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ATP6AP2, also known as (pro)renin receptor, has been shown to be expressed in several tissues including pancreatic ß cells. Whereas ATP6AP2 plays an important role in regulating insulin secretion in mouse pancreatic ß cells, the expression profiles and roles of ATP6AP2 in human pancreatic endocrine cells and neuroendocrine tumor cells remain unclear. Here in this study, we investigated the expression profiles of ATP6AP2 in pancreatic endocrine cells, and found that ATP6AP2 is robustly expressed in pancreatic insulinoma cells as well as in normal ß cells. Although ATP6AP2 was also expressed in low-grade neuroendocrine tumors, it was not or faintly detected in intermediate- and high-grade neuroendocrine tumors. Knockdown experiments of the Atp6ap2 gene in rat insulinoma-derived INS-1 cells demonstrated decreased cell viability accompanied by a significant increase in apoptotic cells. Taken together, these findings suggest that ATP6AP2 plays a role in maintaining cellular homeostasis in insulinoma cells, which could lead to possible therapeutic approaches for endocrine tumors.
Assuntos
Células Secretoras de Insulina , Insulinoma , Tumores Neuroendócrinos , Neoplasias Pancreáticas , ATPases Vacuolares Próton-Translocadoras , Camundongos , Ratos , Animais , Humanos , Células Secretoras de Insulina/metabolismo , Insulinoma/genética , Insulinoma/metabolismo , Tumores Neuroendócrinos/genética , Tumores Neuroendócrinos/metabolismo , Sobrevivência Celular/genética , ATPases Vacuolares Próton-Translocadoras/metabolismo , Receptores de Superfície Celular/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Receptor de Pró-ReninaRESUMO
â¢A case of concurrent primary ovarian clear cell adenocarcinoma and liver angiosarcoma is detailed herein.â¢If a liver tumor is found together with ovarian cancer, it is necessary to determine whether this is a primary hepatic malignancy or metastatic liver cancer.â¢It is important to make a definitive diagnosis by performing a liver biopsy when appropriate.
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INTRODUCTION: There is little evidence regarding the treatment of stage IVB endometrial cancer. Therefore, chemotherapy is more likely to be chosen as the initial and first-line treatment. Pembrolizumab is a new treatment choice for unresectable endometrial cancer after first-line chemotherapy failure. PRESENTATION OF CASE: Herein, we report the case of a 56-year-old patient diagnosed with stage IVB endometrial cancer. After eight cycles of first-line chemotherapy, computed tomography (CT) revealed relapse with re-enlargement of the para-aortic lymph nodes. Since the primary tumour had high microsatellite instability, we switched to pembrolizumab treatment. Pembrolizumab was effective but could not be continued due to adverse events after 10 cycles. Positron emission tomography-CT revealed active cancer in the uterus and para-aortic lymph nodes. DISCUSSION: Since pembrolizumab treatment had to be discontinued, we performed salvage surgery, which achieved complete tumour removal, and the patient has had no evidence of disease for 16 months. CONCLUSION: This is the first case of complete surgical resection after administering pembrolizumab as a second-line treatment for advanced endometrial cancer.
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SUMMARY: Acromegaly is associated with a low quality of life (QoL), which is partially attributable to appearance. However, appearance changes are only partially reversible with treatments of growth hormone excess. This case study describes a 41-year-old Japanese man who presented with mandibular prognathism. Acromegaly was suspected because of the patient's facial features. Subsequent examination revealed a pituitary tumour with elevated levels of growth hormone and insulin-like growth factor 1 (IGF1), confirming a diagnosis of acromegaly. We assessed his QoL with the acromegaly QoL questionnaire (AcroQoL) before transsphenoidal surgery, and all AcroQoL scores were low. Although the pituitary adenoma was resected, his serum IGF1 levels started to increase again and MRI identified a residual pituitary lesion. After lanreotide and pegvisomant injection therapies improved his serum IGF1 levels, we reassessed his AcroQoL scores, however, the results showed worsening scores regarding appearance and personal relationships, and the patient expressed interest in surgery for mandibular prognathism. We performed sagittal split ramus osteotomy (SSRO) with Le Fort I osteotomy, thus, the patient's AcroQoL scores improved. This case shows that SSRO with Le Fort I osteotomy for mandibular prognathism, rather than control of serum IGF1 level alone, improved the patient's AcroQoL score, especially for both psychological well-being and approval of appearance. Acromegaly has many complications, including its negative impact on patients' perception of their appearance and patients' QoL can be improved using multiple options, in addition to controlling growth hormone levels. LEARNING POINTS: The patient's AcroQoL scores worsened despite biochemical normalization of IGF-1 levels. Mandibular prognathism due to acromegaly can be successfully operated by performing sagittal split ramus osteotomy with Le Fort I osteotomy. Frequent monitoring of AcroQoL scores and appropriate response to negative results can improve the overall QoL.
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Advances in imaging technology and its widespread use have increased the number of identified patients with bilateral adrenal incidentalomas. The pathology of bilateral adrenal incidentalomas is gradually elucidated by its increased frequency. Although there is no consensus regarding the optimal management of bilateral adrenal lesions, adrenal lesions that are a suspected adrenocortical carcinoma on the basis of radiological imaging require surgical resection. We report a clinically interesting case of a 59-year-old female with adrenocortical adenoma harboring venous thrombus that mimicked adrenal malignancy. She was referred for evaluation of asymptomatic asymmetric lesions on both adrenal glands. Abdominal computed tomography and magnetic resonance imaging showed a 4.7-cm-diameter heterogenous lesion with peripheral enhancement in the right adrenal gland and a 2.0-cm-diameter homogenous lesion in the left adrenal gland. Adrenal scintigraphy with 131I-adosterol exhibited marked accumulation in the left lesion and slight accumulation in the middle inferior portion of the right lesion. Endocrine data revealed subclinical Cushing syndrome, and the patient underwent right laparoscopic adrenalectomy. The serum cortisol level was not suppressed on an overnight dexamethasone suppression test after the adrenalectomy. The resected tumor revealed a cortisol-producing adrenocortical adenoma harboring an organized and re-canalized venous thrombus, which was associated with focal papillary endothelial hyperplasia. This case illustrates the difficulty with preoperatively diagnosing this heterogeneously enhanced large benign adrenal lesion and differentiating it from adrenocortical carcinoma or angiosarcoma.
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Neoplasias do Córtex Suprarrenal/diagnóstico , Adenoma Adrenocortical/diagnóstico , Trombose Venosa/diagnóstico , Neoplasias do Córtex Suprarrenal/diagnóstico por imagem , Neoplasias do Córtex Suprarrenal/patologia , Adenoma Adrenocortical/diagnóstico por imagem , Adenoma Adrenocortical/patologia , Diagnóstico Diferencial , Feminino , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/patologiaRESUMO
Identification of low-abundance, low-molecular-weight native peptides using non-tryptic plasma has long remained an unmet challenge, leaving potential bioactive/biomarker peptides undiscovered. We have succeeded in efficiently removing high-abundance plasma proteins to enrich and comprehensively identify low-molecular-weight native peptides using mass spectrometry. Native peptide sequences were chemically synthesized and subsequent functional analyses resulted in the discovery of three novel bioactive polypeptides derived from an epidermal differentiation marker protein, suprabasin. SBSN_HUMAN[279-295] potently suppressed food/water intake and induced locomotor activity when injected intraperitoneally, while SBSN_HUMAN[225-237] and SBSN_HUMAN[243-259] stimulated the expression of proinflammatory cytokines via activation of NF-κB signaling in vascular cells. SBSN_HUMAN[225-237] and SBSN_HUMAN[279-295] immunoreactivities were present in almost all human organs analyzed, while immunoreactive SBSN_HUMAN[243-259] was abundant in the liver and pancreas. Human macrophages expressed the three suprabasin-derived peptides. This study illustrates a new approach for discovering unknown bioactive peptides in plasma via the generation of peptide libraries using a novel peptidomic strategy.
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Antígenos de Diferenciação/metabolismo , Proteínas de Neoplasias/metabolismo , Peptídeos/sangue , Animais , Apoptose/efeitos dos fármacos , Apetite/efeitos dos fármacos , Células Cultivadas , Cromatografia Líquida de Alta Pressão , Citocinas/metabolismo , Imunofluorescência , Humanos , Camundongos , Mitose/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , NF-kappa B/metabolismo , Peptídeos/farmacologiaRESUMO
AIMS/INTRODUCTION: Non-alcoholic fatty liver disease is frequently associated with type 2 diabetes, and constitutes an important risk factor for the development of hepatic fibrosis and hepatocellular carcinoma. Because there remains no effective drug therapy for non-alcoholic fatty liver disease associated with type 2 diabetes, we evaluated the efficacy of sodium-glucose cotransporter 2 inhibitor. METHODS AND MATERIALS: In the present pilot, prospective, non-randomized, open-label, single-arm study, we evaluated the effect of 100 mg canagliflozin administered once daily for 12 months on serological markers, body composition measured by bioelectrical impedance analysis method and hepatic fat fraction measured by magnetic resonance imaging in type 2 diabetes patients with non-alcoholic fatty liver disease. RESULTS: Canagliflozin significantly reduced body and fat mass, and induced a slight decrease in lean body or muscle mass that did not reach significance at 6 and 12 months. Reductions in fat mass in each body segment (trunk, arms and legs) were evident, whereas those in lean body mass were not. The hepatic fat fraction was reduced from a baseline of 17.6 ± 7.5% to 12.0 ± 4.6% after 6 months and 12.1 ± 6.1% after 12 months (P < 0.0005 and P < 0.005), whereas serum liver enzymes and type IV collagen concentrations improved. From a mean baseline hemoglobin A1c of 8.7 ± 1.4%, canagliflozin significantly reduced hemoglobin A1c after 6 and 12 months to 7.3 ± 0.6% and 7.7 ± 0.7% (P < 0.0005 and P < 0.01). CONCLUSIONS: Canagliflozin reduced body mass, fat mass and hepatic fat content without significantly reducing muscle mass.