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.     

Genomic and immune microenvironment profiling in a case of metastatic intrathyroid thymic carcinoma

Metastatic intrathyroid thymic carcinoma (ITTC) is a rare cancer with no effective drugs for controlling. This case report has shown genomic and immune microenvironment profiles in metastatic ITTC and emphasized an immunosuppression via a PD‐1/PD‐L1 pathway, possibly strengthening the rationale for immune checkpoint blockade as a novel treatment.     

An assessment of traditional and novel therapies for cellulite.

There are numerous treatments for cellulite including topical, surgical, laser and other therapies. Many of these treatments are expensive. Part of the difficulty in treating cellulite arises from our incomplete understanding of this phenomenon. As noted previously in this journal, there is no consensus as to the etiology of cellulite. This article will focus on both traditional and novel treatments for cellulite and assess their efficacy based on the scientific literature.     

Immediate enamel bond strength of universal adhesives to unground and ground surfaces in different etching modes

The purpose of this study was to determine the immediate bond effectiveness of universal adhesives to unground and ground enamel surfaces in different etching modes, through shear bond strength (SBS) tests and scanning electron microscopy observations. Three universal adhesives, a conventional two‐step self‐etch adhesive, and a conventional single‐step self‐etch adhesive were compared. Human enamel specimens from lower anterior teeth were divided into four groups and subjected to the following treatments: (i) unground enamel in self‐etch mode; (ii) ground enamel in self‐etch mode; (iii) unground enamel in etch‐&‐rinse mode; and (iv) ground enamel in etch‐&‐rinse mode. Bonded assemblies were subjected to SBS testing. All the adhesives showed significantly higher SBS values in etch‐&‐rinse mode than in self‐etch mode, regardless of whether enamel was unground or ground. The influence of the enamel surface condition on SBS was different in different etching modes. Without pre‐etching, all tested materials showed lower SBS values in unground enamel than in ground enamel. In etch‐&‐rinse mode, no significant differences in SBS values were observed between unground enamel and ground enamel for any of the adhesives tested. Phosphoric acid pre‐etching before application of self‐etch adhesives to an unground enamel surface is essential to enhance initial enamel bond effectiveness.     

A comparative study on the effectiveness of losartan/hydrochlorothiazide and telmisartan/hydrochlorothiazide in patients with hypertension

Purpose: Long-term effects of a low-dose hydrochlorothiazide (HCTZ) with losartan (LOS) on uric acid (UA) metabolism as well as glucose metabolism have been studied in hypertensive patients in comparison with those of a low-dose HCTZ with telmisartan (TEL).

Method: Fifty-nine hypertensive patients were allocated to a combination therapy with either losartan (50?mg/day)/HCTZ (12.5?mg/day) (LOS?+?HCTZ group: n?=?37) or telmisartan (40?mg/day)/HCTZ (12.5?mg/day) (TEL?+?HCTZ group: n?=?22), respectively. Before and 1 year after the treatment, blood pressure and biochemical parameters of blood and urine were evaluated.

Results: Both systolic and diastolic blood pressures significantly decreased in two groups, without any statistical differences among them. LOS?+?HCTZ caused no changes in the serum UA level or the ratio of UA clearance to creatinine clearance (CUA/Ccr), whereas TEL?+?HCTZ significantly increased the serum UA level and reduced CUA/Ccr. LOS?+?HCTZ did not influence CUA/Ccr in patients with their serum UA below 5.4?mg/dl, while LOS?+?HCTZ significantly increased CUA/Ccr in patients with their serum UA above 5.5?mg/dl. TEL?+?HCTZ significantly reduced CUA/Ccr in patients with their serum UA below and above 5.4?mg/dl to increase serum UA level significantly. Neither combination therapies caused any changes in fasting plasma glucose, HbA1c and HOMA-R. In patients with their serum UA level above 5.4?mg/dl, TEL?+?HCTZ increased HOMA-R, whereas LOS?+?HCTZ did not.

Conclusions: LOS?+?HCTZ did not influence UA metabolism as well as glucose metabolism, likely because of inhibitory action of losartan on URAT1, although TEL?+?HCTZ were accompanied with impairment of the UA metabolism and glucose metabolism.