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1.
Langmuir ; 40(12): 6330-6341, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38364790

RESUMO

CO2 photoreduction using a semiconductor-based photocatalyst is a promising option for completing a new carbon-neutral cycle. The short lifetime of charges generated owing to light energy is one of the most critical problems in further improving the performance of semiconductor-based photocatalysts. This study shows the structure, electron transmission, and stability of Ti3C2Xy (X = oxo, OH, F, or Cl) MXene combined with a ZrO2 photocatalyst. Using H2 as a reductant, the photocatalytic CO formation rate increased by 6.6 times to 4.6 µmol h-1 gcat-1 using MXene (3.0 wt %)-ZrO2 compared to that using ZrO2, and the catalytic route was confirmed using 13CO2 to form 13CO. In clear contrast, using H2O (gas) as a reductant, CH4 was formed as the major product using Ti3C2Xy MXene (5.0 wt %)-ZrO2 at the rate of 3.9 µmol h-1 gcat-1. Using 13CO2 and H2O, 12CH4, 12C2H6, and 12C3H8 were formed besides H212CO, demonstrating that the C source was the partial decomposition and hydrogenation of Ti3C2Xy. Using the atomic force and high-resolution electron microscopies, 1.6 nm thick Ti3C2Xy MXene sheets were observed, suggesting ∼3 stacked layers that are consistent with the Ti-C and Ti···Ti interatomic distances of 0.218 and 0.301 nm, respectively, forming a [Ti6C] octahedral coordination, and the major component as the X ligand was suggested to be F and OH/oxo, with the temperature increasing by 116 K or higher owing to the absorbed light energy, all based on the extended X-ray absorption fine structure analysis.

2.
J Nippon Med Sch ; 90(4): 308-315, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37690822

RESUMO

Development of surgical support robots began in the 1980s as a navigation and auxiliary device for endoscopic surgery. For remote surgery on the battlefield, a master-slave-type surgical support robot was developed, in which a console surgeon operates the robot at will. The da Vinci surgical system, which currently dominates the global robotic surgery market, received United States Food and Drug Administration and regulatory approval in Japan in 2000 and 2009 respectively. The latest, fourth generation, da Vinci Xi has a good field of view via a three-dimensional monitor, highly operable forceps, a motion scale function, and a tremor-filtered articulated function. Gastroenterological tract robotic surgery is safe and minimally invasive when accessing and operating on the esophagus, stomach, colon, and rectum. The learning curve is said to be short, and robotic surgery will likely be standardized soon. Therefore, robotic surgery training should be systematized for young surgeons so that it can be further standardized and later adapted to a wider range of surgeries. This article reviews current trends and potential developments in robotic surgery.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório , Procedimentos Cirúrgicos Robóticos , Robótica , Estados Unidos , Humanos , Estômago , Reto
3.
J Biosci Bioeng ; 133(4): 329-334, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35123882

RESUMO

Extensive metabolite analysis of Streptomyces rochei 7434AN4 was performed to discover uncharacterized secondary metabolites. A mutant strain of S. rochei, in which two regulatory genes srrC (a tetR-type repressor) and srrY (SARP-type activator) were inactivated, accumulated three 4-monosubstituted γ-butyrolactones YT02-A, YT02-B, and KH01-A, which were not detected in the parent strain. Their structures were identified as 4,10-dihydroxy-10-methyldodecan-4-olide, 4,10-dihydroxy-10-methylundecan-4-olide, and 4-hydroxy-11-oxo-10-methyldodecan-4-olide. A structural comparison indicated that the three butanolides and the signaling molecules, termed S. rochei butenolides (SRBs), could share common C12 or C13 fatty acids for their biosynthesis intermediates, however, these three butanolides did not induce antibiotic production even at 50 µM concentration (1000-folds of the minimum antibiotic-inducing concentration of SRBs) in S. rochei.


Assuntos
Streptomyces , 4-Butirolactona , Antibacterianos , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Regulação Bacteriana da Expressão Gênica , Genes Reguladores , Ligação Proteica , Streptomyces/genética , Streptomyces/metabolismo
4.
Eur J Surg Oncol ; 47(12): 3151-3156, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34315643

RESUMO

BACKGROUND: Circulating tumour DNA (ctDNA) is very useful for purposes of cancer genetics; however, it has some limitations. Recently, ctDNA in body fluids, such as urine, sputum, and pleural effusion, has been investigated. The aim of this study was to evaluate the quantity of ctDNA derived from urine (trans-renal ctDNA) and the accuracy of KRAS mutation detection in relation to disease stage in colorectal cancer. METHODS: Urine, plasma, and tissue samples were collected from consecutively resected colorectal cancer patients. DNA was extracted from each sample and the quantity was determined. From each DNA sample, KRAS mutations were detected using droplet digital PCR. RESULTS: 200 patients participated and KRAS mutations were detected in 84 patients (42.0%) from tumour tissue. The concentration of trans-renal ctDNA (trtDNA) was significantly lower than that of plasma; however, there was no significant difference between the sensitivity using ctDNA and that using trtDNA (29.8% VS 33.3%, p = 0.62). Concordance between these two tests was only 17.5%. Combination analysis (ctDNA + trtDNA) improved the sensitivity to 53.6%, and sensitivity was significantly higher than that of corresponding single assays (p = 0.003). In early cancer stages, trtDNA had greater sensitivity for detecting KRAS mutations than ctDNA (37.7% vs. 21.3%, p = 0.047). Conversely, it was less useful for advanced cancer stages (21.7% vs. 52.2%, p = 0.07). Notably, KRAS mutations were detected using ctDNA or trtDNA in 12 of 116 (10.3%) patients who had no KRAS mutations in their tissue samples. CONCLUSIONS: trtDNA and ctDNA have equal potential and combination analysis significantly improved the sensitivity.


Assuntos
Biomarcadores Tumorais/urina , DNA Tumoral Circulante/urina , Neoplasias Colorretais/genética , Neoplasias Colorretais/urina , Proteínas Proto-Oncogênicas p21(ras)/urina , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/patologia , Feminino , Humanos , Biópsia Líquida , Masculino , Pessoa de Meia-Idade , Mutação , Estadiamento de Neoplasias , Estudos Prospectivos
5.
J Surg Oncol ; 123(1): 286-292, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33022767

RESUMO

BACKGROUND: Neoadjuvant chemotherapy to treat locally advanced rectal cancer is an effective therapeutic strategy for the prevention of local recurrence and distant organ metastasis after surgery. OBJECTIVES: To assess the prognostic significance of histopathological tumor response in rectal cancer patients undergoing neoadjuvant chemotherapy. METHODS: This study included patients with operable rectal cancer who received neoadjuvant chemotherapy using the FOLFOX regimen (5-fluorouracil, l-leucovorin, and oxaliplatin) in a hospital between February 2012 and November 2017. The main outcome measure was disease-free survival with respect to histopathological response to neoadjuvant chemotherapy in resected specimens. RESULTS: The median follow-up was 32 months. Of 48 patients treated with neoadjuvant FOLFOX, 24 (50%) were classified as responders, which included two patients with pathological complete response and 22 patients with partial response. The remaining 24 patients (50%) were classified as nonresponders. Responders had a significantly better 3-year disease-free survival than nonresponders (86% vs. 62%, p = .02). CONCLUSIONS: Patients whose surgical specimens show a pathological complete response or partial response have good oncologic outcomes.


Assuntos
Adenocarcinoma/mortalidade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Recidiva Local de Neoplasia/mortalidade , Neoplasias Retais/mortalidade , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/secundário , Adulto , Idoso , Ensaios Clínicos Fase II como Assunto , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Humanos , Leucovorina/administração & dosagem , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Oxaliplatina/administração & dosagem , Prognóstico , Estudos Prospectivos , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/patologia , Estudos Retrospectivos , Taxa de Sobrevida
6.
J Anus Rectum Colon ; 4(4): 201-205, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33134602

RESUMO

Vascular Ehlers-Danlos syndrome (vEDS) is a rare autosomal dominant connective tissue disease. Patients with vEDS are at a high risk of developing severe complications (such as arterial aneurysm, arterial rupture, intestinal rupture) at an early age. We report a case of colonic perforation in a vEDS patient with no family history of that disease. A 28-year-old man with abdominal pain arrived at our hospital in an ambulance. The preoperative diagnosis was panperitonitis due to gastrointestinal perforation. Although his parents had not suffered from vEDS, he had been diagnosed with the disease at 25 years of age because of his history of arterial dissection. We performed an emergency operation using Hartmann's procedure to construct a descending colostomy. There remains a lack of consensus on surgical management in vEDS patients with gastrointestinal perforation because of the limited number of reported cases.

7.
Int J Clin Oncol ; 25(12): 2075-2082, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32785799

RESUMO

BACKGROUND: Chemotherapy with oxaliplatin is known to induce sinusoidal obstruction syndrome (SOS). In a previous single-center study, we reported that oxaliplatin-induced increase in splenic volume (SV) is strongly indicative of SOS, and that this increase in SV persisted for > 1 year after completing chemotherapy. The aim of this study was to confirm the oxaliplatin-induced SV change in a multicenter study in patients with stage III colon cancer in Japan. METHODS: We enrolled 59 patients who underwent curative resection for stage III colon cancer in the FACOS study in a phase II multi-center clinical study. Participants received mFOLFOX6 or CAPOX as adjuvant chemotherapy. SV change was assessed three times by computed tomographic volumetry: before surgery, on completion of adjuvant chemotherapy, and 1 year after completing adjuvant chemotherapy. RESULTS: SV on completing and 1 year after chemotherapy was significantly higher than that before surgery (P < 0.001). Oxaliplatin-induced SOS persisted for > 1 year after the completion of adjuvant chemotherapy in half of the patients. There was no difference in 3-year disease-free survival with respect to the presence or absence of increased SV. An increase in SV was observed in 72% of patients treated with mFOLFOX6 and 94% of patients treated with CAPOX (P = 0.13). CONCLUSION: This study can be verified the findings observed in our previous single-center study, oxaliplatin-based adjuvant chemotherapy was associated with an increase in SV. Furthermore, this increase can persist for > 1 year. The continuous presence of SOS may have a negative impact on prognosis in patients that develop recurrent disease.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias do Colo/tratamento farmacológico , Oxaliplatina/efeitos adversos , Esplenopatias/induzido quimicamente , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante/efeitos adversos , Neoplasias do Colo/mortalidade , Neoplasias do Colo/patologia , Intervalo Livre de Doença , Feminino , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Humanos , Japão , Leucovorina/efeitos adversos , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/efeitos adversos , Compostos Organoplatínicos/uso terapêutico , Oxaliplatina/administração & dosagem , Prognóstico , Esplenopatias/diagnóstico por imagem
8.
Surg Case Rep ; 6(1): 8, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31915947

RESUMO

BACKGROUND: A transomental hernia is defined as bowel invagination into an abnormal hiatus of the omentum. It is a rare type of internal hernia that is sometimes lethal. We herein report a case of a transomental hernia developing shortly after laparoscopic sigmoidectomy. CASE PRESENTATION: A 71-year-old man underwent laparoscopic sigmoidectomy. He was admitted to our hospital because of abdominal pain and nausea on postoperative day 12. Laboratory investigation showed increased levels of inflammatory markers. Abdominal computed tomography showed a closed loop and mesenteric edema of the small intestine with ascites. We performed an emergency operation under the diagnosis of strangulated bowel obstruction. Operative findings showed internal herniation of strangulated ileal loops through a defect of the omentum with hemorrhagic ascites. The incarcerated small bowel was resected and reconstructed because the ischemic change was irreversible after the reduction. We partially resected the omentum that had formed the defect. The patient's postoperative progress was good, and he was discharged on postoperative day 8. CONCLUSIONS: Almost all internal hernias after intestinal surgery are mesenteric hernias; however, we should bear in mind that the more lethal transomental hernia is also possible. Therefore, immediate surgical exploration should be performed in a timely manner for internal hernias, especially for patients with early-onset symptoms after laparoscopic intestinal surgery.

9.
Gan To Kagaku Ryoho ; 47(13): 2006-2008, 2020 Dec.
Artigo em Japonês | MEDLINE | ID: mdl-33468782

RESUMO

A woman in her 60s underwent lower endoscopy due to a positive fecal occult blood test. A type 2 tumor was found in the cecum, and a biopsy resulted in the diagnosis of adenocarcinoma(tub2). Contrast-enhanced CT showed an enlarged paracolonic lymph node but no distant metastasis, so the patient underwent a laparoscopic-assisted ileocolic resection and D3 lymph node dissection for cecum cancer. The pathology was pT3, pN2b, pM0, pStage Ⅲc, and 12 courses of FOLFOX were administered as adjuvant chemotherapy. Twenty-four months after the completion of adjuvant chemotherapy, an elevated CEA was observed, and a PET-CT was performed, which showed multiple peritoneal disseminated nodules with FDG accumulation. Based on this finding, CAPOX/bevacizumab therapy was introduced, and on completion of 4 courses, the PET-CT showed a decrease in the size of the nodules and the disappearance of FDG accumulation. Based on this, the patient underwent resection. A peritoneal dissemination resection and bilateral ovariectomy were laparoscopically performed, and the patient is currently under observation. In patients with metastatic recurrence of peritoneal dissemination who underwent complete resection, treatment with CAPOX/bevacizumab may allow for disease control and provide a long-term prognosis.


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Neoplasias do Colo/cirurgia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/cirurgia , Feminino , Humanos , Excisão de Linfonodo , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada
10.
Eur J Surg Oncol ; 46(1): 108-114, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31431321

RESUMO

INTRODUCTION: Most patients with colorectal liver metastases, who undergo hepatectomy, experience recurrence. Although the prognosis is poorer for patients with early recurrence (within 6 months after hepatectomy) compared with later recurrence, no biomarker has been identified to predict early recurrence. Minimal residual disease (MRD) in patients who undergo curative surgery is the main cause of recurrence. In cancer patients, long fragment cell-free DNA is detected, and the presence of long fragments of cell-free DNA after surgery can indicate MRD. In this study, we developed a novel biomarker to predict early recurrence of colorectal liver metastases using cell-free DNA. MATERIALS AND METHODS: Forty-one patients with colorectal liver metastases were enrolled. Peripheral blood samples were collected before and at 1 month after hepatectomy. Cell-free DNA was extracted from 1 ml plasma, and the long fragment/ß-globin ratio, which can indicate MRD, was measured by real-time polymerase chain reaction. RESULTS: Three of 21 patients (14.3%) with decreases in the long cell-free DNA fragment/ß-globin ratio after hepatectomy developed early recurrence compared with twelve of 20 patients (60.0%) with an increased ratio (P = 0.002). Patients with a decreased long fragment/ß-globin ratio after hepatectomy had significantly longer recurrence-free survival compared with patients with an increased ratio (366 vs 102 days, P < 0.001). CONCLUSION: The cell-free DNA long fragment/ß-globin ratio may serve as an effective biomarker of early recurrence in patients with colorectal liver metastases, who undergo hepatectomy.


Assuntos
Biomarcadores Tumorais/sangue , Ácidos Nucleicos Livres/sangue , Neoplasias Colorretais/patologia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Adolescente , Adulto , Idoso , Feminino , Hepatectomia , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Neoplasia Residual/patologia , Valor Preditivo dos Testes
11.
Lasers Med Sci ; 35(6): 1289-1297, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31853809

RESUMO

In photodynamic therapy (PDT), singlet oxygen ([Formula: see text]) is the main species responsible for promoting tumor cell death. The determination of the quantum yield (ΦΔ) of a photosensitizer (PS) is important for dosimetry. The purpose of this paper is to quantify the [Formula: see text] generated by the PS by near-infrared spectroscopy (NIRS). The ΦΔ of different PS species were measured by the detection of near-infrared [Formula: see text] luminescence. From the measurement results, the ΦΔ of talaporfin sodium, protoporphyrin IX (PpIX), and lipidated PpIX (PpIX lipid) were measured as 0.53, 0.77, and 0.87, respectively. In addition, the ΦΔ values of PpIX in a hypoxic and oxic solution were evaluated, since tumors are associated with regions of hypoxia. The measured ΦΔ indicated a same value at high (DO: 20%) and low (DO: 1%) oxygen concentrations. Using the measured ΦΔ, the amount of [Formula: see text] generated by the PSs was estimated using [[Formula: see text]] = D*ΦΔ, where D* is the total excited PS concentration. The generated [Formula: see text] amounts were little different at the high and the low oxygen concentrations, and the generated [Formula: see text] amount for each PS was different depending on each ΦΔ. The NIRS measurement determined the ΦΔ of talaporfin sodium, PpIX, and PpIX lipid. The quantitative evaluation based on the measured ΦΔ will support the development of PDT treatment monitoring and design.


Assuntos
Lipídeos/química , Luminescência , Porfirinas/farmacologia , Protoporfirinas/farmacologia , Oxigênio Singlete/análise , Espectroscopia de Luz Próxima ao Infravermelho , Humanos , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Fatores de Tempo
12.
Cancer Sci ; 110(12): 3708-3717, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31648389

RESUMO

The incidence of rare neuroendocrine tumors (NET) is rapidly increasing. Neuroendocrine carcinoma (NEC) is a NET with poorly differentiated histological features, high proliferative properties and associated poor prognoses. As these carcinomas are so rare and, thus, affect only a small number of patients allowing for few cell lines to be derived from patient biopsies, the histological, immunohistochemical, and clinical characteristics associated with colorectal NEC and NEC in other organs have yet to be clearly defined. Herein, we describe the establishment of a novel NEC cell line (SS-2) derived from a tumor resection of the ascending colon from a 59-year-old Japanese woman. The histological, electron microscopic and immunohistochemical features of chromogranin A (CgA) as well as confirmation of synaptophysin positivity in this tumor were typical of those commonly observed in surgically resected colorectal NEC. Further, the Ki-67 labeling index of the resected tumor was >20% and, thus, the tumor was diagnosed as an NEC of the ascending colon. The SS-2 cell line maintained characteristic features to those of the resected tumor, which were further retained following implantation into subcutaneous tissues of nude mice. Additionally, when SS-2 cells were seeded into ultra-low attachment plates, they formed spheres that expressed higher levels of the cancer stem cell (CSC) marker CD133 compared to SS-2 cells cultured under adherent conditions. SS-2 cells may, therefore, contribute to the current knowledge on midgut NEC biological function while providing a novel platform for examining the effects of colorectal NEC drugs, including CSC.


Assuntos
Carcinoma Neuroendócrino/patologia , Colo Ascendente/patologia , Neoplasias do Colo/patologia , Antígeno AC133/análise , Animais , Carcinoma Neuroendócrino/tratamento farmacológico , Linhagem Celular Tumoral , Neoplasias do Colo/tratamento farmacológico , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Transplante de Neoplasias
13.
Cancer Sci ; 110(11): 3497-3509, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31465598

RESUMO

We recruited 56 colorectal cancer patients and compared the mutational spectrum of tumor tissue DNA, circulating cell-free DNA (ccfDNA) and circulating tumor cell (CTC) DNA (ctcDNA) to evaluate the potential of liquid biopsy to detect heterogeneity of cancer. Tumor tissue DNA, ccfDNA, and ctcDNA were extracted from each patient and analyzed using next-generation sequencing (NGS) and digital PCR. To maximize yields of CTC, three antibodies were used in the capture process. From 34 untreated patients, 53 mutations were detected in tumor tissue DNA using NGS. Forty-seven mutations were detected in ccfDNA, including 20 not detected in tissues. Sixteen mutations were detected in ctcDNA, including five not detected in tissues. In 12 patients (35.3%), mutations not found in tumor tissues were detected by liquid biopsy: nine (26.5%) in ccfDNA only and three (8.8%) in ctcDNA only. Combination analysis of the two liquid biopsy samples increased the sensitivity to detect heterogeneity. From 22 stage IV patients with RAS mutations in their primary tumors, RAS mutations were detected in 14 (63.6%) ccfDNA and in eight (36.4%) ctcDNA using digital PCR. Mutations not detected in primary tumors can be identified in ccfDNA and in ctcDNA, indicating the potential of liquid biopsy in complementing gene analysis. Combination analysis improves sensitivity. Sensitivity to detect cancer-specific mutations is higher in ccfDNA compared with ctcDNA.


Assuntos
Ácidos Nucleicos Livres/análise , Neoplasias Colorretais/genética , DNA de Neoplasias/análise , Mutação , Células Neoplásicas Circulantes/química , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/patologia , Análise Mutacional de DNA , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Biópsia Líquida , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Estudos Prospectivos , Proteínas Proto-Oncogênicas p21(ras)/genética
14.
Sci Signal ; 12(587)2019 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-31239324

RESUMO

Kynurenine, which is generated from tryptophan by indoleamine 2,3-dioxygenase 1 (IDO1), binds to the aryl hydrocarbon receptor (AhR). Here, we report that kynurenine was produced by undifferentiated human embryonic stem cells (hESCs) and by induced pluripotent stem cells (iPSCs). In undifferentiated hESCs, kynurenine stimulated the AhR to promote the expression of self-renewal genes. The kynurenine-AhR complex also stimulated the expression of IDO1 and AHR, activating a positive feedback loop. Inhibition of IDO1 activity reduced the proliferation of undifferentiated ESCs but did not stimulate their differentiation. Substantial amounts of free kynurenine were present in the culture medium, providing a paracrine signal for maintenance of the undifferentiated state. Kynurenine was not present in the medium of differentiated ESCs or iPSCs. When ESCs were induced to undergo ectodermal differentiation, the abundance of kynurenine in the medium was reduced through activation of the main kynurenine catabolic pathway mediated by kynurenine aminotransferase 2 (KAT2, also known as AADAT), resulting in the secretion of 2-aminoadipic acid (2-AAA) into the culture medium. Inhibition of KAT2 activity blocked ectodermal differentiation. Thus, kynurenine metabolism plays an important role in the maintenance of the undifferentiated state and in ectodermal differentiation. Furthermore, kynurenine in the culture medium is a biomarker for the undifferentiated state, whereas the presence of 2-AAA in the culture medium is a biomarker of ESCs and iPSCs that have committed to differentiate along the ectoderm lineage.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/biossíntese , Regulação da Expressão Gênica , Células-Tronco Embrionárias Humanas/metabolismo , Cinurenina/metabolismo , Receptores de Hidrocarboneto Arílico/biossíntese , Transdução de Sinais , Diferenciação Celular , Linhagem Celular , Células-Tronco Embrionárias Humanas/citologia , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo
15.
Biol Pharm Bull ; 42(3): 501-506, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30828081

RESUMO

The mechanism underlying the increased pharmacological effects of phenobarbital in rats with glycerol-induced acute renal failure (ARF) was examined. In the experiments, a surgical cannula was inserted in the lateral ventricle of the rats for phenobarbital infusion, and the ARF induction was performed by intramuscular administration of 50% glycerol. The onset time of anesthesia by phenobarbital was determined with the tail flick method. In addition, cerebral microsomes were prepared from excised cerebral cortices of sham and ARF rats, and the cerebral expression of the γ-aminobutyric acid (GABA)A receptor and two cation-chloride transporters, KCC2 and NKCC1, was evaluated by Western blotting, as their functions are involved in the anesthetic effects of phenobarbital. When phenobarbital was infused in the ventricle, anesthesia was induced 2.2-times faster in ARF rats than in sham rats, and there was no detectable increase in the cerebral expression of the GABAA receptor in ARF rats. It was additionally noted that the cerebral expression of KCC2 decreased, whereas that of NKCC1 was unaltered in ARF rats. These findings indicated that the anesthetic effects of phenobarbital are potentiated in ARF rats, probably due to imbalanced cerebral expression of KCC2 and NKCC1, suggesting that altered cation-chloride handling in nerve cells is associated.


Assuntos
Injúria Renal Aguda/induzido quimicamente , Glicerol/toxicidade , Fenobarbital/farmacologia , Injúria Renal Aguda/metabolismo , Anestésicos Intravenosos/farmacologia , Animais , Bumetanida/farmacologia , Diuréticos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Hipnóticos e Sedativos/farmacologia , Masculino , Distribuição Aleatória , Ratos , Ratos Wistar , Receptores de GABA-A/metabolismo , Membro 2 da Família 12 de Carreador de Soluto/genética , Membro 2 da Família 12 de Carreador de Soluto/metabolismo , Simportadores/genética , Simportadores/metabolismo , Uretana/farmacologia , Cotransportadores de K e Cl-
16.
Digestion ; 99(1): 39-45, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30554222

RESUMO

BACKGROUND: Liquid biopsy is a collective term that refers to the analysis of tumor-derived biomarkers isolated from biological fluids of cancer patients. Recently, many authors reported the usefulness of liquid biopsy for the management of malignancy. Summary and Key Messages: The peripheral blood of cancer patients is a pool of cells and/or cell products derived from the primary or metastatic tumor, including circulating tumor cells (CTCs), circulating free (cf) DNA or RNA, and exosomes containing proteins, nucleic acids, and lipids. CTCs are tumor cells that can be isolated from peripheral blood. Free circulating DNA with a tumor-specific mutation is called circulating tumor DNA (ctDNA). Some patients who undergo curative surgery experience recurrent disease, which can be due to the presence of minimal residual disease (MRD). Thus, MRD indicates a high risk of relapse. Detection of ctDNA or CTC after surgery is a direct proof of MRD. Molecular volume (e.g., the number of CTCs and level of ctDNA) might reflect tumor burden, thus high molecular volume may indicate poor prognosis. The most notable application of liquid biopsy in cancer is to understand spatial and temporal heterogeneities. Heterogeneity is one of the causes of refractoriness and hampers prediction of chemotherapeutic effect. Emerging mutations that are not present in primary tumors but are found in their metastases can be detected in ctDNA. Some colorectal cancer patients with wild-type RAS do not respond to epidermal growth factor receptor blockade. In a subset of these patients, RAS mutation is detected in ctDNA, indicating heterogeneity.


Assuntos
Neoplasias Colorretais/sangue , Neoplasias Colorretais/patologia , Biópsia Líquida/métodos , Neoplasia Residual/diagnóstico , Células Neoplásicas Circulantes/metabolismo , Biomarcadores Tumorais/sangue , Colectomia , Neoplasias Colorretais/cirurgia , DNA de Neoplasias/sangue , Humanos
17.
Gan To Kagaku Ryoho ; 46(13): 2143-2145, 2019 Dec.
Artigo em Japonês | MEDLINE | ID: mdl-32156859

RESUMO

Chemoradiotherapy(CRT)for locally recurrent rectal cancer can shrink the tumor and permit R0 resection; however, its effectiveness and safety have not been established. Herein, we report a case of a 60s man with locally recurrent rectal cancer invading the surrounding organs who was administered CRT followed by R0 laparoscopic-assisted abdominoperineal resection( APR). Local recurrence was detected 11 months after laparoscopic-assisted low anterior resection(pT3N0M0, pStage Ⅱ). After tumor shrinkage by CRT(capecitabine 3,000mg/day plus 45 Gy/25 Fr), laparoscopic-assisted APR was performed. The pathological findings showed a pathological complete response(pCR). The patient had not experienced recurrent disease at 6 months after the second surgery. CRT may improve the prognosis of patients with locally recurrent rectal cancer, especially those with possibly unresectable tumors.


Assuntos
Neoplasias Retais , Quimiorradioterapia , Humanos , Masculino , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Prognóstico , Neoplasias Retais/terapia , Resultado do Tratamento
18.
Gan To Kagaku Ryoho ; 46(13): 2386-2388, 2019 Dec.
Artigo em Japonês | MEDLINE | ID: mdl-32156940

RESUMO

Ovarian metastasis of colorectal cancer is associated with poor prognosis. Recent advances in chemotherapy may improve this prognosis. In this retrospective study, we evaluated indicators of poor prognosis for ovarian metastasis of colorectal cancer. Twenty patients, who were diagnosed with ovarian metastasis of colorectal cancer from April 2000 to December 2017, were enrolled. Oophorectomy was performed in 18 of the 20 patients. Postoperative chemotherapy was provided to 13 patients, and molecular targeting agents were administered in 5 patients. Metastases to other organs besides the ovaries, premenopausal condition, undifferentiated histologic type of the primary tumor, and no resection of ovarian metastases were identified as indicators of poor prognosis. The 3-year survival rate was 15%, and the 5-year survival rate was 0%. In conclusion, oophorectomy can improve the prognosis of patients with ovarian metastasis of colorectal cancer. However, prognostic improvement due to molecular target agents was not shown.


Assuntos
Neoplasias Colorretais , Neoplasias Ovarianas , Feminino , Humanos , Tumor de Krukenberg , Neoplasias Ovarianas/secundário , Prognóstico , Estudos Retrospectivos
19.
BMC Gastroenterol ; 18(1): 117, 2018 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-30016941

RESUMO

BACKGROUND: Anastomotic leakage (AL) is the most serious and common complication of surgery for rectal cancer, and associated risk factors remain unknown despite developments in laparoscopic surgery. The present study aimed to determine risk factors for AL after laparoscopic anterior resection (AR) of rectal cancer. METHODS: This retrospective cohort study extracted information from a prospective database of all consecutive colorectal resections that proceeded at Nippon Medical School Hospital between January 2011 and December 2015 (n = 865). We identified 154 patients with rectal cancer treated by elective laparoscopic AR with anastomosis using primary double-stapling. Clinical variables and comorbidity, habits, and surgery-related variables were assessed by univariate and multivariate analyses to determine preoperative risk factors for clinical AL. RESULTS: The overall rate of clinical AL was 11.7% (18 of 154 patients), and 5 (27.8%) of 18 patients required revised laparotomy. Data from males were analyzed because AL occurred only in males. Univariate analysis of male patients (n = 100) significantly associated preoperative creatinine values (p = 0.03) and a history of ischemic heart disease (IHD) (p = 0.012) with AL. The frequency of AL tended to increase (p = 0.06) when patients had low AR (p = 0.06) and transanal drainage. Having AL significantly prolonged hospital stays compared with patients without leakage (36.2 vs. 11.1 days; p <  0.01). Multivariate analysis identified a history of IHD (odds ratio [OR], 4.73; 95% confidence interval [CI], 1.27-17.5; p = 0.025] as an independent risk factor for AL. CONCLUSIONS: Male sex and a history of IHD are possible risk factors for AL after elective laparoscopic rectal cancer surgery.


Assuntos
Fístula Anastomótica/etiologia , Laparoscopia/efeitos adversos , Isquemia Miocárdica/complicações , Neoplasias Retais/complicações , Neoplasias Retais/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anastomose Cirúrgica/efeitos adversos , Creatinina/sangue , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Período Pré-Operatório , Neoplasias Retais/patologia , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais
20.
In Vivo ; 32(4): 937-943, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29936483

RESUMO

BACKGROUND/AIM: The combination of oxaliplatin, leucovorin and fluorouracil (FOLFOX) has been established as postoperative adjuvant chemotherapy for stage III colon cancer. However, the safety and efficacy of neoadjuvant FOLFOX in patients with rectal cancer are still controversial. This prospective pilot study aimed to evaluate the feasibility of neoadjuvant FOLFOX therapy without radiation for baseline resectable rectal cancer (RC). PATIENTS AND METHODS: The study included 30 patients with clinical stage II/III RC between February 2012 and December 2015. The patients were treated with six cycles of FOLFOX followed by elective surgery. The primary endpoint was the R0 resection rate. The secondary endpoints were the scheduled treatment completion rate, adverse events, pathological response and the disease-free survival (DFS) rate. RESULTS: All the patients underwent elective R0 resection after neoadjuvant FOLFOX therapy. The completion rate of the 6-cycle regimen was 93.3% (28/30 patients). Grade 3-4 adverse events occurred in seven patients (23.3%). Pathological complete response was noted in two patients (6.7%). The 3-year DFS rate was 77.5% (95% confidence interval, 61.4%-93.7%). CONCLUSION: Neoadjuvant FOLFOX therapy without radiation is a feasible therapeutic strategy for baseline resectable RC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bevacizumab/administração & dosagem , Neoplasias Retais/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/efeitos adversos , Intervalo Livre de Doença , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Estadiamento de Neoplasias , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Projetos Piloto , Neoplasias Retais/patologia , Neoplasias Retais/radioterapia , Neoplasias Retais/cirurgia
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