Inhibition of ocular angiogenesis by diced small interfering RNAs (siRNAs) specific to vascular endothelial growth factor (VEGF)

The effects of diced small interfering RNAs (siRNAs) designed for vascular endothelial growth factor (VEGF) on the expression of VEGF in human retinal pigment epithelial cell line ARPE-19 cells in vitro and on corneal angiogenesis in vivo were examined. The exposure to diced siRNAs significantly reduced the VEGF mRNA expression in ARPE-19 cells with minimal toxicity. In suture-induced corneal angiogenesis models, diced siRNAs minimized the severity of angiogenesis. Histological analysis displayed no particular tissue damage in the conjunctiva where siRNA was injected. The approach using diced siRNAs can be a new tool for various neovascular ocular diseases.     

Comparison of oncological outcomes between trisegmentectomy and lobectomy for non-small cell lung cancer in the left upper division

BackgroundThe left upper lobe is one of the largest lobes in the lungs and is divided into two anatomical units: the upper division (segments 1+2 and segment 3) and lingula (segments 4 and 5). This anatomical classification is similar to that used for the right upper and middle lobes. Although bilobectomy is not recommended for right upper or middle lobe tumors close to the interlobar plane, lobectomy is often performed for tumors located close to the intersegmental plane in the left upper division. To aid in establishing trisegmentectomy as a standard treatment for clinical N0 non-small cell lung cancer (NSCLC) in the left upper lobe, we aimed to re-assess its feasibility based on oncological outcomes according to tumor location.MethodsWe retrospectively analyzed the data of patients with clinical N0 NSCLC in the left upper division who underwent left upper lobectomy or trisegmentectomy between April 2006 and December 2020. After propensity score matching, oncological outcomes were compared between the trisegmentectomy and lobectomy groups. To verify whether trisegmentectomy was indicated regardless of tumor distance from the intersegmental plane, we compared the recurrence-free survival (RFS) rates following trisegmentectomy between patients with tumors ≤20 and >20 mm from the intersegmental plane.ResultsAfter propensity score matching, 46 patients were included in each group. There was no significant difference in the 5-year RFS rate between the lobectomy and trisegmentectomy groups (75.5% vs. 84.0%, P=0.41). In the trisegmentectomy cohort, the 5-year RFS rate did not significantly differ according to tumor distance from the intersegmental plane (≤20 or >20 mm) measured using three-dimensional computed tomography (79.4% vs. 81.2%, P=0.69). Multivariate analysis indicated that tumor distance from the intersegmental plane was not a significant predictor of RFS (hazard ratio: 1.75, 95% confidence interval: 0.52–5.91, P=0.37).ConclusionsOur analysis suggests that oncological outcomes (i.e., RFS rates) following trisegmentectomy for clinical N0 NSCLC in the left upper division are not significantly inferior to those following lobectomy, even if the tumor is located close to the intersegmental plane.     

Clinical evaluations of pituitary apoplexy in incidental nonfunctional pituitary adenomas

Pituitary apoplexy is an uncommon syndrome that often results in spontaneous hemorrhage or infarction of pituitary tumors or glands. We previously reported pituitary apoplexy occurred most frequently in nonfunctional pituitary adenomas among all types of pituitary incidentalomas. In the present study, we aimed to investigate the characteristics of pituitary apoplexy in patients with incidental nonfunctional pituitary adenomas. 65 patients with pituitary incidentaloma were enrolled. All patients underwent clinical/endocrinological/pathological investigations. As a result, 33 patients were diagnosed with nonfunctional pituitary adenomas. Of these, 12.1% of patients had pituitary apoplexy. There was no difference in tumor diameter, age, or sex between the apoplexy and the non-apoplexy groups. However, the liver enzymes aspartate transaminase and alanine aminotransferase were significantly higher, and plasma sodium and chloride levels were significantly lower in the apoplexy group than in the non-apoplexy group (each P < .05). In addition, low-density lipoprotein-cholesterol was significantly higher in the apoplexy group than in the non-apoplexy group (P < .05). Besides, thyroid-stimulating hormone, luteinizing hormone, follicle-stimulating hormone, and prolactin deficiencies were significantly more frequent in the apoplexy group than in the non-apoplexy group (each P < .05), and growth hormone and adrenocorticotropic hormone deficiencies were more frequent in the apoplexy group than in the non-apoplexy group (P = .09 and.08, respectively). Furthermore, tumor diameter was not associated with pituitary apoplexy, whereas thyroid-stimulating hormone, luteinizing hormone, and follicle-stimulating hormone deficiencies were significantly associated with the apoplexy group (each P < .05). Hence, the present study indicated that pituitary apoplexy could not be related to tumor diameter. Moreover, hormonal deficiencies, hepatic dysfunction, hyponatremia or hypochloremia, and dyslipidemia might be indicators of pituitary apoplexy. There could be the possibility the treatment for dyslipidemia prevents pituitary apoplexy.     

Muscle Biopsy-proven Drug-induced Microscopic Polyangiitis in a Patient with Tuberculosis

We herein report a case of muscle biopsy-proven microscopic polyangiitis (MPA) in a patient with tuberculosis. The patient had developed a persistent fever after the initiation of treatment for tuberculosis and was positive for myeloperoxidase-antineutrophil cytoplasmic antibody (ANCA). However, because conventional symptoms were lacking, determination of the biopsy site was difficult. Based on the findings of a biopsy of the biceps femoris, which confirmed small vessel vasculitis, the patient was diagnosed with MPA. The fever was alleviated by glucocorticoids. Tuberculosis and antituberculosis drugs can cause ANCA-associated vasculitis (AAV). A muscle biopsy is useful for the diagnosis of AAV.     

Factors that affect early postoperative health-related quality of life in patients with gastrointestinal cancer: a three-center cohort study

[Purpose] In this study, we investigated the preoperative and early postoperative health-related quality of life in patients who underwent surgical treatment for gastrointestinal cancer and also the factors that affect postoperative health-related quality of life. [Participants and Methods] The study included 198 patients who underwent elective surgery for gastrointestinal cancer (129 males and 69 females, age: 65.4 ± 11.8 years). Health-related quality of life was evaluated using the Short-Form 36-Item Health Survey version 2 at the following time points: 1–2 days preoperatively (baseline) and 4 weeks postoperatively. [Results] Compared with baseline levels, physical functioning, bodily pain, vitality, as well as physical, social, and emotional role functioning significantly decreased 4 weeks postoperatively. In contrast, compared with baseline levels, mental health significantly improved 4 weeks postoperatively. Physical functioning and general health evaluated 4 weeks postoperatively were significantly associated with income, baseline health-related quality of life, and the 6-minute walk test. [Conclusion] It is important to consider baseline income and health-related quality of life and increase postoperative exercise capacity to improve health-related quality of life in patients who undergo surgical treatment for gastrointestinal cancer.     

TP53 variants in p53 signatures and the clonality of STICs in RRSO samples

ObjectivePrecursor lesions may be identified in fallopian tube tissue after risk-reducing salpingo-oophorectomy (RRSO) in patients with pathogenic variants of BRCA1/2. Serous tubal intraepithelial carcinoma (STIC) is considered a precursor of high-grade serous carcinoma, whereas the significance of the p53 signature remains unclear. In this study, we investigated the relationship between the p53 signature and the risk of ovarian cancer.MethodsWe analyzed the clinicopathological findings and conducted DNA sequencing for TP53 variants of p53 signatures and STIC lesions isolated using laser capture microdissection in 13 patients with pathogenic variants of BRCA1/2 who underwent RRSO and 17 control patients with the benign gynecologic disease.Results TP53 pathogenic variants were detected significantly higher in RRSO group than control (p<0.001). No difference in the frequency of p53 signatures were observed between groups (53.8% vs 29.4%; p=0.17). TP53 sequencing and next-generation sequencing analysis in a patient with STIC and occult cancer revealed 2 TP53 mutations causing different p53 staining for STICs and another TP53 mutation shared between STIC and occult cancer.ConclusionThe sequence analysis for TP53 revealed 2 types of p53 signatures, one with a risk of progression to STIC and ovarian cancer with pathological variants in TP53 and the other with a low risk of progression without pathological variants in TP53 as seen in control.     

AU-1 from Agavaceae plants causes transient increase in p21/Cip1 expression in renal adenocarcinoma ACHN cells in an miR-34-dependent manner

Here, we show that AU-1, spirostanol saponin isolated from Agavaceae plants, causes a transient increase in cyclin-dependent kinase inhibitor (CDKI) p21/Cip1 through the upregulation of miRNAs, miR-34 and miR-21. AU-1 stimulated p21/Cip1 expression without exerting cytotoxicity against different types of carcinoma cell lines. In renal adenocarcinoma ACHN cells, AU-1 transiently elevated the expression level of p21/Cip1 protein without marked increases in p21/Cip1 mRNA levels. Rapid and transient increases in miR-34 and miR-21, both of which are known to upregulate p21/Cip1, were observed in AU-1-treated cells. Inhibitor for miR-34 and for miR-21 significantly blocked the AU-1-caused increase in p21/Cip1, indicating that elevation of p21/Cip1 protein by AU-1 is dependent on these microRNAs. We further clarified that NAD-dependent deacetylase SIRT1, a direct target of miR-34, is decreased by the treatment with AU-1. Furthermore, we found that SIRT1-knockdown increases p21/Cip1 protein levels in an miR-21-dependent manner. On the other hand, ectopic expression of p21/Cip1 resulted in the lowered expression of miR-34 and miR-21, suggesting that reciprocal regulation exists between p21/Cip1 and these miRNAs. We propose that the following feedback network composed of miR-34/SIRT1/miR-21/p21 is triggered by the treatment with AU-1: in cells treated with AU-1, transient elevation of miR-34 leads to the downregulation of SIRT1, thereby miR-21 is freed from SIRT1-dependent suppression. Then, elevated miR-21 upregulates p21/Cip1 protein, followed by the suppression of miR-34 expression.     

Lifestyle intervention might easily improve blood pressure in hypertensive men with the C genotype of angiotensin II type 2 receptor gene

BACKGROUND/OBJECTIVESRecent studies have reported an association of the angiotensin II type 2 receptor (AT2R) 3123Cytosine/Adenine (3123C/A) polymorphism with essential hypertension and cardiovascular diseases. The purpose of the study was to investigate whether the AT2R 3123C/A polymorphism affects blood pressure for free-living hypertensive men during a 5-month intervention period.SUBJECTS/METHODSThe subjects were free-living hypertensive Japanese men aged 40 to 75 years who agreed to intervention in the period from 2004 to 2011. Detection of the AT2R 3123C/A polymorphism was determined by polymerase chain reaction. The dietary intervention was designed to decrease salt level and to increase potassium level through cooking instructions and self-monitoring of the diet. The exercise session consisted of activities such as stretching, resistance training, and walking. Blood pressure, urinary sodium and potassium excretion, dietary and lifestyle data, and non-fasting venous blood sample were collected at baseline and after the intervention period.RESULTSThirty nine subjects were eligible for participation and the follow-up rate was 97.4%. The C allele proportion was 57.9%. AT2R 3123C/A polymorphism was X-chromosome-linked, therefore we analyzed the C and A genotypes. At baseline, no significant differences were observed between the genotype groups. After the intervention, there were no significant differences in lifestyle habit between the groups. Nevertheless, the estimated salt excretion (g/day) was significantly decreased only in the C genotype (13.0-10.3, P = 0.031). No significant change was observed in systolic blood pressure (SBP) (mmHg) in the A genotype, but a significant decrease was observed in the C genotype (150.0-141.5, P = 0.024).CONCLUSTIONSIn the C genotype, it might be easy to improve SBP through lifestyle intervention in free-living hypertensive Japanese men, however generalization could not be achieved by the small sample size.