatment with everolimus triggered the activation of a survival response dependent on PI3K/AKT signalling in vitro, the simultaneous inhibition of SFKs blocked the activation of this unwanted escape signal. These studies might set the ground for the investigation of combined treatment of PETs with SFK and mTOR inhibitors.


Assuntos
Neoplasias das Glândulas Endócrinas/metabolismo , Neoplasias Pancreáticas/metabolismo , Transdução de Sinais/fisiologia , Quinases da Família src/metabolismo , Animais , Antineoplásicos/farmacologia , Neoplasias das Glândulas Endócrinas/tratamento farmacológico , Humanos , Neoplasias Pancreáticas/tratamento farmacológico , Serina-Treonina Quinases TOR/metabolismo
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