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Lee JR  Chung WC  Kim JD  Lee KM  Paik CN  Jung SH  Jung JH  Lee YK  Han SW 《Gut and liver》2011,5(2):149-153

Background/Aims

Gastric epithelial dysplasia is considered a precancerous lesion with a variable clinical course. There is disagreement, however, regarding histology-based diagnoses, which has led to confusion in choosing a therapeutic plan. New objective markers are needed to determine which lesions progress to true malignancy. We measured LINE-1 methylation levels, which have been reported to strongly correlate with the global methylation level in gastric epithelial dysplasia and intramucosal cancer.

Methods

A total of 145 tissue samples were analyzed by two histopathologists. All tissues were excised by therapeutic endoscopic mucosal resection and paired with adjacent normal tissue samples. A modified long interspersed nucleotide elements-combined bisulfite restriction analysis (COBRA-LINE-1) method was used.

Results

Gastric epithelial dysplasia and intramucosal cancer tissues had significantly lower levels of LINE-1 methylation than adjacent normal gastric tissues. High-grade dysplasia and intramucosal cancer were distinguishable from low-grade dysplasia based on LINE-1 methylation levels. Furthermore, the distinction could be determined with high sensitivity and specificity, as shown by the receiver operating characteristic (ROC) curve (AUC, 0.82; 95% confidence interval, 0.74 to 0.88).

Conclusions

LINE-1 methylation levels may provide a diagnostic tool for identifying high-grade dysplasia and intramucosal cancer.  相似文献   

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Background

Animal models of bronchopulmonary dysplasia (BPD) are mainly created by hyperoxia exposure. However, these models do not fully recapitulate BPD pathophysiology as observed in clinical practice. To find a better BPD model, we established a rat 50/10 oxygen-induced retinopathy (OIR) model and analyzed the pathologic features of the lungs.

Methods

The rat OIR model was established by exposing newborn rats (P0) to 50% and 10% oxygen (hyperoxia and hypoxia) on alternating days for 14 days. Lungs were harvested immediately on postnatal day 14 (P14) and on P18 after 4 days of normoxia exposure for hematoxylin and eosin staining, antialpha smooth muscle actin (α-SMA) immunohistochemistry and Picrosirius red staining of collagen. Retinas were obtained to confirm successful model establishment by isolectin B4 staining of retinal vasculature.

Results

OIR rats presented with fewer and enlarged alveoli, and the septal walls were thicker than those in age-matched controls. α-SMA immunohistochemistry indicated increased abundance of myofibroblasts in OIR rats. At P18, α-SMA-positive myofibroblasts were present at extremely low levels from the alveolar walls of control rats, while OIR rats showed myofibroblast persistence. The amount of collagen in OIR rats was also higher than that in control rats at both P14 and P18 as evidenced by Picrosirius red staining.

Conclusions

Alveolar changes observed by hematoxylin and eosin staining, prolonged and stronger α-SMA expression and augmented collagen accumulation resemble the histopathology of BPD, suggesting that the rat 50/10 OIR model is suitable for use in BPD research.  相似文献   

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Background

Although nontuberculous mycobacteria (NTM) lung diseases can occur in association with lung cancer, no study has evaluated the effect of lung cancer treatment on NTM lung diseases. Therefore, the present study aimed to retrospectively examine the effect of lung cancer treatment on NTM lung diseases.

Methods

Patients diagnosed with NTM lung diseases in combination with cytologically or histologically proven lung cancer between January 1, 2010 and October 31, 2014 were enroled. The clinical history of eligible patients was retrospectively reviewed.

Results

Seven hundred twenty-eight patients were diagnosed with NTM lung diseases. Among these patients, 29 (3.9%) also had lung cancer. Of the 29 patients with NTM and lung cancer, 62% had Mycobacterium avium complex as the pathogenic organism. The most common lung cancer histology was adenocarcinoma (62.1%). Anti-cancer cytotoxic chemotherapy was administered to seven patients, and the two patients who did not receive NTM treatment showed worsening of their NTM lung disease.

Conclusion

Whether NTM lung disease should be treated during anti-cancer chemotherapy has not been not clarified by this study. Induction of anti-NTM therapy should be made after careful consideration, because the duration of anti-NTM treatment is long and anti-mycobacterial drugs have extensive effects on anti-cancer drugs. However, we think that anti-NTM therapy should be introduced after consideration of the worsening of symptoms and radiological findings associated with NTM lung disease.  相似文献   

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Background

Gastric emptying (GE) of solids is delayed and autonomic dysfunction is detected in autoimmune gastritis (AIG). The goals of this study were to: (1) compare serum levels of ghrelin and motilin in subjects with delayed and normal GE and (2) investigate whether circulating antimyenteric antibodies (CAA), serum ghrelin levels and motilin levels have any effect on autonomic function.

Materials and Methods

Noninvasive cardiovascular reflex tests were used in order to evaluate the autonomic function. GE was evaluated by a standard 2-hour scintigraphic test. Serum ghrelin and motilin levels were tested by enzyme-linked immunosorbent assay and CAA were tested by immunofluorescence.

Results

The serum ghrelin and motilin levels in the patients with delayed GE (n = 22) were significantly decreased compared to the normal GE patients (n = 19), (67.55 ± 8.81 versus 126.79 ± 25.81 pg/mL, P < 0.001 and 279.59 ± 111.12 versus 500.42 ± 155.95 pg/mL, respectively, P < 0.001). Whereas, the serum ghrelin and motilin levels in the patients with deranged autonomic function (n = 26) were significantly decreased compared to the patients with normal autonomic function (n = 15), (80.73 ± 28.46 versus 127.79 ± 28.06 pg/mL, P < 0.001 and 316.92 ± 160.47 versus 490.20 ± 141.02 pg/mL, P < 0.001, respectively).  None of the patients were positive for CAA.

Conclusions

Ghrelin and motilin levels in AIG subjects with delayed GE and deranged autonomic function were significantly decreased. The decrease in serum ghrelin and plasma motilin levels in AIG suggest their potential role in the delayed GE observed in these subjects.  相似文献   

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Background

Idiopathic pulmonary fibrosis (IPF) is a disease with a worse prognosis than some types of cancer. In patients with IPF, lung cancer is critical because of the associated high mortality rate from its progression and fatal complications from anticancer treatments. Therefore, preventing lung cancer in patients with IPF is primordial. Pirfenidone is an anti-fibrotic agent that reduces the decline in forced vital capacity. This study aimed to assess the effect of pirfenidone in the development of lung cancer in patients with IPF.

Methods

Data from 261 patients with IPF with and without pirfenidone were retrospectively reviewed, and the incidence of lung cancer was analyzed.

Results

In the pirfenidone group, the incidence of lung cancer was significantly lower than in the non-pirfenidone group (2.4% vs. 22.0%, P < 0.0001). Multivariate Cox proportional hazards regression analysis demonstrated that pirfenidone decreased the risk of lung cancer (hazard ratio, 0.11; 95% confidence interval, 0.03 to 0.46; P = 0.003), whereas coexisting emphysema increased the incidence of lung cancer (hazard ratio, 3.22; 95% confidence interval, 1.35 to 7.70; P = 0.009).

Conclusions

Pirfenidone might correlate with a decreased risk of lung cancer in patients with IPF. However, no definite conclusion can be drawn from this retrospective study, and a multicenter, prospective cohort study is still warranted to confirm the effect of pirfenidone on lung cancer in patients with IPF.  相似文献   

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Background

Successful treatment of leukemia requires new medications to combat drug resistance, but the development of novel therapies is an arduous and risky endeavor. Repurposing currently approved drugs or those already in clinical development to treat other indications is a more practical approach. Moreover, combinatorial therapeutics are often more efficacious than single agent therapeutics because the former can simultaneously target multiple pathways that mitigate tumor aggressiveness and induce cancer cell death.

Material and Methods

In this study, we combined the class III antiarrhythmic agent amiodarone and the BH3 mimetic ABT-263 based on data from a prior drug screen to assess the degree of apoptotic induction in 2 human leukemia cell lines.

Results

The combination yielded statistically significant increases in apoptosis in both cell lines by downregulating AKT activity and increasing cleaved caspase-3.

Conclusions

Overall, our findings suggest that combining K+ channel blockers with prosurvival Bcl-2 family inhibitors is a promising therapeutic approach in treating leukemia.  相似文献   

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Background

Residents in the district struck by the Great East Japan Earthquake Tsunami (GEJET) suffered from adverse living conditions and various pulmonary diseases.

Objectives

To evaluate the influence of GEJET, we performed serial assessment of pulmonary function of approximately 10,000 residents in the district struck by GEJET.

Methods

Using a spirometer, we assessed the pulmonary function of approximately 10,000 residents older than 18 years in the Sanriku seacoast, which was struck by the tsunami. Measurements were performed in 2011 and 2012.

Results

We compared FVC (forced vital capacity) % pred. and FEV1 (forced expiratory volume in 1 second) % pred. of subjects between 2011 and 2012, by serial spirometry. Of the 7053 subjects studied, including 2611 men and 4442 women, FVC% pred. and FEV1% pred. were significantly higher in 2012 than in 2011. Physical indices including height, body weight and the body mass index (BMI) did not change significantly during this period. Smoking prevalence changed significantly between 2010, 2011, and 2012. Both FVC% pred. and FEV1% pred. of subjects who had quit smoking increased significantly on spirometry carried out in 2012, compared with those in 2011.

Conclusions

The pulmonary function expressed as FVC% pred. and FEV1% pred. were significantly higher in 2012 than in 2011 among the subjects studied. The changes in the smoking status may be one of the reasons for the increase in values observed. However, other undetermined factors during recovery from a disaster might have resulted in improved pulmonary function.  相似文献   

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Background

In current guidelines, the role of immune checkpoint inhibitors is not yet determined in the treatment strategy for NSCLC harboring ALK translocations.

Case

A 51-year-old woman with lung adenocarcinoma harboring ALK translocation was treated with alectinib until PD. After the second (CDDP/PEM) and third (crizotinib) line treatment, a second biopsy was performed, revealing PD-L1 tumor proportion score of 70–80% and G1202R mutation of ALK. Pembrolizumab was selected for the fourth line, leading to PR for more than 6 months.

Conclusions

While alectinib might induce resistance to ALK-TKI, it could increase PD-L1 positive cells to become sensitive to PD-1/PD-L1 inhibitors.  相似文献   

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Background

Membranoproliferative glomerulonephritis (MPGN) is an uncommon form of glomerulonephritis and it can be particularly difficult to predict outcomes and manage women with this disorder during pregnancy.

Materials and Methods

The management of 3 successful pregnancies in women with MPGN from 1 center and previously described cases from the world literature are reviewed. This includes a number of large studies of pregnancy in women with underlying glomerular disease as well as small case series and individual reports. Courses of these pregnancies, maternal and fetal outcomes, and management, when described, were included in this review.

Results

Some successful outcomes used antiplatelet therapy and plasmapheresis, but high-dose intravenous, followed by oral, corticosteroid therapy was used most frequently in patients with successful outcomes.

Conclusions

The data provided is meant as a guide for clinicians who provide care for women with MPGN who are considering pregnancy or women who present with this disorder while pregnant.  相似文献   

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Background

Alpinetin is a flavonoid isolated from Alpinia katsumadai Hayata that has demonstrated anti-inflammatory, antibacterial and anti-tumor activities. However, alpinetin has not been widely studied in amelioration of inflammatory bowel disease. The study aimed to investigate the role of alpinetin on intestinal epithelial tight junctions, oxidative stress and Nrf2/HO-1 signaling pathway in dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice.

Methods

A total of 40 mice were divided into 5 groups (n = 8/group): control group, DSS group (received 3% DSS), and low, medium and high-dose treatment groups (3% DSS + alpinetin 25, 50 and 100 mg/kg). The disease activity index (DAI), histological scores, epithelial tight junctions, oxidative stress factors, and Nrf2/HO-1 signaling pathway in the colon were determined.

Results

Alpinetin improved DAI, colonic shortening, histological scores and myeloperoxidase activity compared with the DSS group. The expression of occludin and zonula occludens-1 were upregulated by alpinetin, whereas the expression of claudin-2 was reduced. Moreover, alpinetin inhibited the level of malondialdehyde, and increased the level of superoxide dismutase. Nrf2/HO-1 signaling pathways were also found to be activated.

Conclusion

Alpinetin is associated with decreased intestinal inflammation and oxidative stress dose-dependently, and also regulated the expression of tight junctions between cells in UC mice. The findings of our study may shed light on the use of alpinetin in the treatment of UC.  相似文献   

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Background

This study aimed to investigate the expression levels and relationship of bone morphogenetic proteins (BMPs) signaling molecules and microRNA-140 (miR-140) in human osteoarthritis (OA) chondrocytes.

Materials and Methods

Different stage chondrocytes (normal cartilage, mid-stage OA and advanced-stage OA) were isolated from cartilage samples according to Kellgren and Lawrence criteria. The effect of miR-140 on BMPs signaling was evaluated by transfecting miR-140 mimic or inhibitor into chondrocytes. The expression of responsive genes was measured using real-time polymerase chain reaction and Western blotting analysis.

Results

There was a significant reduction in miR-140 and SOX9 expression in OA groups compared to the normal group, and there was a further reduction in the severe OA group compared to the moderate OA group. Compared with the normal group, the expression of ALK1, SMAD1, COL10A1 and MMP3 was higher in the OA groups, whereas the expression of COL2A1 was lower in the OA groups. In the moderate OA group, transfection with miR-140 mimic increased SMAD1, SOX9 and COL2A1 expression, but decreased COL10A1 expression. However, there was an opposite effect after transfecting miR-140 inhibitor with decreased SMAD1, SOX9 and COL2A1 expression, and increased COL10A1 expression. Interestingly, the biological effect of transfecting miR-140 mimic or inhibitor was similar in the severe OA group. SMAD1 and COL2A1 protein production followed the same pattern as their expression profile.

Conclusions

miR-140 suppresses chondrocytes hypertrophy by controlling the BMPs signaling pathway, which highlights the importance of miR-140 in the maintenance of chondrocyte homeostasis and opens up novel avenues in OA therapeutic strategies.  相似文献   

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Background

Bronchoscopy is important to diagnose lung cancer. However, some patients who undergo bronchoscopic procedures develop respiratory tract infections. Little is known about the proportion of pathogen-positive results in bacterial cultures from diagnostic bronchoscopy samples in patients with suspected lung cancer. This study aimed to determine the rate of positive bacterial cultures after diagnostic bronchoscopy in patients with suspected lung cancer and the relationship among culture results, clinical characteristics, and respiratory tract infections.

Methods

We retrospectively reviewed the medical records of all immunocompetent patients who underwent bronchoscopy and had culture and histological samples for the diagnosis of peripheral pulmonary lesions from September 2012 to August 2014 at the National Cancer Center in Tokyo. We analyzed data and classified radiological lesions into the following categories: calcifications, cavitations, low-density areas, margin irregularities, and satellite nodules.

Results

The study population consisted of 328 patients (median age, 69 years). We found that 65.9% of patients had malignant lesions and 4.2% of patients had positive cultures for pathogenic bacteria. The number of calcifications (p = 0.002, 95% CI: 2.17–41.10) was significantly higher in patients with positive bacterial isolates, according to the multivariate analysis, and bacterial culture positivity was not associated with the development of respiratory complications after bronchoscopy. Of the three patients with respiratory complications, all presented with cavitations.

Conclusion

Because of the low prevalence of positive bacterial cultures in patients with suspected lung cancer, bacterial culture may be limited to specific patients, such as those with calcifications. Lesions with cavitation warrant close monitoring.  相似文献   

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Objective

Hepatic fibrosis is characterized by the activation of hepatic stellate cells (HSCs). Focal adhesion kinase (FAK)-phosphatidylinositol 3-kinase (PI3K) signals participate in the activation of HSCs. We evaluated the effect of FAK-related nonkinase (FRNK) on the adhesion and migration of HSCs.

Materials and Methods

Hepatic fibrosis was induced in Sprague-Dawley rats by means of bile duct ligation. Livers were harvested at 1, 2, 3 and 4 weeks after the ligation; livers of sham-operated animals were harvested at 4 weeks after ligation. Histopathologic features were evaluated in liver sections stained with hematoxylin-eosin and Sirius Red stain. HSCs were transfected with FRNK plasmid. The adhesion of HSCs was examined with a toluidine blue colorimetric assay. The migration of HSCs was evaluated by the use of an improved Boyden double-chamber method. Protein and messenger RNA levels in the liver and the HSCs were determined by Western blot analysis and real-time polymerase chain reaction, respectively.

Results

Hematoxylin-eosin staining of the liver documented the presence of fibrosis in the rats. Actin and PI3K expression was increased in parallel with the development of hepatic fibrosis. At the same time, activator protein-1 (AP-1) (c-fos, c-jun) mRNA in the livers was increased. Overexpression of FRNK inhibited the adhesion and migration of HSCs time-dependently. Simultaneously, FRNK inhibited PI3K mRNA and protein expression and c-jun mRNA expression.

Conclusions

FRNK inhibited the adhesion and migration of HSCs by decreasing the expressions of the FAK-PI3K-AP-1 signal pathway.  相似文献   

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Background

The management of skin toxicity is crucial for efficient afatinib treatment, but the role of tetracycline class antibiotics (TCs) in managing these rashes is relatively unknown.

Methods

We reviewed the clinical records of patients who were administered afatinib for the treatment of non-small cell lung cancer harboring epidermal growth factor receptor mutations between October 2014 and November 2016. Twenty-five patients, who received TCs for the management of afatinib-related skin disorders, were enrolled.

Results

Minocycline was administered orally to participants. Afatinib-related toxic effects, such as rash, diarrhea, and paronychia, were observed in 92%, 92%, and 40% of cases, respectively. Although 24% of diarrhea and 4% of paronychia cases were rated grade 3 or higher, no severe cases of rash were observed during afatinib treatment. Of the 18 afatinib dose reductions, 14 (78%), three (17%), and one (6%) resulted from diarrhea, paronychia, and stomatitis, respectively; no patients required a dose reduction because of rash. When minocycline treatment started, 21 patients (84%) had a rash of grade 1 or less, and three patients had a grade 2 rash. A response to afatinib was observed in 18 patients (72%) and the median duration of afatinib administration was 501 days. An adverse event related to minocycline (grade 1 nausea) was observed in one patient.

Conclusions

A large proportion of the study patients started minocycline before grade 2 rash development and the severity of afatinib-related rash was lower than that previously reported. Oral TCs may be beneficial, especially if started early.  相似文献   

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Background

Several studies have reported that viral infections are related to lung cancer. We previously reported the involvement of Torque teno virus (TTV) in patients with lung cancer and idiopathic pulmonary fibrosis. However, the role of TTV in lung cancer growth, and its influence on changes in TTV DNA titers due to idiopathic pulmonary fibrosis (IPF) in lung cancer patients are poorly understood.

Methods

Serum TTV DNA titers were measured in serum samples obtained from patients with lung cancer. Forty-eight patients with primary lung cancer, including 8 patients with IPF, were enrolled. Serum TTV DNA titers were quantitated before and after chemotherapy. In addition, patients were classified into two groups according to the presence or absence of IPF, and clinical characteristics were compared between these two groups.

Results

Among the 33 patients with partial response to treatment or stable disease in the lung cancer, the mean TTV DNA titer in 28 patients without IPF had significantly decreased after chemotherapy. In contrast, the mean TTV DNA titer in the 5 patients with IPF tended to increase after chemotherapy. In the 15 patients with progressive lung cancer, TTV DNA titers were significantly elevated in those with and without IPF.

Conclusion

In lung cancer patients without IPF, changes in TTV titers may be correlated with tumor growth. However, in lung cancer patients with IPF, TTV titers were not consistently associated with chemotherapy responses. Therefore, IPF may have an influence on changes in TTV DNA titers.  相似文献   

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Background

It is well known that ultrasound-guided needle-aspiration (USGNA) for intrapulmonary subpleural lesion in contact with the pleura is useful and safe, and its diagnostic yield is high. However, reports concerned with the analyses of cases with intrapulmonary subpleural lesion which could not be diagnosed using USGNA are limited. The objective of this study is to clarify the radiological properties of subpleural primary lung cancer which obstruct diagnosis by USGNA.

Methods

The consecutive cases with subpleural primary lung cancer whose radiological properties could be confirmed by thoracic computed tomography (CT) without contrast enhancement (CE), and examined by USGNA at our hospital between January 1999 and December 2014 have been analyzed. All cases were given pathological diagnoses of primary lung cancer. The diagnostic yield by USGNA was calculated, and the properties of the lesions of the subjects were analyzed by means of thoracic CT without CE images and pathological findings.

Results

87 consecutive cases (41–86 year olds, 75 males, 12 females) were analyzed. The overall diagnostic yield by USGNA was 86.2%. There was no statistically significant difference regarding the diagnostic yield concerning radiological properties such as cavities, small airspaces and low density areas in the lesions and their sizes. However, the diagnostic yield for the cases with squamous cell carcinoma was statistically significantly low (p=0.02).

Conclusion

Although the diagnostic yield of USGNA is not distorted by the radiological properties of lesions, it is statistically significantly low in cases with squamous cell carcinoma.  相似文献   

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