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1.
Int J Colorectal Dis ; 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34850277

RESUMO

PURPOSE: This study aimed to analyze the effect of ascitic carcinoembryonic antigen (CEA) levels on the long-term oncologic outcomes of colorectal cancer (CRC) following curative treatment. METHODS: A total of 191 patients with stage II/III CRC were included. CEA was analyzed on the peritoneal fluid samples taken at the start of each surgery. Long-term oncologic outcomes were analyzed using known risk factors for recurrence in CRC. RESULT: Multivariate analysis of recurrence showed that lymphatic invasion (hazards ratio (HR) 2.7, 95% confidence interval (CI) 1.1-7, p = 0.038), vascular invasion (HR 2.8, 95% CI 1.2-6.3, p = 0.013), mucinous cancer (HR 3.6, 95% CI 1.3-10.1, p = 0.017), and peritoneal fluid CEA exceeding 5 ng/dl (odds ratio 3.1, 95% CI 1.2-7.7, p = 0.017) were significant risk factors. There were 14 patients with liver metastasis, 11 of whom had high ascitic CEA levels and no peritoneal metastasis. Additionally, eight had lung metastasis, and seven of them had high ascitic CEA levels. CONCLUSION: High ascitic CEA levels showed significantly lower disease-free survival and were significantly associated with distant metastasis in the lung and liver.

2.
Genes Genomics ; 2021 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-34800260

RESUMO

BACKGROUND: Cisplatin (CP) is an effective anticancer drug broadly used for various types of cancers, but it has shown ototoxicity that results from oxidative stress. Berberine has been reported for its anti-oxidative stress suggesting its therapeutic potential for many diseases such as colitis, diabetes, and vascular dementia. OBJECTIVE: Organ of Corti of postnatal day 3 mouse cochlear explants were used to compare hair cells after the treatment with cisplatin alone or with berberine chloride (BC) followed by CP. METHODS: We investigated the potential of the anti-oxidative effect of BC against the cisplatin-induced ototoxicity. We observed a reduced aberrant bundle of stereocilia in hair cells in CP with BC pre-treated group. Caspase-3 immunofluorescence and TUNEL assay supported the hypothesis that BC attenuates the apoptotic signals induced by CP. Reactive oxygen species level in the mitochondria were investigated by MitoSOX Red staining and the mitochondrial membrane potentials were compared by JC-1 assay. RESULTS: BC decreased ROS generation with preserved mitochondrial membrane potentials in mitochondria as well as reduced DNA fragmentation in hair cells. In summary, our data indicate that BC might act as antioxidant against CP by reducing the stress in mitochondria resulting in cell survival. CONCLUSION: Our result suggests the therapeutic potential of BC for prevention of the detrimental effect of CP-induced ototoxicity.

3.
Asian J Surg ; 2021 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-34815142

RESUMO

PURPOSE: The purpose of this study was to investigate the clinical features and risk factors of late anastomotic leakage (AL) in a homogeneous cohort with elective sphincter-sparing surgery (SSS) with ileostomy after neoadjuvant chemoradiotherapy (nCRT) for rectal cancer. METHODS: Data from a total of 359 patients who underwent elective rectal cancer surgery between Jan 2017 and May 2020 were retrospectively reviewed. Patients were classified into early and late AL groups, referring to onset of AL occurring within or after 30 post-operative days, respectively. We analyzed clinical, pathological, and inflammatory features of both AL and risk factors of stoma reversal failure and late AL. RESULTS: A total of 85 patients with SSS with ileostomy after nCRT were classified into 8 (9.4%) patients of early AL and 16 (18.8%) of late AL. Unlike early AL patients, late AL group showed lower neutrophil-lymphocyte ratio (NLR) (P < 0.001) and did not need an invasive intervention at the time of diagnosis. 50% (5/10) patients needed reformation of ileostomy. (P = 0.048) Failure of stoma reversal is associated with advanced stages, high NLR ratio (≥3), and inflammatory lesions seen around anastomosis in radiologic findings, which was confirmed as the risk factor of late AL. CONCLUSION: Late AL, with different clinical features, showed a higher incidence than early AL in patients who underwent surgery after nCRT and also had a higher stoma reformation rate. Careful evaluation using laboratory and radiological findings before an ileostomy closure is performed to prevent late AL.

4.
Ann Surg Treat Res ; 101(4): 221-230, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34692594

RESUMO

Purpose: Intrathecal analgesia (ITA) and transverse abdominis plane block (TAPB) are effective pain control methods in abdominal surgery. However, there is still no gold standard for postoperative pain control in minimally invasive colorectal surgery. This study aimed to investigate whether the analgesic effect could be increased when TAPB, which can further reduce wound somatic pain, was administered in low-dose morphine ITA patients. Methods: Patients undergoing elective colorectal surgery were randomized into an ITA with TAPB group or an ITA group. Patients were evaluated for pain 0, 8, 16, 24, and 48 hours after surgery. The primary outcome was the total morphine milligram equivalents administered 24 hours after surgery. The secondary outcomes were pain scores, ambulatory variables, inflammation markers, hospital stay duration, and complications within 48 hours after surgery. Results: A total of 64 patients were recruited, and 55 were compared. There was no significant difference in morphine use over the 24 hours after surgery in the 2 groups (ITA with TAPB, 15.3 mg vs. ITA, 10.2 mg; P = 0.270). Also, there was no significant difference in pain scores. In both groups, the average pain score at 24 and 48 hours was 2 points or less, showing effective pain control. Conclusion: ITA for pain control in patients with colorectal surgery is an effective pain method, and additional TAPB was not effective.

5.
Antioxidants (Basel) ; 10(10)2021 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-34679662

RESUMO

Drug-induced hearing loss is a major type of acquired sensorineural hearing loss. Cisplatin and aminoglycoside antibiotics have been known to cause ototoxicity, and excessive accumulation of intracellular reactive oxygen species (ROS) are suggested as the common major pathology of cisplatin- and aminoglycoside antibiotics-induced ototoxicity. Fursultiamine, also called thiamine tetrahydrofurfuryl disulfide, is a thiamine disulfide derivative that may have antioxidant effects. To evaluate whether fursultiamine can prevent cisplatin- and kanamycin-induced ototoxicity, we investigated their preventive potential using mouse cochlear explant culture system. Immunofluorescence staining of mouse cochlear hair cells showed that fursultiamine pretreatment reduced cisplatin- and kanamycin-induced damage to both inner and outer hair cells. Fursultiamine attenuated mitochondrial ROS accumulation as evidenced by MitoSOX Red staining and restored mitochondrial membrane potential in a JC-1 assay. In addition, fursultiamine pretreatment reduced active caspase-3 and TUNEL signals after cisplatin or kanamycin treatment, indicating that fursultiamine decreased apoptotic hair cell death. This study is the first to show a protective effect of fursultiamine against cisplatin- and aminoglycoside antibiotics-induced ototoxicity. Our results suggest that fursultiamine could act as an antioxidant and anti-apoptotic agent against mitochondrial oxidative stress.in cochlear hair cells.

6.
Nutr Clin Pract ; 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34609767

RESUMO

BACKGROUND: Although body composition (BC) can be measured easily using bioelectrical impedance analysis (BIA), there are few studies of serial BC measurements in colorectal cancer (CRC). The purpose of the present study was to observe the serial change of BC in patients with CRC surgery from the initiation to the end of chemotherapy and to evaluate its clinical usefulness. METHODS: From July 2018 to November 2019, patients undergoing elective CRC surgery were enrolled. All clinical data were reviewed retrospectively. BIA data were collected prospectively at four time points (initial, discharge day, first chemotherapy, and 6 months later). BC was measured using a commercial BIA device. RESULTS: A total of 160 patients were enrolled, and 110 (68.8%) patients were followed. Most BC measurements, such as weight, body mass index, skeletal muscle mass, skeletal muscle index, and fat mass index, were lowest at the first chemotherapy and rebounded after 6 months. Phase angle (PhA) and the ratio of extracellular water to total body water (ECW/TBW) were "V" shaped and inverted "V" shaped, respectively, and the peaks were on discharge days. This pattern of BC showed significant difference according to sarcopenia, old age (>70 years), and advanced stage (III or IV). The change of PhA and ECW/TBW sensitively pattern differences according to clinical aspect. CONCLUSIONS: Using BIA, serial BC measurements were taken to establish a pattern based on clinical characteristics. PhA showed the most sensitive change according to the patient's clinical aspect.

8.
Endocrinol Metab (Seoul) ; 36(5): 1142-1146, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34674507

RESUMO

It has been suggested that the coronavirus disease 2019 (COVID-19) pandemic has had a negative impact on glycemic control in patients with type 2 diabetes mellitus (T2DM). However, no study has examined yearly trends in glycated hemoglobin (HbA1c) levels after the start of the COVID-19 outbreak. Here, we performed a retrospective analysis of HbA1c concentrations during the early period of the COVID-19 outbreak (COVID-19 cohort) and then compared the yearly trend in the mean HbA1c level, along with fluctuations in HbA1c levels, with those during previous years (non-COVID-19 cohorts). We observed that the mean HbA1c level in patients with T2DM increased during the first 6 months of the COVID-19 outbreak. After 6 months, HbA1c levels in the COVID-19 cohort returned to levels seen in the non-COVID-19 cohorts. The data suggest that vulnerable patients with T2DM should be monitored closely during the early period of a pandemic to ensure they receive appropriate care.


Assuntos
COVID-19/epidemiologia , Diabetes Mellitus Tipo 2/sangue , Hemoglobina A Glicada/análise , Controle Glicêmico/tendências , Adulto , Glicemia/análise , COVID-19/diagnóstico , COVID-19/virologia , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/epidemiologia , Surtos de Doenças/estatística & dados numéricos , Feminino , Humanos , Masculino , Estudos Retrospectivos , SARS-CoV-2/genética , Fatores de Tempo
9.
Exp Mol Med ; 53(9): 1390-1401, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34552205

RESUMO

Obesity is now recognized as a disease. This study revealed a novel role for pyruvate dehydrogenase kinase (PDK) in diet-induced hypertrophic obesity. Mice with global or adipose tissue-specific PDK2 deficiency were protected against diet-induced obesity. The weight of adipose tissues and the size of adipocytes were reduced. Adipocyte-specific PDK2 deficiency slightly increased insulin sensitivity in HFD-fed mice. In studies with 3T3-L1 preadipocytes, PDK2 and PDK1 expression was strongly increased during adipogenesis. Evidence was found for epigenetic induction of both PDK1 and PDK2. Gain- and loss-of-function studies with 3T3-L1 cells revealed a critical role for PDK1/2 in adipocyte differentiation and lipid accumulation. PDK1/2 induction during differentiation was also accompanied by increased expression of hypoxia-inducible factor-1α (HIF1α) and enhanced lactate production, both of which were absent in the context of PDK1/2 deficiency. Exogenous lactate supplementation increased the stability of HIF1α and promoted adipogenesis. PDK1/2 overexpression-mediated adipogenesis was abolished by HIF1α inhibition, suggesting a role for the PDK-lactate-HIF1α axis during adipogenesis. In human adipose tissue, the expression of PDK1/2 was positively correlated with that of the adipogenic marker PPARγ and inversely correlated with obesity. Similarly, PDK1/2 expression in mouse adipose tissue was decreased by chronic high-fat diet feeding. We conclude that PDK1 and 2 are novel regulators of adipogenesis that play critical roles in obesity.

10.
BMB Rep ; 54(11): 563-568, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34488935

RESUMO

Cancer cells predominantly generate energy via glycolysis, even in the presence of oxygen, to support abnormal cell proliferation. Suppression of PDHA1 by PDK1 prevents the conversion of cytoplasmic pyruvate into Acetyl-CoA. Several PDK inhibitors have been identified, but their clinical applications have not been successful for unclear reasons. In this study, endogenous PDHA1 in A549 cells was silenced by the CRISPR/Cas9 system, and PDHA1WT and PDHA13SD were transduced. Since PDHA13SD cannot be phosphorylated by PDKs, it was used to evaluate the specific activity of PDK inhibitors. This study highlights that PDHA1WT and PDHA13SD A549 cells can be used as a cell-based PDK inhibitor-distinction system to examine the relationship between PDH activity and cell death by established PDK inhibitors. Leelamine, huzhangoside A and otobaphenol induced PDH activity-dependent apoptosis, whereas AZD7545, VER-246608 and DCA effectively enhanced PDHA1 activity but little toxic to cancer cells. Furthermore, the activity of phosphomimetic PDHA1 revealed the complexity of its regulation, which requires further in-depth investigation. [BMB Reports 2021; 54(11): 563-568].

11.
Surg Endosc ; 2021 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-34370125

RESUMO

BACKGROUND: In the field of rectal cancer surgery, there remains ongoing debate on the merits of high ligation (HL) and low ligation (LL) of the inferior mesenteric artery (IMA) in terms of perfusion and anastomosis leakage. Recently, infrared fluorescence of indocyanine green (ICG) imaging has been used to evaluate perfusion status during colorectal surgery. OBJECTIVE: The purpose of this study is to compare the changes in perfusion status between HL and LL through quantitative evaluation of ICG. METHODS: Patients with rectosigmoid or rectal cancer were randomized into a high or LL group. ICG was injected before and after IMA ligation, and region of interest (ROI) values were measured by an image analysis program (HSL video©). RESULTS: From February to July 2020, 22 patients were enrolled, and 11 patients were assigned to each group. Basic demographics were similar between the two groups, except for albumin level and cardiac ejection fraction. There were no significant differences in F_max between the two groups, but T_max was significantly higher and Slope_max was significantly lower in the HL group than in the LL group. Anastomosis leakage was significantly associated with neoadjuvant chemoradiation and F_max. CONCLUSION: After IMA ligation, T_max increased and Slope_max decreased significantly in the HL group. However, the intensity of perfusion status (F_max) did not change according to the level of IMA ligation.

12.
Cancers (Basel) ; 13(16)2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34439344

RESUMO

The objective of this study was to characterize circulating tumor DNA (ctDNA) mutations in colorectal cancer (CRC) patients and evaluate their prognostic values during treatment. Forty-nine patients with CRC planned for operation were enrolled. A total of 115 plasma samples were collected pre-operation, post-operation, and post-chemotherapy. ctDNA analysis was performed using next-generation sequencing (NGS) including 14 genes. In 22 (44.9%) out of 49 patients, at least one mutation (40 total mutations) was detected in the initial plasma sample. The median sum of variant allele frequency was 0.74% (range: 0.10-29.57%). TP53 mutations were the most frequent (17 of 49 patients, 34.7%), followed by APC (18.4%), KRAS (12.2%), FBXW7 (8.2%), NRAS (2.0%), PIK3CA (2.0%), and SMAD4 (2.0%). After surgery, five (14.3%) out of 35 patients harbored ctDNA mutation. All five patients experienced relapse or metastasis during follow-up. It was noteworthy that all three patients with persistent ctDNA relapsed after R0 resection. After chemotherapy, ctDNA analysis was performed for 31 patients, all of which were ctDNA-negative. Analytical and clinical performances of NGS to utilize ctDNA in CRC were determined. Results revealed that postoperative ctDNA might serve as a marker for identifying risk of recurrence, thus contributing to patient-oriented treatment strategies.

13.
Biomedicines ; 9(8)2021 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-34440092

RESUMO

We evaluated the prognostic impact of vascular invasion (VI) compared with nodal (N) stage and developed a new staging system including VI in colon cancer. Patients who underwent curative resection with stage II-III colon cancer were assigned to VI and non-VI groups; the latter was subclassified as N0, N1, and N2; a new TNVM staging was devised by adding the V-stage. Among the 2243 study participants, the VI group independently showed worse oncological outcomes than the N1 group (disease-free survival (DFS), hazard-ratio (HR) 1.704, 1.267-2.291; overall survival (OS), HR 2.301, 1.582-3.348). The 5-year DFS in the VI group was 63.4% [N1b (74.6%), p = 0.003; N2a (69.7%), p = 0.126; and N2b (56.8%), p = 0.276], and the 5-year OS was 76.6% [N1b (84.9%), p = 0.004; N2a (83.0%), p = 0.047; and N2b (76.1%), p = 0.906]. Thus, we considered VI as N2a in TNVM staging; 78 patients (3.5%) underwent upstaging. The 5-year OS rates of stage IIB and IIC increased from 88.6% and 65.9% in TNM staging to 90.5% and 85.7% in TNVM staging, respectively. In stage II-III colon cancer, VI had a similar prognostic impact as the N2 stage without VI. The incorporation of the V-stage into the conventional TNM staging facilitates better prediction of prognosis.

14.
BMB Rep ; 54(8): 431-436, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34353426

RESUMO

In recent years, restoring anti-tumor immunity has garnered a growing interest in cancer treatment. As potential therapeutics, immune checkpoint inhibitors have demonstrated benefits in many clinical studies. Although various methods have been applied to suppress immune checkpoints to boost anti-tumor immunity, including the use of immune checkpoint inhibitors, there are still unmet clinical needs to improve the response rate of cancer treatment. Here, we show that acetate can suppress the expression of poliovirus receptor (PVR/CD155), a ligand for immune checkpoint, in colon cancer cells. We demonstrated that acetate treatment could enhance effector responses of CD8+ T cells by decreasing the expression of PVR/CD155 in cancer cells. We also found that acetate could reduce the expression of PVR/CD155 by deactivating the PI3K/AKT pathway. These results demonstrate that acetate-mediated expression of PVR/ CD155 in cancer cells might potentiate the anti-tumor immunity in the microenvironment of cancer. Our findings indicate that maintaining particular acetate concentrations could be a complementary strategy in current cancer treatment. [BMB Reports 2021; 54(8): 431-436].

15.
Ann Coloproctol ; 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34284558

RESUMO

Purpose: The aim of this study was to evaluate the safety and feasibility of applying enhanced recovery after surgery (ERAS) protocol in elderly colorectal cancer patients. Methods: The medical records of patients who underwent elective colorectal cancer surgery at our institution, from January 2017 to December 2017, were reviewed. Patients were divided into 2 groups: the young group (YG, patients aged 70 and under 70 years) and the old group (OG, patients over 70 years old). Perioperative outcomes and length of hospital stay were compared between both groups. Results: In total, 335 patients were enrolled; 237 were YG and 98 were OG. Despite the poorer baseline characteristics of OG, the perioperative outcomes were similar. Length of hospital stay was not different between the groups (YG, 5 days vs. OG, 5 days; P=0.320). When comparing the postoperative complications using the comprehensive complication index (CCI), there was no significant difference (YG, 8.0±13.2 vs. OG, 11.7±23.0; P=0.130). In regression analysis, old age (>70 years) was not a risk factor for high CCI in all patients. In multivariate analysis, C-reactive protein (CRP) level on postoperative day (POD) 3 to 4 was the only strong predictive factor for high CCI in elderly patients. Conclusion: Implementing the ERAS protocol in patients aged >70 years is safe and feasible. High CRP (≥6.47 mg/dL) on POD 3 to 4 can be used as a safety index to postpone discharge in elderly patients.

16.
Front Med (Lausanne) ; 8: 685032, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34222291

RESUMO

Age-related macular degeneration (AMD) is a leading cause of blindness in the elderly, and oxidative damage to retinal pigment epithelial (RPE) cells plays a major role in the pathogenesis of AMD. Exposure to high levels of atmospheric particulate matter (PM) with an aerodynamic diameter of <2.5 µm (PM2.5) causes respiratory injury, primarily due to oxidative stress. Recently, a large community-based cohort study in the UK reported a positive correlation between PM2.5 exposure and AMD. Sulforaphane (SFN), a natural isothiocyanate found in cruciferous vegetables, has known antioxidant effects. However, the protective effects of SNF in the eye, especially in the context of AMD, have not been evaluated. In the present study, we evaluated the effect of SFN against PM2.5-induced toxicity in human RPE cells (ARPE-19) and elucidated the molecular mechanism of action. Exposure to PM2.5 decreased cell viability in ARPE-19 cells in a time- and dose-dependent manner, potentially due to elevated intracellular reactive oxygen species (ROS). SFN treatment increased ARPE-19 cell viability and decreased PM2.5-induced oxidative stress in a dose-dependent manner. PM2.5-induced downregulation of serum- and glucocorticoid-inducible kinase 1 (SGK1), a cell survival factor, was recovered by SFN. PM2.5 treatment decreased the enzymatic activities of the antioxidant enzymes including superoxide dismutase and catalase, which were restored by SFN treatment. Taken together, these findings suggest that SFN effectively alleviates PM2.5-induced oxidative damage in human ARPE-19 cells via its antioxidant effects, and that SFN can potentially be used as a therapeutic agent for AMD, particularly in cases related to PM2.5 exposure.

17.
Korean J Intern Med ; 36(4): 942-948, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34092049

RESUMO

BACKGROUND/AIMS: Coronavirus disease 2019 (COVID-19) is a global pandemic that had affected more than 13,000 people in South Korea by July 2020. To prevent spread of COVID-19, tele-prescription was permitted temporarily. This study investigated the impact of tele-prescription on glycemic control in patients with type 2 diabetes. METHODS: Glycated hemoglobin (HbA1c) concentrations were retrospectively analyzed in patients with type 2 diabetes who were treated with tele-prescription because of COVID-19 and those who were treated by face-to-face care (non-tele-prescription group) enrolled at the same period of time. Mean HbA1c concentrations and mean change in HbA1c concentration (ΔHbA1c) were compared in these two groups. RESULTS: The mean HbA1c levels of patients were significantly higher after than before the tele-prescription period (7.46% ± 1.24% vs. 7.27% ± 1.13%, p < 0.05). Mean ΔHbA1c was significantly higher in the tele-prescription than in the non-tele-prescription group (0.19% ± 0.68% vs. 0.04% ± 0.95%, p < 0.05). HbA1c was significantly greater in patients taking fewer oral hypoglycemic agents, no insulin, fewer comorbidities (e.g., coronary artery disease, cerebrovascular accident, and diabetic neuropathy), and higher baseline HbA1c. CONCLUSION: Tele-prescription may worsen glycemic control in patients with type 2 diabetes during public health crises.


Assuntos
COVID-19 , Diabetes Mellitus Tipo 2 , Glicemia , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Hemoglobina A Glicada/análise , Controle Glicêmico , Humanos , Hipoglicemiantes/uso terapêutico , Prescrições , República da Coreia/epidemiologia , Estudos Retrospectivos , SARS-CoV-2
18.
Int J Mol Sci ; 22(10)2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-34065602

RESUMO

Resistance to anticancer therapeutics occurs in virtually every type of cancer and becomes a major difficulty in cancer treatment. Although 5-fluorouracil (5FU) is the first-line choice of anticancer therapy for gastric cancer, its effectiveness is limited owing to drug resistance. Recently, altered cancer metabolism, including the Warburg effect, a preference for glycolysis rather than oxidative phosphorylation for energy production, has been accepted as a pivotal mechanism regulating resistance to chemotherapy. Thus, we investigated the detailed mechanism and possible usefulness of antiglycolytic agents in ameliorating 5FU resistance using established gastric cancer cell lines, SNU620 and SNU620/5FU. SNU620/5FU, a gastric cancer cell harboring resistance to 5FU, showed much higher lactate production and expression of glycolysis-related enzymes, such as lactate dehydrogenase A (LDHA), than those of the parent SNU620 cells. To limit glycolysis, we examined catechin and its derivatives, which are known anti-inflammatory and anticancer natural products because epigallocatechin gallate has been previously reported as a suppressor of LDHA expression. Catechin, the simplest compound among them, had the highest inhibitory effect on lactate production and LDHA activity. In addition, the combination of 5FU and catechin showed additional cytotoxicity and induced reactive oxygen species (ROS)-mediated apoptosis in SNU620/5FU cells. Thus, based on these results, we suggest catechin as a candidate for the development of a novel adjuvant drug that reduces chemoresistance to 5FU by restricting LDHA.


Assuntos
Catequina/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Fluoruracila/farmacologia , Lactato Desidrogenase 5/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Apoptose/efeitos dos fármacos , Catequina/análogos & derivados , Linhagem Celular Tumoral , Glicólise/efeitos dos fármacos , Humanos , Espécies Reativas de Oxigênio/metabolismo , Estômago/efeitos dos fármacos , Neoplasias Gástricas/metabolismo
19.
Ann Coloproctol ; 37(4): 232-238, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34167189

RESUMO

PURPOSE: The objective of this study was to compare the perioperative outcomes between single-incision laparoscopic appendectomy (SILA) and 3-port conventional laparoscopic appendectomy (CLA) in enhanced recovery after surgery (ERAS) protocol. METHODS: Of 101 laparoscopic appendectomy with ERAS protocol cases for appendicitis from March 2019 to April 2020, 54 patients underwent SILA with multimodal analgesic approach (group 1) while 47 patients received CLA with multimodal analgesic approach (group 2). SILA and CLA were compared with the single institution's ERAS protocol. To adjust for baseline differences and selection bias, operative outcomes and complications were compared after propensity score matching (PSM). RESULTS: After 1:1 PSM, well-matched 35 patients in each group were evaluated. Postoperative hospital stays for patients in group 1 (1.2 ± 0.8 vs. 1.6 ± 0.8 days, P = 0.037) were significantly lesser than those for patients in group 2. However, opioid consumption (2.0 mg vs. 1.4 mg, P=0.1) and the postoperative scores of visual analogue scale for pain at 6 hours (2.4±1.9 vs. 2.8 ± 1.4, P = 0.260) and 12 hours (2.4 ± 2.0 vs. 2.9 ± 1.5, P = 0.257) did not show significant difference between the 2 groups. CONCLUSION: SILA resulted in shortening the length of hospitalization without increase in complications or readmission rates compared to CLA with ERAS protocol.

20.
Arch Toxicol ; 95(9): 3071-3084, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34191077

RESUMO

Acute liver injury results from the complex interactions of various pathological processes. The TGF-ß superfamily plays a crucial role in orchestrating fibrogenic response. In contrast to TGF-ß1, a role of TGF-ß2 in hepatic fibrogenic response has not been fully investigated. In this study, we showed that TGF-ß2 gene expression and secretion are induced in the liver of CCl4 (1 ml/kg)-treated WT mice. Studies with hepatocyte specific ERRγ knockout mice or treatment with an ERRγ-specific inverse agonist, GSK5182 (40 mg/kg), indicated that CCl4-induced hepatic TGF-ß2 production is ERRγ dependent. Moreover, IL6 was found as upstream signal to induce hepatic ERRγ and TGF-ß2 gene expression in CCl4-mediated acute toxicity model. Over-expression of ERRγ was sufficient to induce hepatic TGF-ß2 expression, whereas ERRγ depletion markedly reduces IL6-induced TGF-ß2 gene expression and secretion in vitro and in vivo. Promoter assays showed that ERRγ directly binds to an ERR response element in the TGF-ß2 promoter to induce TGF-ß2 transcription. Finally, GSK5182 diminished CCl4-induced fibrogenic response through inhibition of ERRγ-mediated TGF-ß2 production. Taken together, these results firstly demonstrate that ERRγ can regulate the TGF-ß2-mediated fibrogenic response in a mouse model of CC14-induced acute liver injury.

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