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1.
J Nippon Med Sch ; 2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34840222

RESUMO

Kyphosis makes abdominal surgery difficult. Here, we report a case of rectal cancer in a patient with kyphosis on whom laparoscopic surgery was adequately performed owing to preoperative simulation. An 81-year-old woman with rectal cancer was admitted to our department, and laparoscopic surgery was planned. On physical examination, the patient showed severe kyphosis. To adequately perform laparoscopic surgery, a detailed and thorough preoperative simulation was conducted. 1) Simulations of port arrangement and anatomy with 3-D CT, 2) body position simulation, 3) selection of surgical instruments, 4) preoperative discussion with the anesthesiologist were conducted. We planned to insert the first port from the umbilical region for pneumoperitoneum and the camera port from the ventral region under pneumoperitoneum. We planned to insert the ports on the right side of the patient's body from caudal regions, considering the location of the inferior mesenteric artery and the limited degrees and space due to the costal arch and the promontorium. Beach chair position was planned. We used a fan-shaped retractor and a sponge-made retractor to remove the small intestine from the surgical view. We discussed with the anesthesiologist preoperatively, and decided to keep the pneumoperitoneum pressure under 8 mmHg during the operation considering the respiratory function. Lower anterior resection with D2 lymph node dissection was performed without any intraoperative complications, and at 2 years post-surgery, the patient was healthy with no signs of recurrence. Laparoscopic surgery may be a good choice in patients with kyphosis, and we believe that preoperative simulation will result in an uneventful surgery.

2.
Shokuhin Eiseigaku Zasshi ; 62(5): 162-165, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-34732642

RESUMO

Cyanogenic glycosides in loquat (Eriobotrya japonica) seeds, which are used in so-called health foods, pose a public concern in Japan due to their potential health risks. Several pretreatment methods, such as the steam distillation and Conway microdiffusion methods, have been established for the determination of cyanogenic glycoside concentrations in foods. However, these methods are time-consuming and have extremely low throughput. Therefore, we developed a simple and rapid method, called the purge method, to analyze cyanide compounds in seed-derived food products. Under this method, the aqueous extract of cyanogenic glycosides is treated with ß-glucosidase in a midget impinger, after which the liberated cyanide is purged into an absorbing solution. The concentration of cyanide in the adsorbent is then quantified using 4-pyridinecarboxylic acid-pyrazolone reagent. A single-laboratory method validation study was performed using amygdalin at a concentration of 10 ppm as cyanide ion. The validation parameter results (trueness, 83.9%; repeatability, 1.18%; intermediate precision, 4.67%) indicated that the developed method was suitable, precise and accurate. The purge method was used to analyze cyanide concentrations in commercially available food samples. Of the 10 samples tested (loquat seed powder, apricot kernel powder, and plum seed powder), three samples were found to contain cyanogenic glycosides at concentrations of >10 ppm as hydrogen cyanide, with the highest concentration detected being 861 ppm. These results clearly demonstrated the applicability of our method in determining cyanogenic glycosides in seed-derived food samples.


Assuntos
Amigdalina , Cianetos/análise , Glicosídeos , Japão , Pós
3.
J Cell Biol ; 220(11)2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34499080

RESUMO

Arg (R)-rich dipeptide repeat proteins (DPRs; poly(PR): Pro-Arg and poly(GR): Gly-Arg), encoded by a hexanucleotide expansion in the C9ORF72 gene, induce neurodegeneration in amyotrophic lateral sclerosis (ALS). Although R-rich DPRs undergo liquid-liquid phase separation (LLPS), which affects multiple biological processes, mechanisms underlying LLPS of DPRs remain elusive. Here, using in silico, in vitro, and in cellulo methods, we determined that the distribution of charged Arg residues regulates the complex coacervation with anionic peptides and nucleic acids. Proteomic analyses revealed that alternate Arg distribution in poly(PR) facilitates entrapment of proteins with acidic motifs via LLPS. Transcription, translation, and diffusion of nucleolar nucleophosmin (NPM1) were impaired by poly(PR) with an alternate charge distribution but not by poly(PR) variants with a consecutive charge distribution. We propose that the pathogenicity of R-rich DPRs is mediated by disturbance of proteins through entrapment in the phase-separated droplets via sequence-controlled multivalent protein-protein interactions.

4.
J Pestic Sci ; 46(3): 267-273, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34566460

RESUMO

We investigated the relative sensitivity of duckweed Lemna minor and six species of algae to seven herbicides, using an efficient high-throughput microplate-based toxicity assay. First, we assessed the sensitivity of L. minor to the seven herbicides, and then we compared its sensitivity to that of previously published data for six algal species based on EC50 values. For five herbicides, the most sensitive species differed: L. minor was most sensitive to cyclosulfamuron: Raphidocelis subcapitata was most sensitive to pretilachlor and esprocarb: Desmodesmus subspicatus was most sensitive to pyraclonil; and Navicula pelliculosa was most sensitive to pyrazoxyfen. Simetryn was evenly toxic to all species, whereas 2,4-D was evenly less toxic, with only small differences in species sensitivity. These results suggested that a single algal species cannot represent the sensitivity of the primary producer assemblage to a given herbicide. Therefore, to assess the ecological effects of herbicides, aquatic plant and multispecies algal toxicity data sets are essential.

5.
J Nippon Med Sch ; 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34526470

RESUMO

Small intestinal metastasis from lung cancer is a relatively rare occurrence, and often causes intestinal obstruction, gastrointestinal perforation, and/or gastrointestinal bleeding making it is an oncological emergency. Many patients have been reported to undergo emergency surgery owing to the rapid progression of the intestinal metastatic lesion; however, information regarding the changes that occur in such metastases over time remains lacking. Therefore, we analyzed 4 patients who had small intestinal metastases arising from lung cancer, who were treated during a 10-year period (January 2011 to December 2020), and whose tumor diameter changes were recorded. The average tumor volume growth rate was 1.48 (1.31-1.78) -fold, and the median observation period was 22 (4-39) days, showing a rapid increase. Histopathologically, in patients with a high degree of primary tumor atypia, rapid tumor growth caused by intratumoral hemorrhage may occur. This was considered to be one of the factors responsible for the rapid increase in tumor volume.

6.
Front Oncol ; 11: 732743, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34589434

RESUMO

Background: Patient participation in colorectal cancer (CRC) screening via a stool test and colonoscopy is suboptimal, but participation can be improved by the development of a blood test. However, the suboptimal detection abilities of blood tests for advanced neoplasia, including advanced adenoma (AA) and CRC, limit their application. We aimed to investigate the proteomic landscape of small extracellular vesicles (sEVs) from the serum of patients with colorectal neoplasia and identify specific sEV proteins that could serve as biomarkers for early diagnosis. Materials and Methods: We enrolled 100 patients including 13 healthy subjects, 12 non-AAs, 13 AAs, and 16 stage-I, 15 stage-II, 16 stage-III, and 15 stage-IV CRCs. These patients were classified as normal control, early neoplasia, and advanced neoplasia. The sEV proteome was explored by liquid chromatography-tandem mass spectrometry. Generalized association plots were used to integrate the clustering methods, visualize the data matrix, and analyze the relationship. The specific sEV biomarkers were identified by a decision tree via Orange3 software. Functional enrichment analysis was conducted by using the Ingenuity Pathway Analysis platform. Results: The sEV protein matrix was identified from the serum of 100 patients and contained 3353 proteins, of which 1921 proteins from 98 patients were finally analyzed. Compared with the normal control, subjects with early and advanced neoplasia exhibited a distinct proteomic distribution in the data matrix plot. Six sEV proteins were identified, namely, GCLM, KEL, APOF, CFB, PDE5A, and ATIC, which properly distinguished normal control, early neoplasia, and advanced neoplasia patients from each other. Functional enrichment analysis revealed that APOF+ and CFB+ sEV associated with clathrin-mediated endocytosis signaling and the complement system, which have critical implications for CRC carcinogenesis. Conclusion: Patients with colorectal neoplasia had a distinct sEV proteome expression pattern in serum compared with those patients who were healthy and did not have neoplasms. Moreover, the six identified specific sEV proteins had the potential to discriminate colorectal neoplasia between early-stage and advanced neoplasia. Collectively, our study provided a six-sEV protein biomarker panel for CRC diagnosis at early or advanced stages. Furthermore, the implication of the sEV proteome in CRC carcinogenesis via specific signaling pathways was explored.

7.
PLoS One ; 16(9): e0257000, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34516553

RESUMO

PURPOSE: To investigate the dynamics of the healing process after therapeutic subthreshold micropulse laser (SMPL) for diabetic macular edema (DME) using polarization-sensitive optical coherence tomography (PS-OCT). METHODS: Patients with treatment-native or previously-treated DME were prospectively imaged using PS-OCT at baseline, 1, 2, 3, and 6 months. The following outcomes were evaluated: changes in the entropy value per unit area (pixel2) in the retinal pigment epithelium (RPE) on the B-scan image; changes in the entropy value in each stratified layer (retina, RPE, choroid) based on the ETDRS grid circle overlaid with en face entropy mapping, not only the whole ETDRS grid area but also a sector irradiated by the SMPL; and the relationship between edema reduction and entropy changes. RESULTS: A total of 11 eyes of 11 consecutive DME patients were enrolled. No visible signs of SMPL treatment were detected on PS-OCT images. The entropy value per unit area (pixel2) in the RPE tended to decrease at 3 and 6 months from baseline (35.8 ± 17.0 vs 26.1 ± 9.8, P = 0.14; vs 28.2 ± 18.3, P = 0.14). Based on the en face entropy mapping, the overall entropy value did not change in each layer in the whole ETDRS grid; however, decrease of entropy in the RPE was observed at 2, 3, and 6 months post-treatment within the SMPL-irradiated sectors (P < 0.01, each). There was a positive correlation between the change rate of retinal thickness and that of entropy in the RPE within the SMPL-irradiated sector at 6 months (r2 = 0.19, P = 0.039). CONCLUSION: Entropy measured using PS-OCT may be a new parameter that facilitates objective monitoring of SMPL-induced functional changes in the RPE that could not previously be assessed directly. This may contribute to a more promising therapeutic evaluation of DME. CLINICAL TRIAL: This clinical study was registered in UMIN-CTR (ID: UMIN000042420).


Assuntos
Corioide/diagnóstico por imagem , Retinopatia Diabética/diagnóstico por imagem , Entropia , Fotocoagulação a Laser/métodos , Edema Macular/diagnóstico por imagem , Epitélio Pigmentado da Retina/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Corioide/patologia , Corioide/cirurgia , Retinopatia Diabética/patologia , Retinopatia Diabética/cirurgia , Feminino , Angiofluoresceinografia , Humanos , Edema Macular/patologia , Edema Macular/cirurgia , Masculino , Projetos Piloto , Estudos Prospectivos , Refração Ocular , Epitélio Pigmentado da Retina/patologia , Epitélio Pigmentado da Retina/cirurgia , Tomografia de Coerência Óptica , Acuidade Visual/fisiologia
8.
Proc Natl Acad Sci U S A ; 118(35)2021 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-34426493

RESUMO

Cellular senescence causes a dramatic alteration of chromatin organization and changes the gene expression profile of proinflammatory factors, thereby contributing to various age-related pathologies through the senescence-associated secretory phenotype (SASP). Chromatin organization and global gene expression are maintained by the CCCTC-binding factor (CTCF); however, the molecular mechanism underlying CTCF regulation and its association with SASP gene expression remains unclear. We discovered that noncoding RNA (ncRNA) derived from normally silenced pericentromeric repetitive sequences directly impairs the DNA binding of CTCF. This CTCF disturbance increases the accessibility of chromatin and activates the transcription of SASP-like inflammatory genes, promoting malignant transformation. Notably, pericentromeric ncRNA was transferred into surrounding cells via small extracellular vesicles acting as a tumorigenic SASP factor. Because CTCF blocks the expression of pericentromeric ncRNA in young cells, the down-regulation of CTCF during cellular senescence triggers the up-regulation of this ncRNA and SASP-related inflammatory gene expression. In this study, we show that pericentromeric ncRNA provokes chromosomal alteration by inhibiting CTCF, leading to a SASP-like inflammatory response in a cell-autonomous and non-cell-autonomous manner and thus may contribute to the risk of tumorigenesis during aging.

9.
Graefes Arch Clin Exp Ophthalmol ; 259(11): 3351-3357, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34379184

RESUMO

PURPOSE: To determine the relationship between fluoroquinolone susceptibility of gram-positive cocci (GPC) isolated from patients with bacterial keratitis and the age of the patients or the date of onset. METHODS: Bacterial isolates were obtained from corneal lesions of patients with infectious keratitis treated between January 2008 and December 2016. The fluoroquinolone susceptibility of GPC was assessed, and a retrospective review of microbiological records was performed. Fluoroquinolone susceptibility was measured through broth microdilution in accordance with protocols of the Clinical and Laboratory Standards Institute. Statistical analysis was performed using a generalized estimating equation and cubic spline to determine the association between fluoroquinolone susceptibility of GPC isolated from corneal lesions and patient age. RESULTS: Of the 1200 bacterial isolates, 471 GPC were identified. They included Staphylococcus epidermidis (45.6%), other coagulase-negative Staphylococcus sp. (17.8%), and Staphylococcus aureus (18.3%). Levofloxacin susceptibility of GPC exhibited a negative relationship with age and had an odds ratio of 0.893 (95% confidence interval, 0.825-0.967) for every 10 years of age. A non-adjusted cubic spline curve was well correlated with year-adjusted data in a generalized additive model, and the levofloxacin susceptibility of GPC was initially stable but gradually declined after 40 years of age, before re-stabilizing again after 70 years of age. CONCLUSION: The fluoroquinolone susceptibility of GPC isolated from corneal lesions of infectious keratitis is high in children under 15 years of age and declines with an increase in age of patients using a generalized estimating equation and cubic spline.


Assuntos
Infecções Oculares Bacterianas , Cocos Gram-Positivos , Ceratite , Fatores Etários , Idoso , Antibacterianos/farmacologia , Criança , Infecções Oculares Bacterianas/diagnóstico , Infecções Oculares Bacterianas/tratamento farmacológico , Infecções Oculares Bacterianas/epidemiologia , Fluoroquinolonas/farmacologia , Humanos , Ceratite/diagnóstico , Ceratite/tratamento farmacológico , Ceratite/epidemiologia , Testes de Sensibilidade Microbiana , Estudos Retrospectivos
10.
FEBS Lett ; 595(19): 2522-2532, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34418081

RESUMO

Azurocidin (AZU1) is an antimicrobial protein secreted by neutrophils that acts as a chemoattractant for monocytes and macrophages and a permeabilizer of vascular endothelial cells. We previously identified AZU1 to be specifically present in extracellular vesicles (EVs) obtained from renal cell carcinoma (RCC) tissues. Here, we examined the relationship between N-linked glycosylation and AZU1 loading into small EVs (SEVs). Inhibition of N-linked glycosylation by introducing mutations in three glycosylation sites inhibited AZU1 loading into SEVs. Furthermore, SEVs released from AZU1-wild-type cells increased the Ca2+ concentration in endothelial cells and the endothelial permeability, whereas SEVs released from AZU1-mutant cells had no significant effect. Anti-AZU1 antibodies diminished the effect of SEVs on endothelial cell sheets. Collectively, we found that N-linked glycosylation of AZU1 directs its loading into SEVs, thereby enabling AZU1-positive SEVs to function as potent permeabilizers of endothelial cells and leading to enhanced transendothelial migration of RCC cells.


Assuntos
Peptídeos Catiônicos Antimicrobianos/metabolismo , Proteínas Sanguíneas/metabolismo , Carcinoma de Células Renais/patologia , Vesículas Extracelulares/metabolismo , Neoplasias Renais/patologia , Linhagem Celular Tumoral , Glicosilação , Humanos , Invasividade Neoplásica , Transporte Proteico
11.
Artigo em Inglês | MEDLINE | ID: mdl-34297034

RESUMO

OBJECTIVES: We aimed to identify disease-specific surface proteins on extracellular vesicles (EVs) as novel serum biomarkers of polymyositis and dermatomyositis (PM/DM). METHODS: We performed liquid chromatography-tandem mass spectrometry (LC/MS) on purified EVs from sera of 10 PM/DM, 23 patients with other autoimmune diseases and 10 healthy controls (HC). We identified membrane proteins preferentially present in EVs of PM/DM patients by bioinformatics and biostatistical analyses. We developed EV sandwich ELISA for directly detecting serum EVs expressing disease-specific membrane proteins and evaluated their clinical utility using sera of 54 PM/DM, 24 rheumatoid arthritis (RA), 20 systemic lupus erythematosus (SLE), 13 systemic sclerosis, 25 Duchenne and Becker muscular dystrophy (DMD/BMD) patients, and 36 HC. RESULTS: LC/MS analysis identified 1,220 proteins in serum EVs. Of these, Plexin D1 was enriched in those from PM/DM patients relative to HC or patients without PM/DM. Using a specific EV sandwich ELISA, we found that levels of Plexin D1-positive EVs (Plexin D1+ EVs) in serum were significantly greater in PM/DM patients than in HC, RA or SLE, or DMD/BMD patients. Serum levels of Plexin D1+ EVs were greater in those PM/DM patients with muscle pain or weakness. Serum levels of Plexin D1+ EVs were significantly correlated with levels of aldolase (rs=0.481), white blood cells (rs=0.381), neutrophils (rs=0.450), and platelets (rs=0.408) in PM/DM patients. Finally, serum levels of Plexin D1+ EVs decreased significantly in patients with PM/DM in clinical remission after treatment. CONCLUSION: We have identified levels of circulating Plexin D1+ EVs as a novel serum biomarker for PM/DM.

12.
Eur J Surg Oncol ; 2021 Jul 22.
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.

13.
Rep Pract Oncol Radiother ; 26(3): 495-501, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34277107

RESUMO

Background: 3-dimensional intra-cone beam computed tomography (intra-CBCT ) could be a potentially powerful tool for use with arc irradiation such as volumetric modulated arc therapy. The aim of the study was to evaluate the image quality of intra-cone beam computed tomography (intra-CBCT ) for arc irradiation with various imaging condition. Materials and methods: Two types of intra-CBCT imaging techniques were evaluated - intra-fractional CBCT with flattening filtered (FF) beam (intra-FF CBCT ) and that with flattening filter free (FFF) beam (intra-FFF CBCT ). For the intra-MV beams, four different field sizes (2 cm × 2 cm, 5 cm × 5 cm, 10 cm × 10 cm, and 20 cm × 20 cm) were used with dose rates of 500 MU/min and 1600 MU/min, for 6 MV FF and 6 MV FFF, respectively. For all image acquisitions, two rotation angles (full-arc and half-arc) were investigated. Thereafter, the linearity, contrast-to-noise ratio (CNR), and uniformity index (UI) of intra-CBCT image were compared with those of conventional CBCT image. Results: All acquisition conditions had good linearity of the CT value (R2 > 0.99). For CNR, the change rates from conventional CBCT ranged from 0.6-33.7% for a 2 cm × 2 cm beam, whereas that for a 20 cm × 20 cm beam ranged from 62.7-82.3%. Similarly, the UI increased from 1.5% to 7.0% as the field size increased. Conclusion: Quality of intra-CBCT image was affected by the field size and acquisition angle. Image quality of intra-CBCT was worse than that of conventional CBCT, but it was better under a smaller field and wider correction angle and would be acceptable for clinical use.

14.
Cancer Chemother Pharmacol ; 88(3): 513-524, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34114067

RESUMO

BACKGROUND: Osteosarcoma (OS) is a malignant bone tumor primarily affecting children and adolescents. The prognosis of chemotherapy-refractory OS patients is poor. We developed a tumor suppressor p53-expressing oncolytic adenovirus (OBP-702) that exhibits antitumor effects against human OS cells. Here, we demonstrate the chemosensitizing effect of OBP-702 in human OS cells. MATERIALS AND METHODS: The in vitro and in vivo antitumor activities of doxorubicin (DOX) and OBP-702 were assessed using parental and DOX-resistant OS cells (U2OS, MNNG/HOS) and a DOX-resistant MNNG/HOS xenograft tumor model. RESULTS: DOX-resistant OS cells exhibited high multidrug resistant 1 (MDR1) expression, which was suppressed by OBP-702 or MDR1 siRNA, resulting in enhanced DOX-induced apoptosis. Compared to monotherapy, OBP-702 and DOX combination therapy significantly suppressed tumor growth in the DOX-resistant MNNG/HOS xenograft tumor model. CONCLUSION: Our results suggest that MDR1 is an attractive therapeutic target for chemoresistant OS. Tumor-specific virotherapy is thus a promising strategy for reversing chemoresistance in OS patients via suppression of MDR1 expression.


Assuntos
Neoplasias Ósseas/tratamento farmacológico , Doxorrubicina/farmacologia , Terapia Viral Oncolítica/métodos , Osteossarcoma/tratamento farmacológico , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Animais , Antibióticos Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Osteossarcoma/genética , Osteossarcoma/patologia , Proteína Supressora de Tumor p53/genética , Ensaios Antitumorais Modelo de Xenoenxerto
15.
Eur J Surg Oncol ; 47(11): 2880-2887, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34103245

RESUMO

BACKGROUND: High preoperative carcinoembryonic antigen (CEA) is a well-known risk factor for stage II-III colorectal cancer (CRC); however, in most cases, cancer does not recur. Conversely, postoperative CEA (post-CEA) is occasionally measured, and high post-CEA patients often develop recurrence; however, the clinical significance of post-CEA testing is unknown. The purpose of this study was to determine whether post-CEA elevation might indicate a poor prognosis for stage II-III CRC patients who underwent curative surgery. PATIENTS AND METHODS: 482 patients with pathological stage II-III CRC were included. Univariate and multivariate analyses were performed to evaluate post-CEA levels. RESULTS: Multivariate analysis showed that elevated post-CEA (hazard ratio (HR): 3.14, P < 0.001), pathological lymph node metastasis (pN+), and pathological T4 (pT4) are associated with poor recurrence-free survival (RFS), and that elevated post-CEA (HR: 3.12; P = 0.002), pN+, pT4, age >70, and smoking are independently associated with poor overall survival. Subgroup analysis among stage III patients, in combination with the risk classification of the International Duration Evaluation of Adjuvant Chemotherapy (IDEA) study, showed that elevated post-CEA is a significant indicator of poor prognosis for RFS in both low-risk (73.8% vs. 21.2%, P < 0.001) and high-risk (49.9% vs. 25.0%, P = 0.04) groups. CONCLUSIONS: Post-surgical CEA elevation is independently associated with poor prognosis in stage II-III CRC. Adding post-CEA levels to the IDEA risk classification may provide a more reliable indicator of the need for individualized surveillance and adjuvant chemotherapeutic strategies.

16.
Am J Ophthalmol Case Rep ; 22: 101088, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33937582

RESUMO

Purpose: The aim of this report was to describe a case of cataract surgery and Descemet stripping automated endothelial keratoplasty (DSAEK) after cytomegalovirus (CMV) corneal endotheliitis and bullous keratopathy (BK) following immunosuppressive treatment for Mooren's ulcer. Observations: A 64-year-old man was referred to our hospital because of peripheral ulcerative keratitis in his left eye. He had a history of trabeculectomy for open angle glaucoma in his left eye. He was diagnosed with Mooren's ulcer and treated with topical betamethasone and tacrolimus with systemic cyclosporine. The corneal ulcer improved, but the peripheral cornea thinned from 6 to 12 and 0-2 o'clock. Five months later, cells were observed in the left anterior chamber, and real-time polymerase chain reaction examination of the aqueous humor showed CMV-DNA-positive results. The patient was diagnosed with CMV corneal endotheliitis, and oral ganciclovir was administered. Fifteen months after the initial presentation, BK appeared with decreased vision to 20 cm/n. d. After confirmation of negative CMV-DNA in the aqueous humor, DSAEK was performed following cataract surgery. The postoperative visual acuity recovered to 0.3. Mooren's ulcer exacerbation and CMV corneal endotheliitis did not recur postoperatively. Conclusions and Importance: This is the first report of a case in which a patient with Mooren's ulcer developed BK due to CMV corneal endotheliitis and required DSAEK. Cataract surgery and DSAEK could be performed without issue by creating the main wound and side ports in a manner that avoids the thinned parts of the cornea.

17.
Cell Host Microbe ; 29(6): 941-958.e10, 2021 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-33989515

RESUMO

Infection with CagA-producing Helicobacter pylori plays a causative role in the development of gastric cancer. Upon delivery into gastric epithelial cells, CagA deregulates prooncogenic phosphatase SHP2 while inhibiting polarity-regulating kinase PAR1b through complex formation. Here, we show that CagA/PAR1b interaction subverts nuclear translocation of BRCA1 by inhibiting PAR1b-mediated BRCA1 phosphorylation. It hereby induces BRCAness that promotes DNA double-strand breaks (DSBs) while disabling error-free homologous recombination-mediated DNA repair. The CagA/PAR1b interaction also stimulates Hippo signaling that circumvents apoptosis of DNA-damaged cells, giving cells time to repair DSBs through error-prone mechanisms. The DSB-activated p53-p21Cip1 axis inhibits proliferation of CagA-delivered cells, but the inhibition can be overcome by p53 inactivation. Indeed, sequential pulses of CagA in TP53-mutant cells drove somatic mutation with BRCAness-associated genetic signatures. Expansion of CagA-delivered cells with BRCAness-mediated genome instability, from which CagA-independent cancer-predisposing cells arise, provides a plausible "hit-and-run mechanism" of H. pylori CagA for gastric carcinogenesis.


Assuntos
Antígenos de Bactérias/metabolismo , Proteína BRCA1/metabolismo , Proteínas de Bactérias/metabolismo , Células Epiteliais/metabolismo , Instabilidade Genômica , Infecções por Helicobacter/microbiologia , Helicobacter pylori/metabolismo , Neoplasias Gástricas/microbiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Carcinogênese/metabolismo , Linhagem Celular , Quebras de DNA de Cadeia Dupla , Células Epiteliais/microbiologia , Feminino , Regulação Neoplásica da Expressão Gênica , Helicobacter pylori/patogenicidade , Interações Hospedeiro-Patógeno , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Pessoa de Meia-Idade , Fosforilação , Proteína Tirosina Fosfatase não Receptora Tipo 11/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais , Estômago/microbiologia , Proteína Supressora de Tumor p53/metabolismo
18.
Cancers (Basel) ; 13(8)2021 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-33920416

RESUMO

The lack of noninvasive biomarkers that can be used for tumor monitoring is a major problem for soft-tissue sarcomas. Here we describe a sensitive analytical technique for tumor monitoring by detecting circulating extracellular vesicles (EVs) of patients with synovial sarcoma (SS). The proteomic analysis of purified EVs from SYO-1, HS-SY-II, and YaFuSS identified 199 common proteins. DAVID GO analysis identified monocarboxylate transporter 1 (MCT1) as a surface marker of SS-derived EVs, which was also highly expressed in SS patient-derived EVs compared with healthy individuals. MCT1+CD9+ EVs were also detected from SS-bearing mice and their expression levels were significantly correlated with tumor volume (p = 0.003). Furthermore, serum levels of MCT1+CD9+ EVs reflected tumor burden in SS patients. Immunohistochemistry revealed that MCT1 was positive in 96.7% of SS specimens and its expression on the cytoplasm/plasma membrane was significantly associated with worse overall survival (p = 0.002). Silencing of MCT1 reduced the cellular viability, and migration and invasion capability of SS cells. This work describes a new liquid biopsy technique to sensitively monitor SS using circulating MCT1+CD9+ EVs and indicates the therapeutic potential of MCT1 in SS.

19.
Graefes Arch Clin Exp Ophthalmol ; 259(8): 2309-2316, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33929590

RESUMO

PURPOSE: To investigate how the central visual field would be changed after fornix-based trabeculectomy with mitomycin C in Japanese normal-tension glaucoma (NTG) patients monitored for more than 10 years including before surgery. METHODS: This is a retrospective cohort study. We identified twenty-eight eyes of 28 NTG cases regularly monitored for more than 5 years and examined static visual field (VF) tests for more than five times before and after fornix-based trabeculectomy (including combined surgery). Based on preoperative data for 6.3 years, we evaluated postoperative changes for 6.0 years in 10-2 VF and 30-2 VF. RESULTS: Six patients were male and 22 females, the mean age was 57.9 years, and the mean deviation was - 13.7 decibels. After surgery, mean IOP decreased from 13.9 to 9.0 mmHg (P ≤ 0.01), and medication score also did. The rate of 10-2 VF deterioration was significantly suppressed from - 1.0 dB/year preoperatively to - 0.4 dB/year postoperatively (P ≤ 0.01). And when 30-2 VF was divided into six relevant sectors, the rate of deterioration at cecocentral and arcuate areas of the superior hemifield was suppressed postoperatively (P ≤ 0.01 and P = 0.042, respectively). CONCLUSION: Based on long-term preoperative data, a significant positive change in 10-2 VF was observed after fornix-based trabeculectomy with mitomycin C in Japanese NTG patients with a mean IOP of 13.9 mmHg. Central vision could be expected to be maintained for NTG patients even if its preoperative IOP is low after successful trabeculectomy.


Assuntos
Glaucoma de Baixa Tensão , Trabeculectomia , Feminino , Humanos , Pressão Intraocular , Japão/epidemiologia , Glaucoma de Baixa Tensão/cirurgia , Masculino , Pessoa de Meia-Idade , Mitomicina , Estudos Retrospectivos , Esclera , Campos Visuais
20.
PLoS One ; 16(4): e0249526, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33831057

RESUMO

Extracellular vesicles (EVs) in body fluids constitute heterogenous populations, which mirror their diverse parental cells as well as distinct EV-generation pathways. Various methodologies have been proposed to differentiate EVs in order to deepen the current understanding of EV biology. Equilibrium density-gradient centrifugation has often been used to separate EVs based on their buoyant densities; however, the standard conditions used for the method do not necessarily allow all EVs to move to their equilibrium density positions, which complicates the categorization of EVs. Here, by prolonging ultracentrifugation time to 96 h and fractionating EVs both by floating up or spinning down directions, we allowed 111 EV-associated protein markers from the whole saliva of three healthy volunteers to attain equilibrium. Interestingly, the determined buoyant densities of the markers drifted in a specimen-specific manner, and drift patterns differentiated EVs into at least two subclasses. One class carried classical exosomal markers, such as CD63 and CD81, and the other was characterized by the molecules involved in membrane remodeling or vesicle trafficking. Distinct patterns of density drift may represent the differences in generation pathways of EVs.


Assuntos
Biomarcadores/metabolismo , Centrifugação com Gradiente de Concentração/métodos , Vesículas Extracelulares/metabolismo , Saliva/metabolismo , Adulto , Humanos
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