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1.
IJU Case Rep ; 6(6): 428-432, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37928296

RESUMO

Introduction: Orthotopic kidney transplantation is an option when heterotopic kidney transplantation into the iliac fossa is inappropriate. We report a case of orthotopic kidney transplantation following stenting of both external iliac arteries to treat arteriosclerosis obliterans. Case presentation: A 56-year-old woman on hemodialysis for end-stage kidney disease underwent living-donor kidney transplantation. Desensitization therapy was administered because of her history of sensitization by pregnancy. Stents had been placed previously in both external iliac arteries. The left kidney was removed via an oblique lumbar incision. The two graft arteries were conjoined and anastomosed to the native renal artery end-to-end. The urinary tract was reconstructed by uretero-ureterostomy with ureteral stent placement. Renal function improved promptly after surgery. Conclusion: Preoperative imaging of vascular anatomy is important for successful orthotopic kidney transplantation in patients who have previously undergone stenting of both external iliac arteries for arteriosclerosis obliterans.

2.
Plant Cell Physiol ; 64(12): 1534-1550, 2023 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-37464897

RESUMO

Glucosinolates (GSLs) are sulfur (S)-rich specialized metabolites present in Brassicales order plants. Our previous study found that GSL can function as a S source in Arabidopsis seedlings via its catabolism catalyzed by two ß-glucosidases (BGLUs), BGLU28 and BGLU30. However, as GSL profiles in plants vary among growth stages and organs, the potential contribution of BGLU28/30-dependent GSL catabolism at the reproductive growth stage needs verification. Thus, in this study, we assessed growth, metabolic and transcriptional phenotypes of mature bglu28/30 double mutants grown under different S conditions. Our results showed that compared to wild-type plants grown under -S, mature bglu28/30 mutants displayed impaired growth and accumulated increased levels of GSL in their reproductive organs and rosette leaves of before-bolting plants. In contrast, the levels of primary S-containing metabolites, glutathione and cysteine decreased in their mature seeds. Furthermore, the transport of GSL from rosette leaves to the reproductive organs was stimulated in the bglu28/30 mutants under -S. Transcriptome analysis revealed that genes related to other biological processes, such as ethylene response, defense response and plant response to heat, responded differentially to -S in the bglu28/30 mutants. Altogether, these findings broadened our understanding of the roles of BGLU28/30-dependent GSL catabolism in plant adaptation to nutrient stress.


Assuntos
Arabidopsis , Arabidopsis/genética , Arabidopsis/metabolismo , Glucosinolatos/metabolismo , Folhas de Planta/genética , Folhas de Planta/metabolismo , Perfilação da Expressão Gênica , Enxofre/metabolismo
3.
Transplant Proc ; 55(4): 744-747, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37236866

RESUMO

BACKGROUND: The left kidney is typically selected for laparoscopic donor nephrectomy. In contrast, right kidney donation raises concerns for donor safety, and venous anastomosis may be difficult to achieve due to the short renal vein. We investigated the safety and operative outcomes of right donor nephrectomy compared with those of the left. METHODS: We retrospectively analyzed the clinical records of living donor-kidney transplant donors and evaluated operative outcomes such as operative time, ischemic time, blood loss, and surgical complications in the donor. RESULTS: We identified 79 donors (left:right = 62:17 cases) between May 2020 and March 2023. There were no significant differences between the 2 groups regarding age, sex, body mass index, and number of renal arteries. Although the operative time (left and right: 190 and 225 minutes, excluding waiting time; P = .009) and warm ischemic time (left and right: 143 and 193 seconds, P = .021) were significantly longer on the right side, the total ischemic time (82 and 86 minutes, P = .463) and blood loss (left and right: 35 and 25 mL, P = .159) were comparable between the groups. There were no significant differences between the groups regarding the surgical complications. CONCLUSIONS: Operative outcomes were similar in both donor sides in the retroperitoneoscopic donor nephrectomies. The right side should be considered for donation in this operative procedure.


Assuntos
Laparoscopia , Doadores Vivos , Humanos , Estudos Retrospectivos , Rim , Nefrectomia/efeitos adversos , Nefrectomia/métodos , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Coleta de Tecidos e Órgãos/efeitos adversos
4.
IJU Case Rep ; 4(5): 307-309, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34497991

RESUMO

INTRODUCTION: After kidney transplantation, patients should be treated with caution and monitored for surgical complications. Among the possible surgical complications, strangulation ileus after kidney transplantation is rare. CASE PRESENTATION: A 59-year-old woman who had undergone kidney transplantation at 41 years of age presented to our hospital with lower abdominal pain. She was diagnosed with strangulation ileus and underwent emergency surgery. In the lower right abdomen, the small intestine was compressed by cord-like tissue running from the intraperitoneal space to the retroperitoneal space. We confirmed that the cord-like tissue was the ureter of the transplanted kidney. The necrotic small intestine was resected, and ureter-ureteral anastomosis of the ureter of the transplanted kidney was performed. CONCLUSION: All surgical procedures, including ureteroneocystostomy, require careful attention. The occurrence of some postoperative surgical complications can be prevented by carefully performing the kidney transplantation procedure.

5.
World Neurosurg ; 155: e704-e715, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34500101

RESUMO

OBJECTIVE: Cortical spreading depolarization (CSD), cortical spreading ischemia (CSI), and early brain injury are involved in the occurrence of delayed brain ischemia after subarachnoid hemorrhage (SAH). We tested whether local application of magnesium (Mg) sulfate solution suppressed CSD and CSI, and decreased brain damage in a rat SAH-mimicking model. METHODS: Nitric oxide synthase inhibitor L-NG-nitroarginine methyl ester (L-NAME) and high concentration potassium solution were topically applied to simulate the environment after SAH. We irrigated the parietal cortex with artificial cerebrospinal fluid (ACSF), containing L-NAME (1 mM), K+ (35 mM), and Mg2+ (5 mM). Forty-five rats were divided into 3 groups: sham surgery (sham group), L-NAME + [K+]ACSF (control group), and L-NAME + [K+]ACSF + [Mg2+] (Mg group). CSD was induced by topical application with 1 M KCl solution in 3 groups. The effects of Mg administration on CSD and cerebral blood flow were evaluated. Histological brain tissue damage, body weight, and neurological score were assessed at 2 days after insult. RESULTS: Mg solution significantly shortened the total depolarization time, and reduced CSI, histological brain damage, and brain edema compared with those of the control group (P < 0.05). Body weight loss was significantly suppressed in the Mg group (P < 0.05), but neurological score did not improve. CONCLUSIONS: Local application of Mg suppressed CSI and reduced brain damage in a rat SAH-mimicking model. Mg irrigation therapy may be beneficial to suppress brain damage due to CSI after SAH.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Depressão Alastrante da Atividade Elétrica Cortical/efeitos dos fármacos , Modelos Animais de Doenças , Sulfato de Magnésio/administração & dosagem , Hemorragia Subaracnóidea/tratamento farmacológico , Analgésicos/administração & dosagem , Animais , Isquemia Encefálica/patologia , Isquemia Encefálica/fisiopatologia , Circulação Cerebrovascular/efeitos dos fármacos , Circulação Cerebrovascular/fisiologia , Depressão Alastrante da Atividade Elétrica Cortical/fisiologia , Masculino , Soluções Farmacêuticas/administração & dosagem , Ratos , Ratos Sprague-Dawley , Hemorragia Subaracnóidea/patologia , Hemorragia Subaracnóidea/fisiopatologia
6.
Plant Signal Behav ; 16(10): 1945212, 2021 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-34227899

RESUMO

Here we compare mineral accumulation and global gene expression patterns between two metal hyperaccumulator plants - Noccaea japonica, originating from Ni-rich serpentine soils, and Noccaea caerulescens (ecotype Ganges), originating from Zn/Pb-mine soils - under excess Ni conditions. Significant differences in the accumulation of K, P, Mg, B, and Mo were explained by the expression levels of specific transporters for each mineral. We previously showed that total Ni accumulation in the whole plant is higher in N. caerulescens than in N. japonica. Here we found a similar tendency for Fe under excess Ni; however, the expression of iron-regulated transporter 1 (IRT1), which encodes the primary Fe uptake transporter and causes excess Ni uptake in Arabidopsis thaliana, was higher in N. japonica. NjIRT1 has a point mutation at Asp100, which is essential for Fe transport, and so might lack its Fe and possibly Ni transport function. Noccaea japonica might have lost its IRT1 function, which would prevent excess Ni uptake via IRT1 in Ni-rich soils, and come to rely on other transporters.


Assuntos
Brassicaceae/genética , Brassicaceae/metabolismo , Minerais/metabolismo , Níquel/metabolismo , Arabidopsis/metabolismo , Transcriptoma
7.
Urol Case Rep ; 38: 101661, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33868946

RESUMO

Ipilimumab and nivolumab combination therapy is effective against unresectable or metastatic renal cell carcinoma. However, it is associated with many immune-related adverse events, including hypophysitis that is difficult to diagnose early because of non-specific initial symptoms. Herein, we report the case of a 54-year-old man with metastatic renal cell carcinoma who developed hypophysitis after receiving ipilimumab and nivolumab combination therapy. The initial symptom was headache. However, endocrine tests showed decreased levels of cortisol, free thyroxine and thyroid-stimulating hormone. Moreover, magnetic resonance imaging revealed pituitary enlargement. Accordingly, we diagnosed hypophysitis and immediately started hydrocortisone replacement therapy, which improved the symptoms.

8.
Front Plant Sci ; 11: 610, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32582232

RESUMO

A number of metal hyperaccumulator plants, including nickel (Ni) hyperaccumulators, have been identified in the genus Noccaea. The ability to accumulate Ni in shoots varies widely among species and ecotypes in this genus; however, little is known about the molecular mechanisms underlying this intra- and inter-specific variation. Here, in hydroponic culture, we compared Ni accumulation patterns between Noccaea japonica, which originated in Ni-enriched serpentine soils in Mt. Yubari (Hokkaido, Japan), and Noccaea caerulescens ecotype Ganges, which originated in zinc/lead-mine soils in Southern France. Both Noccaea species showed extremely high Ni tolerance compared with that of the non-accumulator Arabidopsis thaliana. But, following treatment with 200 µM Ni, N. caerulescens showed leaf chlorosis, whereas N. japonica did not show any stress symptoms. Shoot Ni concentration was higher in N. caerulescens than in N. japonica; this difference was due to higher efficiency of root-to-shoot Ni translocation in N. caerulescens than N. japonica. It is known that the vacuole Ni transporter IREG2 suppresses Ni translocation from roots to shoots by sequestering Ni in the root vacuoles. The expression level of the IREG2 gene in the roots of N. japonica was 10-fold that in the roots of N. caerulescens. Moreover, the copy number of IREG2 per genome was higher in N. japonica than in N. caerulescens, suggesting that IREG2 expression is elevated by gene multiplication in N. japonica. The heterologous expression of IREG2 of N. japonica and N. caerulescens in yeast and A. thaliana confirmed that both IREG2 genes encode functional vacuole Ni transporters. Taking these results together, we hypothesize that the elevation of IREG2 expression by gene multiplication causes the lower root-to-shoot Ni translocation in N. japonica.

9.
Urol Case Rep ; 29: 101105, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31908963

RESUMO

We present a 78-year-old male with renal cell carcinoma who developed myasthenia gravis complicated by myositis after nivolumab administration, which was verified by the presence of antibodies against the acetylcholine receptor. The initial symptom was posterior neck pain, and biochemical examination of blood showed elevated levels of hepatic enzymes and creatine phosphokinase. The level of antibody against the acetylcholine receptor increased 4.1-fold. His condition progressed rapidly resulting in respiratory failure 15 days after conservative therapy.

10.
BMC Nephrol ; 20(1): 403, 2019 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-31703636

RESUMO

BACKGROUND: The renal function of the remaining kidney in living donors recovers up to 60~70% of pre-donation estimated-glomerular filtration rate (eGFR) by compensatory hypertrophy. However, the degree of this hypertrophy varies from donor to donor and the factors related to it are scarcely known. METHODS: We analyzed 103 living renal transplantations in our institution and divided them into two groups: compensatory hypertrophy group [optimal group, 1-year eGFR ≥60% of pre-donation, n = 63] and suboptimal compensatory hypertrophy group (suboptimal group, 1-year eGFR < 60% of pre-donation, n = 40). We retrospectively analyzed the factors related to suboptimal compensatory hypertrophy. RESULTS: Baseline eGFRs were the same in the two groups (optimal versus suboptimal: 82.0 ± 13.1 ml/min/1.73m2 versus 83.5 ± 14.8 ml/min/1.73m2, p = 0.588). Donor age (optimal versus suboptimal: 56.0 ± 10.4 years old versus 60.7 ± 8.7 years old, p = 0.018) and uric acid (optimal versus suboptimal: 4.8 ± 1.2 mg/dl versus 5.5 ± 1.3 mg/dl, p = 0.007) were significantly higher in the suboptimal group. The rate of pathological chronicity finding on 1-h biopsy (ah≧1 ∩ ct + ci≧1) was much higher in the suboptimal group (optimal versus suboptimal: 6.4% versus 25.0%, p = 0.007). After the multivariate analysis, the pathological chronicity finding [odds ratio (OR): 4.8, 95% confidence interval (CI): 1.3-17.8, p = 0.021] and uric acid (per 1.0 mg/dl, OR: 1.5, 95% CI: 1.1-2.2, p = 0.022) were found to be independent risk factors for suboptimal compensatory hypertrophy. CONCLUSION: Chronicity findings on baseline biopsy and higher uric acid were associated with insufficient recovery of the post-donated renal function.


Assuntos
Taxa de Filtração Glomerular/fisiologia , Falência Renal Crônica/cirurgia , Rim/fisiopatologia , Doadores Vivos , Nefrectomia , Recuperação de Função Fisiológica/fisiologia , Fatores Etários , Doença Crônica , Feminino , Hemoglobinas Glicadas/análise , Humanos , Hipertrofia/fisiopatologia , Rim/patologia , Falência Renal Crônica/sangue , Falência Renal Crônica/fisiopatologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/patologia , Complicações Pós-Operatórias/fisiopatologia , Estudos Retrospectivos , Ureia/sangue , Ácido Úrico/metabolismo
11.
World Neurosurg X ; 2: 100025, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31218296

RESUMO

BACKGROUND: Internal carotid artery (ICA) aneurysm may be a good target for supraorbital keyhole clipping. We discuss the surgical indications and risks of keyhole clipping for ICA aneurysms based on long-term clinical and radiologic results. METHODS: This was a retrospective analysis of 51 patients (aged 35-75 years, mean 62 years) with ICA aneurysms (mean 5.8 ± 1.8 mm) who underwent clipping via the supraorbital keyhole approach between 2005 and 2017. Neurologic and cognitive functions were examined by several methods, including the modified Rankin Scale and Mini-Mental Status Examination. The state of clipping was assessed 1 year and then every few years after the operation. RESULTS: Complete clipping was confirmed in 45 patients (88.2%), dog-ear remnants behind the clip persisted in 4 patients, and wrapping was performed in 2 patients. Mean duration of postoperative hospitalization was 3.4 ± 6.9 days. The mean clinical follow-up period was 6.6 ± 3.2 years. The overall mortality was 0, and overall morbidity (modified Rankin Scale score ≥2 or Mini-Mental Status Examination <24) was 3.9%. Completely clipped aneurysms did not show any recurrence during the mean follow-up period of 6.3 ± 3.1 years, but the 2 (3.9%) aneurysms with neck remnants showed regrowth. CONCLUSIONS: The risk of neck remnant behind the clip blade is a drawback of supraorbital keyhole clipping. The surgical indication requires preoperative simulation and careful checking of the clip blade state is essential.

12.
No Shinkei Geka ; 45(11): 985-990, 2017 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-29172204

RESUMO

The spread of human immunodeficiency virus(HIV)infection may result in an increased likelihood of surgery in patients with HIV infection. We treated a patient with intracranial malignant lymphoma associated with acquired immunodeficiency syndrome(AIDS)caused by HIV infection. The recommendations of the countermeasure manual for AIDS were followed. Only surgical staff without finger injury or inflammation were permitted to be involved in the operation. All staff were dressed in a waterproof, full-body surgical gown, and wore double gloves, double foot covers, and an N95 mask. The surgery could be performed safely with such infection control measures. Histological examination revealed a diffuse large B-cell lymphoma. The patient was referred to the Division of Infectious Diseases and Respiratory Medicine for chemotherapy.


Assuntos
Síndrome da Imunodeficiência Adquirida/complicações , Neoplasias Encefálicas/cirurgia , Linfoma Difuso de Grandes Células B/cirurgia , Biópsia , Neoplasias Encefálicas/etiologia , Neoplasias Encefálicas/patologia , Craniotomia , Humanos , Linfoma Difuso de Grandes Células B/etiologia , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
13.
No Shinkei Geka ; 45(4): 345-350, 2017 Apr.
Artigo em Japonês | MEDLINE | ID: mdl-28415060

RESUMO

We report a case of foramen magnum meningioma manifesting as hypoglossal nerve palsy. A 72-year-old woman presented with progressive hypoglossal nerve palsy and lingual atrophy on the left side. Gadolinium-enhanced T1-weighted magnetic resonance imaging revealed a heterogeneously enhanced mass lesion with dural tail sign partially extending into the hypoglossal canal. The transcondylar approach was performed to expose the hypoglossal canal and resect the tumor completely. Histological examination revealed a transitional meningioma. The postoperative course was uneventful. Hypoglossal nerve palsy improved gradually after the operation.


Assuntos
Forame Magno/cirurgia , Doenças do Nervo Hipoglosso/cirurgia , Neoplasias Meníngeas/cirurgia , Meningioma/cirurgia , Neoplasias da Base do Crânio/cirurgia , Idoso , Feminino , Forame Magno/patologia , Humanos , Doenças do Nervo Hipoglosso/diagnóstico , Imageamento por Ressonância Magnética/métodos , Neoplasias Meníngeas/diagnóstico , Meningioma/diagnóstico , Neoplasias da Base do Crânio/diagnóstico , Resultado do Tratamento
14.
Int J Mol Sci ; 16(5): 9420-30, 2015 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-25923075

RESUMO

Excessive accumulation of nickel (Ni) can be toxic to plants. In Arabidopsis thaliana, the Fe²âº transporter, iron (Fe)-regulated transporter1 (IRT1), mediates Fe uptake and also implicates in Ni²âº uptake at roots; however, the underlying mechanism of Ni²âº uptake and accumulation remains unelucidated. In the present study, we found that zinc (Zn) deficient conditions resulted in increased accumulation of Ni in plants, particularly in roots, in A. thaliana. In order to elucidate the underlying mechanisms of Ni uptake correlating zinc condition, we traced 63Ni isotope in response to Zn and found that (i) Zn deficiency induces short-term Ni²âº absorption and (ii) Zn²âº inhibits Ni²âº uptake, suggesting competitive uptake between Ni and Zn. Furthermore, the Zrt/Irt-like protein 3 (ZIP3)-defective mutant with an elevated Zn-deficient response exhibited higher Ni accumulation than the wild type, further supporting that the response to Zn deficiency induces Ni accumulation. Previously, expression profile study demonstrated that IRT1 expression is not inducible by Zn deficiency. In the present study, we found increased Ni accumulation in IRT1-null mutant under Zn deficiency in agar culture. These suggest that Zn deficiency induces Ni accumulation in an IRT1-independen manner. The present study revealed that Ni accumulation is inducible in response to Zn deficiency, which may be attributable to a Zn uptake transporter induced by Zn deficiency.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/fisiologia , Proteínas de Transporte de Cátions/metabolismo , Níquel/metabolismo , Zinco/deficiência , Zinco/fisiologia , Ágar , Proteínas de Arabidopsis/genética , Transporte Biológico , Proteínas de Transporte de Cátions/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Hidroponia , Ferro/química , Mutação , Raízes de Plantas/metabolismo
15.
No Shinkei Geka ; 42(11): 1035-8, 2014 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-25351799

RESUMO

An 81-year-old man presented with poor visual acuity of the left eye, swelling of the left eyelid, and elevation of the left intraocular pressure after contusion of the left palpebral portion. CT revealed left ocular proptosis and left intraorbital hematoma. Traumatic optic neuropathy was suspected, and emergent optic nerve decompression was performed through extradural anterior clinoidectomy followed by optic canal release. Postoperatively, his left visual acuity was markedly improved and the elevated intraocular pressure decreased. Postoperative CT demonstrated improvement of the left ocular proptosis and decompression of the optic nerve. Emergent optic canal release has been recommended in patients who have suffered visual dysfunction caused by optic canal fracture or intraorbital hematoma. The advantages of extradural anterior clinoidectomy followed by optic canal release include a shorter surgical route and easy identification of the optic nerve, resulting in fewer surgical complications. In addition, this procedure can achieve intraorbital decompression. We recommend extradural anterior clinoidectomy followed by optic canal release as a safe and reliable procedure for optic nerve decompression in patients with traumatic optic neuropathy.


Assuntos
Descompressão Cirúrgica , Procedimentos Neurocirúrgicos , Doenças do Nervo Óptico/cirurgia , Traumatismos do Nervo Óptico/cirurgia , Acuidade Visual/fisiologia , Idoso de 80 Anos ou mais , Descompressão Cirúrgica/métodos , Humanos , Masculino , Procedimentos Neurocirúrgicos/métodos , Doenças do Nervo Óptico/etiologia , Traumatismos do Nervo Óptico/complicações , Traumatismos do Nervo Óptico/diagnóstico , Resultado do Tratamento
16.
No Shinkei Geka ; 42(11): 1051-6, 2014 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-25351802

RESUMO

A primary intraosseous cavernous hemangioma located at the sphenoid bone with extensive involvement of the orbital roof and the lateral wall of the orbit is very rare. A 48-year-old woman presented with progressive right exophthalmos and diplopia. CT showed a bony mass lesion in the right sphenoid bone extending to the orbital bone. MRI showed an abnormal lesion in the sphenoid bone, which was heterogeneously enhanced with gadolinium. All of the abnormal bone was surgically removed, and histological examination confirmed a cavernous angioma. We also present a brief clinical and radiological review of seven previously reported cases.


Assuntos
Hemangioma Cavernoso/cirurgia , Neoplasias Orbitárias/cirurgia , Osso Esfenoide/cirurgia , Feminino , Hemangioma Cavernoso/patologia , Humanos , Pessoa de Meia-Idade , Neoplasias Orbitárias/secundário , Resultado do Tratamento
17.
Anal Sci ; 30(7): 751-8, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25007935

RESUMO

Metabolomic studies conducted for evaluating cancer pathogenesis and progression by monitoring the amino acids metabolic balance hold great promise for assessing current and future anticancer treatments. We performed a comprehensive quantification of 21 amino acids concentrations in cultured human colorectal adenocarcinoma cells treated with the anticancer drugs 5-fluorouracil, irinotecan, and cisplatin. A precolumn fluorescence derivatization-HPLC method involving 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate was used. Amino acid concentration data were analyzed by principal-component analysis and partial least-squares multivariate statistical methods to represent samples on two-dimensional graphs. The hierarchical cluster analysis and linear discriminant analysis were used to classify the samples on the score plots. Unlike the cluster analysis approach, the linear discrimination analysis classification successfully distinguished anticancer drug-treated samples from the untreated controls. Moreover, three candidate amino acids (serine, aspartic acid, and methionine) were identified from the loading plots as potential biomarkers. Our proposed method might be able to evaluate the effectiveness of anticancer therapy even in small laboratories or medical institutions.


Assuntos
Aminoácidos/metabolismo , Antineoplásicos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Metabolômica , Aminoácidos/análise , Linhagem Celular Tumoral , Cromatografia Líquida de Alta Pressão , Humanos , Indicadores e Reagentes , Espectrometria de Fluorescência
18.
Pharm Res ; 30(11): 2880-90, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23812637

RESUMO

PURPOSE: The expression of a multispecific organic anion transporter, OATP1B3/SLCO1B3, is associated with clinical prognosis and survival of cancer cells. The aims of present study were to investigate the involvement of epigenetic regulation in mRNA expression of a cancer-type variant of OATP1B3 (Ct-OATP1B3) in cancer cell lines. METHODS: The membrane localization and transport functions of Ct-OATP1B3 were investigated in HEK293 cells transiently expressing Ct-OATP1B3. DNA methylation profiles around the transcriptional start site of Ct-OATP1B3 in cancer cell lines were determined. The effects of a DNA methyltransferase inhibitor and siRNA knockdown of methyl-DNA binding proteins (MBDs) on the expression of Ct-OATP1B3 mRNA were investigated. RESULTS: 5'-RACE identified the TSS of Ct-OATP1B3 in PK-8 cells. Ct-OATP1B3 was localized on the plasma membrane, and showed the transport activities of E217ßG, fluvastatin, rifampicin, and Gd-EOB-DTPA. The CpG dinucleotides were hypomethylated in Ct-OATP1B3-positive cell lines (DLD-1, TFK-1, PK-8, and PK-45P) but were hypermethylated in Ct-OATP1B3-negative cell lines (HepG2 and Caco-2). Treatment with a DNA methyltransferase inhibitor and siRNA knockdown of MBD2 significantly increased the expression of Ct-OATP1B3 mRNA in HepG2 and Caco-2. CONCLUSIONS: Ct-OATP1B3 is capable of transporting its substrates into cancer cells. Its mRNA expression is regulated by DNA methylation-dependent gene silencing involving MBD2.


Assuntos
Regulação Neoplásica da Expressão Gênica , Neoplasias/genética , Transportadores de Ânions Orgânicos Sódio-Independentes/genética , Linhagem Celular , Linhagem Celular Tumoral , Metilação de DNA , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Epigênese Genética , Humanos , Neoplasias/metabolismo , Transportadores de Ânions Orgânicos Sódio-Independentes/metabolismo , Interferência de RNA , RNA Mensageiro/genética , Membro 1B3 da Família de Transportadores de Ânion Orgânico Carreador de Soluto
19.
Plant Signal Behav ; 7(3): 329-31, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22476458

RESUMO

Excessive amounts of nickel (Ni) can be toxic for plants. Recently, we reported that IRT1, the primary iron (Fe) uptake transporter in roots, meditates excess Ni accumulation in Arabidopsis thaliana. We also found that Ni exposure increases IRT1 expression in roots, suggesting that Ni uptake is further induced by Ni stress. Here, we show that Ni exposure induces expression of not only IRT1, but also FRO2, a ferric reductase in the root epidermis, and FIT, a transcription factor regulating the expression of genes involved in Fe homeostasis including IRT1 and FRO2. This result suggests that Ni accumulation induces an Fe-deficient response and leads to the induction of IRT1. Our findings suggest that excess Ni causes Fe deficiency at the molecular level and induces Fe deficiency signaling in plant cells.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/efeitos dos fármacos , Arabidopsis/metabolismo , Proteínas de Transporte de Cátions/metabolismo , Deficiências de Ferro , Níquel/farmacologia , Proteínas de Arabidopsis/genética , Proteínas de Transporte de Cátions/genética , FMN Redutase/genética , FMN Redutase/metabolismo , Ferro/metabolismo
20.
Plant Cell Physiol ; 52(8): 1433-42, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21742768

RESUMO

Nickel (Ni) is an essential nutrient for plants, but excessive amounts can be toxic. Ni competes with iron (Fe) in vivo, raising the possibility that Ni is competitively taken up via the Fe uptake system in plants. Here, we show evidence that AtIRT1, the primary Fe(2+) uptake transporter in the root, mediates Ni accumulation in Arabidopsis thaliana. In hydroponic cultures, excess Ni exposure increased Fe accumulation and the relative transcription level of AtIRT1 in roots, indicating that excess Ni induces AtIRT1 expression in roots. An Fe-deficient treatment increased Ni accumulation in plants, suggesting that excess Ni was absorbed via the Fe uptake system, which was induced by Fe starvation. Moreover, Ni accumulation under Fe-deficient conditions was markedly lower in AtIRT1-defective mutants than in the wild-type, Col-0. Furthermore, AtIRT1 showed Ni(2+) uptake activity in a yeast expression system. These data demonstrate that AtIRT1 transports Ni(2+) in roots, and strongly suggest that Ni accumulation is further accelerated by AtIRT1 that is expressed in response to excess Ni.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Proteínas de Transporte de Cátions/metabolismo , Ferro/metabolismo , Níquel/metabolismo , Raízes de Plantas/metabolismo , Adaptação Fisiológica/efeitos dos fármacos , Adaptação Fisiológica/genética , Arabidopsis/efeitos dos fármacos , Arabidopsis/genética , Arabidopsis/fisiologia , Proteínas de Arabidopsis/genética , Proteínas de Transporte de Cátions/genética , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Hidroponia , Ferro/farmacologia , Mutação/genética , Níquel/toxicidade , Fenótipo , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/genética , Saccharomyces cerevisiae/citologia , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/metabolismo
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