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OBJECTIVE: Pituitary neuroendocrine tumours (PitNETs) are the second most common type of intracranial tumour. Several studies have explored the prognostic factors for PitNETs. However, prognostic factors for postoperative PitNET recurrence remain not fully understood. This study aimed to explore potential prognostic factors for PitNET recurrence, such as surrounding tissue invasion and the extent of surgical resection in patients with postoperative PitNETs. METHODS: We included 106 patients who underwent PitNET surgery between 2013 and 2018, dividing them into two groups: those with recurrence and those without recurrence. Tumours were classified based on demographics, neuroradiological, and immunohistological characteristics. Univariate and multivariate analyses were used to determine factors predicting recurrence. Kaplan-Meier plots and log-rank tests were used to analyse each independent factor based on the cumulative 5-year recurrence rate. RESULTS: During the 5-year follow-up period, 29.2% of the patients (n = 31) had disease recurrence. Univariate analysis showed that predictors of recurrence included cavernous and sphenoid sinus invasions, optic chiasm compression, larger tumour volume, giant adenoma >4 cm, and gross total resection (GTR). Multivariate analysis showed that lactotroph tumour type, sphenoid sinus invasion, and GTR were independent predictors. Kaplan-Meier analysis revealed significant differences in the 5-year recurrence rate among the three independent predictors, with significantly lower recurrence rate in patients with lactotroph tumours and GTR, and a significantly higher recurrence risk in patients with sphenoid sinus invasion. CONCLUSIONS: Lactotroph tumour type, sphenoid sinus invasion, and GTR are independent predictors of postoperative PitNET recurrence. This study provides insights into the factors affecting postoperative PitNET recurrence.
PitNETs are the second most common intracranial tumour typePrognostic factors for postoperative PitNET recurrence remain not fully understoodWe explored potential prognostic factors in patients with postoperative PitNETsProlactin secretion and GTR failure were independent recurrence predictorsProliferative factors did not correlate with recurrence.
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Hepatotoma is the leading type of primary liver cancer in adults and third cause of death in the world. Hydroxytyrosol is a natural phenol existing in olive (Olea europaea L.). Hydroxytyrosol is the chief ingredient of olive oil, which was early deemed to be the most robust antioxidant in olive oil. Hydroxytyrosol is known to inhibit various types of cancer by different methods. This study was aimed to delineate the action of hydroxytyrosol on viability and [Ca2+]i in HepG2 hepatoma cells. Fura-2 was used to detect [Ca2+]i, and WST-1 assays were applied to explore cell cytotoxicity. Hydroxytyrosol elicited [Ca2+]i raises. Eliminating external Ca2+ diminished the Ca2+ signal by 30%. Hydroxytyrosol-evoked Ca2+ influx was diminished by 20% by three inhibitors of store-operated Ca2+ channels and by a protein kinase C activator and an inhibitor. In the absence of Ca2+, thapsigargin eradicated hydroxytyrosol-provoked [Ca2+]i raises. Suppression of phospholipase C (PLC) with U73122, a PLC inhibitor, did not inhibit hydroxytyrosol-elicited [Ca2+]i raises. Hydroxytyrosol reduced cell viability. This cytotoxic action was not reversed by preincubation with BAPTA/AM, a cytosolic Ca2+ binder. In sum, in HepG2 hepatoma cells, hydroxytyrosol elicited [Ca2+]i raises by provoking PLC-unrelated discharge of Ca2+ from ER and Ca2+ influx through PKC-sensitive store-operated Ca2+ entry. In addition, hydroxytyrosol elicited Ca2+-dissociated cytotoxicity.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Olea , Apoptose , Cálcio/metabolismo , Sinalização do Cálcio , Carcinoma Hepatocelular/tratamento farmacológico , Linhagem Celular Tumoral , Sobrevivência Celular , Etanol , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Olea/metabolismo , Fenóis , Álcool Feniletílico/análogos & derivados , Fosfolipases Tipo C/metabolismoRESUMO
Tectorigenin, a traditional Chinese medicine, is isolated from the flower of plants such as Pueraria thomsonii Benth. It is an O-methylated isoflavone, a type of flavonoid. Previous studies have shown that tectorigenin evoked various physiological responses in different models, but the effect of tectorigenin on cytosolic-free Ca2+ levels ([Ca2+]i) and cytotoxicity in renal tubular cells is unknown. Our research explored if tectorigenin changed Ca2+ signal transduction and viability in Madin-Darby Canine Kidney (MDCK) renal tubular cells. [Ca2+]iin suspended cells were measured by applying the fluorescent Ca2+-sensitive probe fura-2. Viability was explored by using water-soluble tetrazolium-1 as a fluorescent dye. Tectorigenin at concentrations of 5-50 µM induced [Ca2+]irises. Ca2+ removal reduced the signal by approximately 20%. Tectorigenin (50 µM) induced Mn2+ influx suggesting of Ca2+ entry. Tectorigenin-induced Ca2+ entry was inhibited by 10% by three inhibitors of store-operated Ca2+ channels, namely, nifedipine, econazole, and SKF96365. In Ca2+-free medium, treatment with the endoplasmic reticulum Ca2+ pump inhibitor thapsigargin inhibited 83% of tectorigenin-evoked [Ca2+]irises. Conversely, treatment with tectorigenin abolished thapsigargin-evoked [Ca2+]irises. Inhibition of phospholipase C with U73122 inhibited 50% of tectorigenin-induced [Ca2+]irises. Tectorigenin at concentrations between 10 and 60 µM killed cells in a concentration-dependent fashion. Chelation of cytosolic Ca2+ with 1,2-bis (2-aminophenoxy)ethane-N, N, N', N'-tetraacetic acid/acetoxy methyl did not reverse tectorigenin's cytotoxicity. Our data suggest that, in MDCK cells, tectorigenin evoked [Ca2+]irises and induced cell death that was not associated with [Ca2+]irises. Therefore, tectorigenin may be a Ca2+-independent cytotoxic agent for kidney cells.
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Sinalização do Cálcio , Animais , Apoptose , Cálcio , Linhagem Celular Tumoral , Sobrevivência Celular , Cães , Isoflavonas , Fosfolipases Tipo CRESUMO
PURPOSE: PACNS has a broad spectrum of clinical manifestations without typical features, and its clinical diagnosis is challenging. We report an elderly patient of cerebellar PACNS (Primary angiitis of central nervous system) presented as a brain tumor by MRI, and primary angiitis was proven by pathology. CASE REPORT: We report an 81-year-old female who complained about vertigo for 3 weeks with right arm dysmetria. There were no other neurologic symptoms/signs, and the patient was free from headache. Brain CT showed a space-occupying lesion over the right cerebellum, and a high-grade glioma was suspected by brain MRI and MRS. The pathologic result of brain biopsy showed granulomatous variant of PACNS. The patient received immunosuppressant therapy as long-term therapy, and had favorable response during a 2-year follow up. CONCLUSION: Due to variations in clinical presentation and nonspecific findings on imaging studies, PACNS is not easily diagnosed, especially in the aged population. PACNS should be considered as one of the differential diagnoses of any CNS dysfunction. PACNS is also an exclusionary diagnosis, so although brain biopsy is limited for its low sensitivity, its application is still important to exclude the possibility of other diseases. Although there have been reports of fulminant cases, PACNS can be treated successfully with immunosuppressant as maintaining therapy.
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Vasculite do Sistema Nervoso Central , Idoso de 80 Anos ou mais , Cerebelo , Feminino , Humanos , Imageamento por Ressonância Magnética , NeoplasiasRESUMO
Niflumic acid, a drug used for joint and muscular pain, affected Ca²âº signaling in different models. However, the effect of niflumic acid on Ca²âº homeostasis and Ca²âº-related physiology in human osteosarcoma cells is unknown. This study examined the effect of niflumic acid on cytosolic free Ca²âº concentrations ([Ca²âº]i) in MG63 human osteosarcoma cells. Intracellular Ca²âº concentrations in suspended cells were monitored by using the fluorescent Ca²âº-sensitive dye fura- 2. Cell viability was examined by using 4-[3-[4-lodophenyl]-2-4(4-nitrophenyl)-2H-5-tetrazolio- 1,3-benzene disulfonate] water soluble tetrazolium-1 (WST-1). In MG63 cells, niflumic acid at concentrations of 250-750 µM evoked [Ca²âº]i rises concentration-dependently. Niflumic acid-evoked Ca²âº entry was confirmed by Mn²âº-induced quenching of fura-2 fluorescence. This entry was inhibited by nifedipine, econazole, SKF96365, the protein kinase C (PKC) activator phorbol 12-myristate 13 acetate (PMA), but was not affected by the PKC inhibitor GF109203X. In Ca²âº- free medium, treatment with the endoplasmic reticulum Ca²âº pump inhibitor thapsigargin (TG) inhibited niflumic acid-evoked [Ca²âº]i rises. Conversely, treatment with niflumic acid abolished TG-evoked [Ca²âº]i rises. Inhibition of phospholipase C (PLC) with U73122 also partly reduced niflumic acid-evoked [Ca²âº]i rises. Niflumic acid killed cells at 200-500 µM in a concentration-dependent fashion. Chelating cytosolic Ca²âº with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid/ AM (BAPTA/AM) did not reverse niflumic acid-induced cytotoxicity. Collectively, our data suggest that in MG63 cells, niflumic acid induced [Ca²âº]i rises by evoking PLC-dependent Ca²âº release from the endoplasmic reticulum, and Ca²âº entry via PKC-sensitive store-operated Ca²âº entry. Niflumic acid also induced Ca²âº-independent cell death.
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Neoplasias Ósseas , Osteossarcoma , Apoptose , Cálcio , Sinalização do Cálcio , Linhagem Celular Tumoral , Sobrevivência Celular , Humanos , Ácido Niflúmico , Fosfolipases Tipo CRESUMO
M-3M3FBS (2,4,6-trimethyl-N-(meta-3-trifluoromethyl-phenyl)-benzenesulfonamide is a presumed phospholipase C activator which induced Ca²âº movement and apoptosis in different cell models. How- ever, the effect of m-3M3FBS on cytosolic free Ca²âº concentrations ([Ca²âº]i) and apoptosis in SCM1 human gastric cancer cells is unclear. This study explored whether m-3M3FBS elevated basal [Ca²âº]i levels in suspended cells by using fura-2 as a Ca²âº-sensitive fluorescent dye. M-3M3FBS at concentrations between 5-50 µM increased [Ca²âº]i in a concentration-dependent manner. The Ca²âº signal was reduced by half by removing extracellular Ca²âº. M-3M3FBS-induced Ca²âº influx was inhibited by nifedipine, econazole, SK&F96365, aristolochic acid, and GF109203X. In Ca²âº-free medium, 50 µM m-3M3FBS pretreatment inhibited the [Ca²âº]i rise induced by the endoplasmic reticulum Ca²âº pump inhibitor thapsigargin. Conversely, pretreatment with thapsigargin partly reduced m-3M3FBS-induced [Ca²âº]i rise. Suppression of inositol 1,4,5-trisphosphate production with U73122 did not change m-3M3FBS- induced [Ca²âº]i rise. At concentrations between 25 and 50 µM m-3M3FBS killed cells in a concentration- dependent manner. The cytotoxic effect of m-3M3FBS was not reversed by prechelating cytosolic Ca²âº with acetoxy-methyl ester of bis-(o-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid (BAPTA/AM). Annexin V/propidium iodide staining data suggest that m-3M3FBS induced apoptosis at 25 and 50 µM. M-3M3FBS also increased levels of superoxide. Together, in human gastric cancer cells, m-3M3FBS induced a [Ca²âº]i rise by inducing phospholipase C-independent Ca²âº release from the endoplasmic reticulum and Ca²âº entry via protein kinase C-sensitive store-operated Ca²âº channels. M-3M3FBS induced cell death that might involve apoptosis via reactive oxygen species production.
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Apoptose/efeitos dos fármacos , Cálcio/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Sulfonamidas/farmacologia , Fosfolipases Tipo C/fisiologia , Linhagem Celular Tumoral , Humanos , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologiaRESUMO
The effect of 2,4,6-trimethyl-N-(meta-3-trifluoromethyl-phenyl)-benzenesulfonamide (m-3M3FBS), a presumed phospholipase C activator, on cytosolic free Ca² ⺠concentrations ([Ca² ⺠]i ) in HA59T human hepatoma cells is unclear. This study explored whether m-3M3FBS elevated basal [Ca² ⺠]i levels in suspended cells by using fura-2 as a Ca² ⺠-sensitive fluorescent dye. M-3M3FBS at concentrations of 10- 50 µM increased [Ca² ⺠]i in a concentration-dependent fashion. The Ca² ⺠signal was reduced partly by removing extracellular Ca² ⺠. M-3M3FBS-induced Ca² ⺠influx was inhibited by nifedipine, econazole, SK&F96365, aristolochic acid, and GF109203X. In Ca² ⺠-free medium, 50 µM m-3M3FBS pretreatment inhibited the [Ca² ⺠]i rise induced by the endoplasmic reticulum Ca² ⺠pump inhibitor thapsigargin. Conversely, pretreatment with thapsigargin partly reduced m-3M3FBS-induced [Ca² ⺠]i rise. Inhibition of inositol 1,4,5-trisphosphate formation with U73122 did not alter m-3M3FBS-induced [Ca² ⺠]i rise. At concentrations between 10 and 40 µM m-3M3FBS killed cells in a concentration-dependent manner. The cytotoxic effect of m-3M3FBS was not reversed by prechelating cytosolic Ca² ⺠with 1,2-bis(2- aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA). Annexin V/propidium iodide staining data suggest that m-3M3FBS induced apoptosis in a concentration-dependent manner. M-3M3FBS also increased levels of reactive oxygen species. Together, in human hepatoma cells, m-3M3FBS induced a [Ca² ⺠]i rise by inducing phospholipase C-independent Ca² ⺠release from the endoplasmic reticulum and Ca² ⺠entry via protein kinase C-sensitive store-operated Ca² ⺠channels. M-3M3FBS induced cell death that might involve apoptosis via mitochondrial pathways.
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Sinalização do Cálcio/efeitos dos fármacos , Cálcio/metabolismo , Sulfonamidas/farmacologia , Fosfolipases Tipo C/metabolismo , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Espécies Reativas de Oxigênio/metabolismoRESUMO
The atypical spindle cell/pleomorphic lipomatous tumor (ASPLT) was classified as a new tumor by the World Health Organization (WHO) in 2020. The tumor is benign and commonly occurs in the limbs. Paraspinal presentations are rare. A 38-year-old man presented at our clinic complaining of sudden onset back pain. No neurological deficit was found. The magnetic resonance imaging (MRI) revealed a well-defined heterogeneous mass in the left psoas muscle, from L1 to L3 extending over the L1 and L2 neuroforamen. The tumor was totally excised. Pathology led to an ASPLT diagnosis. Clinical symptoms improved and there was no postsurgical neurological deficit. This case of ASPLT, located in an uncommon location and present an unusual cluster of symptoms, could be treated by surgical excision, usually the first-treatment strategy. Totally, removal was achieved because there was a clear morphological margin. The risk of metastatic dissemination was minimal, though there remains a nonnegligible risk of local recurrence.
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BACKGROUND: The occurrence of postoperative complications within 30 days (PC1M) of a craniotomy for the removal of a primary malignant brain tumor has been associated with a poor prognosis. However, it is still unclear to early predict the occurrence of PC1M. This study aimed to identify the potential perioperative predictors of PC1M from its preoperative, intraoperative, and 24-h postoperative parameters. METHODS: Patients who had undergone craniotomy for primary malignant brain tumor (World Health Organization grades III and IV) from January 2011 to December 2020 were enrolled from a databank of Kaohsiung Veterans General Hospital, Taiwan. The patients were classified into PC1M and nonPC1M groups. PC1M was defined according to the classification by Landriel et al. as any deviation from an uneventful 30-day postoperative course. In both groups, data regarding the baseline characteristics and perioperative parameters of the patients, including a new marker-kinetic estimated glomerular filtration rate, were collected. Logistic regression was used to analyze the predictability of the perioperative parameters. RESULTS: The PC1M group included 41 of 95 patients. An American Society of Anesthesiologists score of > 2 (aOR, 3.17; 95% confidence interval [CI], 1.19-8.45; p = 0.021), longer anesthesia duration (aOR, 1.16; 95% CI, 0.69-0.88; p < 0.001), 24-h postoperative change in hematocrit by > - 4.8% (aOR, 3.45; 95% CI, 1.22-9.73; p = 0.0019), and 24-h postoperative change in kinetic estimated glomerular filtration rate of < 0 mL/min (aOR, 3.99; 95% CI, 1.52-10.53; p = 0.005) were identified as independent risk factors for PC1M via stepwise logistic regression analysis. When stratified according to the age of ≥ 65 years (OR, 11.55; 95% CI, 1.30-102.79; p = 0.028), the reduction of kinetic estimated glomerular filtration rate was more robustly associated with a higher risk of PC1M. CONCLUSIONS: Four parameters were demonstrated to significantly influence the risk of PC1M in patients undergoing primary malignant brain tumor removal. Measuring and verifying these markers, especially kinetic estimated glomerular filtration rate, would help early recognition of PC1M risk in clinical care.
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Background: Infections caused by multi-drug-resistant Gram-negative bacteria (MDR-GNB) are an emerging problem globally. Colistin is the last-sort antibiotic for MDR-GNB, but its toxicity limits its clinical use. We aimed to test the efficacy of colistin-loaded micelles (CCM-CL) against drug-resistant Pseudomonas aeruginosa and compare their safety with that of free colistin in vitro and in vivo. Materials and methods: We incorporated colistin into chelating complex micelles (CCMs), thus producing colistin-loaded micelles (CCM-CL), and conducted both safety and efficacy surveys to elucidate their potential uses. Results: In a murine model, the safe dose of CCM-CL was 62.5%, which is much better than that achieved after the intravenous bolus injection of 'free' colistin. With a slow drug infusion, the safe dose of CCM-CL reached 16 mg/kg, which is double the free colistin, 8 mg/kg. The area under the curve (AUC) levels for CCM-CL were 4.09- and 4.95-fold higher than those for free colistin in terms of AUC0-t and AUC0-inf, respectively. The elimination half-lives of CCM-CL and free colistin groups were 12.46 and 102.23 min, respectively. In the neutropenic mice model with carbapenem-resistant Pseudomonas aeruginosa pneumonia, the 14-day survival rate of the mice treated with CCM-CL was 80%, which was significantly higher than the 30% in the free colistin group (p < 0.05). Conclusions: Our results showed that CCM-CL, an encapsulated form of colistin, is safe and effective, and thus may become a drug of choice against MDR-GNB.
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The effect of the natural product diindolylmethane on cytosolic Ca(2+) concentrations ([Ca(2+)](i)) and viability in PC3 human prostate cancer cells was explored. The Ca(2+)-sensitive fluorescent dye fura-2 was applied to measure [Ca(2+)](i). Diindolylmethane at concentrations of 20-50 µM induced [Ca(2+)](i) rise in a concentration-dependent manner. The response was reduced partly by removing Ca(2+). Diindolylmethane-evoked Ca(2+) entry was suppressed by nifedipine, econazole, SK&F96365, protein kinase C modulators and aristolochic acid. In the absence of extracellular Ca(2+), incubation with the endoplasmic reticulum Ca(2+) pump inhibitor thapsigargin or 2,5-di-tert-butylhydroquinone (BHQ) inhibited or abolished diindolylmethane-induced [Ca(2+)](i) rise. Incubation with diindolylmethane also inhibited thapsigargin or BHQ-induced [Ca(2+)](i) rise. Inhibition of phospholipase C with U73122 reduced diindolylmethane-induced [Ca(2+)](i) rise. At concentrations of 50-100 µM, diindolylmethane killed cells in a concentration-dependent manner. This cytotoxic effect was not altered by chelating cytosolic Ca(2+) with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA). Annexin V/PI staining data implicate that diindolylmethane (50 and 100 µM) induced apoptosis in a concentration-dependent manner. In conclusion, diindolylmethane induced a [Ca(2+)](i) rise in PC3 cells by evoking phospholipase C-dependent Ca(2+) release from the endoplasmic reticulum and Ca(2+) entry via phospholipase A(2)-sensitive store-operated Ca(2+) channels. Diindolylmethane caused cell death in which apoptosis may participate.
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Sinalização do Cálcio/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Homeostase/efeitos dos fármacos , Neoplasias da Próstata/metabolismo , Cálcio/metabolismo , Linhagem Celular Tumoral , Retículo Endoplasmático/efeitos dos fármacos , Retículo Endoplasmático/metabolismo , Fura-2/farmacologia , Humanos , Indóis/farmacologia , Masculino , Tapsigargina/farmacologia , Fosfolipases Tipo C/metabolismoRESUMO
Celecoxib has been shown to have an antitumor effect in previous studies, but the mechanisms are unclear. Ca(2+) is a key second messenger in most cells. The effect of celecoxib on cytosolic free Ca(2+) concentrations ([Ca(2+)](i)) in human suspended PC3 prostate cancer cells was explored by using fura-2 as a fluorescent dye. Celecoxib at concentrations between 5 and 30 µM increased [Ca(2+)](i) in a concentration-dependent manner. The Ca(2+) signal was reduced partly by removing extracellular Ca(2+). Celecoxib-induced Ca(2+) influx was not blocked by L-type Ca(2+) entry inhibitors or protein kinase C/A modulators [phorbol 12-myristate 13-acetate (PMA), GF109203X, H-89], but was inhibited by the phospholipase A(2) inhibitor, aristolochic acid. In Ca(2+)-free medium, 30 µM of celecoxib failed to induce a [Ca(2+)](i) rise after pretreatment with thapsigargin (an endoplasmic reticulum [ER] Ca(2+) pump inhibitor). Conversely, pretreatment with celecoxib inhibited thapsigargin-induced Ca(2+) release. Inhibition of phospholipase C with U73122 did not change celecoxib-induced [Ca(2+)](i) rises. Celecoxib induced slight cell death in a concentration-dependent manner, which was enhanced by chelating cytosolic Ca(2+) with BAPTA. Collectively, in PC3 cells, celecoxib induced [Ca(2+)](i) rises by causing phospholipase C-independent Ca(2+) release from the ER and Ca(2+) influx via non-L-type, phospholipase A(2)-regulated Ca(2+) channels. These data may contribute to the understanding of the effect of celecoxib on prostate cancer cells.
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Cálcio/metabolismo , Inibidores de Ciclo-Oxigenase 2/farmacologia , Neoplasias da Próstata/tratamento farmacológico , Pirazóis/farmacologia , Sulfonamidas/farmacologia , Canais de Cálcio Tipo L/metabolismo , Celecoxib , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Inibidores de Ciclo-Oxigenase 2/administração & dosagem , Relação Dose-Resposta a Droga , Retículo Endoplasmático/metabolismo , Corantes Fluorescentes/química , Fura-2/química , Humanos , Masculino , Fosfolipases A2/metabolismo , Neoplasias da Próstata/patologia , Pirazóis/administração & dosagem , Sulfonamidas/administração & dosagemRESUMO
A 58-year-old woman experienced relapsing acute longitudinally extensive transverse myelitis that developed rapidly in 3 days after lumbar surgery. The patient had a history of systemic lupus erythematosus with acute transverse myelitis and had undergone plasmapheresis 16 years ago. New neurologic deficits including paraplegia of the lower limbs, sensory alterations, and bowel incontinence presented 3 days postoperatively. Magnetic resonance imaging revealed a long-segment hyperintense signal over the thoracic spine on T2-weighted imaging. Intravenous pulse therapy with high-dose corticosteroid was first used for 5 days but was ineffective. Plasmapheresis after pulse therapy resulted in improved neurologic deficit. The patient then underwent 6 months of rehabilitation therapy but was partially wheelchair bound. She no longer had bladder and bowel incontinence.
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Incontinência Fecal , Lúpus Eritematoso Sistêmico , Mielite Transversa , Corticosteroides/uso terapêutico , Feminino , Humanos , Pessoa de Meia-Idade , Mielite Transversa/diagnóstico por imagem , Mielite Transversa/etiologia , Mielite Transversa/terapia , Recidiva Local de NeoplasiaRESUMO
OBJECTIVE: Ependymomas are rare central nervous system tumors. The current treatment strategy is gross total tumor removal. Whether adjuvant therapy will be beneficial is controversial. We retrospectively analyzed 3 cases of World Health Organization (WHO) grade III posterior fossa anaplastic ependymomas treated with different treatment modalities. We aimed to identify possible treatment options for infratentorial WHO grade III anaplastic ependymoma in adults. METHODS: We performed a retrospective analysis of 3 patients diagnosed with infratentorial anaplastic ependymomas in our institution from 2016 to 2020. The demographic data were documented. This case series of 3 patients does not meet the Department of Health and Human Services definition of research and does not need Institutional Review Board approval. All patients' informed consents have been obtained. RESULTS: One patient underwent subtotal tumor resection combined with adjuvant radiotherapy and Gamma Knife radiosurgery while the other 2 patients underwent gross total tumor removal combined with Gamma Knife radiosurgery or adjuvant radiotherapy. Tumors recurred in the first patient 20 months later, while the other 2 patents did not develop recurrence. The modified Rankin scale scores of these patients were 1, 0, and 0. All patients are followed up with regular magnetic resonance imaging at our facility. CONCLUSIONS: The strategy for treating WHO grade III anaplastic ependymomas is controversial, but gross total tumor resection remains the key element. Adjuvant stereotactic radiosurgery after tumor removal might be considered if radiotherapy is not an option. The role of chemotherapy is unclear, and the use of chemotherapy should be tailored to individual patients.
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Ependimoma , Neoplasias Infratentoriais , Adulto , Ependimoma/diagnóstico por imagem , Ependimoma/cirurgia , Humanos , Neoplasias Infratentoriais/diagnóstico por imagem , Neoplasias Infratentoriais/cirurgia , Radioterapia Adjuvante , Estudos RetrospectivosRESUMO
Effect of the carcinogen thapsigargin on human prostate cancer cells is unclear. This study examined if thapsigargin altered basal [Ca²âº](i) levels in suspended PC3 human prostate cancer cells by using fura-2 as a Ca²âº-sensitive fluorescent probe. Thapsigargin at concentrations between 10 nM and 10 µM increased [Ca²âº](i) in a concentration-dependent fashion. The Ca²âº signal was reduced partly by removing extracellular Ca²âº indicating that Ca²âº entry and release both contributed to the [Ca²âº](i) rise. This Ca²âº influx was inhibited by suppression of phospholipase A2, but not by inhibition of store-operated Ca²âº channels or by modulation of protein kinase C activity. In Ca²âº-free medium, pretreatment with the endoplasmic reticulum Ca²âº pump inhibitor 2,5-di-(t-butyl)-1,4-hydroquinone (BHQ) nearly abolished thapsigargin-induced Ca²âº release. Conversely, pretreatment with thapsigargin greatly reduced BHQ-induced [Ca²âº](i) rise, suggesting that thapsigargin released Ca²âº from the endoplasmic reticulum. Inhibition of phospholipase C did not change thapsigargin-induced [Ca²âº](i) rise. At concentrations of 1-10 µM, thapsigargin induced cell death that was partly reversed by chelation of Ca²âº with BAPTA/AM. Annexin V/propidium iodide staining data suggest that apoptosis was partly responsible for thapsigargin-induced cell death. Together, in PC3 human prostate cancer cells, thapsigargin induced [Ca²âº](i) rises by causing phospholipase C-independent Ca²âº release from the endoplasmic reticulum and Ca²âº influx via phospholipase A2-sensitive Ca²âº channels. Thapsigargin also induced cell death via Ca²âº-dependent pathways and Ca²âº-independent apoptotic pathways.
Assuntos
Sinalização do Cálcio/efeitos dos fármacos , Cálcio/metabolismo , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Tapsigargina/farmacologia , Apoptose/efeitos dos fármacos , Ácidos Aristolóquicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Estrenos/farmacologia , Fluorescência , Fura-2/metabolismo , Humanos , Espaço Intracelular/efeitos dos fármacos , Espaço Intracelular/metabolismo , Masculino , Manganês/metabolismo , Neoplasias da Próstata/enzimologia , Pirrolidinonas/farmacologia , Fosfolipases Tipo C/metabolismoRESUMO
The effect of the environmental contaminant, bisphenol A, on cytosolic free Ca(2+) concentrations ([Ca(2+)](i)) in Madin-Darby canine kidney (MDCK) cells is unclear. This study explored whether bisphenol A changed basal [Ca(2+)](i) levels in suspended MDCK cells by using fura-2 as a Ca(2+)-sensitive fluorescent dye. Bisphenol A, at concentrations between 50 and 300 µM, increased [Ca(2+)](i) in a concentration-dependent manner. The Ca(2+) signal was reduced, partly, by removing extracellular Ca(2+). Bisphenol A induced Mn(2+) influx, leading to quenching of fura-2 fluorescence, suggesting Ca(2+) influx. This Ca(2+) influx was inhibited by phospholipase A2 inhibitor aristolochic acid, store-operated Ca(2+) channel blockers nifedipine and SK&F96365, and protein kinase C inhibitor GF109203X. In Ca(2+)-free medium, pretreatment with the mitochondrial uncoupler, carbonylcyanide m-chlorophenylhydrazone (CCCP), and the endoplasmic reticulum Ca(2+) pump inhibitors, thapsigargin or 2,5-di-tert-butylhydroquinone (BHQ), inhibited bisphenol A-induced Ca(2+) release. Conversely, pretreatment with bisphenol A abolished thapsigargin (or BHQ)- and CCCP-induced [Ca(2+)](i) rise. Inhibition of phospholipase C with U73122 abolished bisphenol-induced [Ca(2+)](i) rise. Bisphenol A caused a concentration-dependent decrease in cell viability via apoptosis in a Ca(2+)-independent manner. Collectively, in MDCK cells, bisphenol A induced [Ca(2+)](i) rises by causing phospholipase C-dependent Ca(2+) release from the endoplasmic reticulum and mitochondria and Ca(2+) influx via phospholipase A2-, protein kinase C-sensitive, store-operated Ca(2+) channels.
Assuntos
Sinalização do Cálcio/efeitos dos fármacos , Cálcio/metabolismo , Disruptores Endócrinos/toxicidade , Túbulos Renais/efeitos dos fármacos , Fenóis/toxicidade , Animais , Compostos Benzidrílicos , Técnicas de Cultura de Células , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Interpretação Estatística de Dados , Diploide , Cães , Relação Dose-Resposta a Droga , Citometria de Fluxo , Túbulos Renais/citologia , Túbulos Renais/enzimologia , Túbulos Renais/metabolismo , Inibidores de Fosfolipase A2 , Fosfolipases Tipo C/antagonistas & inibidoresRESUMO
The effect of the antidepressant paroxetine on cytosolic free Ca2+ concentrations ([Ca2+]i) in OC2 human oral cancer cells is unclear. This study explored whether paroxetine changed basal [Ca2+]i levels in suspended OC2 cells by using fura-2 as a Ca2+-sensitive fluorescent dye. Paroxetine at concentrations between 100-1,000 microM increased [Ca2+]i in a concentration-dependent manner. The Ca2+ signal was reduced by 50% by removing extracellular Ca2+. Paroxetine-induced Ca2+ influx was inhibited by the store-operated Ca2+ channel blockers nifedipine, econazole and SK&F96365, and protein kinase C modulators. In Ca2+-free medium, pretreatment with the endoplasmic reticulum Ca2+ pump inhibitor thapsigargin abolished paroxetine-induced [Ca2+]i rise. Inhibition of phospholipase C with U73122 did not alter paroxetine-induced [Ca2+]i rise. Paroxetine at 10-50 microM induced cell death in a concentration-dependent manner. The death was not reversed when cytosolic Ca2+ was chelated with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid. Propidium iodide staining suggests that apoptosis plays a role in the death. Collectively, in OC2 cells, paroxetine induced [Ca2+]i rise by causing phospholipase C-independent Ca2+ release from the endoplasmic reticulum and Ca2+ influx via store-operated Ca2+ channels in a manner regulated by protein kinase C and phospholipase A2. Paroxetine (up to 50 microM) induced cell death in a Ca2+-independent manner.
Assuntos
Apoptose/efeitos dos fármacos , Cálcio/metabolismo , Neoplasias Bucais/metabolismo , Paroxetina/farmacologia , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Linhagem Celular Tumoral , Estrenos/farmacologia , Humanos , Neoplasias Bucais/patologia , Fosfolipases A2/fisiologia , Proteína Quinase C/fisiologia , Pirrolidinonas/farmacologiaRESUMO
A 30-year-old woman experienced nasal stuffiness followed by a progressive headache and reduced visual acuity for 3 weeks. She underwent an endoscopic endonasal transsphenoidal approach for pituitary spindle cell oncocytoma 13 months before the present admission. Magnetic resonance imaging revealed an intrasellar cystic lesion with a suprasellar extension. After endoscopic endonasal transsphenoidal approach for tumor removal, the histologic findings of inflammatory infiltration showed a pituitary abscess. Microscopy revealed mites and fungal hyphae. Cultures from the abscess showed Staphylococcus hyicus, Stenotrophomonas maltophilia, and Aspergillus sp. The patient received a 6-week antibiotic treatment, which completely resolved the clinical symptoms and cleared the magnetic resonance imaging findings.
Assuntos
Abscesso Encefálico/cirurgia , Endoscopia/métodos , Infestações por Ácaros/cirurgia , Ácaros , Procedimentos Neurocirúrgicos/métodos , Doenças da Hipófise/cirurgia , Adulto , Animais , Antibacterianos/uso terapêutico , Aspergilose/diagnóstico por imagem , Aspergilose/tratamento farmacológico , Abscesso Encefálico/diagnóstico por imagem , Feminino , Humanos , Imageamento por Ressonância Magnética , Doenças da Hipófise/diagnóstico por imagem , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/cirurgia , Infecções Estafilocócicas/diagnóstico por imagem , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/cirurgia , Stenotrophomonas maltophilia , Resultado do TratamentoRESUMO
A 73-year-old woman having a throat lump sensation and dysphagia for the past several months presented at our otorhinolaryngology outpatient clinic. A physical examination disclosed a protruding subepithelial mass over the right tonsil fossa. The mass was not tender and had no mucosal lesions or signs of active infection. Therefore, we arranged face and neck computed tomography scans, which reported a solitary osseous lesion over the anterior-right aspect of the C1-2 joint. Considering the rarity and unfamiliar anatomy of this disease, we built a 3D-printed model to assist with the surgical rehearsal of the procedure as well as with a preoperation discussion with the patient and her family. We arranged a combined Otolaryngology-Neurosurgery department approach after discussion with the neurosurgeon and successfully removed the lesion without sacrificing the overlying longus capitis muscle. The pathology examination revealed no evidence of malignancy. The final diagnosis was cervical spine solitary osteochondroma. The patient had a complete recovery of both oral cavity and normal swallowing function. No tumor recurred during the 3-year follow-up. On the basis of this case, in-house 3D-printing technology can offer a rapid, reliable model for an interdisciplinary team to use to enhance personalized presurgical planning, thus providing better patient engagement during hospitalization.
RESUMO
OBJECTIVE: This study aimed to create a prediction model with a radiographic score, serum, and cerebrospinal fluid (CSF) values for the occurrence of shunt-dependent hydrocephalus (SDHC) in patients with aneurysmal subarachnoid hemorrhage (aSAH) and to review and analyze literature related to the prediction of the development of SDHC. METHODS: Sixty-three patients with aSAH who underwent external ventricular drain insertion were included and separated into 2 subgroups: non-SDHC and SDHC. Patient characteristics, computed tomography scoring system, and serum and CSF parameters were collected. Multivariate logistic regression was conducted to illustrate a nomogram for determining the predictors of SDHC. Furthermore, we sorted and summarized previous meta-analyses for predictors of SDHC. RESULTS: The SDHC group had 42 cases. Stepwise logistic regression analysis revealed 3 independent predictive factors associated with a higher modified Graeb (mGraeb) score, lower level of estimated glomerular filtration rate group, and lower level of CSF glucose. The nomogram, based on these 3 factors, was presented with significant predictive performance (area under curve = 0.895) for SDHC development, compared with other scoring systems (AUC = 0.764-0.885). In addition, a forest plot was generated to present the 12 statistically significant predictors and odds ratio for correlations with the development of SDHC. CONCLUSIONS: First, the development of a nomogram with combined significant factors had a good performance in estimating the risk of SDHC in primary patient evaluation and assisted in clinical decision making. Second, a narrative review, presented with a forest plot, provided the current published data on predicting SDHC.